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Discordance between the degree of osteopenia and the prevalence of spontaneous vertebral fractures in Crohn's disease
Abstract
A high prevalence of osteoporosis has been noted in Crohn's disease, but data about fractures are scarce.
The relationship between low bone mineral density and the prevalence of vertebral fractures was studied in 271 patients with ileo-caecal Crohn's disease in a large European/Israeli study. One hundred and eighty-one currently steroid-free patients with active Crohn's disease (98 completely steroid-naive) and 90 steroid-dependent patients with inactive or quiescent Crohn's disease were investigated by dual X-ray absorptiometry scan of the lumbar spine, a standardized posterior/anterior and lateral X-ray of the thoracic and lumbar spine, and an assessment of potential risk factors for osteoporosis.
Thirty-nine asymptomatic fractures were seen in 25 of 179 steroid-free patients (14.0%; 27 wedge, 12 concavity), and 17 fractures were seen in 13 of 89 steroid-dependent patients (14.6%; 14 wedge, three concavity). The prevalence of fractures in steroid-naive patients was 12.4%. The average bone mineral density, expressed as the T-score, of patients with fractures was not significantly different from that of those without fractures (-0.759 vs. -0.837; P=0.73); 55% of patients with fractures had a normal T-score. The bone mineral density was negatively correlated with lifetime steroids, but not with previous bowel resection or current disease activity. The fracture rate was not correlated with the bone mineral density (P=0.73) or lifetime steroid dose (P=0.83); in women, but not in men, the fracture rate was correlated with age (P=0.009).
The lack of correlation between the prevalence of fractures on the one hand and the bone mineral density and lifetime steroid dose on the other necessitates new hypotheses for the pathogenesis of the former.
... Therefore, it is important to address the mechanisms of osteoporosis in patients with CD to prevent and treat bone loss [2]. Osteoporotic fractures have a negative impact not only on disease may also be present without glucocorticoid treatment [1,[10][11][12]13,14]; therefore, the effect of the disease itself has to be taken into account. Cytokines produced by inflamed intestine in CD may affect bone and hence contribute to bone loss in patients with CD [15]. ...
... From 23 patients screened during two years only 7 fulfilled the stringent criteria (see below). In another study investigating steroid-free CD patients with active or symptomatic disease, the authors were able to include 99 patients from 34 centers, therefore only around 3 for each center, showing the difficulty of this inclusion criterion [11]. Hence glucocorticoids decisively influence bone metabolism and bone turnover returned to normal in patients not before 4 weeks after cessation of glucocorticoid therapy [22]. ...
... As shown also in our patients with different diseases the duration or the cumulative glucocorticoid dosage per se were not causal for decreased BMD [43]. BMD is only in part responsible for bone disease in GC therapy [11]. ...
Background
Crohn’s disease (CD) is associated with a higher prevalence of osteoporosis, a complication that is recognized as a significant cause of morbidity. Its pathogenesis is controversial, but the activity of CD is one contributing factor.
Methods
We stimulated SCP-1 cells (mesenchymal stem cell line) under osteogenic conditions with serum from adult patients with CD in the symptomatic phase (SP) and in remission (R) and with control sera. Concentrations of IL-6, IL-1 beta, and TNF alpha in the sera were measured. Patients were classified as normal or osteopenic/osteoporotic based on bone mineral density (BMD) T-score measurements. After 14 days in culture, protein expression and gene ontology (GO) annotation analysis was performed.
Results
Cytokine concentrations (IL-6, IL-1 beta, TNF alpha) varied within sera groups. None of the cytokines were significantly increased in the symptomatic phase compared to remission. Protein analysis revealed 17 proteins regulated by the SP versus R phase sera of disease. A linear relationship between CDAI (Crohn’s disease activity index) and normalized protein expression of APOA1 and 2, TTR, CDKAL1 and TUBB6 could be determined. Eleven proteins were found to be differentially regulated comparing osteoporosis-positive and osteoporosis-negative sera. Gene annotation and further analysis identified these genes as part of heme and erythrocyte metabolism, as well as involved in hypoxia and in endocytosis. A significant linear relationship between bone mineral density and normalized protein expression could be determined for proteins FABP3 and TTR.
Conclusion
Our explorative results confirm our hypothesis that factors in serum from patients with CD change the protein expression pattern of human immortalized osteoblast like cells. We suggest, that these short time changes indeed influence factors of bone metabolism.
... W części badań wartości BMD były jednakowe w obu tych lokalizacjach [5,26,43,50,51], w innych znacząco niższe w kręgach lędźwiowych [22,55] lub znacząco niższe w kości udowej [33]. Wartości BMD chorych na ChZJ mężczyzn i kobiet były takie same [22,26,33,43,50,55,68,74,75] lub znamiennie niższe u mężczyzn, niż u kobiet [1,5,97,90,103,107]. Część badaczy obserwowało obniżone wartości BMD u pacjentów z niskim wskaźnikiem BMI [5,22,33,55,68,90,107]. ...
... Spośród danych klinicznych o przebiegu ChZJ z występowaniem obniżonych wartości BMD wiązał się czas trwania choroby [5,51,50,55,101,103]. Tylko w pojedynczych badaniach obserwowano związek z wiekiem zachorowania [103,22], nasileniem objawów klinicznych [74], lokalizacją i zakresem zmian zapalnych w przewodzie pokarmowym [74,33], przebytą resekcją odcinkową przewodu pokarmowego [22,55,101,107]. Negatywny wpływ terapii glikokortykosteroidami na BMD wykazano w części prac [1,5,22,90,97,107]. W analizie ok. ...
... Pozostałe badania opisywały liczące 150-300 serie pacjentów z ChLC, bez grup kontrolnych. Jedno z nich było wieloośrodkowe [97], pozostałe jednoośrodkowe. Podawana w nich częstość występowania złamań kręgów to 14-26%. ...
Malabsorption, nutritional deficits, systemic influence of proinflammatory cytokines
and glucocorticoid treatment are well known risk factors for osteoporosis in
general population. All of these factors can exist simultaneously in patients with
inflammatory bowel diseases (IBD). Prevalence of osteoporosis and other manifestations
of metabolic bone diseases (MBD) in this group of patients has not been
unequivocally established. In the scientific literature only limited data exist on
polish patients with IBD. The widespread vitamin D deficiency in Poland could
make IBD patients more prone to MBD.
MBD can manifest clinically as low-energy fractures that are often associated
with poor quality of life, disability and increased mortality. The fracture risk of
in IBD patients is unknown. In the general population the risk can be reliably
estimated using the FRAX algorithm, however only few studies in IBD patients
utilized this algorithm.
In the current study a cross-sectional analysis of 60 IBD patients from a university
medical centre has been performed. Main inclusion criteria were clinical,
endoscopic and histopathological evidence of IBD and at least 5-year history were
enrolled. During the study detailed clinical data, bone densitometry, laboratory
studies were obtained and the 10-year risk of major osteoporotic fracture was
calculated. The results were compared with the results observed in an age- and
sex-matched control group that consisted of 28 healthy individuals.
In the IBD group osteoporosis was diagnosed in 31%, vitamin D deficiency
in 83%, secondary hyperparathyroidism in 27%, 45% had abnormal biochemical
bone turnover markers. Based on FRAX results nearly half of the patients (47%)
were classified as moderate to high risk of fractures. In the control group 54%
had vitamin D deficiency, 18% had secondary hyperparathyroidism and 39% had
abnormal biochemical bone turnover markers.
The results of the study showed an increased risk of osteoporosis in IBD patients
(OR=4,9) and increased risk of vitamin D deficiency (OR=4,3) compared
to the controls. The FRAX-derived 10-year absolute fracture risk was more than
2-times higher in IBD patients compared to the controls. The results also suggested
that development of MBD in IBD patients is predominantly due to vitamin D deficiency.
MBD is thus an important clinical problem affecting IBD patients. Further
studies on the topic are warranted and preventive and therapeutic measures should
be undertaken by the treating physicians.
... Studies assessing the risk of fracture in IBD are scarce and controversial and use different methodologies [8][9][10][11][12], and those analyzing possible risk factors associated with the appearance of these fractures are much more limited. Most are focused on patients with Crohn's disease (CD) [8][9][10][11] and evaluate the prevalence of fractures in patients with low bone mass, which introduces an important bias [8]. ...
... Studies assessing the risk of fracture in IBD are scarce and controversial and use different methodologies [8][9][10][11][12], and those analyzing possible risk factors associated with the appearance of these fractures are much more limited. Most are focused on patients with Crohn's disease (CD) [8][9][10][11] and evaluate the prevalence of fractures in patients with low bone mass, which introduces an important bias [8]. Other studies evaluate the prevalence of vertebral crush fractures only in the IBD group without quantifying these fractures in a control group with similar characteristics [8][9][10][11][12]. ...
... Most are focused on patients with Crohn's disease (CD) [8][9][10][11] and evaluate the prevalence of fractures in patients with low bone mass, which introduces an important bias [8]. Other studies evaluate the prevalence of vertebral crush fractures only in the IBD group without quantifying these fractures in a control group with similar characteristics [8][9][10][11][12]. ...
A prospective study was performed to compare the prevalence of morphometric vertebral fractures (MVF) between patients with inflammatory bowel disease (IBD) and healthy subjects and to identify predictive factors of fracture.
A total of 107 patients with IBD (53 with Crohn's disease and 54 with ulcerative colitis) and 51 healthy subjects participated in the study. Information about anthropometric parameters, toxins, previous fractures, and parameters related to this disease were evaluated. The index of vertebral deformity, bone mass density (BMD), and biochemical parameters were calculated.
A total of 72 fractures were detected in 38.32% of patients with IBD, and 10 fractures were detected in 13.73% of healthy subjects; the risk of fracture in patients with IBD was higher than that in control subjects (OR, 4.03; 95% CI, 1.652-9.847; p < 0.002). We found no correlation between fracture and BMD in patients with IBD (lumbar spine, r = -0.103, p = 0.17 and femoral neck, r = -0.138, p = 0.07). Corticosteroid treatment was not associated with prevalent vertebral fractures nor with taking corticosteroids (r = 0.135, p = 0.14) or the duration for which they were taken (r = 0.08, p = 0.38), whereas this relationship was present in the controls (r = -0.365, p = 0.01). In the multivariate analysis, none of the measured parameters were significantly predictive of fracture, only to manifested IBD. Hypovitaminosis D was observed in 55.14% of patients with IBD.
The prevalence of morphometric vertebral fractures is higher in patients with IBD than in the healthy population, without association with BMD or corticoid treatment. Simply having IBD was proven to be a predictive factor of fracture. We observed a high incidence of hypovitaminosis D in patients with IBD.
... It is well established that inflammatory diseases, including CD, can induce alterations in BMD, resulting in either osteopaenia or osteoporosis [26]. Stockbrugger et al. demonstrated the discordance between the low BMD and high frequency of vertebral fractures in a cohort of CD patients [27]. The TBS, being evaluated directly from DXA scans, has the potential to complement BMD in the detection of bone texture changes and, therefore, the prediction of bone microarchitectural deterioration. ...
... Bernstein and colleagues demonstrated that subjects with IBD were at a 40% increased risk of fracture and had an overall increased prevalence of osteoporosis compared with age-matched, sex-matched and geographically matched controls [10]. Furthermore, a significant number of fractures in IBD patients are asymptomatic and many fractures are underreported [27]. ...
Objectives:
Osteoporosis and osteopaenia are known chronic complications of inflammatory bowel diseases. The trabecular bone score (TBS) provides an indirect measurement of bone microarchitecture, independent of bone mineral density (BMD).
Patients and methods:
The study was designed as a case-control study with the aim to assess and compare bone quantity and quality in patients with Crohn's disease (CD). We purposefully excluded postmenopausal women and patients on long-term corticosteroid therapy.
Results:
The cohort consisted of 50 CD patients and 25 healthy controls who matched in age, sex, weight, or vitamin D status. There was no significant difference between CD patients versus controls in the mean lumbar BMD of 0.982±0.119 versus 0.989±0.12 g/cm and the mean TBS score of 1.37±0.12 versus 1.38±0.12. We observed significantly lower TBS, but not lumbar BMD, in CD patients with stricturing (B2, 1.36±0.08) or penetrating (B3, 1.32±0.11) disease compared with those with luminal disease (B1, 1.42±0.11; P=0.003 and <0.0001, respectively). We also observed lower mean±SD TBS in patients on versus not on anti-tumour necrosis factor-α therapy: 1.341±0.138 versus 1.396±0.099, respectively. However, the difference between these groups failed to reach statistical significance (P=0.11). No similar finding was seen comparing lumbar BMD in these groups.
Conclusion:
For the first time, it was observed that TBS, but not BMD, correlates with the severity of CD. Our results therefore suggest that TBS can potentially help to identify high fracture risk CD patients better than BMD alone.
... Researchers from the Netherlands studied spontaneous vertebral fractures in (a) steroid-free patients with active Crohn's disease and (b) steroid-dependent patients with inactive or quiescent Crohn's disease [30]. ...
Atraumatic fractures (ATFs) are a fragility fracture subtype with occasional medicolegal issues. ATFs are defined as fractures because of a “low-energy mechanism that is usually considered incapable of producing a fracture.” They are an underreported disorder, with epidemiological variations. ATF phenomena were previously reported not only in older adults, but also in children, young adults, older adults, and animals.
This study is a short retrospective case series exploring atraumatic fractures in a tertiary care university hospital. Over a period of two years, a total of seven ATF cases were identified. However, only five fulfilled the inclusion criteria. Local causes of pathologic fractures (e.g., metastasis) and elder abuse or neglect were excluded. Comparison of the cases’ clinical profile, fracture profile, and management was done.
All five cases were frail females with significant osteotoxic burdens from medications and multi-morbidities. ATF presentations included typical (as pain) and atypical (as painless, loud crack, and sudden giveaway) symptomatology. One ATF had a coincident unexplained aseptic fever. Three cases had more than one fracture (fracture cascade), confirmed and followed up by x-rays. All the cases were managed conservatively except for one case that underwent hip hemiarthroplasty. Plans of care included managing the osteotoxic multi-morbidities burden, focusing on the whole body, not only on the fracture or bone. The study provided insights about challenges in presentations of ATF (as the bone fracture acute phase reaction: osteogenic aseptic fever). Risk factors are classically assumed to be osteoporosis, but it is usually systemic and multifactorial. A high risk of fracture warning sign could help decrease ATF occurrence or fracture cascades. Four ATF categories were detected to help healthcare systems identify high-risk patients and raise awareness among medical staff, families, and caregivers. Future studies of the at-risk groups are needed to understand ATF knowledge gaps, challenges, and the best treatments.
