Figure 1 - available via license: Creative Commons Attribution 4.0 International
Content may be subject to copyright.
Hip MRI reveals a right femur subtrochanteric fracture (arrows). MRI\u200A=\u200Amagnetic resonance imaging.
Source publication
Bisphosphonates have been commonly used for the treatment of osteoporosis. However, there have been recent case reports of atypical fractures citing their long-term use, which inhibits the turnover of bone components.
A 64-year-old woman visited the outpatient clinic with pain in her right thigh and ambulation difficulty. We found fractures at both...
Similar publications
Rib fractures are one of main causes of chest or flank pain when related to an osteoporotic vertebral compression fracture (OVCF). The authors investigated the incidence and risk factors of rib fracture in 284 patients with OVCF using bone scans and evaluated the feasibility as to whether bone scans could be utilized as a useful screening tool. Hot...
Background and purpose — Patients with osteoporosis who present with an acute onset of back pain often have multiple fractures on plain radiographs. Differentiation of an acute osteoporotic vertebral fracture (AOVF) from previous fractures is difficult. The aim of this study was to investigate the incidence of concomitant AOVFs and previous OVFs in...
Osteocytes are contained within spaces called lacunae and play a central role in bone remodelling. Administered frequently to prevent osteoporotic fractures, antiresorptive agents such as bi-sphosphonates suppress osteocyte apoptosis and may be localized within osteocyte lacunae. Bisphosphonates also reduce osteoclast viability and thereby hinder t...
Citations
... Bisphosphonates are commonly used for the treatment of osteoporosis and have recently been associated with atypical fractures after prolonged exposure. Kim et al (6) published a case of a 64-year-old woman who presented with bilateral atypical femoral and L4 pedicle fractures after a 3-year treatment with intravenous ibandronate. ...
of atypical femoral fractures is a known complication of chronic bisphosphonate therapy; however, the finding of atraumatic lumbar pedicle fractures without a prior history of spinal surgery or contralateral spondylolysis is rare. While a few cases of osteoporotic pedicle fractures associated with adjacent vertebral compression fractures have been reported, only a single case of isolated atraumatic bilateral pedicle fractures has been published in a patient who had been on chronic risedronate therapy of 10-year duration. Case Report: The present case report illustrates a 63-year-old man who developed isolated atraumatic bilateral lumbar pedicle fractures after 3 years and 5 months on alendronate treatment. The patient’s past medical history had been significant for osteoporosis with a lumbar spine T-score of -2.7. At the time of initial diagnosis, a comprehensive work-up for secondary causes of osteoporosis proved to be negative; this was followed by initiation of bisphosphonate treatment with 70 mg of alendronate once per week. Ten months after starting bisphosphonate therapy, he underwent magnetic resonance imaging (MRI) of the lumbar spine for low back pain that had not responded to conservative management, with imaging not revealing any evidence of pedicle fractures or pedicle stress reaction. He was again seen in the spine clinic, for atraumatic exacerbation of his chronic low back pain with concurrent right lower extremity radiation, 6 months after stopping bisphosphonate therapy. Since the patient failed to respond to conservative management over the ensuing 6 months, a repeat MRI was obtained, which showed new acute/subacute bilateral L5 pedicle fractures. Conclusion: An isolated atraumatic lumbar pedicle fracture may be an additional type of atypical fracture associated with chronic bisphosphonate therapy in an osteoporotic patient. Key words: Chronic low back pain, bisphosphonate, alendronate, pedicle fracture Pain Medicine
... Commonly, these symptoms were transient in duration and mild to moderate in intensity, and according to NSAID, the incidence and intensity of such an APR could be efficiently impeded (Ding et al., 2017). Additionally, the atypical femoral fracture (AFF), an unusual atraumatic or minimal-trauma fracture, has also been reported with increasing frequency in long-term diphosphonate users since the first case reports were published in 2005 (Kim et al., 2015). A unique case of AFF after diphosphonate therapy was discovered in 2014, but the patient had a successful recovery through conservative treatment (Pazianas & Smith, 2014). ...
Background
This study aimed to draw a series of scientific maps to quantitatively and qualitatively evaluate hot spots and trends in postmenopausal osteoporosis research using bibliometric analysis.
