Questioning the association between bisphosphonates and atypical femoral fractures

Ann N Y Acad Sci. 2015 Jan;1335(1):1-9. doi: 10.1111/nyas.12551. Epub 2014 Oct 7.

Abstract

Bisphosphonates are the first-line treatment for osteoporosis. Structurally, they are stable analogues of pyrophosphate and therefore exhibit a high affinity for bone mineral. They reduce bone loss by attenuating the ability of the osteoclast to resorb bone, decreasing activation frequency, and the rate of remodeling. Large prospective randomized placebo-control trials provide unequivocal evidence for a reduction in the incidence of fractures. Impressively, 40 years since their first use in patients, the safety profile of bisphosphonates has been equally reassuring. Questions have arisen lately as to whether bisphosphonates could cause atypical fractures, a rare type of atraumatic or minimal trauma femur fracture occurring below the great trochanter. This question has prompted calls for a broader examination of the long-term effects of bisphosphonate use. An attempt by the Food and Drug Administration to garner consensus and provide definitive views was not successful. This has led to continued anxiety among treating physicians and patients alike, resulting in an overall reduction in prescriptions for bisphosphonates and for osteoporosis therapies in general. Here, we provide an overview of the current data on atypical fractures and bisphosphonate use.

Keywords: atypical femur fractures; bisphosphonates; femoral shaft fractures; fragility fractures; low-energy femoral fractures; subtrochanteric fractures.

Publication types

  • Review

MeSH terms

  • Animals
  • Bone Density Conservation Agents / adverse effects*
  • Diphosphonates / adverse effects*
  • Femoral Fractures / chemically induced*
  • Femoral Fractures / diagnostic imaging*
  • Femoral Fractures / epidemiology
  • Humans
  • Osteoporosis / diagnostic imaging
  • Osteoporosis / drug therapy
  • Osteoporosis / epidemiology
  • Radiography
  • United States / epidemiology
  • United States Food and Drug Administration / legislation & jurisprudence

Substances

  • Bone Density Conservation Agents
  • Diphosphonates