... A prospective study across multiple countries suggested that about 12%-22% of IBD patients had asymptomatic vertebral fractures, including 19.6% (44/224) in Canada, 21.8% (34/156) in Germany, and 12.2% (22/179) in Israel (60)(61)(62). It remains unclear whether the reduction in BMD among CD patients is correlated with the occurrence of fractures or osteoporosis. ...
Introduction
Over the past few years, multiple observational studies have speculated a potential association between inflammatory bowel disease (IBD), which includes ulcerative colitis (UC) and Crohn’s disease (CD), and osteoporosis. However, no consensus has been reached regarding their interdependence and pathogenesis. Herein, we sought to further explore the causal associations between them.
Methods
We validated the association between IBD and reduced bone mineral density in humans based on genome-wide association studies (GWAS) data. To investigate the causal relationship between IBD and osteoporosis, we performed a two-sample Mendelian randomization study using training and validation sets. Genetic variation data for IBD, CD, UC, and osteoporosis were derived from published genome-wide association studies in individuals of European ancestry. After a series of robust quality control steps, we included eligible instrumental variables (SNPs) significantly associated with exposure (IBD/CD/UC). We adopted five algorithms, including MR Egger, Weighted median, Inverse variance weighted, Simple mode, and Weighted mode, to infer the causal association between IBD and osteoporosis. In addition, we evaluated the robustness of Mendelian randomization analysis by heterogeneity test, pleiotropy test, leave-one-out sensitivity test, and multivariate Mendelian randomization.
Results
Genetically predicted CD was positively associated with osteoporosis risk, with ORs of 1.060 (95% CIs 1.016, 1.106; p = 0.007) and 1.044 (95% CIs 1.002, 1.088; p = 0.039) for CD in the training and validation sets, respectively. However, Mendelian randomization analysis did not reveal a significant causal relationship between UC and osteoporosis (p > 0.05). Furthermore, we found that overall IBD was associated with osteoporosis prediction, with ORs of 1.050 (95% CIs 0.999, 1.103; p = 0.055) and 1.063 (95% CIs 1.019, 1.109; p = 0.005) in the training and validation sets, respectively.
Conclusion
We demonstrated the causal association between CD and osteoporosis, complementing the framework for genetic variants that predispose to autoimmune disease.
... We found moderately statistically significant correlations between TBS and LS BMD as well as between TBS and hip BMD, indicating that the TBS could provide complementary information for the detection of bone damage in patients. Stockbrugger et al. 19 showed discordance between decreased BMD and the prevalence of vertebral fractures, raising the need for an additional parameter. The TBS could improve the identification of risk fracture. ...
Inflammatory bowel disease (IBD) patients have a significant risk of developing bone loss. The trabecular bone score (TBS) is a relatively new parameter used to provide information on bone quality. The study cohort included 81 patients with IBD and 81 healthy controls. Blood tests, dual-energy x-ray absorptiometry (DXA), including TBS, were assessed. Harvey–Bradshaw Index (HBI) for Crohn's disease (CD) and the Partial Mayo Score for ulcerative colitis (UC) were used for evaluation of clinical disease activity. Compared with the healthy controls, the IBD patients had lower lumbar spine (LS) bone mineral density (BMD) (1.06 ± 0.18 vs. 1.16 ± 0.15 g/cm2, p < 0.005), hip BMD (0.88 ± 0.13 vs. 0.97 ± 0.13 g/cm2, p < 0.005) and TBS (1.38 ± 0.1 vs. 1.43 ± 0.1, p < 0.005) values. The patients with stricturing CD had lower TBS (1.32 ± 0.13 vs. 1.40 ± 0.9, p = 0.03) and LS BMD (0.92 ± 0.19 vs. 1.07 ± 0.1, p = 0.01) values compared with those with non-stricturing CD. Multivariate regression model analysis identified HBI as independent factor associated with TBS. Our results support that all DXA parameters are lower in patients with IBD than in healthy patients. Moreover, TBS is a valuable tool for assessment of bone impairment in active CD.
... Among IBD patients, a prevalence of osteopenia ranging from 32 to 50% and of osteoporosis from 5 to 37% have been reported in several studies [8,[51][52][53][54]. Interestingly, Reffitt et al. [55] have observed that bone mineral density improves with long-lasting stable remission; IBDs, however, appear to be associated with vertebral fractures independently of DEXA values [56]. In particular, IBD patients have a significantly higher risk of vertebral fractures, but not that of other sites, when compared to healthy controls (OR = 2.26, 95% CI 1.04-4.09) ...
Extraintestinal manifestations are the cause of morbidity and affect the quality of life of patients with inflammatory bowel diseases (IBDs). Musculoskeletal manifestations, in particular, spondyloarthritis and osteoporosis, are the most frequent extraintestinal manifestation of IBDs. The diagnosis and management of the musculoskeletal manifestation of IBDs relies on imaging. Conventional radiography, magnetic resonance imaging, computed tomography, and ultrasound can help to detect pathological signs of spondyloarthritis, both peripheral and with axial involvement. Dual-energy X-ray absorptiometry is the gold standard for identifying the presence of osteoporosis, whereas conventional radiology and computed tomography can reveal occult vertebral fractures. The aim of this narrative review is to describe the imaging of musculoskeletal manifestations of IBDs.
... In the majority of IBD patients, who are primarily young adults aged 20-40 years, the lumbar spine BMD has been found to be significantly reduced. [9,[29][30][31] Studies have demonstrated that being in a state of stable remission for 3 years helps to normalize the bone density of IBD patients. [32] Treatment with anti-TNF agents may improve bone density due to the reduction of chronic inflammation. ...
Extraintestinal manifestations (EIMs) are common in inflammatory bowel disease (IBD), in both Crohn's disease and ulcerative colitis. Almost any organ system can be affected, including the musculoskeletal, dermatologic, renal, hepatopancreatobiliary, pulmonary and ocular systems. However, the musculoskeletal and dermatologic systems are the most commonly involved sites of manifestations. While some manifestations such as peripheral arthritis and erythema nodosum have an association with IBD activity, others such as axial arthropathy, pyoderma gangrenosum and primary sclerosing cholangitis have an independent disease course. This review provides a summary of the most common EIMs in IBD and their prevalence and management.
... The presence of osteoporosis is one (but not the only) risk factor for fractures of the spine and peripheral long bones. In recent studies, vertebral fractures have been documented in patients with reduced and normal bone density, challenging the concept that osteoporosis is the main risk factor for vertebral fractures in young patients with IBD (298)(299)(300). The strongest predictor of future fracture is a prior vertebral fracture. ...
This paper is the second in a series of two publications relating to the European Crohn’s and Colitis Organisation (ECCO) evidence based consensus on the diagnosis and management of Crohn’s disease and concerns the surgical management of Crohn’s disease as well as special situations including management of perianal Crohn’s disease and extraintestinal manifestations. Diagnostic approaches and medical management of Crohn’s disease of this ECCO Consensus are covered in the first paper
... risk of fragility fractures in the absence low BMD for reasons that are not completely understood [37] . The etiology of osteoporosis and osteopenia in IBD is multifactorial; risk factors include; corticosteroid use, age, malnutrition, vitamin D deficiency, calcium malabsorption, immobilization, degree of underlying GI inflammation and lower levels of sex hormones [38] . ...
We aim to review the literature and provide guidance on preventive health measures in inflammatory bowel
disease (IBD). Structured searches were performed in PubMed, MEDLINE, EMBASE, Web of Science and
Cochrane Library from January 1976 to June 2016 using the following keywords: (inflammatory bowel
disease OR Crohn’s disease OR ulcerative colitis) AND(health maintenance OR preventive health OR health
promotion). Abstracts of the articles selected from each of these multiple searches were reviewed, and those
meeting the inclusion criteria (that is, providing data regarding preventive health or health maintenance in
IBD patients) were recorded. Reference lists from the selected articles were manually reviewed to identify
further relevant studies. Patients with IBD are at increased risk of developing adverse events related
to the disease course, therapeutic interventions, or non-adherence to medication. Recent studies have
suggested that IBD patients do not receive preventive services with the same thoroughness as patients with
other chronic diseases. Preventive health measures can avert morbidity and improve the quality of life of
patients with IBD. Gastroenterologists and primary care physicians (PCPs) should have an up to date working
knowledge of preventive health measures for IBD patients. A holistic approach and better communication
between gastroenterologists and PCPs with explicit clarification of roles will prevent duplication of services
and streamline care.
... 15 A retrospective study of a Caucasian population showed a 40% increase in the risk of fracture compared to healthy controls. 16 CD seems to be associated with a slightly higher risk than UC does for osteoporosis and subsequent fractures, although this has been disputed in some studies. 17 With the advent of dual-energy X-ray absorptiometry (DXA), it is easy to measure bone mineral density (BMD) non-invasively. ...
Patients with inflammatory bowel disease are at increased risk of developing disorder in bone and mineral metabolism The study was aimed to determine if inflammatory bowel disease (IBD) is a risk factor for osteoporosis in 103 adult patients. We included 103 IBD patients, 67 patients with Crohn’s disease (CD) and 36 with ulcerative colitis (UC). Bone mineral density was measured by dual-energy X-ray absorptiometry. We used T score to express bone loss (osteopenia: -2.5 SD <-1 SD, osteoporosis: T <-2.5 SD). Plain x-rays were examined to search for vertebral compression or spontaneous fractures before DEXA. Among the 103 patients, 47.7% exhibited osteopenia of the femoral neck and 62.3% of the lumbar spine, with no significant difference between CD and UC. The prevalence of osteoporosis of the lumbar spine was significantly higher in CD patients (41.2% versus 8.7%). Osteoporosis is frequent in IBD patients, especially in CD patients. Female gender, malnutrition (body mass index <20 kg/m2), disease course (>2 years) and active disease would be risk factors of bone mineral loss in IBD.
... Osteoporosis identifies patients at above average risk for fractures of the spine and peripheral long bones; they should receive treatment since the fracture risk increases about twofold for each standard deviation decline in BMD below the population mean 66,67 . Vertebral fractures have been documented in patients with both reduced and normal bone density, challenging the concept that osteoporosis is the main risk factor for vertebral fractures in young patients with IBD [68][69][70] . No linear association between lumbar bone density and spontaneous fracture risk exists. ...
This is the first European Crohn’s and Colitis Organisation [ECCO] consensus guideline that addresses extra-intestinal manifestations [EIMs] in inflammatory bowel disease [IBD]. It has been drafted by 21 ECCO members from 13 European countries. Although this is the first ECCO consensus guideline that primarily addresses EIMs, it is partly derived from, updates, and replaces previous ECCO consensus advice on EIMs, contained within the consensus guidelines for Crohn’s disease1 [CD] and ulcerative colitis2 [UC]. The strategy to define consensus was similar to that previously described in other ECCO consensus guidelines [available at www.ecco-ibd.eu]. Briefly, topics were selected by the ECCO guidelines committee [GuiCom]. ECCO members were selected to form working groups. Provisional ECCO Statements and supporting text were written following a comprehensive literature review, then refined following two voting rounds which included national representative participation by ECCO’s 35 member countries. The level of evidence was graded according to the Oxford Centre for Evidence-based Medicine [www.cebm.net]. The ECCO Statements were finalised by the authors at a meeting in Vienna in October 2014 and represent consensus with agreement of at least 80% of participants. Complete consensus [100% agreement] was reached for most statements. The supporting text was then finalised under the direction of each working group leader [VA, SV, FC, MH] before being integrated by the two consensus leaders [MH, FC]. This consensus guideline is pictorially represented within the freely available ECCO e-Guide [http://www.e-guide.ecco-ibd.eu/].
Up to 50% of patients with inflammatory bowel disease [IBD] experience at least one extra-intestinal manifestation [EIM], which can present before IBD is diagnosed.34,5,6 EIMs adversely impact upon patients’ quality of life and some, such as primary sclerosing cholangitis [PSC] or venous thromboembolism [VTE], can be life-threatening. The probability of developing EIMs increases with disease duration and in patients who already have one EIM.7 …
... In the general population it is estimated that only one-third of spine fractures are diagnosed. Similarly, approximately 14% of all spine fractures in CD patients were asymptomatic in a European/Israeli study [21] . The fracture rate was very similar in patients with low bone mass compared to patients with normal BMD. ...
Low bone mineral density is an established, frequent, but often neglected complication in patients with inflammatory bowel disease (IBD). Data regarding the diagnosis, therapy and follow-up of low bone mass in IBD has been partially extrapolated from postmenopausal osteoporosis; however, the pathophysiology of bone loss is altered in young patients with IBD. Fracture, a disabling complication, is the most important clinical outcome of low bone mass. Estimation of fracture risk in IBD is difficult. Numerous risk factors have to be considered, and these factors should be weighed properly to help in the identification of the appropriate patients for screening. In this editorial, the authors aim to highlight the most important clinical aspects of the epidemiology, prevention, diagnosis and treatment of IBD-related bone loss.
... La presencia de osteoporosis es un ----aunque no el único----factor de riesgo de fracturas de columna vertebral y de huesos largos periféricos. En estudios recientes, las fracturas vertebrales se han documentado en pacientes con densidad ósea normal y reducida, desafiando el concepto de que la osteoporosis es el principal factor de riesgo para fracturas vertebrales en pacientes jóvenes con EII [254][255][256] . El predictor más fuerte de futuras fracturas es una fractura vertebral previa. ...
... Interestingly, the increased fracture risk associated with GC therapy (compared to osteoporosis in general) can only be partially explained by the decline in bone mineral density (BMD). Thus, despite similar BMD levels, patients receiving GCs have a greater fracture risk than patients suffering from other forms of osteoporosis [3,27,28]. The daily GC dose is a better predictor of fracture risk than the cumulative dose [28,29]. ...
Glucocorticoids (GCs) are highly effective in the treatment of inflammatory and autoimmune conditions but their therapeutic use is limited by numerous adverse effects. Recent insights into the mechanisms of action of both endogenous and exogenous GCs on bone cells have unlocked new approaches to the development of effective strategies for the prevention and treatment of GC-induced osteoporosis. Furthermore, topical studies in rodents indicate that the osteoblast-derived peptide, osteocalcin, plays a central role in the pathogenesis of GC-induced diabetes and obesity. These exciting findings mechanistically link the detrimental effects of GCs on bone and energy metabolism. In this article we review the physiology and pathophysiology of GC action on bone cells, and discuss current and emerging concepts regarding the molecular mechanisms underlying adverse effects of GCs such as osteoporosis and diabetes.
