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

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.

Figure 1.

The results for each type of drug were categorized according to study design and fracture type. Abbreviation: atypical femur fracture.

Figure 2.

Decision tree with considerations for medical management after atypical femur fracture (AFF). aDefinition may vary across countries, eg, a hip BMD T-score ≤ –2.5 SD, older age (70–75 years), a recent fragility fracture, other strong risk factors for fracture, or a FRAX fracture risk score that is above country-specific thresholds (95). dRaloxifene or bazedoxifene are preferably prescribed in relatively young postmenopausal women who are at low risk of hip fractures and deep vein thrombosis (94), or in women in whom the use of teriparatide is contraindicated. ^eIn case of intolerance to SERMs, hormone replacement therapy or tibolone could be considered in women with a low risk of deep vein thrombosis and breast cancer, without a history of myocardial infarction or stroke (94). bSwitching denosumab to teriparatide may result in progressive BMD loss. cBe aware that antiresorptive therapy may be needed after stopping denosumab. ^fCalcitonin can be prescribed in patients who are not eligible for bisphosphonates, SERMs, hormone replacement therapy, tibolone, abaloparatide, or teriparatide.