Medical Management of Patients After Atypical Femur Fractures: a Systematic Review and Recommendations From the European Calcified Tissue Society

J Clin Endocrinol Metab. 2020 May 1;105(5):1682-1699. doi: 10.1210/clinem/dgz295.

Abstract

Context: Atypical femur fractures (AFFs) are serious adverse events associated with bisphosphonates and often show poor healing.

Evidence acquisition: We performed a systematic review to evaluate effects of teriparatide, raloxifene, and denosumab on healing and occurrence of AFF.

Evidence synthesis: We retrieved 910 references and reviewed 67 papers, including 31 case reports, 9 retrospective and 3 prospective studies on teriparatide. There were no RCTs. We pooled data on fracture union (n = 98 AFFs on teriparatide) and found that radiological healing occurred within 6 months of teriparatide in 13 of 30 (43%) conservatively managed incomplete AFFs, 9 of 10 (90%) incomplete AFFs with surgical intervention, and 44 of 58 (75%) complete AFFs. In 9 of 30 (30%) nonoperated incomplete AFFs, no union was achieved after 12 months and 4 (13%) fractures became complete on teriparatide. Eight patients had new AFFs during or after teriparatide. AFF on denosumab was reported in 22 patients, including 11 patients treated for bone metastases and 8 without bisphosphonate exposure. Denosumab after AFF was associated with recurrent incomplete AFFs in 1 patient and 2 patients of contralateral complete AFF. Eight patients had used raloxifene before AFF occurred, including 1 bisphosphonate-naïve patient.

Conclusions: There is no evidence-based indication in patients with AFF for teriparatide apart from reducing the risk of typical fragility fractures, although observational data suggest that teriparatide might result in faster healing of surgically treated AFFs. Awaiting further evidence, we formulate recommendations for treatment after an AFF based on expert opinion.

Keywords: anabolics; antiresorptives; osteoporosis.

Publication types

  • Practice Guideline
  • Systematic Review

MeSH terms

  • Bone Density Conservation Agents / adverse effects
  • Denosumab / therapeutic use
  • Diphosphonates / adverse effects
  • Europe / epidemiology
  • Femoral Fractures / chemically induced
  • Femoral Fractures / diagnostic imaging
  • Femoral Fractures / drug therapy*
  • Femoral Fractures / epidemiology
  • Humans
  • Osteoporotic Fractures / chemically induced
  • Osteoporotic Fractures / diagnosis
  • Osteoporotic Fractures / epidemiology
  • Osteoporotic Fractures / prevention & control
  • Practice Patterns, Physicians' / standards
  • Raloxifene Hydrochloride / therapeutic use
  • Risk Assessment
  • Risk Factors
  • Societies, Medical / standards
  • Teriparatide / therapeutic use

Substances

  • Bone Density Conservation Agents
  • Diphosphonates
  • Teriparatide
  • Denosumab
  • Raloxifene Hydrochloride