... [28][29][30] Few data are available on the prevalence of asymptomatic fractures in patients with osteopenia or osteoporosis; however it might be assumed, that low trauma fractures occur in 14-22% of patients with IBD. 11,31 As our study did not comprise a screening for asymptomatic fractures, our results most likely underestimate the actual risk of (asymptomatic) pathologic fractures in patients with IBD. ...
Background and aims: Osteoporosis is a frequent complication of inflammatory bowel disease (IBD). It may be related to IBD itself or to its therapy. In this study, the quality of care regarding diagnosis and treatment of osteoporosis was examined.
Methods: In this retrospective, monocentric study 293 consecutive patients with IBD (98 ulcerative colitis, 195 Crohn's disease) were included. Information on age, gender, weight, nicotine abuse, course, disease pattern and medication was assessed, results of dual X-ray absorptiometry (DEXA-scan) were evaluated.
Results: DEXA-scan was performed in 174 patients (59 male, 115 female). Bone mineral density (BMD) was impaired in 38.5% of these patients. Male patients were diagnosed more often with osteopenia or osteoporosis than females (55.9% vs. 29.6%, p = 0.03) and had a risk of bone disease comparable to postmenopausal women. Additionally, duration of corticosteroid treatment and IBD were identified as risk factors for osteoporosis. Follow up DEXA-scan demonstrated an overall deterioration of BMD in patients with normal baseline results.
Conclusions: While in general, women are considered at higher risk for osteoporosis, male patients had a higher risk of impaired BMD, especially when under treatment with corticosteroids. The high incidence of reduced BMD supports the recommendation to screen patients with IBD at an early stage of disease, although a possible bias has to be considered for patients at a tertial referral centre for IBD. Patients with normal baseline DEXA-scan were still at risk to develop bone disease and it seems advisable to monitor patients with IBD for reduced BMD continually.
... In recent studies, vertebral fractures have been documented in patients with both reduced and normal bone density; challenging the concept that osteoporosis is the main risk factor for vertebral fractures in young patients with IBD. [254][255][256] The strongest predictor of future fracture is a prior vertebral fracture. There is, therefore, a need for prospective studies in young and premenopausal IBD patients to establish a valid assessment tool like the FRAX index used for postmenopausal women. ...
### 8.1 General
Proctocolectomy with ileal pouch-anal anastomosis (IPAA) is the procedure of choice for most patients with ulcerative colitis (UC) requiring colectomy.1 Pouchitis is a non-specific inflammation of the ileal reservoir and the most common complication of IPAA in patients with UC.2–7 Its frequency is related to the duration of follow up, occurring in up to 50% of patients 10 years after IPAA in large series from major referral centres.1–9 The cumulative incidence of pouchitis in patients with an IPAA for familial adenomatous polyposis is much lower, ranging from 0 to 10%.10–12 Reasons for the higher frequency of pouchitis in UC remain unknown. Whether pouchitis more commonly develops within the first years after IPAA or whether the risk continues to increase with longer follow up remains undefined.
### Statement 8A
The diagnosis of pouchitis requires the presence of symptoms, together with characteristic endoscopic and histological abnormalities [EL3a, RG B]. Extensive UC, extraintestinal manifestations (i.e. PSC), being a non-smoker, p-ANCA positive serology and NSAID use are possible risk factors for pouchitis [EL3b, RG D]
#### 8.1.1 Symptoms
After proctocolectomy with IPAA, median stool frequency is 4 to 8 bowel movements,1–4,13,14 with about 700 mL of semiformed/liquid stool per day,2,13,14 compared to a volume of 200 mL/day in healthy people. Symptoms related to pouchitis include increased stool frequency and liquidity, abdominal cramping, urgency, tenesmus and pelvic discomfort.2,15 Rectal bleeding, fever, or extraintestinal manifestations may occur. Rectal bleeding is more often related to inflammation of the rectal cuff (“cuffitis,” Section 1.4),16 than to pouchitis. Faecal incontinence may occur in the absence of pouchitis after IPAA, but is more common in patients with pouchitis. Symptoms of pouch dysfunction in patients with IPAA may be caused by conditions other than pouchitis, including Crohn's disease of the pouch,17–19 cuffitis16 and an irritable pouch …
... before menopause). Moreover, it is also possible that vertebral fractures occur in IBD children but these may be asymptomatic and hence are undiagnosed (Stockbrugger et al., 2002). ...
Disease-associated undernutrition of all types is very common in paediatric inflammatory bowel disease (IBD). Recent weight loss remains one of the triad of clinical manifestations and a cornerstone for the diagnosis of Crohn's disease (CD), although significantly fewer patients now present as being underweight. Recent evidence suggests that the introduction of medical treatment will quickly restore body weight, although this does not reflect concomitant changes in body composition. CD children present with features of nutritional cachexia with normal fat stores but depleted lean mass. Poor bone health, delayed puberty and growth failure are additional features that further complicate clinical management. Suboptimal nutritional intake is a main determinant of undernutrition, although activation of the immune system and secretion of pro-inflammatory cytokines exert additional independent effects. Biochemically low concentrations of plasma micronutrients are commonly reported in IBD patients, although their interpretation is difficult in the presence of an acute phase response and other indices of body stores adequacy are needed. Anaemia is a common extraintestinal manifestation of the IBD child. Iron-deficient anaemia is the predominant type, with anaemia of chronic disease second. Decreased dietary intake, as a result of decreased appetite and food aversion, is the major cause of undernutrition in paediatric IBD. Altered energy and nutrient requirements, malabsorption and increased gastrointestinal losses are additional factors, although their contribution to undernutrition in paediatric CD needs to be studied further.
... These studies have been performed in IBD-centers in Canada (44/224 patients 20%), 12 Germany (34/156 patients 22%) 13 and Europe and Israel (25/179 patients 14%). 14 Surprisingly the incidence of vertebral fractures in these patients does not correlate with the degree of bone loss. Two of these 3 studies demonstrated a clear discordance between the degree of bone loss and the prevalence of vertebral fractures in patients with Crohn's disease. ...
Half of all patients with inflammatory bowel disease show a significant reduction of their bone mass during the course of their chronic inflammatory disease. In contrast to women with postmenopausal osteoporosis these patients are much younger and a significant subgroup develops vertebral fractures which are mostly asymptomatic.
The activity of the chronic inflammatory disease and the steroid treatment leads to bone loss predominantly through the TNFα-driven osteoprotegerin system. Clinical useful genetic markers to identify patients at risk for fractures have not been developed so far. Long-term clinical remission leads in most patients to normalisation of the bone density. Patients with reduced bone density should be substituted with calcium and vitamin D. Patients with vertebral fractures should receive bisphosphonates.
Background
Joint involvement is a common extraintestinal manifestation of Crohn’s Disease (CD) that may require total knee arthroplasty (TKA). There is a paucity of evidence regarding the relationship between CD and postoperative outcomes after TKA surgery. This study seeks to evaluate the impact of CD on 90-day and ≥2-year follow-up postoperative outcomes of TKA patients.
Methods
We retrospectively analyzed the Statewide Planning and Research Cooperative System database (2009–2013) and isolated ICD-9 codes for TKA patients (8154), while excluding those with any revision of knee replacements (0080–0084) and split into 2 groups with or without CD (5550–5559). Patient demographics and postoperative outcomes were compared. Logistic regression analyses with covariates (sex, race, Deyo score, age, and insurance) were utilized to evaluate the association of CD with 90-day and overall postoperative outcomes.
Results
A total of 89,134 TKA patients were identified, 244 of whom had CD. Significant differences in age, race distribution, insurance, and Deyo score (all, p < 0.05) were found. Multivariable analysis demonstrated CD was an independent risk factor for 90-day and overall medical complications, surgical complications, and readmission. Univariate and multivariable analyses report CD had significant increased rates and was a predictor, respectively, of overall blood transfusions (OR 1.5 [95% CI 1.1–2.0] p < 0.01), acute renal failure (OR 1.7 [95% CI 1.1–2.6] p = 0.03), and pulmonary embolism (OR 2.5 [95% CI 1.3–4.6] p = 0.01).
Conclusion
Patients with CD undergoing TKA have increased risk both 90-day and overall surgical and medication complications, as well as readmissions compared to patients without CD.
Osteoporosis is described as secondary when low bone mineral density or an increased risk of fragility fracture is caused by factors other than aging or postmenopausal status. A large number of factors cause secondary osteoporosis, including adverse effects of drug therapy, endocrine disorders, immobilization, rheumatological conditions, disorders of the gastrointestinal or biliary tract, haematological conditions and renal disease. The prevalence of secondary causes of osteoporosis varies according to the population studied, as many as 50–55% of men and 40–50% of premenopausal women presenting with established osteoporosis have been found to have other conditions that may have contributed to their bone loss. This chapter emphasizes the importance of identification and treatment of secondary osteoporosis and discusses familiar and less well-known causes.
Objective:
The aim of our study was to examine longitudinal changes in bone mineral density (BMD) of children and adolescents with Crohn's disease, and risk factors related to low BMD.
Patients and methods:
All patients aged from 2 to 18 years with CD who underwent dual-energy X-ray absorptiometry (DXA) at diagnosis and at the end of follow-up between 1999 and 2018 were considered for inclusion in this retrospective study. Factors related to changes in BMD at diagnosis and during follow-up were investigated.
Results:
193 patients had the 2 DXA required.At diagnosis 36 patients (18.7%) had a low BMD.At the end of follow-up, 31 patients (16%).164 patients did not have the 2 DXA required.In included CD, BMD values were lower in lumbar spine (LS) than in total body less head (TBLH), as well at diagnosis (p < 0.0001) or at the end of follow-up (p = 0.001).At diagnosis, only growth impairment or low BMI was associated with low BMD (p < 0.0001), only cumulative dose of corticosteroid at the end of follow-up (p = 0.01).
Conclusion:
The high prevalence of low BMD in children and adolescents with IBD highlights the importance of evaluating BMD in these patients at the time of diagnosis and throughout the course of their treatment. Special attention must be given to patients with height delay or low BMI at diagnosis. Long-term glucocorticoid therapy is the main clinical risk factor associated with low BMD at the end of follow-up.
Background
A high prevalence of osteopenia and osteoporosis is observed in patients with Inflammatory Bowel Disease (IBD).
Objective
The aim of our study was to investigate the prevalence of bone loss, bone remodeling and risk factors in Tunisian patient with IBD.
Patients and Methods
The study included 40 patients with IBD and 32 age- and sex-matched healthy controls subjects. All participants underwent bone densitometry by dual energy X-ray absorptiometry at the femoral neck and lumbar spine. Serum levels of 25-hydroxy vitamin D (25(OH)D), parathyroid hormone (PTH), osteocalcin(OC), and urinary degradation products of C-terminal telopeptide of type I collagen (CTXI) were measured in all participants to assess the bone metabolism status.
Results
Twelve (30%) patients were normal, 32.5% were osteopenic and 37.5% were osteoporotic. Osteoporosis was more frequent in IBD patients than controls (p=0.0001). Age and inflammation were associated with low bone mineral density (BMD). Mean calcium, phosphorus and alkaline phosphatase levels were similar in both groups. Median 25(OH) D levels were significantly lower in IBD patients compared with controls (p=0.0001). Median urinary CTXI levels were significantly higher in IBD patients compared with healthy controls (p=0.007). No significant differences between IBD patients and controls concerning the median serum OC and PTH levels were found.
Conclusion
In our study, there is a high prevalence of low BMD in IBD patients and an increase in bone resorption without a change of bone formation. Low BMI and hypovitaminoses D were identified as risk factors for low BMD.
Background:
Studies assessing the risk of fractures in inflammatory bowel diseases (IBD) have shown controversial results.
Goals:
We performed a systematic review and meta-analysis to assess the risk of fractures in IBD.
Study:
Electronic databases were searched for cohort studies assessing the risk of fractures in IBD. The outcomes were the risk of overall fractures and at specific sites, and the association between the risk of fractures and the proportion of patients with corticosteroid use or osteoporosis.
Results:
Ten studies including 470,541 patients were identified. The risk of overall fractures in IBD patients was similar to controls [odds ratio (OR), 1.08; P=0.70; 95% confidence interval (CI), 0.72-1.62) with moderate heterogeneity (I=74.4%) which appeared to be due to the variable power and outcomes among the studies. The OR of fractures at the spine was significantly elevated at 2.21 (P<0.0001; 95% CI, 1.39-3.50) with low heterogeneity (I=26.1%). Meta-regression showed a correlation with the proportion of patients with steroid use. Risks of fractures at other sites (hip, rib, and wrist) were not elevated. Patients with fractures were more commonly on steroids compared with those without fractures (OR, 1.47; P=0.057; 95% CI, 0.99-2.20; I<0.0001%), but there was no correlation with osteoporosis.
Conclusions:
IBD patients had no increased risk of overall fractures, but were at significantly increased risk of fractures at the spine, which was associated with steroid use. Strict surveillance and prevention of spine fractures are indicated in patients with IBD.
Glucocorticoid-induced osteoporosis (GIO) is the second most common form of osteoporosis and is the most common iatrogenic form of the disease. Fractures may occur in 30% to 50% of patients receiving chronic glucocorticoid therapy and many are asymptomatic, possibly due to glucocorticoid-induced analgesia. In addition to fractures, glucocorticoid administration is the most common cause of nontraumatic osteonecrosis. The absence of severe underlying disease or the presence of youth does not convey protection from glucocorticoid-induced bone disease. A devastating accompaniment of long-term glucocorticoid therapy is osteonecrosis (also known as aseptic necrosis, avascular necrosis, or ischemic necrosis). Under some circumstances (vasculitis, rheumatoid arthritis, lupus, status asthmaticus, inflammatory bowel disease), high-dose glucocorticoid therapy is an emergency; the clinician always hopes that the course of treatment will be brief, and, therefore, does not address the complications of these drugs. © 2013 American Society for Bone and Mineral Research. All rights reserved.
