DXA summary for changes in lumbar spine BMD from pre-operative to...

Trabecular bone score, bone marrow fat and vertebral fractures in cushing syndrome

Article

Full-text available

Feb 2023
ENDOCRINE

Objective Prediction of fragility fractures in Cushing syndrome (CS) is a challenge since dual energy X-ray absorptiometry (DXA) measurement of bone mineral density (BMD) does not capture all the alterations in bone microstructure induced by glucocorticoid excess. In this study we investigated the relationship between trabecular bone score (TBS), bone marrow fat (BMF) and vertebral fractures (VFs) in endogenous CS. Design Cross-sectional. Methods Thirty subjects (7 M and 23 F, mean age 44.8 ± 13.4 yrs, range: 25–71) with active hypercortisolism were evaluated for VFs by quantitative morphometry, BMD and TBS by lumbar spine DXA and BMF by single-voxel magnetic resonance spectroscopy of vertebral body of L3. Results Subjects with VFs (17 cases; 56.7%) had higher BMF (P = 0.014) and lower BMD T-score (P = 0.012) and TBS (P = 0.004) as compared to those without VFs. Prevalence of VFs resulted to be significantly higher in individuals with impaired TBS as compared to those with normal TBS (77.8% vs. 25.0%; P = 0.008). Among patients with VFs, only 6 (35.3%) had either osteoporosis or “low BMD for age”. In logistic regression analysis, impaired TBS maintained the significant association with VFs [odds ratio (OR) 6.60, 95% C.I. 1.07–40.61; P = 0.042] independently of BMF (OR 1.03, 95% C.I. 0.99–1.08; P = 0.152). Conclusions TBS might be more accurate than BMF in identifying subjects with active CS and skeletal fragility at risk of VFs. Significance statement Excess in glucocorticoids is associated with alterations in bone remodeling and metabolism, leading to fragility fractures regardless of bone mineral density, making more challenging for the clinician the identification of high-risk population and the definition of preventing strategies. In this context, instrumental parameters suggestive of bone quality alterations and predictive of increased fracture risk are needed. In this study, we found CS patients to have bone quality alterations as indicated by the decreased trabecular bone score and increased bone marrow fat, as measured by DEXA and MRI respectively. Both parameters were associated with high risk of VFs, and were inversely correlated, although TBS seems to be more accurate than BMF in fractures prediction in this clinical setting.

Novel approaches to bone comorbidity in Cushing’s disease: an update

Article

Full-text available

Jul 2022
PITUITARY

Skeletal complications are frequent and clinically relevant findings in Cushing's disease (CD) since an uncoupled suppressed bone formation and enhanced bone resorption leads to a marked skeletal damage with a rapid increase of fracture risk. Reduced Bone Mineral Density (BMD) has been consistently reported and osteopenia or osteoporosis are typical findings in patients with CD. Vertebral Fractures (VFs) are frequently reported and may occur even in patients with an only mild reduction of BMD, representing nowadays a still under- or misdiagnosed comorbidity of these patients being frequently asymptomatic. A novel approach combining different available tools such as BMD evaluation and vertebral morphometry, in order to improve diagnosis, management, and follow-up of bone comorbidity in all patients affected by CD, is needed. This approach is foreseen to be a crucial part of management of patients with CD, particularly in Pituitary Tumor Center of Excellence since VFs, the landmark of the bone involvement, may occur early in the history of the disease and may represent a relevant risk factor for further fractures, reduced quality of life and survival and need for pharmacologic prevention and treatment.