Methods
Scientific papers published on postmenopausal osteoporosis were extracted from the Web of Science Core Collection and PubMed database. Extracted information was analyzed quantitatively with bibliometric analysis by CiteSpace, the Online Analysis Platform of Literature Metrology and Bibliographic Item Co-Occurrence Matrix Builder (BICOMB). To explore the hot spots in this field, co-word biclustering analysis was conducted by gCLUTO based on the major MeSH terms/MeSH subheading terms-source literatures matrix.
Results
We identified that a total of 5,247 publications related to postmenopausal osteoporosis were published between 2013 and 2017. The overall trend decreased from 1,071 literatures in 2013 to 1,048 literatures in 2017. Osteoporosis International is the leading journal in the field of postmenopausal osteoporosis research, both in terms of impact factor score (3.819) and H-index value (157). The United States has retained a top position and has exerted a pivotal influence in this field. The University of California, San Francisco was identified as a leading institution for research collaboration, and Professors Reginster and Kanis have made great achievements in this area. Eight research hot spots were identified.
Conclusions
Our study found that in the past few years, the etiology and drug treatment of postmenopausal osteoporosis have been research hot spots. They provide a basis for the study of the pathogenesis of osteoporosis and guidelines for the drug treatment of osteoporosis.
... Generally, conservative treatment is only an option for cases of incomplete fracture 13 , but AFF rarely heals spontaneously and most patients require surgery 14,15 . Specifically, teriparatide appears to promote AFF healing 16 , so weight-bearing gait rehabilitation during teriparatide treatment 17,18 might be a good conservative treatment option for some patients. We believe that teriparatide therapy enhanced the bone union in our patient. ...
An 82-year-old woman had been taking alendronate for 5 years and 5 months, which had been prescribed for osteoporosis at a local clinic. Severe left thigh pain began without any trauma. X-ray, computed tomography and magnetic resonance imaging findings showed atypical femoral fracture（AFF）. Treatment with teriparatide and weight-bearing therapy was selected. Bone union was achieved without surgery. Teriparatide has been reported to promote AFF healing. At four years and 9 months from the beginning of treatment, our patient has no left femoral pain and no impairment to activities of daily living. Careful follow-up will be necessary as long-term outcomes of conservative AFF treatment have not been reported to date.
... Several authors have reported on successful conservative approaches for incomplete AFFs [29,30]. However, recognizing that a large proportion of incomplete AFFs will progress to complete fractures without surgical fixation mandates prophylactic surgical intervention [7,8]. ...
Little evidence is available on how to treat incomplete atypical fractures of the femur. When surgery is chosen, intramedullary nailing is the most common invasive technique. However, this approach is adopted from the treatment of other types of ordinary femoral fracture and does not aim to prevent the impending complete fracture by interrupting the mechanism underlying the pathology. We suggest a different surgical approach that intends to counteract the underlying biomechanical conditions leading to a complete atypical fracture and thus could be better suited in selected cases. Here, we share an alternative surgical approach and present two cases treated accordingly.
... The duration of bisphosphonate treatment ranged from 0.04 to 20 years. Concomitant glucocorticoid use could be assessed in 272 patients, 20,21,24,26,28,30,31,33,36,37,40,41,44,46,48,50,51,[54][55][56][57][60][61][62][63][64][65][66][67][68][69][70][71][72]74,75,77,79,80,86,[88][89][90][91][92][93][94] and was given to 49 patients (18%). Complete fracture. ...
Aims:
Treatment guidelines for atypical femoral fractures associated with bisphosphonates have not been established. We conducted a systematic review of the treatment of atypical femoral fractures first, to evaluate the outcomes of surgical fixation of complete atypical fractures and secondly, to assess whether prophylactic surgery is necessary for incomplete atypical fractures.
Materials and methods:
Case reports and series were identified from the PubMed database and were included if they described the treatment of atypical femoral fractures. In total, 77 publications met our inclusion criteria and 733 patients with 834 atypical complete or incomplete femoral fractures were identified.
Results:
For complete fractures, internal fixation was predominantly achieved by intramedullary nailing. The mean time to healing post-operatively was 7.3 months (2 to 31). Revision surgery for nonunion or implant failure was needed in 77 fractures (12.6%). A greater percentage of fractures treated with plate fixation (31.3%) required revision surgery than those treated with intramedullary nailing (12.9%) (p < 0.01). Non-operative treatment of incomplete fractures failed and surgery was eventually needed in nearly half of the patients (47%), whereas prophylactic surgery was successful and achieved a 97% rate of healing.