Una riduzione più o meno marcata della densità minerale ossea (BMD) può talvolta comparire in corso di varie malattie gastrointestinali, epatobiliari e pancreatiche, sia per il ridotto assorbimento di calcio e di vitamina D, sia per una significativa perdita fecale di calcio e di calcidiolo. La sua prevalenza e la sua tipologia variano con la durata, il tipo e la severità del malassorbimento, e anche la sua importanza clinica si correla con la causa e con la gravità della patologia di base. Con sempre maggior frequenza si osservano quadri clinici in cui la sintomatologia propria del malassorbimento è talora assai sfumata e in cui l’osteoporosi ol’osteopenia possono rappresentarne il primo indicatore significativo: la loro patogenesi prende origine da uno stato di ipocalcemia cronica che determina una maggiore increzione di paratormone (PTH), che a sua volta induce un maggiore riassorbimento osseo e, di conseguenza, una demineralizzazione scheletrica; a livello renale l’iperincrezione paratiroidea determina una maggiore escrezione di fosfati, una riduzione della calciuria e una più elevata produzione di 1,25(OH)2D3.
Crohn's disease and ulcerative colitis are associated with an increased risk of osteoporosis and bone fractures. Initialstudies suggested very high rates of osteoporosis in IBD based on bone mineral density (BMD) measurements;however, more recent studies suggest that BMD is often normal in IBD and average short-term changes are small.Doctors managing patients with IBD will have to consider a variety of risk factors and not just BMD measurements inassessing fracture risk. The evolution of knowledge regarding receptor for activated factor of nuclear factor kappa B (RANK), its ligand RANKLand osteoprotegerin (OPG) that serves as a decoy receptor, has enhanced our understanding of osteoporosis and alsoT cell immunobiology. Recent clinical studies in subjects with IBD have revealed that serum OPG levels may be elevated and inflamedintestinal tissue secretes OPG. It is suspected that OPG levels are elevated as a counter-regulatory response to lowBMD as serum OPG levels in IBD have been found to be inversely associated with BMD. OPG may ultimately prove tobe a useful therapeutic target for managing both low bone mass and colitis in patients with IBD. Currently, an underpinning of therapy for all IBD patients should include supplemental calcium and vitamin D,particularly for patients using corticosteroids. Postmenopausal women and men over age 50 years should be considered for BMD screening (in conjunction with anassessment of other risk factors for fracture) and if this suggests high fracture risk then pharmacological interventionmay be appropriate. Those with spontaneous or low-impact fractures that are typical for osteoporotic fractures (e.g.,hip fractures, one or more moderate to severe vertebral compression fractures) should be considered to haveestablished disease with high risk for further fractures and also require intervention.
The chapter discusses aetiology of malnutrition in inflammatory bowel disease (IBD). It focuses on protein energy malnutrition (PEM), altered body composition, micronutrient deficiencies and poor bone health. In children, growth failure and pubertal development delay can be additional outcomes of poor nutritional status which further complicate disease management. Reduced dietary intake, altered energy/nutrient metabolism, increased gastrointestinal nutrient losses and drug– nutrient interactions are all implicated in the origins of malnutrition in IBD. Short stature and faltering linear growth are commonly encountered in IBD, and frequently precede disease diagnosis. Two predominant types of anaemia have been identified in the context of IBD. Iron deficiency anaemia and the anaemia of chronic disease account for the majority of cases, with the first being more common in children and the latter in adults.
Weight loss and nutritional depletion are common features of inflammatory bowel disease. Our aim was to assess body composition in patients with Crohn’s disease (CD) and ulcerative colitis (UC) and to evaluate possible differences between the patient groups and healthy subjects.MethodsA total of 60 patients with CD, 60 patients with UC, and 60 healthy subjects were investigated. Each group consisted of 24 men and 36 women. Body composition was measured by dual x-ray absorptiometry and Z scores were obtained by comparison to age- and sex-matched normal values.ResultsBone mineral content and lean body mass were significantly lower in patients with CD compared with patients with UC and healthy subjects. The body composition of CD men was more strongly affected than that of women. UC patients had significantly higher fat mass and body mass index than patients with CD and healthy subjects. There was no difference in the percentage of fat mass between the two patient groups. Corticosteroid treatment and smoking had a negative impact on bone mineral content and lean body mass in CD patients independently of each other.ConclusionsCD was associated with disturbances in body composition: both bone mineral content and lean body mass were significantly reduced, especially in men with CD. Corticosteroid therapy and smoking had a significant influence on body composition in patients with CD. When studying the effects of inflammatory bowel disease on body composition and nutritional status, patients with CD and UC should be evaluated separately.
Objectives
To evaluate the prevalence of osteopenia and osteoporosis in patients with inflammatory bowel disease (IBD) and to study the factors involved in their pathogenesis.Methods
One hundred consecutive patients with IBD (57 women, mean age 41 years) were included in this study. Data were collected about their life habits, disease characteristics of medication use (mainly corticosteroids). Bone turnover markers were analyzed and the presence of osteoporosis or osteopenia was assessed with total hip and lumbar spine bone densitometry (DXA).ResultsOsteopenia percentages ranged from 37% (t-score measured by lumbar spine DXA) to 39% (hip DXA t-score). The prevalence of osteoporosis ranged from 2% (t-score measured by hip DXA) to 15% (lumbar spine DXA t-score). In the multivariate analysis, diagnosis of Crohn's disease (vs. ulcerative colitis; odds ratio 2.9, 95% CI 1-8.7) and the number of flares controlled by the cumulative dose of steroids (number of flares ≥3: odds ratio 8.7; 95%CI 1.6-45) were associated with a higher risk of osteopenia/osteoporosis. None of the analytical parameters significantly correlated with bone mineral density values.Conclusions
The prevalence of osteopenia/osteoporosis is higher in patients with IBD (mainly those with Crohn's disease) than in the general population. Changes in bone metabolism seem to be more closely related to the inflammatory activity of IBD than to the steroid dose per se. Bone turnover markers did not correlate with the presence of osteopenia and osteoporosis.
To investigate the impact of inflammatory bowel disease (IBD) on bone status, a cross-sectional study was conducted including 102 Brazilian patients with ulcerative colitis or Crohn’s disease. Our results demonstrated the higher prevalence of low bone mass and fragility fractures in Brazilian patients compared with other populations with IBD.
Introduction
The prevalence of low bone mass and fractures in Brazilian patients with Crohn’s disease (CD) and ulcerative colitis (UC) was investigated.
Methods
Patients with CD or UC answered a questionnaire detailing clinical risk factors for fracture. Bone mineral density (BMD) and quantitative ultrasound (QUS) measurements were performed in all patients. Spine X-ray was performed to determine the prevalence of vertebral fractures. Non-vertebral fracture data were obtained from medical history.
Results
A total of 61 women and 41 men (mean age 41.2 years) were included. Fractures were observed in 40.8% and 33.3% of the UC and CD patients respectively. 31.9% and 7.2% of the patients had vertebral and non-vertebral fractures respectively. Weight and body mass index were higher in patients with fracture than in those without (p < 0.01), while other clinical variables did not differ significantly between groups. Densitometric osteoporosis was detected in 14.7% of the population. Osteoporosis was more prevalent among men than women (p = 0.014). CD patients had significantly lower BMD values than UC patients. BMD and QUS values were not associated with fractures.
Conclusion
We observed a high prevalence of vertebral fractures (37.1%) in a young Brazilian IBD population. BMD and QUS were not associated with fracture in these patients.
Patients with inflammatory bowel disease are at increased risk of developing disorder in bone and mineral metabolism The study was aimed to determine if inflammatory bowel dis-ease (IBD) is a risk factor for osteoporosis in 103 adult patients. We included 103 IBD patients, 67 patients with Crohn's disease (CD) and 36 with ulcerative colitis (UC). Bone mineral density was measured by dual-energy X-ray absorptiometry. We used T score to express bone loss (osteopenia: -2.5 SD <T<-1 SD, osteoporosis: T <-2.5 SD). Plain x-rays were examined to search for vertebral com-pression or spontaneous fractures before DEXA. Among the 103 patients, 47.7% exhibit-ed osteopenia of the femoral neck and 62.3% of the lumbar spine, with no significant differ-ence between CD and UC. The prevalence of osteoporosis of the lumbar spine was signifi-cantly higher in CD patients (41.2% versus 8.7%). Osteoporosis is frequent in IBD patients, especially in CD patients. Female gender, malnutrition (body mass index <20 kg/m 2), disease course (>2 years) and active disease would be risk factors of bone mineral loss in IBD.
La situation des femmes ménopausées ostéoporotiques est très hétérogène en termes de comorbidités et l’existence de ces pathologies associées est souvent un frein à la prise en charge de l’ostéoporose. Il paraît donc important de bien étudier quelles sont les pathologies susceptibles de modifier le cours évolutif de l’ostéoporose, en majorant le risque de fracture ultérieure ou en conduisant à l’apparition de fractures multiples. Pour essayer de répondre à cette question, nous avons analysé la littérature concernant les pathologies les plus fréquentes chez les adultes de plus de 50 ans, en privilégiant les méta-analyses publiées. À côté des facteurs de risque maintenant « classiques », l’analyse de la littérature montre, de façon indirecte, le rôle aggravant d’un certain nombre de pathologies : les maladies inflammatoires digestives ou articulaires avec ou sans corticothérapie associée, les cancers du sein et de la prostate traités par chimiothérapie ou hormonothérapie, le diabète (surtout de type I) et la maladie cœliaque. Les études consacrées à l’insuffisance rénale modérée et à la dépression, moins convaincantes en raison d’insuffisances méthodologiques, vont cependant dans la même direction. En pratique, ces pathologies doivent être prises en compte dans l’évaluation du risque de fracture et la décision thérapeutique.
Context:
Low bone mineral density (BMD) is common in patients with inflammatory bowel diseases.
Objective:
The objective of the study was to assess the prevalence and the predictors of low BMD (osteoporosis or osteopenia) and fragility fractures among men with ulcerative colitis.
Design:
This was a retrospective database analysis.
Setting:
The study was conducted at a nationwide Veterans Affairs health care system.
Patients:
Male ulcerative colitis patients who were followed up in the Veterans Affairs system between 2001 and 2011 were identified using the International Classification of Diseases, ninth revision (ICD-9).
Main outcome measures:
We identified patients with low BMD and fragility fractures using ICD-9 codes. Steroid exposure was assessed using pharmacy data. A multivariate analysis was used to identify the independent effect of systemic steroids on the risk of low BMD and fragility fractures.
Results:
We identified 34 665 patients. Among them, 31% used steroids. The prevalence of low BMD was 15.8% and 7.1% among those who used and did not use steroids, respectively (P < .001). Prevalence of fragility fractures was 7.9%, 4.4%, and 1.1% for those with osteoporosis and osteopenia and those without low BMD, respectively (P < .001). Steroid exposure showed a dose-response pattern, patients who had cumulative prednisone exposure of greater than 11 136 mg (10th decile) were more likely to develop low BMD (odds ratio 8.9, P < .001) and fragility fractures (odds ratio 1.8, P < .001) as compared with non-steroid users after controlling for other possible predictors.
Conclusion:
In this nationwide cohort, the prevalence of low BMD was higher than what was reported for the general male population. There was a strong correlation between the cumulative steroid use and the risk of low BMD. Both steroids and low BMD were independent risk factors for fragility fractures.
Osteoporosis is a common problem in thalassemics. As the most affected bone is spinal vertebrae, theoretically, it should have the greatest risk of fracture. However, vertebral fracture (VF) in thalassemics was rarely reported. Screening for asymptomatic VF in thalassemics has not been reported. We, therefore, evaluated prevalence of VF in adolescents and young adults with thalassemia. A total of 150 patients with thalassemia, aged 10 years and older were enrolled. Lateral thoracolumbar spine radiography was evaluated. Twenty patients (13%) had VF and 6 of 20 (30%) had multiple VFs. The 2 most common sites of VF were lumbar 1 and thoracic 12 vertebrae. Comparing with the group without VF, thalassemics with VF were older, had more severe degree of thalassemia, history of splenectomy and previous non-VF, more iron chelation use, and longer duration of blood transfusion, but had lower pretransfused hematocrit. Multivariate analysis revealed 2 predictive factors for VF, having severe thalassemia and aged 20 years or older (odds ratio 5.7 and 5.0, respectively). In conclusion, unrecognized asymptomatic VF in thalassemics was not uncommon. Risk factors associated with VF included severe thalassemia and age 20 years or older. Screening for VF in the high-risk patient should be considered.
Background:
We analyzed the characteristics associated with increased risk of osteoporosis in patients with Crohn's disease in Malta.
Method:
Eighty-three patients with histologically and endoscopically confirmed Crohn's disease underwent a DEXA bone density scan and their phenotypic characteristics were analyzed.
Results:
There was a significant association between body mass index and bone mineral density (P = 0.004) and a significant difference in the T scores of patients according to age at diagnosis (Montreal Classification: P = 0.0006) with patients diagnosed <17 years (n = 13) having lower T scores than those diagnosed at older age groups (n = 70). There was a significant difference between the T scores of patients on infliximab (n = 33) and those not on biological therapy (n = 50, P = 0.0058). Patients with high cumulative corticosteroid doses (>10 mg/d for >3 mo, n = 18) had lower bone mineral densities than patients who received smaller corticosteroid doses (P = 0.013). There was however no significant difference in the T scores of patients according to disease location (P = 0.18), disease type (P = 0.64), gender (P = 0.30), and history of ileal resection (P = 0.68). There was also no significant correlation between disease duration and T scores (hip) (P = 0.61).
Conclusions:
Low body mass index, early disease onset, high corticosteroid doses and, anti-tumor necrosis factor α therapy are associated with increased risk of osteoporosis. Lower T scores in patients on infliximab occur as patients receiving this therapy have more severe inflammation, which is associated with elevated osteoclastogenic factors, rather than as a side-effect of the anti-tumor necrosis factor-α therapy.
Background:
The World Health Organization has recently developed the fracture risk assessment tool (FRAX) based on clinical risk factors and bone mineral density (BMD) for evaluation of the 10-year probability of a hip or a major osteoporotic fracture. The aim of this study was to evaluate the use of the FRAX tool in Greek patients with inflammatory bowel disease (IBD).
Methods:
FRAX scores were applied to 134 IBD patients [68 Crohn's disease (CD); 66 ulcerative colitis (UC)] who underwent dual-energy X-ray absorptiometry scans at the femoral neck and lumbar spine during the period 2007-2012. Calculation of the FRAX scores, with or without BMD, was made through a web-based probability model used to compute individual fracture probabilities according to specific clinical risk factors.