Glucocorticoids and Trabecular Bone Score

Article

Full-text available

Oct 2020

TBS (Trabecular Bone Score) is the latest tool for clinicians to evaluate bone micro-architecture based on a pixel greyscale, which is provided by lumbar dual-energy X-ray absorptiometry (DXA). Its use enhances fracture prediction in addition to DXA-BMD (Bone Mineral Density). This is independent of fracture risk assessment (FRAX) and DXA results. We present a narrative review regarding the connection between TBS and Glucocorticoids (GC), either as a drug used for different conditions or as a tumor-produced endogenous excess. TBS is a better discriminator for GC-induced vertebral fractures compared to DXA-BMD. This aspect is similarly available for patients with osteoporosis diagnosed by DXA. TBS is inversely correlated with the cumulative dose of GC (systemic or inhaled), with disease duration, and positively correlated with respiratory function in patients with asthma. Low TBS values are found in females with a T-score at the hip within the osteoporosis range, with diabetes mellitus, or who use GC. Lumbar TBS is a screening tool in menopausal women with type 2 diabetes mellitus. TBS is an independent parameter that provides information regarding skeleton deterioration in diabetic patients receiving GC therapy in a manner complementary to DXA-BMD. TBS might become an essential step regarding the adrenalectomy decision in patients with adrenal incidentaloma in whom autonomous cortisol secretion might damage bone micro-architecture. TBS currently represents a standard tool of fracture risk evaluation in patients receiving GC therapy or with endogenous Cushing’s syndrome, a tool easy to be applied by different practitioners since GCs are largely used

The changes of standard DXA measurements and TBS depending on outcomes of neurosurgical treatment in patients with Cushing's diseaseFig. 1. Changes in trabecular bone index and bone mineral density in patients with NIR after neurosurgical intervention

Article

Full-text available

Apr 2019

BACKGROUND:Patients with endogenous hypercortisolism have reduced bone mineral density (BMD) and trabecular bone score (TBS) that are the causes of secondary osteoporosis and low-traumatic fractures. It is well known that radical treatment (neurosurgery or radiosurgery) of Cushings disease leads to a decline of cortisol levels in all body fluids to normal values. However, it is still uncertain whether bone tissue structure, and particularly its microarchitecture, does recover in remission of the disease. AIMS:To evaluate an influence of hormone activity (presence or absence of remission) in patients with Cushing's disease on changes of bone structure measurements in accordance with DXA values (TBS, BMD, T- and Z-scores), as well as significance of such changes in 12 and 24 months after neurosurgical treatment. MATERIALS AND METHODS:In patients with confirmed active Cushing's disease (ACTH-producing pituitary adenoma) (n = 44) and in control group of healthy volunteers (n = 40), BMD in lumbar spine (L1-L4) and simultaneously TBS, in cut-off points before neurosurgical treatment (in both groups) and in 12 and 24 months after it (only in patients), were assessed. We diagnosed presence or absence of disease remission at cut-offs. All measurements were performed using a GE iDXA device (GE Healthcare Lunar, Madison, Wisconsin, USA). The TBS was calculated simultaneously from taken BMD scans, blinded to clinical outcome using TBS iNsight software v2.1 (Medimaps, Merignac, France). The activity of Cushings disease was evaluated using late-night salivary cortisol (LNSC, at 23:00). To determine the differences in DXA and TBS values before and after neurosurgical intervention depending on remission occurrence, covariate analysis (ANCOVA) was applied. RESULTS:There were found significant changes in TBS, BMD and T-score values in 12 months after neurosurgical treatment associated with presence or absence of disease remission (p = 0.039, 0.046 and 0.048, respectively). No differences in Z-score as well as in all measurements in 24 months, that might be associated with remission occurrence, were revealed. The gain in all DXA measurements (including TBS) during 24 months of observation period was statistically significant when analyzing data using Students paired t-test. However, the values corresponding to the age references had not been achieved for the specified time interval. CONCLUSIONS:Patients with Cushings disease have lower TBS values. In remission conditions TBS is getting significantly higher. The increase in BMD and TBS occurs during 24 months after achieving remission of Cushings disease but doesnt lead to a full restoration of normal bone mass and microstructure throughout observation period of 24 months.

The risk factors for fractures and trabecular bone-score value in patients with endogenous Cushing's syndrome