Conclusion:
Intramedullary nailing is the first-line treatment for a complete fracture, although the risk of delayed healing and revision surgery seems to be higher than with a typical femoral fracture. Non-operative treatment does not appear to be a reliable way of treating an incomplete fracture: prophylactic intramedullary nailing should be considered if the patient is in intractable pain. Radiographs of the opposite side should be obtained routinely looking for an asymptomatic fracture. Bisphosphonates must be discontinued but ongoing metabolic management in the form of calcium and/or vitamin D supplements is advisable. Teriparatide therapy can be considered as an alternative treatment. Cite this article: Bone Joint J 2017;99-B:295-302.
... Long-term pamidronate in a young patient has been described in another report [42] as inducing an osteopetrotic state mimicking the characteristic bone-in-bone radiological sign. While no fractures are reported in that case, Whytes's patient's bilateral vertebral pedicle fractures have also been observed in three separate BP exposed individuals [43,44,45], respectively after 3 years of IV ibandronate, after 4 years of weekly alendronate, and after 10 years of risedronate. In addition, another atraumatic 3-level bilateral pedicle fracture in an elderly man, previously diagnosed two years before as osteoporotic, was reported in 2006. ...
Aims: Responding to the steadily increasing number of unusual subtrochanteric and mid-shaft
femoral (ST/FS) fractures in persons treated with the bisphosphonate drugs since the index cases
were described in 2003, the American Society of Bone and Mineral Research (ASBMR) convened
a committee tasked with finding a precise definition. Their present definition, a composite from two
publications, includes the morphological characteristics of low trauma, origin as an insufficiency
fracture, transverse/oblique orientation with/without comminution, cortical thickening, and beaking
at the cortex when complete. These fractures must occur in mid-femur, below the lesser trochanter
and above the supracondylar flare. They became known as Atypical Femur Fractures (AFFs).
The index cases included about an equal number of fractures meeting this definition and similar
fractures in other locations. Despite this, attention was focused on the ST/FS definition and a large
number of publications ensued describing these. However, publications in the medical literature as
early as 1986 contained descriptions of non-femur fractures associated with bisphosphonate
therapy and the number of these reported has grown slowly contemporaneously with reports of
femur fractures meeting the ASBMR definition.
The present authors have been following the development of these non-AFF bisphosphonate-associated
fractures since 2005 and have collected a large amount of historical and current
information on the subject. We find that many useful inferences about the phenomenon can be
derived from consideration of it as a systemic rather than localized effect. We aim to provide a
summary of this subset up to the present time and to discuss the implications of these data.
Methodology: We queried the OVID Medline database as detailed below.
Results and Discussion: We identified 102 individual or case series which reported more than
166 atypical non-AFF fractures. In the Discussion, we review the current state of the evidence
upon which the assumed antifracture benefit of the drugs rests and show that these atypical
fractures, when added to the AFFs, reduce even more the typically claimed benefit-to-harm ratio.
Conclusion: We intend this review as a resource for individuals wishing to follow developments in
this field. We also present our conclusions about the implications of the accumulated evidence and
the general state of associated knowledge.
Postmenopausal osteoporosis is a systemic metabolic disease that chronically endangers public health and is typically characterized by low bone mineral density and marked bone fragility. The excessive bone resorption activity of osteoclasts is a major factor in the pathogenesis of osteoporosis; therefore, strategies aimed at inhibiting osteoclast activity may prevent bone decline and attenuate the process of osteoporosis. Casticin (Cas), a natural compound, has anti‑inflammatory and antitumor properties. However, the role of Cas in bone metabolism remains largely unclear. The present study found that the receptor activator of nuclear factor‑κΒ (NF‑κB) ligand‑induced osteoclast activation and differentiation were inhibited by Cas. Tartrate‑resistant acid phosphatase staining revealed that Cas inhibited osteoclast differentiation, and bone resorption pit assays demonstrated that Cas affected the function of osteoclasts. Cas significantly reduced the expression of osteoclast‑specific genes and related proteins, such as nuclear factor of activated T cells, cytoplasmic 1 and c‑Fos at the mRNA and protein level in a concentration‑dependent manner. Cas inhibited osteoclast formation by blocking the AKT/ERK and NF‑κB signaling pathways, according to the intracellular signaling analysis. The microcomputed tomography and tissue staining of tibiae from ovariectomized mice revealed that Cas prevented the bone loss induced by estrogen deficiency and reduced osteoclast activity in vivo. Collectively, these findings indicated that Cas may be used to prevent osteoporosis.