Results:
The median 10-year probability of a major osteoporotic fracture for IBD patients based on clinical data was 7.1%, and including the BMD was 6.2%. A significant overestimation with the first method was found (P = 0.01). Both scores with and without BMD were significantly higher in CD patients compared with UC patients (P = 0.02 and P = 0.005, respectively). The median 10-year probability of hip fracture based on clinical data was 0.8%, and including the BMD was 0.9%. The score with use of BMD was significantly higher in CD compared with UC patients (P = 0.04).
Conclusions:
CD patients have significantly higher FRAX scores and possibly fracture risk compared with UC patients. The clinical FRAX score alone seems to overestimate the risk of osteoporotic fracture in Greek IBD patients.
IntroductionClinical FeaturesBone HistomorphometryDirect Effects of Glucocorticoids on Bone CellsIndirect Effects of Glucocorticoids on Bone CellsOsteonecrosisManagement of GI0
Patients with inflammatory bowel disease (IBD) are at high risk of developing osteoporosis. Our objective was to determine the usefulness of IBD guidelines in identifying patients at risk for developing osteoporosis.
We utilized institutional repository to identify patients seen in IBD center and extracted data on demographics, disease history, conventional, and nonconventional risk factors for osteoporosis and Dual Energy X-ray Absorptiometry (DXA) findings.
59% of patients (1004/1703) in our IBD cohort had at least one risk factor for osteoporosis screening. DXA was documented in 263 patients with indication of screening (provider adherence, 26.2%), and of these, 196 patients had DXA completed ("at-risk" group). Ninety-five patients not meeting guidelines-based risk factors also had DXA completed ("not at-risk" group). 139 (70.9%) patients in "at-risk" group had low BMD, while 51 (53.7%) of "not-at-risk" patients had low BMD. Majority of the patients with osteoporosis (83.3%) missed by the current guidelines had low BMI. Multivariate logistic regression analysis showed that low BMI was the strongest risk factor for osteoporosis (OR 3.07; 95% CI, 1.47-6.42; P = 0.003).
Provider adherence to current guidelines is suboptimal. Low BMI can identify majority of the patients with osteoporosis that are missed by current guidelines.
Although a strong relationship exists between areal bone mineral density (aBMD) derived from dual-energy X-ray absorptiometry (DXA) and bone strength, the predictive validity of aBMD for osteoporotic vertebral fractures remains suboptimal. The diagnostic sensitivity of DXA may be improved by assessing aBMD within vertebral subregions, rather than relying on an estimate derived from the total area of the vertebra. The objective of this study was to validate a method of measuring subregional vertebral aBMD in vitro using lateral-projection DXA against subregional volumetric BMD (vBMD) measured with peripheral quantitative computed tomography (pQCT). A mixed set of 49 lumbar and thoracic vertebrae from 25 donors were scanned using lateral-projection DXA and pQCT. aBMD and apparent vBMD were measured in 7 vertebral regions (1 total area and 6 subregions) from the lateral DXA scan. vBMD was calculated in anatomically equivalent regions from pQCT scan data, using a customised software program designed to increase efficiency of the analysis process. Significant differences in densitometric parameters between subregions were observed by DXA and pQCT (P < 0.01). Subregional vBMD derived from pQCT was explained by a significant proportion of the variance in DXA-derived aBMD (R
2 = 0.51–0.67, P < 0.05) and apparent vBMD (R
2 = 0.64–0.75, P < 0.05). These results confirm the validity of measuring aBMD in vertebral subregions using lateral-projection DXA. The clinical significance should now be explored.
To evaluate the prevalence of osteopenia and osteoporosis in patients with inflammatory bowel disease (IBD) and to study the factors involved in their pathogenesis.
One hundred consecutive patients with IBD (57 women, mean age 41 years) were included in this study. Data were collected about their life habits, disease characteristics of medication use (mainly corticosteroids). Bone turnover markers were analyzed and the presence of osteoporosis or osteopenia was assessed with total hip and lumbar spine bone densitometry (DXA).
Osteopenia percentages ranged from 37% (t-score measured by lumbar spine DXA) to 39% (hip DXA t-score). The prevalence of osteoporosis ranged from 2% (t-score measured by hip DXA) to 15% (lumbar spine DXA t-score). In the multivariate analysis, diagnosis of Crohn's disease (vs. ulcerative colitis; odds ratio 2.9, 95% CI 1-8.7) and the number of flares controlled by the cumulative dose of steroids (number of flares ≥ 3: odds ratio 8.7; 95%CI 1.6-45) were associated with a higher risk of osteopenia/osteoporosis. None of the analytical parameters significantly correlated with bone mineral density values.
The prevalence of osteopenia/osteoporosis is higher in patients with IBD (mainly those with Crohn's disease) than in the general population. Changes in bone metabolism seem to be more closely related to the inflammatory activity of IBD than to the steroid dose per se. Bone turnover markers did not correlate with the presence of osteopenia and osteoporosis.
The co-morbidity profile varies widely across postmenopausal women with osteoporosis, and comorbidities often adversely affect the management of osteoporosis. There is a need for detailed information on the co-morbidities that may affect the course of osteoporosis by increasing the risk of subsequent fractures or inducing multiple fractures. We consequently reviewed the literature on the most common co-morbidities in adults older than 50 years of age, with special attention to published meta-analyses. We found that osteoporosis severity was increased not only by conventional risk factors, but also by a number of conditions including inflammatory bowel and joint diseases with or without glucocorticoid therapy, breast cancer and prostate cancer treated with chemotherapy or hormone therapy, diabetes (chiefly type 1), and celiac disease. Studies suggest an adverse impact of moderate renal failure and depression, although their methodological weaknesses preclude definitive conclusions. In practice, these co-morbidities should be taken into account when evaluating the fracture risk and making treatment decisions.
Although patients with inflammatory bowel disease (IBD) are at increased risk of osteoporosis, low bone mineral density (BMD) alone confers only a modest increase in risk of fracture. The FRAX score, developed by the WHO, is a free web-based clinical scale assessing the 10-year fracture risk and need for lifestyle advice/reassurance, dual X-ray absorptiometry (DEXA) scanning or preventive treatment.
To assess the accuracy of pre-BMD FRAX scores in identifying at risk IBD patients needing BMD measurement (intermediate risk) and/or therapy (high risk).
We calculated FRAX scores retrospectively in 116 consecutive IBD out-patients (81 Crohn's disease, 35 ulcerative colitis), who were having DEXA scans in 2005-2009 because they were considered at risk of osteoporosis.
On DEXA scans, 47% (38/81) and 12% (10/81) patients with Crohn's disease were osteopaenic and osteoporotic, respectively; equivalent figures for patients with UC were 34% (12/35) and 14% (5/35). The clinical FRAX score alone, when compared with the FRAX score including the BMD result, had a sensitivity of 100% (95% CI: 70-100%), specificity of 40% (95% CI: 31-50%), positive predictive value of 16% (95% CI: 9-27%) and negative predictive value of 100% (95% CI: 90-100%) in identifying those patients needing BMD measurement (intermediate risk) or preventive therapy (high risk).
In patients with IBD perceived to be at risk of osteoporosis and/or osteopaenia, the clinical FRAX score alone can predict accurately the risk of osteoporotic fracture, and thereby reduce the need for DEXA scans and unnecessary anti-osteoporosis treatment.
PROCEEDINGS OF THE INTERNATIONAL SYMPOSIUM ON IN VIVO BODY COMPOSITION STUDIES, 28 SEPTEMBER - 1 OCTOBER 1986, BROOKHAVEN NATIONAL LABORATORY, UPTON, NEW YORK, USA.
Quantitative computed tomography was used to examine the prevalence of spinal trabecular osteoporosis and single photon absorptiometry was used to examine that of radial cortical bone in 75 unselected patients with small or large intestinal inflammatory bowel disease. Twenty three patients (30.7%) had cortical and/or trabecular osteoporosis as defined by a bone mineral content more than two standard deviations below the age and sex-matched control mean value. Of these, 18 had cortical osteoporosis (8 male) and 12 trabecular osteoporosis (6 male). Seven patients (3 male) had both cortical and trabecular osteoporosis. Six patients had radiological evidence of one or more vertebral crush fractures. three females, aged 34, 38 and 42 years, had clinically severe osteoporosis with multiple vertebral crush fractures, bone pain, kyphosis and height loss. All the were amenorrhoeic and had received high dose steroids. These results demonstrate that the prevalence of both spinal trabecular and peripheral cortical osteoporosis is increased in patients with inflammatory bowel disease and that severe clinical osteoporosis may occur in young amenorrhoeic females.
The prevalence of osteoporosis in patients with inflammatory bowel disease (IBD) has not been accurately established. Using single photon absorptiometry of the radius and vertebral quantitative computerised tomography we have determined the prevalence of cortical and trabecular osteoporosis in 73 unselected patients, 29 male, with large or small bowel IBD. Osteoporosis (bone mineral content (BMC) > 2 SD below the normal mean) was demonstrated in 22 patients ( 11 female), with mean age 43 years (range 21-77). Six had both cortical and trabecular osteoporosis, 12 cortical only and 4 trabecular only. Three females aged 33, 38 and 39 years had severe clinical osteoporosis with back pain, vertebral fractures and height loss; all were amenorrhoeic. Two other patients had one or more vertebral fractures. All but 2 patients with osteoporosis had small bowel IBD with previous resections and 14 had received large doses of steroids (> 10 gm total dose). In these patients with IBD, cortical and/or trabecular osteoporosis was present in 29%, with severe clinical disease in 3 young females. Patients with small bowel IBD, previous resections and high steroid dosage, appear to be mainly at risk. Within this category, premenopausal females with amenorrhoea may develop severe clinical osteoporosis and oestrogen replacement therapy should be considered in such patients.
Bone mineral density of the radius was measured by single-photon absorptiometry in 50 patients with inflammatory bowel disease. Thirty-three had Crohn's disease and 17 ulcerative colitis; 25 were women. The mean age was 45 years (range, 18-70 years). Measurements were repeated in 39 of them after a mean follow-up period of 7.9 years (range, 7.1-8.2 years). In female patients the mean (95% confidence interval) annual change in radial bone mineral density was -0.74% (-1.34% to -0.14%) (P = 0.022), the greatest bone loss occurring in postmenopausal women (mean, -1.16% (-2.01% to -0.30%)). In male patients the mean annual rate of bone loss was -0.07% (-0.41% to 0.28%) (P = NS). Patients with abnormally low values at the first measurement remained osteopenic at the second measurement, whilst some others with normal values initially showed increased rates of bone loss and had a subnormal bone mineral density after the follow-up period. These results show increased rates of cortical bone loss in some patients with inflammatory bowel disease and emphasize the need to monitor bone mass in these patients so that prophylactic measures can be instituted.
The rate of spinal trabecular bone loss during one year was measured in 54 patients with inflammatory bowel disease. The mean change in spinal bone mineral content was -5.1 mg/ml K2HPO4, representing 3% of the initial bone mineral content. The rate of bone loss showed a significant negative correlation with body mass index (r = -0.276, p less than 0.05) but no other significant correlations were found with other clinical or biochemical indices, including the total amount of prednisolone taken during the course of the study. Eleven patients had bone loss greater than 15 mg/ml/year; these included four non-steroid treated patients, two of whom had disease confined to the large bowel. The results indicate rapid rates of bone loss in some patients with inflammatory bowel disease over the course of one year. Although steroid therapy and malnutrition are likely to be contributory factors in some patients, other, as yet unidentified, risk factors also operate. The rapid bone loss observed in some patients emphasises the need for effective prophylactic regimes.
Bone mineral content in spinal trabecular and peripheral cortical bone was measured in 75 unselected patients with small and/or large intestinal inflammatory bowel disease. Osteoporosis, defined as a bone mineral content greater than 2 SD below the age and sex matched normal mean value was present in 23 patients (30.6%). Three amenorrhoeic females aged 34, 38, and 42 years had severe clinical osteoporosis and a further three patients had one or more vertebral crush fractures. Eighteen of the 23 patients with osteoporosis had small intestinal disease with one or more resections and the mean lifetime steroid dose in those with osteoporosis was significantly higher than in those with normal bone mineral content. Bone mineral content in spinal trabecular bone showed significant negative correlations with lifetime steroid dose and serum alkaline phosphatase and a significant positive correlation with serum albumin. Peripheral cortical bone mineral content was positively correlated with body weight, height and body mass index. We conclude that the prevalence of osteoporosis is increased in patients with inflammatory bowel disease, severe clinical osteoporosis developing in some relatively young patients. The pathogenesis of this bone loss is probably multifactorial; steroid therapy is likely to be an important contributory factor.
Serial measurements of spinal trabecular and radial cortical bone density were made over 4 years in 70 patients with inflammatory bowel disease. Mean rates of bone loss for the cohort differed little from rates reported in normal populations; however, some patients showed increased rates of loss, including patients whose bone density at entry to the study was already well below normal. There was a significant correlation between the amount of corticosteroid prescribed and spinal trabecular bone loss in males, but no significant correlation with other clinical parameters. Increased rates of bone loss emphasise the need for bone densitometry and prophylactic measures in patients with inflammatory bowel disease.
Reduced bone mineral density in patients with inflammatory bowel disease is thought to be due to disturbances in calcium homeostasis or the effects of corticosteroid treatment.
To assess the prevalence and mechanism of reduced bone mineral density in 79 patients with inflammatory bowel disease (44 with Crohn's disease, 35 with ulcerative colitis) who did not have significant risk factors for low bone densities.
Dual x ray absorptiometry was used to measure bone mineral density and serum and urinary markers of osteoblast (alkaline phosphatase, procollagen 1 carboxy terminal peptide and osteocalcin) and osteoclast (pyridinoline, deoxypyridinoline, and type 1 collagen carboxy terminal peptide) activities to assess bone turnover.
There was a high prevalence of low bone mineral density (prevalence of T scores < -1.0 from 51%-77%; T scores < -2.5 (osteoporosis) from 17%-28%) with hips being more often affected than vertebrae (p < 0.001). Reduced bone mineral density did not relate to concurrent or past corticosteroid intake, or type, site, or severity of disease. Whereas calcium homeostasis was normal, bone markers showed increased bone resorption without a compensatory increase in bone formation.
The greater prevalence of reduced hip bone mineral density, as opposed to vertebral, mineral density and the pattern of a selective increase in bone resorption contrasts with that found in other known causes of metabolic bone disease.
Patients with inflammatory bowel disease are at risk of developing metabolic bone disease.
To compare bone mineral density in patients with Crohn's disease with patients with ulcerative colitis and healthy subjects, and to evaluate possible risk factors for bone loss in inflammatory bowel disease.
