Bisphosphonates and atypical subtrochanteric fractures of the femur

Abstract

ObjectivesBisphosphonates are widely used as first-line treatment for primary and secondary prevention of fragility fractures. Whilst they have proved effective in this role, there is growing concern over their long-term use, with much evidence linking bisphosphonate-related suppression of bone remodelling to an increased risk of atypical subtrochanteric fractures of the femur (AFFs). The objective of this article is to review this evidence, while presenting the current available strategies for the management of AFFs.MethodsWe present an evaluation of current literature relating to the pathogenesis and treatment of AFFs in the context of bisphosphonate use.ResultsSix broad themes relating to the pathogenesis and management of bisphosphonate-related AFFs are presented. The key themes in fracture pathogenesis are: bone microdamage accumulation; altered bone mineralisation and altered collagen formation. The key themes in fracture management are: medical therapy and surgical therapy. In addition, primary prevention strategies for AFFs are discussed.ConclusionsThis article presents current knowledge about the relationship between bisphosphonates and the development of AFFs, and highlights key areas for future research. In particular, studies aimed at identifying at-risk subpopulations and organising surveillance for those on long-term therapy will be crucial in both increasing our understanding of the condition, and improving population outcomes.Cite this article: N. Kharwadkar, B. Mayne, J. E. Lawrence, V. Khanduja. Bisphosphonates and atypical subtrochanteric fractures of the femur. Bone Joint Res 2017;6:144–153. DOI: 10.1302/2046-3758.63.BJR-2016-0125.R1.

Secondary Fracture Prevention: Consensus Clinical Recommendations from a Multistakeholder Coalition

“…(124,125) Patients who are Asian, (114,117) relatively younger (<65 to 70 years old), (124,126) with higher bone mineral density, (127) or have used glucocorticoids for 1 year or more (128) may also have an increased AFF risk. Metabolic factors, such as impaired response of parathyroid hormone to hypocalcemia, and bone mechanical/geometric factors (eg, neck-shaft angle) have been suggested as contributing to the risk of AFF.…”

“…(124,125) Patients who are Asian, (114,117) relatively younger (<65 to 70 years old), (124,126) with higher bone mineral density, (127) or have used glucocorticoids for 1 year or more (128) may also have an increased AFF risk. (21,114,124,125) Dual-energy X-ray absorptiometry technology is a useful evaluation technique for detecting cortical thickening in the spectrum of AFF (130,131) and some newer densitometers can provide a single energy image of almost the entire femur. (129) It should be noted that in around 70% of the AFF cases reviewed by an expert task force, patients reported a prodrome of thigh or hip pain.…”

Adult-onset hypophosphatasia diagnosed following bilateral atypical femoral fractures in a 55-year-old woman

“…Adult-onset HPP can be a consequence of both autosomal dominant and autosomal recessive inheritance of TNSALP mutations, and has characteristically variable penetrance and severity (12 (Table 1) (9). There have been several cases of bilateral ASFFs documented in the literature, however the vast majority of these are associated with bisphosphonate use, which is thought to contribute to the accumulation of bone microdamage and cause dysregulation of bone mineralisation, bone turnover, collagen cross-linking and bone vascularity in some patients (8,(16)(17)(18). Whilst this case represents an unusual injury pattern for a patient with HPP, approximately 18% of the adultonset form of disease is diagnosed following a fracture, with 23% of all patients having sustained a femoral fracture at some point in their life (19).…”

“…These are defined as any fracture meeting four out of five of the major criteria described by the American Society for Bone and Mineral Research (ASBMR) task force in 2013 (Table 1) (7). They are most commonly associated with the use of bisphosphonates, which are thought to have adverse effects on bone biology in a small proportion of patients (8,9). Outcomes following these fractures are generally poor with 25% patients surviving less than two years and greater than half of all patients failing to return to their previous level of functioning in this time (10).…”

<em>Lactobacillus helveticus</em> (ATCC 27558) upregulates <em>Runx2</em> and <em>Bmp2</em> and modulates bone mineral density in ovariectomy-induced bone loss rats

“…However, this therapy causes some side effects including atypical subtrochanteric fractures11 and osteonecrosis of the jaw 12. The other therapy for osteoporosis is hormone replacement therapy (HRT) 13.…”