Article

Full-text available

Nov 2015

Introduction: The aim was to estimate the risk factors for fracture in subjects with endogenous Cushing's syndrome (CS) and to evaluate the value of the TBS in these patients. Methods: All enrolled patients with CS (n = 182) were interviewed in relation to low-traumatic fractures and underwent lateral X-ray imaging from T4 to L5. BMD measurements were performed using a DXA Prodigy device (GEHC Lunar, Madison, Wisconsin, USA). The TBS was derived retrospectively from existing BMD scans, blinded to clinical outcome, using TBS iNsight software v2.1 (Medimaps, Merignac, France). Urinary free cortisol (24hUFC) was measured by immunochemiluminescence assay (reference range, 60-413 nmol/24 h). Results: Among enrolled patients with CS (149 females; 33 males; mean age, 37.8 years (95 % confidence interval, 34.2-39.1); 24hUFC, 2370 nmol/24 h (2087-2632), fractures were confirmed in 81 (44.5 %) patients, with 70 suffering from vertebral fractures, which were multiple in 53 cases; 24 patients reported non-vertebral fractures. The mean spine TBS was 1.207 (1.187-1.228), and TBS Z-score was -1.86 (-2.07 to -1.65); area under the curve (AUC) was used to predict fracture (mean spine TBS) = 0.548 (95 % CI, 0.454-0.641)). In the final regression model, the only predictor of fracture occurrence was 24hUFC levels (p = 0.001), with an increase of 1.041 (95 % CI, 1.019-1.063), calculated for every 100 nmol/24-h cortisol elevation (AUC (24hUFC) = 0.705 (95 % CI, 0.629-0.782)). Conclusions: Young patients with CS have a low TBS. However, the only predictor of low traumatic fracture is the severity of the disease itself, indicated by high 24hUFC levels.

Osteoporosis and arthropathy in functioning pituitary tumors

Chapter

Jan 2021

Pituitary adenomas are relatively rare endocrine conditions; approximately two-thirds of the tumors are hormone secreting. Although, in general, pituitary adenomas are histologically benign, patients experience severe morbidity due to mass effects of the tumor, systemic complications of hormonal overproduction, and hypopituitarism, resulting in an increased overall mortality and decreased quality of life in these patients. Early diagnosis and effective treatment are cornerstones in the management of functioning pituitary tumors, since appropriate therapy can improve many systemic comorbid conditions considerably. However, during the last years, there is increasing awareness for late manifestations of transient hormone excess despite long-term remission, as is the case for skeletal complications. In this chapter, we outline the skeletal manifestations of patients with functioning pituitary tumors, focusing on osteoporosis and arthropathy. We summarize current pathophysiological ideas, the clinical picture with its determinants before and after adequate treatment, and a disease-specific approach to the skeletal complications.

Osteopathy in mild adrenal Cushing’s syndrome and Cushing disease

Article

Mar 2021
BEST PRACT RES CL EN

Pathophysiology and effects of endogenous glucocorticoid (GC) excess on skeletal endpoints as well as awareness and management of bone fragility are reviewed. Cushing’s syndrome (CS) increase the risk of fracture affecting prevalently bone quality. Bone antiresorptive agents (SERMs, bisphosphonates and denosumab) as well as teriparatide increase bone mineral density and in some instances reduce fracture risk. Awareness and management of bone health in CS can be improved.

Assessment of vertebral microarchitecture in overt and mild Cushing's syndrome using trabecular bone score

Article

May 2018
CLIN ENDOCRINOL

Objective Osteoporotic fractures associated with Cushing's syndrome (CS) may occur despite normal bone mineral density (BMD). Few studies have described alterations in vertebral microarchitecture in glucocorticoid‐treated patients and during CS. Trabecular bone score (TBS) estimates trabecular microarchitecture from dual‐energy X‐ray absorptiometry acquisitions. Our aim was to compare vertebral BMD and TBS in patients with overt CS and mild autonomous cortisol secretion (MACE), and following cure of overt CS. Setting University hospital. Design Monocentric retrospective cross‐sectional and longitudinal studies of consecutive patients. Patients 110 patients were studied: 53 patients had CS (35, 11 and 7 patients with Cushing's disease, bilateral macronodular adrenal hyperplasia and ectopic ACTH secretion respectively); 39 patients had MACE (10 patients with a late post‐operative recurrence of Cushing's disease and 29 patients with adrenal incidentalomas); 18 patients with non‐secreting adrenal incidentalomas. 14 patients with overt CS were followed for up to 2 years after cure. Results Vertebral osteoporosis at BMD and degraded microarchitecture at TBS were found in 24% and 43% of patients with CS, respectively (p<0.03). As compared to patients with non‐secreting incidentalomas, patients with MACE had significantly decreased TBS (p< 0.04) but not BMD. Overt fragility fractures tended to be associated with low TBS (p = 0.07) but not with low BMD. TBS, but not BMD values, decreased with the intensity of hypercortisolism independently of its etiology (p <0.01). Following remission of CS, TBS improved more markedly and rapidly than BMD (10% vs 3%, respectively; p< 0.02). Conclusion TBS may be a promising, non‐invasive, widely available and inexpensive complementary tool for the routine assessment of the impact of CS and MACE on bone in clinical practice. This article is protected by copyright. All rights reserved.