60 patients with Crohn's disease, 60 with ulcerative colitis, and 60 healthy subjects were investigated. Each group consisted of 24 men and 36 women.
Lumbar spine, femoral neck, and total body bone mineral density were measured by dual x ray absorptiometry (DXA), and Z scores were obtained by comparison with age and sex matched normal values.
Mean Z scores were significantly lower in patients with Crohn's disease compared with patients with ulcerative colitis and healthy subjects. Patients with ulcerative colitis had bone mineral densities similar to healthy subjects. Use of corticosteroids, body mass index (BMI), and sex were significant predictor variables for bone mineral density in Crohn's disease. In ulcerative colitis only body mass index and sex were of significant importance. Disease localisation and small bowel resections had no influence on bone mineral density in patients with Crohn's disease.
Patients with Crohn's disease have reduced bone mineral density. Several factors are probably involved, but the reduction is associated with corticosteroid therapy. When studying skeletal effects of inflammatory bowel disease, patients with Crohn's disease and those with ulcerative colitis should be evaluated separately.
In spite of the accumulating evidence of an increased prevalence of osteopenia and osteoporosis in patients with inflammatory bowel diseases (IBD), the time course of bone loss is not well described, and there is little knowledge about factors indicating an increased risk of rapid bone loss.
We conducted a follow-up study in 80 IBD patients (45 men and 25 premenopausal and 10 postmenopausal women), 19 with ulcerative colitis and 61 with Crohn disease, with a mean follow-up time of 568 +/- 60 days, to assess bone loss, risk factors of rapid bone loss, and value of bone markers to predict bone loss. Bone mineral density was measured by dual-energy X-ray absorptiometry, bone formation by bone alkaline phosphatase (BAP), and bone resorption by N-terminal telopeptide of type-I collagen (NTX) and free deoxypyridinoline (DPD).
Bone density changes per year were 0.46% +/- 3% at the spine, 0.06% +/- 5.1% at the femoral neck, -1.1% +/- 7.7% at the triangle of Ward, and -0.52% +/- 1.86% at total body level. Type and duration of disease, sex, age, and level of NTX, DPD, and BAP at base line did not show significant differences between patients who lost and those who did not lose bone mass. Bone loss was significantly higher in patients with (n = 28) than in those without steroids (n = 52) at the femoral neck and Ward triangle but not at the spine and total body.
Change in bone mass in IBD patients during short-term follow-up is low on average, but there is great heterogeneity within the population, which cannot be explained by the use of steroids alone. Bone loss cannot be predicted by analysis of bone markers.
Needing a single index of degree of illness in Crohn's disease, the National CooperativeCrohn's Disease Study group collected data prospectively from 187 visits of 112 patients with Crohn's disease of the small bowel, colon, or both. Information on 18 predictor variables was gathered at each visit. In addition, the attending physician rated his over-all evaluation of how well the patient was doing and compared the patient's status with that at the previous visit. A multiple regression computer program was utilized to derive an equation for prediction of the physician's over-all ratings from a subset of the predictor variables fulfilling a combination of constraints. This equation, numerically simplified and utilizing eight selected variables, is the Crohn's Disease Activity Index. Index values of 150 and below are associated with quiescent disease; values above that indicate active disease, and values above 450 are seen with extremely severe disease.
The construct validity and the test-retest reliability of a self-administered questionnaire about habitual physical activity were investigated in young males (n = 139) and females (n = 167) in three age groups (20 to 22, 25 to 27, and 30 to 32 yr) in a Dutch population. By principal components analysis three conceptually meaningful factors were distinguished. They were interpreted as: 1) physical activity at work; 2) sport during leisure time; and 3) physical activity during leisure time excluding sport. Test-retest showed that the reliability of the three indices constructed from these factors was adequate. Further, it was found that level of education was inversely related to the work index, and positively related to the leisure-time index in both sexes. The subjective experience of work load was not related to the work index, but was inversely related to the sport index, and the leisure-time index in both sexes. The lean body mass was positively related to the work index, and the sport index in males, but was not related to the leisure-time index in either sex. These differences in the relationships support the subdivision of habitual physical activity into the three components mentioned above.
Reduced bone mineral density (BMD) has been reported in 3-77% of patients with inflammatory bowel disease (IBD). The majority of these studies are cross-sectional and from tertiary referral centres. The aim of our study was to estimate the prevalence of metabolic bone disease and of symptomatic fractures in a population of patients with Crohn's disease (CD) living in a well-defined geographic area. Patients with CD living in three adjacent municipalities within the IBD South-Limburg study area were investigated. BMD was measured by dual X-ray absorptiometry (DXA) of the femoral neck, lumbar spine and total body. The population comprised of 181 CD patients. 23 of whom were excluded. One-hundred-and-nineteen (75%) of the 158 eligible patients (37 males, 82 females with a mean age of 42 years (17-78)) were investigated. Osteopenia of lumbar spine and/or femoral neck was found in 45% of patients. Osteoporosis was found in another 13% of patients. Mean BMD (T-score) of femoral neck was significantly lower than of lumbar spine (P < 0.001). Male CD patients and patients aged under 18 at diagnosis are more at risk of having a low bone mass at the lumbar spine (P < 0.001) and total body (P = 0.018). The prevalence of osteoporosis in postmenopausal CD patients (29%) was significantly higher than in premenopausal patients (3%) (odds ratio: 12). Twenty-nine of 119 (24%) patients had a history of symptomatic fractures. Osteopenia and osteoporosis are frequent in CD and should have the full attention of the treating physician.
The European Vertebral Osteoporosis Study (EVOS) is one of the largest studies to investigate the prevalence of osteoporosis related vertebral fractures in a population based cross-sectional study. One of the main tasks was to create standards and logistics to obtain uniform and comparable radiographs in all 36 European centers. Furthermore the central reading of the X-rays and the morphometry of the vertebral bodies were 2 important challenges. This paper describes the standardized patient positioning and making of the radiographs as well as their morphomerty, reading, and evaluation.
Although corticosteroid therapy is associated with the development of osteopenia, it is unclear whether the cause of osteopenia in inflammatory bowel disease (Crohn's disease and ulcerative colitis) is related to corticosteroid therapy or other disease-related variables. Patients with Crohn's disease (a diffuse gastrointestinal disease) could have greater osteopenia than patients with ulcerative colitis because of small bowel disease and secondary malabsorption of calcium and vitamin D. A cross-sectional analysis of consecutive patients with Crohn's disease and ulcerative colitis was undertaken. Bone density was determined by measurements of the L2-L4 spine, the total hip, and Ward's triangle using dual energy X-ray absorptiometry (DXA). A number of clinical parameters were recorded prior to bone density evaluation and analyzed by univariate and subsequently multivariate analysis to determine possible predictors of osteopenia. Of the 26 patients with Crohn's disease, diminished bone density (a Z score of at least -1) was found at the hip in 64% and at the spine in 44%; and of the 23 patients with ulcerative colitis diminished bone density was found at the hip in 43% and at the spine in 48%. Among all the variables tested, only corticosteroid use was a statistically significant predictor of diminished bone density (p = 0.025 for the spine and hip and p = 0.005 for Ward's triangle). Disease diagnosis (Crohn's disease compared with ulcerative colitis) did not predict or correlate with diminished bone density. No obvious associations were seen between the measurements of any serum hormones or biochemistries and bone density, although the patients using corticosteroids had lower serum calcium levels than the nonusers.(ABSTRACT TRUNCATED AT 250 WORDS)
Objective:
The mechanism of bone loss in patients with inflammatory bowel disease (IBD) is not completely understood. The aim of this study was to assess indices of bone turnover and bone mineral density (BMD) in the lumbar spine and femoral neck in IBD patients.
Methods:
Sixty-three patients with Crohn's disease and 41 with ulcerative colitis were studied. Serum bone-specific alkaline phosphatase (B-ALP), osteocalcin, parathyroid hormone (PTH), 25 hydroxyvitamin D, interleukin-6 (IL-6), and urinary N-telopeptide cross linked type 1 collagen (NTX) were determined. BMD of the lumbar spine and femoral neck was determined by dual x-ray absorptiometry in 59 patients.
Results:
In the femoral neck 42% of the patients had osteopenia (-2.5 SD < BMD T score < -1 SD) and another 41% had osteoporosis (BMD T score < -2.5). In the spine 34% of the patients had osteopenia and additional 42% had osteoporosis. BMD T scores were lower in the femoral neck compared to the spine. Reduced BMD was unrelated to gender, disease type, lifetime corticosteroid dose, but inversely correlated with disease duration (r = -0.36, p < 0.05). Serum IL-6 was higher in IBD patients compared to controls. A reduced level of osteocalcin, a marker of bone formation, was present in 7% of patients and an increase in NTX, a marker of bone resorption, in 25% of them. Osteoporotic IBD patients (spine or hip BMD T score < -2.5) had increased serum IL-6, osteocalcin and PTH level compared to nonosteoporotic patients.
Conclusions:
There is a high prevalence of reduced BMD at the spine and femoral neck in IBD patients, which is more severe in the hip. Bone turnover in osteoporotic IBD patients is associated with an increase in osteocalcin, PTH and IL-6. IL-6 may play a role in the pathogenesis of bone loss in IBD.
Histological examination of bone from 25 patients with small-intestinal resection showed that 9 (36%) had osteomalacia, which was severe in 5 and mild in 4. The serum-alkaline-phosphatase concentration was raised in all patients with severe osteomalacia, but serum calcium, phosphate, and alkaline-phosphatase concentrations were normal in the 4 patients with mild disease, 2 of whom had symptoms. Osteomalacia was diagnosed radiologically in only 3 patients. Osteomalacia appears to be commoner in patients with small-intestinal resection than has previously been thought, and bone biopsy is essential if all cases are detected. Although high-dose parenteral vitamin-D therapy is usually effective in the treatment of osteomalacia after small-intestinal resection, our findings showed that oral vitamin-D metabolites and their analogues may also be effective. This has important practical advantages.
Needing a single index of degree of illness in Crohn's disease, the National Cooperative Crohn's Disease Study group collected data prospectively from 187 visits of 112 patients with Crohn's disease of the small bowel, colon, or both. Information on 18 predictor variables was gathered at each visit. In addition, the attending physician rated his over-all evaluation of how well the patient was doing and compared the patient's status with that at the previous visit. A multiple regression computer program was utilized to derive an equation for prediction of the physician's over-all ratings from a subset of the predictor variables fulfilling a combination of constraints. This equation, numerically simplified and utilizing eight selected variables, is the Crohn's Disease Activity Index. Index values of 150 and below are associated with quiescent disease; values above that indicate active disease, and values above 450 are seen with extremely severe disease.
To assess the prevalence and risk factors for low bone mineral density in inflammatory bowel disease, we studied 61 consecutive patients, mean age 36 +/- 11 years. Twenty-seven had a Crohn's disease and 34 ulcerative colitis (including 13 with ileoanal anastomosis). Three patients, two women and one man (32, 70, and 45 years old, respectively) had vertebral crush fractures. Bone mineral density measured by dual energy x-ray absorptiometry at spine and femoral level was more than 2 SD below normal values in 23% of the patients, all of them having received steroid therapy. Eighteen patients (29%) had never received steroid therapy; their bone mineral density was not different than those who had. Univariate analysis showed a positive correlation between bone mineral density and body weight or oral calcium intakes, and a negative correlation with steroid daily dose. After ileoanal anastomosis, bone mineral density was not different from other groups and showed a positive correlation with time elapsed since coloproctectomy. We concluded that bone mineral density is low in patients with inflammatory bowel disease and exposes them to the risk of bone fracture. Bone mineral density after ileoanal anastomosis may increase with time after surgery.
The epidemiology of ulcerative colitis (UC) in Stockholm County over a 25-year period, 1955-1979, was investigated. There were 1,274 cases--681 males and 593 females. The proportion of patients with proctitis, left-sided, and total extent of disease remained constant over the study period, as did the time interval between onset of symptoms and definite diagnosis. The incidence increased over the first 20 years followed by a plateau and was 4.3 per 10(5) inhabitants at the end of the study period. The peak incidence in relation to age increased, but remained in the 3rd and 4th decade throughout the study period. In a population-based study of UC the overall prevalence of extracolonic diagnoses was 21%. Seventy percent of patients with extracolonic diagnoses had extensive colitis whereas among the patients without extracolonic diagnoses only 28% had extensive colitis (p less than 0.001). The extracolonic diagnoses were classified into two major groups, activity-related and autoimmune, the former is related to the extent and activity of UC and responds to both medical and surgical treatment, whereas the latter is unaffected by medical and surgical treatment for UC. A total of 364 diagnoses were distributed among 271 UC patients. The prevalence of extracolonic diagnoses was higher in familial UC (p less than 0.05), but was distributed as UC in general mostly with activity-related diagnoses. The familial occurrence of inflammatory bowel disease (IBD) was investigated among 963 patients with UC. There was a general prevalence of 7.9% for familial IBD. In 80% one relative was affected, in most cases this was a first degree relative with UC. Sibship was the most common relationship. No concordance for UC was found among three pairs of monozygotic twins. The prevalence of UC in first degree relatives of index patients was 15 times higher than in non-relatives. The age at onset was significantly lower among patients with a family history for UC; they also had a higher prevalence of total colitis. The prevalence of Crohn's disease (CD) in first degree relatives of index patients with UC was almost 3.5 times higher than in non-relatives. Complex segregation analysis of 124 families with UC where two or more individuals were affected points to a rare additive major gene with a low penetrance as the cause of the disease with. About 20% of the affected were heterozygotes for the gene. There was no evidence for multifactorial inheritance. The prevalence of IBD was found to be 13.4% in a population-based study on patients with CD.(ABSTRACT TRUNCATED AT 400 WORDS)
The construct validity and the test-retest reliability of a self-administered questionnaire about habitual physical activity were investigated in young males (n = 139) and females (n = 167) in three age groups (20 to 22, 25 to 27, and 30 to 32 yr) in a Dutch population. By principal components analysis three conceptually meaningful factors were distinguished. They were interpreted as: 1) physical activity at work; 2) sport during leisure time; and 3) physical activity during leisure time excluding sport. Test-retest showed that the reliability of the three indices constructed from these factors was adequate. Further, it was found that level of education was inversely related to the work index, and positively related to the leisure-time index in both sexes. The subjective experience of work load was not related to the work index, but was inversely related to the sport index, and the leisure-time index in both sexes. The lean body mass was positively related the the work index, and the sport index in males, but was not related to the leisure-time index in either sex. These differences in the relationships support the subdivision of habitual physical activity into the three components mentioned above.
