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.

Does Teriparatide Improve Fracture Union?: A Systematic Review

“…There are several studies that TPTD treatment can aid fracture healing in patients with AFF. [57][58][59][60] One retrospective study compared 2 groups, AFFs were treated TPTD (n=21) and not-TPTD (n=24) groups. All TPTD group showed faster healing time (5.4±1.5 vs. 8.6±4.7 months; P=0.012), and low frequency of delayed healing or nonunion (P=0.012).…”

“…[67,68] The European Calcified Tissue Society suggested the use of TPTD after surgery of AFFs, even though strong evidence for improved fracture union is lacking. [59] However, there is a clear need for RCTs to evaluate whether TPTD enhances the union of AFF may contribute to the risk of AFF.…”

Bisphosphonate-related atypical femoral fractures: A novel strategy to improve patient outcomes

“…There is an increasing body of evidence to suggest that teriparatide after intramedullary nailing can promote faster healing of AFFs and a normalisation of bone turnover markers within 2 years of treatment. 23 –25…”

A Spontaneous Atypical Femoral Fracture after 2 decades of antiresorptive therapy

“…Despite having stopped bisphosphonates 3 years prior to admission, this prolonged course likely contributed to her fracture risk. Replacement with Denosumab, which has also been linked with AFFs, was also a contributory factor [5], although the link between AFFs and Bisphosphonates is better established [3].…”

“…Following surgery, teriparatide was initiated for bone protection with escalation of Vitamin D dosage. Amid uncertainty regarding how to treat patients after they have sustained an AFF and given that bone agents have potential positive and negative effects on fracture healing, recent recommendations, not supported by randomised data, from the European Calcified Tissue Society describe probable beneficial effects on healing time of surgically treated AFFs with teriparatide, although non-union at one year can still occur [5].…”