Pituitary Diseases and Bone

Article

Apr 2018
ENDOCR REV

Neuroendocrinology of bone is a new area of research based on the evidence that pituitary hormones may directly modulate bone remodeling and metabolism. Skeletal fragility associated with high risk of fractures is a common complication of several pituitary diseases such as hypopituitarism, Cushing disease, acromegaly and hyperprolactinemia. As in other forms of secondary osteoporosis, pituitary diseases generally affect bone quality more than bone quantity and fractures may occur even in the presence of normal or low-normal bone mineral density as measured by dual-energy X-ray absorptiometry, making difficult the prediction of fractures in these clinical settings. Treatment of pituitary hormone excess and deficiency generally improves skeletal health, although some patients remain at high risk of fractures and treatment with bone-active drugs may become mandatory. Aim of this review will be to discuss the physiological, pathophysiological and clinical insights of the bone involvement in pituitary diseases.

Trabecular bone score as one of the new methods of non-invasive evaluation of bone microarchitecture in patients with Cushing’s syndrome

Article

Full-text available

Aug 2015

Objective - to evaluate the value of trabecular bone score and risk factors of fractures in patients with Cushing’s syndrome (CS). Material and methods. One hundred eighty two patients with laboratory-confirmed Cushing’s syndrome were enrolled. All patients underwent measurement of bone mineral density (BMD) at the lumbar spine (LI-LIV), femoral neck and total hip using DXA Prodigy (GEHC Lunar, Madison, WI, USA). Trabecular bone score (TBS) was assessed retrospectively on the basis of already existing DXA images using software TBS iNsight software v2.1 (Medimaps, Merignac, France). Each patient was interviewed for the presence of low-traumatic fractures during the active stage of the disease. A lateral X-ray of the thoracic and lumbar spine ThIV-LV was performed to estimate vertebral fractures. Twenty-four hours urinary free cortisol (24hUFC) was measured by imunochemiluminescence assay VITROS ECi with the preliminary extraction with diethyl ether (reference values 60-413 nmol/24 h). Results. Among 182 patients with CS (149 women, 33 men), Cushing’s disease was confirmed in 151 cases, 9 patients diagnosed with benign adrenal tumor and 22 - ACTH-ectopic syndrome. The median of age - 35 (Q25-Q75 27-49) years, body mass index - 29 (26-33) kg/m2, 24hUFC - 1760 (985-2971) nmol/24h. Fractures were confirmed in 80 (44%) cases, 70 patients suffered from vertebral fractures, which were multiple in 53 cases; 23 patients had non-vertebral fractures. Median of trabecular bone score was 1.205 (1.102-1.307), which is much lower than expected in healthy volunteers (>1.350), while the decrease in bone mineral density (BMD) did not correspond to the severity and prevalence of osteoporosis fractures: LI-LIV Z-score - 1.7 (2.5-0.73); femoral neck Z-score - 1 (-1.6- -0.4). However, when using binary logistic regression analysis (adjusted for sex, age, body mass index, bone mineral density, trabecular bone score and 24hUFC) revealed that the most significant predictor of fracture is high levels of 24hUFC (p=0.001) . The high prevalence of vertebral fractures in patients with CS most likely influenced the results of trabecular bone score and its ability to predict fractures. Conclusion. Patients with active CS have low trabecular bone score, rather than bone mineral density, which reflects deterioration in bone microarchitecture. The low-traumatic fracture occurrence depends on the severity of CS reflected in 24hUFC levels.

DXA summary for changes in lumbar spine BMD from pre-operative to 5years post-surgery: initially to 8months post-surgery treatment with calcium and vitamin D alone, then TPTD for the next 2years then one infusion with zoledronate.

Citations