To assess the rate of bone loss in patients with inflammatory bowel disease, we prospectively studied 35 patients (17 women) aged 36 +/- 13 (range 17-60) years, 14 of whom had Crohn's disease and 21 with ulcerative colitis (including 12 with ileoanal anastomosis). Bone mineral density was measured by dual-energy X-ray absorptiometry at the lumbar spine and femoral neck. The follow-up was 19 +/- 8 months. During this period, 14 patients received oral steroids. Lumbar bone density changes expressed as a percentage per year were -3.1 +/- 4.9%, -6.4 +/- 7.5% and +2.0 +/- 4.0% in Crohn's disease and ulcerative colitis without and with ileoanal anastomosis respectively (p = 0.007). The same pattern was observed at the femoral neck. Mean annual lumbar bone density changes were -6.2 +/- 7.0% and +0.9 +/- 3.9% in patients with and without steroids during follow-up (p = 0.002). We conclude that patients with inflammatory bowel disease are at risk of lumbar and femoral bone loss. However, bone loss is not observed in patients with ileoanal anastomosis.
To assess the prevalence of and risk factors for low bone mineral density in inflammatory bowel disease (IBD), 152 IBD patients and 73 healthy controls were studied. Sixty seven patients had ulcerative colitis, 78 had Crohn's disease (52 of them (66.7%) had ileal disease), and seven had indeterminate colitis. Bone mineral density values (g/cm2) measured by dual energy x ray absorbtiometry at the spine (L2-L4), the femoral neck, Ward's triangle, and the trochanter were 1.177, 0.948, 0.850, and 0.838 in the patients and 1.228 (p = 0.034), 1.001 (p = 0.009), 0.889 (NS), and 0.888 (p = 0.012) in the control group, respectively. The type or extent of the disease or previous small bowel resection did not have any significant effect on the bone mineral density values. There was a weak, but statistically significant negative correlation between bone mineral density and the total lifetime corticosteroid dose (in the lumbar spine r = -0.164, p = 0.04, the femoral neck r = -0.185, p = 0.02, Ward's triangle r = -0.167, p = 0.04, and the trochanter r = -0.237, p = 0.003). The patients whose lifetime corticosteroid dose (prednisone/prednisolone) was more than 10 g had especially low bone mineral density (p < 0.05 compared with the groups with no or less than 5 g of corticosteroid). The patients who had never taken peroral corticosteroids did not have decreased bone mineral density. In conclusion, IBD patients have significantly lower bone mineral density values than healthy controls, but the difference is not so great as has been reported previously. Low bone mineral density values in these patients are related to high lifetime corticosteroid doses.
Patients with inflammatory bowel disease are at risk for osteopenia. To study the metabolic bone status of these patients, a cross-sectional study was conducted.
Eighty-four patients (49 women, 35 men) with inflammatory bowel disease, 34 of whom had Crohn's disease and 50 ulcerative colitis (including 18 with prior coloproctectomy and ileoanal anastomosis), underwent clinical, dietary, and spine radiological assessments. Bone metabolism was assessed by measuring serum levels of calcium, phosphate, parathyroid hormone (1-84), 25-hydroxyvitamin D3, 1,25-dihydroxyvitamin D3, and osteocalcin. Lumbar and femoral neck bone mineral densities were measured by dual energy X-ray absorptiometry.
Serum osteocalcin level was decreased in 29 patients (34%), 12 of whom had never undergone steroid therapy. The other biochemical markers of bone metabolism were in the normal range. Thirty-six patients (43%) had osteopenia, and 6 patients (7%) had vertebral crush fractures. Osteopenia was observed in 27 patients (52%) and 9 patients (28%) with and without corticosteroid therapy, respectively. No patient had clinical or biological signs of osteomalacia. Analysis of bone density (lumbar Z score) by a multiple regression analysis showed a statistically significant correlation with age, cumulative corticosteroid doses, sedimentation rate, and osteocalcin level (R2 = 0.76; P = 0.05).
The results suggest that bone turnover in inflammatory bowel disease is characterized by low bone formation in the presence of normal levels of calcium-regulating hormones.
The pathogenesis of low bone mineral density in patients with inflammatory bowel disease is unclear, and the relevance of secondary osteopenic influences is controversial. Our aim was to study bone mineral density in newly diagnosed patients.
Bone mineral density and biochemical parameters of bone metabolism were measured in 15 patients with Crohn's disease and 15 patients with ulcerative colitis, all of whom were newly diagnosed. Lumbar and forearm bone mineral densities were measured by dual energy x-ray absorptiometry, and Z scores were obtained by comparison with age- and sex-matched normal values. Twenty-three patients had repeat measurements 1 year later, and 20 had received systemic steroids.
At diagnosis, the mean Z score for patients with Crohn's disease (spine, -1.06 +/- 0.86; forearm, -1.04 +/- 0.86) was significantly lower than that for patients with ulcerative colitis (spine, -0.03 +/- 1.16; forearm, 0.11 +/- 1.24). Inflammatory activity, disease localization, body mass index, smoking habits, sex, physical activity, or biochemical parameters did not account for this difference. Spine and forearm Z scores were significantly correlated. Mean Z scores after 1 year were not significantly different from initial Z scores.
At diagnosis, low bone mineralization is a feature of Crohn's disease but not ulcerative colitis. Treatment with corticosteroids did not result in further bone loss in 1 year.
Beginning 1982, our group has been performing the technique of ileal pouch-anal anastomosis, changing the procedure for achieving better functional results, less morbidity and making it easier. Fifty patients operated on for ulcerative colitis and "polyposis coli" were grouped as follows: Group I (28): proctocolectomy, mucosectomy, handsewn anastomosis and temporary ileostomy; Group II (13): proctocolectomy without mucosectomy, leaving a rectal stump up to just the level of the puborectalis, instrumental anastomosis and no-ileostomy; Group III (9): Same as Group II but with the implant of an endoluminal prosthesis to defunction the pouch. From our results it is concluded that, provided an adequate selection of patients is done, the best technique is the one performed in Group III due to its simplicity, no morbidity related to the ileostomy, no risk of fistula and probably better functional results than in Group II.
This chapter summarizes current evidence that supports a role for local factors acting both directly and as mediators of systemic hormones. Differences in the production of, or response to, local factors are important in the pathogenesis of osteoporosis. Since these local factors often act in concert and are often coordinately regulated, it seems likely that the relevant differences will involve multiple local factors in most patients. This hypothesis is particularly attractive because there is so little difference in the levels of systemic hormones in osteoporotic patients compared to that seen in age-matched controls. A plausible hypothesis would be that the production or activity of local factors changes to varying degrees with age and estrogen deficiency and that the individuals with severe osteoporosis are those who have large increases in bone resorbing factors; loss of inhibitors of resorption; large increases in inhibitors of formation; and loss of stimulators of bone formation. Another critical factor in the pathogenesis of osteoporosis is peak bone mass. It is quite possible that the genetic determinants of peak bone mass involve effects on local factors, particularly growth factors. Moreover, the effect of weight-bearing activity on peak bone mass is likely to be mediated by local factors. Regulation involves contributions from marrow cells of both the hematopoietic and the mesenchymal lineages as well as bone cells themselves. There is some evidence for a decrease in the number of osteogenic stem cells in the marrow with age, and this could account in part for age-related decreases in bone formation. It is likely that the pathogenesis of severe osteoporosis will be heterogeneous; that is, there will be patients with different patterns of abnormalities involving different systemic hormones and local factors.
Some patients with inflammatory bowel disease have reduced bone mineral density, but the risk factors for osteoporosis in these patients are unclear.
To evaluate the effect of smoking and other lifestyle factors on bone mineral density in patients with inflammatory bowel disease, we studied 67 patients with ulcerative colitis, 78 with Crohn's disease, 7 with indeterminate colitis, and 73 healthy control subjects. Bone mineral density of the lumbar spine and the proximal femur was measured, using dual-energy X-ray absorptiometry. Measures of smoking and other lifestyle factors were assessed in an interview.
The female ex- or current smokers with inflammatory bowel disease (n = 38) had lower age- and sex-adjusted Z-scores of bone mineral density than the female patients who had never smoked (n = 34) (Z-scores in the lumbar spine, -0.277 (1.283) (mean (standard deviation)) and 0.487 (1.056), respectively; p = 0.008; and in the femoral neck, -0.626 (1.055) and -0.013 (1.019); p = 0.015). These differences were not explained by the type or treatment of the disease, the menstrual history, or the use of estrogen preparations. In male patients no differences in bone mineral density were found between ex- or current smokers and non-smokers. Coffee drinking and alcohol consumption were not associated with bone mineral density in these patients.
Smoking is associated with low bone mineral density in women with inflammatory bowel disease. This association is not related to the body mass index, the medical treatment, or the type of disease.
Osteoporosis is known to be a significant complication of Crohn's disease in adult patients. The association of osteoporosis and the development of vertebral compression fractures is well delineated. This case report describes 5 pediatric patients with Crohn's disease in whom vertebral compression fractures associated with a marked reduction in bone density developed. As in adults, the association of osteoporosis and Crohn's disease in pediatric patients is multifactorial, including corticosteroid use, calcium and vitamin D homeostasis, malnutrition, alteration in sex hormones, and site of disease. At the time of diagnosis of the vertebral fractures, the patients' ages ranged from 10.6 to 16.8 years, they had persistent and severe back pain, and 3 of 5 patients had a decrease in height. They were taking 13.7-41.6 mg/day of corticosteroid, and all 5 patients had terminal ileal involvement. Bone mineral density measured by dual-energy x-ray absorptiometry was well below 2SD from the mean in all patients (z-score, -2.31 to -5.11). Because of the high morbidity and mortality associated with fractures that result from low bone mineral density, medical care of all pediatric patients with Crohn's disease should include an evaluation of bone mineral density.
In patients with inflammatory bowel disease (IBD), accelerated bone loss and osteopenia have been found. Potential etiologies of these bone abnormalities have included malnutrition, poor calcium intake or absorption, and the use of corticosteroids. Recent studies have suggested that circulating pro-inflammatory cytokines, which are produced in inflamed bowel, can have a profound effect on bone metabolism, particularly bone resorption. Our aim was to characterize the effects of serum from subjects with IBD on bone metabolism in an in vitro bone culture system.
Organ cultures of fetal rat parietal bones were treated with sera from 9 subjects with Crohn's disease, 7 with ulcerative colitis, and 10 controls with functional bowel disease (age range of all subjects 7-16 years). Patients were also classified by disease activity, serum albumin level, erythrocyte sedimentation rate (ESR), and serum interleukin (IL) 6 levels. The effects of sera on bone formation and resorption were quantified.
Compared with control serum, serum from patients with Crohn's disease significantly decreased bone dry weight (p < 0.01) and calcium content (p < 0.001) during 96 h of culture, while serum from ulcerative colitis patients had no effect. While no difference in collagen synthesis was noted between any of the three experimental groups, noncollagen protein synthesis was lower in the ulcerative colitis group than in the control group or those with Crohn's disease (p < 0.05). DNA content was similar in all groups. There was no significant effect of serum from any experimental group on bone resorption. There was no demonstrable relationship between clinical disease activity, ESR, or serum IL-6 levels and measures of bone metabolism. Histologic evaluation of cultured bone showed marked differences between control subjects and Crohn's disease patients, with the latter being characterized by disorganization of mineral and osteoid and morphologically abnormal osteoblasts.
Serum from children with IBD has a significantly different effect than control serum on an in vitro model of bone metabolism. Our data suggest that circulating factors may affect osteoblasts and bone formation, leading to bone loss. Further work will be required to further characterize the nature of these factors and develop treatment strategies to minimize their effects.
A reduced bone mineral density has been reported in inflammatory bowel disease (IBD).
To assess the mechanisms of bone disease in IBD.
We studied in 90 patients (61 with Crohn's disease, 22 with ulcerative colitis, 7 with indeterminate colitis) biochemical markers of bone metabolism in serum and bone mineral density by peripheral quantitative computed tomography at the forearm.
Forty-five percent of the patients had a reduced bone density (Z score < -1). Serum calcium was normal in most patients, vitamin D deficiency was documented in 17%. Osteocalcin, a serum marker of bone formation, was decreased in 26% (1.2 +/- 0.1 ng/ml), whereas the carboxyterminal cross-linked telopeptide of type I collagen (ICTP), a recently described serum parameter of bone breakdown, was stimulated in 38% (10.4 +/- 2.3 microg/L). Of 33 patients with increased ICTP levels, 19 showed a decreased bone density (Z score < -1), and 2 of them never received steroids. An active status of the underlying disease in most patients with increased ICTP levels suggests a direct effect of the underlying IBD. In the whole series of patients with a history of active disease (n = 34), 47% had signs of an increased bone degradation (ICTP > 5 microg/L; mean, 12.9 +/- 4.7 microg/L). Data derived from a retrospective survey of 245 patients with IBD suggest that the prevalence of bone fractures in IBD is unexpectedly high, particularly in patients with a long duration of disease, frequent active phases, and high cumulative doses of corticosteroid intake.
Several mechanisms may be involved in IBD-associated bone disease: (1) a high inflammatory activity directly induces bone degradation via yet unknown pathways, (2) treatment with corticosteroids may exert catabolic effects on the bone, or (3) malabsorption and vitamin D deficiency may activate bone turnover.
In Europe there is a 3-fold variation, according to geographical center, in risk of vertebral deformity in men and women over the age of 50. We investigated the relationship between bone density, as assessed by dual-energy X-ray absorptiometry (DEXA) of the spine and hip and prevalent vertebral deformities in 13 of the 36 centers participating in the European Vertebral Osteoporosis Study (EVOS). Each center recruited an age-stratified sample of men and women aged 50 years and over, and of those who agreed to densitometry, 288/2088 women and 233/1908 men were found to have one or more deformities of the vertebrae between T4 and L4 as assessed by the McCloskey algorithm. DEXA was in each case performed on L2-L4, the proximal femur, or both. Bone densitometry results were cross-calibrated between centers using the European Spine Phantom prototype and results expressed as bone mineral density (BMD, g/cm2). In both genders, subjects with deformities involving loss of anterior vertebral body height alone comprised over 20% of the total with deformities and these related poorly to BMD. Other classes of deformity were found by logistic regression to relate significantly to BMD in one or both genders, with odds ratios for the risk of any of these ranging from 1.67 to 2.11 for a 1 SD reduction in bone density at spine, femoral neck, or trochanter (p < 0.001). Adjusting for anthropometric variables and BMD did not remove the effect of age on risk which rose 1.67- to 1.78-fold per decade according to gender. The greater unadjusted rate of increase in deformity risk with age in women was attributable to their faster rate of bone loss with age; after adjusting for age, body mass index (BMI), and BMD at the trochanter in grams per square centimeter, men had a 2-fold higher risk of deformity than women. Analysis of the relationship between mean bone density and the prevalence of deformity in each center demonstrated no significant differences between centers in either gender, after adjusting for BMD, age, and BMI together with an a posteriori statistical adjustment for imperfect cross-calibration of densitometers. It is concluded that BMD is an important determinant of deformity risk in both genders. Together with age, BMD explains much of the differences in risk both between the sexes and between individual geographical centers in Europe.
