Sounds like it's at the level of some case reports. I wonder if it's related to Vitamin D deficiency:
Drug Saf. 2009;32(9):775-85. doi: 10.2165/00002018-200932090-00002.
Low-energy femoral fractures associated with the long-term use of bisphosphonates: a case series from a Swiss university hospital.
Ing-Lorenzini K,
Desmeules J,
Plachta O,
Suva D,
Dayer P,
Peter R.
Division of Clinical Pharmacology and Toxicology, Regional Pharmacovigilance Centre, University Hospitals of Geneva, Geneva, Switzerland.
BACKGROUND: Bisphosphonates are effective and well tolerated anti-resorptive drugs used for the treatment of osteoporosis. However, some concerns about their potential long-term negative effects are emerging. OBJECTIVE: We report a series of patients with a history of bisphosphonate treatment admitted to our institution with a low-energy subtrochanteric fracture. PATIENTS AND METHODS: Eight patients fulfilling these two criteria within the last 2 years were included in our retrospective analysis. All cases were reported to the Swiss National Pharmacovigilance Centre. RESULTS: All patients presented with a typical radiological pattern consisting of a cortical thickening at the lateral femoral subtrochanteric cortex with a horizontal fracture line originating precisely at this level. Four patients eventually developed a stress fracture or complete fracture of the contralateral femur. Two patients demonstrated delayed healing of their fracture. Five patients had been on alendronate therapy for a period ranging from 16 months to 8 years, two had been on ibandronate for 4 months and 1 year, respectively, after changing from alendronate, and one patient had been on pamidronate until 1 year before the fracture occurred. Seven patients were also receiving long-term proton pump inhibitor (PPI) treatment which could have contributed to the increased risk of fracture. Four patients were receiving both PPI and long-term corticosteroid treatment. The hypothesis of a negative pharmacodynamic interaction between bisphosphonates, PPIs and corticosteroids which could lead to a decrease in bone strength after long-term use needs further investigation. CONCLUSION: Prescribers should be aware of the possibility of these rare adverse reactions and the prolonged use of bisphosphonates should be reconsidered until long-term robust safety data are available.
PMID: 19670917 [PubMed - indexed for MEDLINE]
J Bone Joint Surg Am. 2009 Nov;91(11):2556-61.
Bilateral low-energy simultaneous or sequential femoral fractures in patients on long-term alendronate therapy.
Capeci CM,
Tejwani NC.
Department of Orthopaedic Surgery, New York University Hospital for Joint Diseases, 301 East 17th Street, Suite 1401, New York, NY 10003, USA.
craig.capeci@nyumc.org
BACKGROUND: While alendronate therapy has been shown to decrease the risk of vertebral and femoral neck fractures in postmenopausal osteoporotic patients, recent reports have associated long-term alendronate therapy with unilateral low-energy subtrochanteric and diaphyseal femoral fractures in a small number of patients. To our knowledge, there has been only one report of sequential bilateral femoral fractures in patients on long-term bisphosphonate therapy. METHODS: We retrospectively reviewed the case log of the senior author over the last four years to identify patients who presented with a subtrochanteric or diaphyseal femoral fracture after a low-energy mechanism of injury (a fall from standing height or less) and who had been taking alendronate for more than five years. Radiographs were reviewed, and the fracture patterns were recorded. Serum calcium levels were recorded when available. RESULTS: Seven patients who sustained low-energy bilateral subtrochanteric or diaphyseal femoral fractures while on long-term alendronate therapy were identified. One patient presented with simultaneous bilateral diaphyseal fractures, two patients had sequential subtrochanteric fractures, and four patients had impending contralateral subtrochanteric stress fractures noted at the time of the initial fracture. Of the latter four, one patient had a fracture through the stress site and the other three patients had prophylactic stabilization of the site with internal fixation. No patient had discontinued alendronate therapy prior to the second fracture. All patients were women with an average age of sixty-one years, and they had been on alendronate therapy for an average of 8.6 years. All fractures were treated with reamed intramedullary nailing and went on to union at an average of four months. CONCLUSIONS: In patients on long-term alendronate therapy who present with a subtrochanteric or diaphyseal femoral fracture, we recommend radiographs of the contralateral femur and consideration of discontinuing alendronate in consultation with an endocrinologist. If a contralateral stress fracture is found, prophylactic fixation should be considered.
PMID: 19884427 [PubMed - indexed for MEDLINE]
J Bone Miner Res. 2010 Jan 14. [Epub ahead of print]
Increased prevalence of bisphosphonate-related osteonecrosis of the jaw with vitamin D deficiency in rats.
Hokugo A,
Christensen R,
Chung E,
Sung E,
Felsenfeld AL,
Sayre JW,
Garrett N,
Adams JS,
Nishimura I.
The Jane and Jerry Weintraub Center for Reconstructive Biotechnology, UCLA School of Dentistry, Los Angeles, CA.
Necrotic bone exposure in the oral cavity has recently been reported in patients treated with nitrogen-containing bisphosphonates as part of their therapeutic regimen for multiple myeloma or metastatic cancers to bone. It has been postulated that systemic conditions associated with cancer patients combined with tooth extraction may increase the risk of osteonecrosis of the jaw (ONJ). The objective of this study was to establish an animal model of bisphosphonate-related ONJ by testing the combination of these risk factors. The generation of ONJ lesions in rats resembling human diseases was achieved under the confluence of intravenous injection of zoledronate (ZOL; 35 microg/Kg every 2 weeks), maxillary molar extraction and vitamin D deficiency (VitD(-)). The prevalence of ONJ in the VitD(-)/ZOL group was 66.7%, which was significantly higher (p < 0.05, Fisher exact test) than the Control (0%), VitD(-) (0%) and ZOL alone (14.3%) groups. Similar to human patients, rat ONJ lesions prolonged the oral exposure of necrotic bone sequestra and were uniquely associated with pseudoepitheliomatous hyperplasia. The number of TUNEL positive osteoclasts significantly increased on the surface of post-tooth extraction alveolar bone of the VitD(-)/ZOL group, where sustained inflammation was depicted by 18F-fluorodeoxyglucose microPET. ONJ lesions were found to be associated with dense accumulation of mixed inflammatory/immune cells. These cells composed of neutrophils and lymphocytes appeared to juxtapose apoptotic osteoclasts. It is suggested that the pathophysiological mechanism(s) underpinning ONJ may involve the interaction between bisphosphonates and compromised vitamin D functions in the realm of skeletal homeostasis and innate immunity. (c) 2010 American Society for Bone and Mineral Research.
PMID: 20200938 [PubMed - as supplied by publisher]
MED ALERT: Fosamax MAY promote bone breaks!
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