To ascertain whether patients with Crohn's disease treated with azathioprine maintained bone mineral mass better than patients treated with steroids alone.
Retrospective study.
University Hospital of Malmö, Sweden.
A total of 59 patients with ileocolonic, ileocaecal or colonic Crohn's disease.
Bone mass was assessed by dual photon X-ray absorptiometry at the level of L2-L4.
Patients treated with a high lifetime dose of steroids (> 5 g prednisolone) had significantly (P = 0.011) lower Z-score of L2-L4 (-0.87 +/- 1.11; 11 SD) than steroid-treated patients, who had received a low dose of prednisolone (< 5 g) (0.08 +/- 1.16 SD). Azathioprine did not negatively influence the steroid effect on bone mineral density.
Azathioprine does not seem to affect bone mineral density by itself. However, by being steroid-saving, it seems to conserve bone mineral mass in patients with Crohn's disease.
In postmenopausal women, the serum concentrations of endogenous sex hormones and vitamin D might influence the risk of hip and vertebral fractures. In a study of a cohort of women 65 years of age or older, we compared the serum hormone concentrations at base line in 133 women who subsequently had hip fractures and 138 women who subsequently had vertebral fractures with those in randomly selected control women from the same cohort. Women who were taking estrogen were excluded. The results were adjusted for age and weight.
The women with undetectable serum estradiol concentrations (<5 pg per milliliter [18 pmol per liter]) had a relative risk of 2.5 for subsequent hip fracture (95 percent confidence interval, 1.4 to 4.6) and subsequent vertebral fracture (95 percent confidence interval, 1.4 to 4.2), as compared with the women with detectable serum estradiol concentrations. Serum concentrations of sex hormone-binding globulin that were 1.0 microg per deciliter (34.7 nmol per liter) or higher were associated with a relative risk of 2.0 for hip fracture (95 percent confidence interval, 1.1 to 3.9) and 2.3 for vertebral fracture (95 percent confidence interval, 1.2 to 4.4). Women with both undetectable serum estradiol concentrations and serum sex hormone-binding globulin concentrations of 1 microg per deciliter or more had a relative risk of 6.9 for hip fracture (95 percent confidence interval, 1.5 to 32.0) and 7.9 for vertebral fracture (95 percent confidence interval, 2.2 to 28.0). For those with low serum 1,25-dihydroxyvitamin D concentrations (< or =23 pg per milliliter [55 pmol per liter]), the risk of hip fracture increased by a factor of 2.1 (95 percent confidence interval, 1.2 to 3.5).
Postmenopausal women with undetectable serum estradiol concentrations and high serum concentrations of sex hormone-binding globulin have an increased risk of hip and vertebral fracture.
Low bone mineral density (BMD) is common in patients with Crohn's disease; however, the pathogenesis of bone loss and risk factors for osteoporosis are not established. Our aim was to evaluate the clinical, dietary, and nutritional determinants of BMD in Crohn's disease. A cross-sectional analysis of 117 patients with Crohn's disease was undertaken. All patients underwent a clinical and dietary evaluation including assessment of nutritional state and life-style. BMD was measured at the hip and lumbar spine by dual-energy x-ray absorptiometry; and z scores obtained by comparison with age- and sex-matched normal values for the healthy UK population. Multiple regression analysis was used to assess associations between BMD and potential risk factors, allowing for possible confounding variables. Thirteen (11%) patients had osteoporosis (z score < -2), with osteopenia (z score < -1, > -2) in a further 34 (29%). Patients with jejunal disease had significantly lower BMD at the spine (P = 0.03) and femoral neck (P = 0.02) than those with disease at other sites. Mean BMD was significantly lower at the hip of patients with previous bowel resection (diff in means = 0.53, 95% CI -0.97, -0.08, P = 0.02), but type of surgery was not significant. Active disease, menstrual history, diet, level of physical activity, and smoking were not associated with low bone mass. At the lumbar spine, body weight (P < 0.0001), male sex (P < 0.0001), and current prednisolone use (P < 0.02) were independently predictive of low bone mass. Body weight (P < 0.0001), male sex (P < 0.0001), and cumulative steroid dose (P = 0.02) were predictive at the femoral neck. The major determinants of BMD in Crohn's disease are body weight, current steroid use, and cumulative steroid dose. Men with Crohn's disease are at greatest risk of osteoporosis, with jejunal involvement and previous bowel resection also contributing to the low bone mineral density.
We conducted this study to assess bone mineral density and to evaluate conceivable predictive factors for bone loss in patients with Crohn's disease.
One hundred-thirteen patients with Crohn's disease and 113 healthy subjects, individually matched for gender, age, and body weight were investigated. The group consisted of 68 women and 45 men. The median duration of Crohn's disease was 6 yr. Two-thirds of the patients had been subjected to intestinal resection. Seventy-seven percent had at some time been treated with corticosteroids. Bone mineral density in the lumbar spine, the hip, and the total body skeleton was measured by dual-energy X-ray absorptiometry (DEXA).
In patients with Crohn's disease bone mineral density was not different from that of healthy controls except for a regional decrease in bone mineral density of the hip in female patients. The strongest predictors of bone mineral density were gender, age, and body weight. Corticosteroid use was only a weak predictor of diminished bone density. Duration of disease and intestinal resection had no predictive value for bone mineral density.
Gender, age, and body weight are the major determinants of bone mineral density in patients with Crohn's disease. As in healthy individuals, the combined effect of these factors account for up to 50% of the variability in bone mineral density.
The effect of nifedipine administration (10 mg) on esophageal acid exposure time was investigated in 11 non-reflux esophagitis (non-RE) patients and 11 grade C (Los Angeles classification) reflux esophagitis (RE) patients. In each subject, esophageal pH monitoring was performed, with the subject in the supine position, preprandially (1 h) and 3-h postprandially after oral administration of a placebo in the morning and oral administration of nifedipine (10 mg) in the afternoon on the same day. In the non-RE patients, there was no difference in the esophageal acid exposure time between administration of the placebo and that of nifedipine. In patients with RE, the esophageal acid exposure time after the administration of nifedipine was significantly (P<0.05) longer than that after the placebo. In patients with severe RE, the severity of RE may worsen with nifedipine administration.
To study fracture rates and risk factors for fractures in patients with Crohn's disease and ulcerative colitis.
998 self administered questionnaires were issued to members of the Danish Colitis/Crohn Association, and 1000 questionnaires were issued to randomly selected control subjects. 845 patients (84.5%) and 645 controls (65.4%) returned the questionnaire (p<0.01). 817 patients and 635 controls could be analysed.
Analysis was performed on 383 patients with Crohn's disease (median age 39, range 8-82 years; median age at diagnosis 26, range 1-75 years), 434 patients with ulcerative colitis (median age 39, range 11-86 years; median age at diagnosis 29, range 10-78 years), and 635 controls (median age 43, range 19-93 years, p<0.01). The fracture risk was increased in female patients with Crohn's disease (relative risk (RR) = 2.5, 95% confidence interval (CI) 1.7-3.6), but not in male patients with Crohn's disease (RR = 0.6, 95% CI 0.3-1.3) or in patients with ulcerative colitis (RR = 1.1, 95% CI 0.8-1.6). An increased proportion of low energy fractures was observed in patients with Crohn's disease (15.7% versus 1.4 % in controls, 2p<0. 01), but not in patients with ulcerative colitis (5.4%, 2p=0.30). The increased fracture frequency in Crohn's disease was present for fractures of the spine, feet, and toes and fractures of the ribs and pelvis. Fracture risk increased with increasing duration of systemic corticosteroid use in Crohn's disease (2p=0.028), but not in ulcerative colitis (2p=0.50).
An increased risk of low energy fractures was observed in female patients with Crohn's disease, but not in male patients with Crohn's disease or in patients with ulcerative colitis.
Reduced bone mineral density (BMD) is common in patients with inflammatory bowel disease (IBD), but the factors associated with its longitudinal rate of change have not been established. We prospectively assessed the rate of change in BMD, and its association with biochemical markers of bone turnover.
Twenty-two patients with Crohn's disease and 14 ulcerative colitis patients age 37.1 +/- 11.6 yr were followed for 2 yr. Lumbar spine (L2-L4) and femoral neck BMD were measured by dual x-ray absorptiometry at baseline and 24 months. Bone-specific alkaline phosphatase, osteocalcin, urinary N-telopeptide crosslinked type 1 collagen (NTx), parathyroid hormone, and 25-hydroxyvitamin-D were determined at baseline.
At baseline, 59% of Crohn's patients and 43% of ulcerative colitis patients were osteoporotic, with spine or femoral neck BMD T-score < -2.5. Spine BMD, and spine and femoral neck T-scores were lower and disease duration was longer in nine patients with ileal resection compared with nonoperated patients (0.84 +/- 0.15 g/cm2 vs 0.96 +/- 0.11 g/cm2, -3.0 +/- 1.5 vs -1.7 +/- 1.3, -3.2 +/- 1.5 vs -2.2 +/- 1.0, respectively; all p < 0.05). At 24 months, 13/36 (36%) and 14/36 (39%) patients experienced spinal and femoral neck bone loss, respectively, with mean annual percent BMD changes of -2.0% and -1.5%, respectively. NTx, a bone resorption marker, inversely correlated with spinal BMD rate of change (r = -0.4, p < 0.05). Using quartiles analysis, patients with the highest NTx (Q4) experienced the greatest decrease in spine BMD compared with patients with the lowest NTx (Q1).
Spine and femoral neck bone loss continues over time in more than one-third of IBD patients. Increased NTx level predicts spinal bone loss in IBD patients.
When the World Health Organization (WHO) guidelines for the definition of osteoporosis in postmenopausal women were identified similar proposals were not developed for men as there was insufficient evidence about the relationship between bone density and fracture in men. We have therefore examined the relationship between bone density and vertebral fracture in men and women attending for assessment of possible osteoporosis. Two hundred and sixty-four women (age 64 [SD 10] years) and 37 men (age 55 [10] years) were studied. Bone density was measured in the lumbar spine and femoral neck by dual-energy X-ray absorptiometry and expressed both as bone mineral density (BMD; g/cm2) and as T-scores. In both sexes there was a sigmoid relationship between the cumulative frequency of vertebral fracture and bone density at both sites. There was a linear relationship between the log odds of fracture and bone mass for both sexes and both sites (r = 0.97-0.99; p < 0.0001). The slope of these lines was significantly steeper for men than women. The BMD at which there was 50% risk of fracture was higher in men than women (0.908 vs 0.844 g/cm2). The difference between the slopes was similar when the bone mass was expressed as a T-score. However, the T-score associated with 50% prevalence of fracture was similar in the two sexes (F: -2.77 vs M: -2.60). We conclude that although there is a different relationship between bone density and fracture in the two sexes the current WHO definition of osteoporosis in postmenopausal women can be appropriately applied to men.
Vertebral fractures (VFX) are caused by low bone mass and microstructural deterioration of bone tissue. The latter is not well defined. We investigated bone structure in transiliac biopsy specimens from 88 volunteers. Biopsy specimens were obtained at baseline in the Multiple Outcomes of Raloxifene Evaluation trail, a prospective study in osteoporotic (BMD < or = -2.5 T score) postmenopausal women without or with VFX on standardized lateral spinal radiographs. Bone biopsy specimens were embedded in methylmethacrylate (MMA). Histomorphometry was done in 8 microns (U.S.A.) or 5 microns (Europe) Goldner stained sections. Vertebral fracture status (yes/no) was the outcome variable in logistic regression models adjusted for age and biopsy specimen origin (U.S.A. vs. Europe). Patients with and without VFX (26/62) were similar regarding age (69.2 +/- 5.2 years vs. 67.3 +/- 6.7 years), bone volume (BV/TV; 17.7 +/- 4.7% vs. 19.0 +/- 5.8%), and bone surface (BS/TV; 2.7 +/- 0.6 mm2/mm3 vs. 2.8 +/- 0.6 mm2/mm3). A lower cortical thickness (C.Th; 652 +/- 267 microns vs. 822 +/- 325 microns), total strut length (TSL; 826 +/- 226 microns/mm2 vs. 922 +/- 256 microns/mm2), node-to-loop (Nd-Lp) strut length (10.1 +/- 10.3% vs. 15.0 +/- 13.6%), together with a higher node-to-terminus (Nd-Tm) strut length (45.6 +/- 9.7% vs. 39.1 +/- 9.3%) were each associated with prevalent VFX (0.01 < p < 0.10). Differences in BV/TV did not explain these associations. In conclusion, cortical thinning and disruption of trabecular lattice are possible pathogenic mechanisms in patients with VFX.
The diagnosis of osteoporosis is based on bone mass measurement. To avoid the errors associated with the measurement of spinal bone density the total hip has been accepted as the standard measurement site. This information is not available for many early measurements. We have assessed whether it is possible to derive clinically useful information about total hip bone mineral density (BMD) from measurements at other hip sites. The bone mass measurements of 46 patients participating in a current trial of therapy for osteoporosis were reviewed. The total hip BMD as directly measured was compared with that obtained from the formula: Total hip BMD = 0.48×Neck BMD + 0.62×Trochanteric BMD + 0.03. In 30 patients with follow-up data the rate of change in hip BMD over a year was also determined by both methods. In the pretreatment state there was good agreement between the two measures (r
2 = 0.96, SEE 0.012 g/cm2). If the formula was used to compute a change in total hip BMD, the agreement between both methods remained good. However, the standard error of the estimate of the change represented 59% of the observed change. This indicates that the error associated with this estimate is too great to allow clinically meaningful conclusions to be drawn from calculated total hip BMD. We conclude that, whilst it may be possible to obtain reasonable point estimates of total hip BMD from other measures in the hip, these estimates are too imprecise to allow conclusions about change in BMD to be made.