Shane Elizabeth, Burr David, Abrahamsen Bo, Adler Robert A, Brown Thomas D, Cheung Angela M, Cosman Felicia, Curtis Jeffrey R, Dell Richard, Dempster David W, Ebeling Peter R, Einhorn Thomas A, Genant Harry K, Geusens Piet, Klaushofer Klaus, Lane Joseph M, McKiernan Fergus, McKinney Ross, Ng Alvin, Nieves Jeri, O'Keefe Regis, Papapoulos Socrates, Howe Tet Sen, van der Meulen Marjolein C H, Weinstein Robert S, Whyte Michael P
Author affiliations appear on pp. 15-20.
J Bone Miner Res. 2014 Jan;29(1):1-23. doi: 10.1002/jbmr.1998. Epub 2013 Oct 1.
Bisphosphonates (BPs) and denosumab reduce the risk of spine and nonspine fractures. Atypical femur fractures (AFFs) located in the subtrochanteric region and diaphysis of the femur have been reported in patients taking BPs and in patients on denosumab, but they also occur in patients with no exposure to these drugs. In this report, we review studies on the epidemiology, pathogenesis, and medical management of AFFs, published since 2010. This newer evidence suggests that AFFs are stress or insufficiency fractures. The original case definition was revised to highlight radiographic features that distinguish AFFs from ordinary osteoporotic femoral diaphyseal fractures and to provide guidance on the importance of their transverse orientation. The requirement that fractures be noncomminuted was relaxed to include minimal comminution. The periosteal stress reaction at the fracture site was changed from a minor to a major feature. The association with specific diseases and drug exposures was removed from the minor features, because it was considered that these associations should be sought rather than be included in the case definition. Studies with radiographic review consistently report significant associations between AFFs and BP use, although the strength of associations and magnitude of effect vary. Although the relative risk of patients with AFFs taking BPs is high, the absolute risk of AFFs in patients on BPs is low, ranging from 3.2 to 50 cases per 100,000 person-years. However, long-term use may be associated with higher risk (∼100 per 100,000 person-years). BPs localize in areas that are developing stress fractures; suppression of targeted intracortical remodeling at the site of an AFF could impair the processes by which stress fractures normally heal. When BPs are stopped, risk of an AFF may decline. Lower limb geometry and Asian ethnicity may contribute to the risk of AFFs. There is inconsistent evidence that teriparatide may advance healing of AFFs.
双膦酸盐类药物（BPs）和地诺单抗可降低脊柱和非脊柱骨折的风险。服用BPs的患者以及使用地诺单抗的患者中均有股骨转子下区域和股骨干非典型股骨骨折（AFFs）的报道，但未接触这些药物的患者中也会发生此类骨折。在本报告中，我们回顾了自2010年以来发表的关于AFFs的流行病学、发病机制和药物治疗的研究。这些新证据表明，AFFs是应力性或不全性骨折。最初的病例定义经过修订，以突出区分AFFs与普通骨质疏松性股骨干骨折的影像学特征，并就其横向取向的重要性提供指导。将骨折无粉碎的要求放宽，以包括最小程度的粉碎。骨折部位的骨膜应力反应从次要特征变为主要特征。与特定疾病和药物暴露的关联从次要特征中去除，因为认为应寻找这些关联，而不是将其纳入病例定义。影像学复查研究一致报告AFFs与BP使用之间存在显著关联，尽管关联强度和效应大小各不相同。虽然发生AFFs的患者服用BPs的相对风险较高，但服用BPs的患者发生AFFs的绝对风险较低，每10万人年为3.2至50例。然而，长期使用可能与更高风险相关（每10万人年约100例）。BPs定位于正在发生应力性骨折的区域；抑制AFF部位的靶向皮质内重塑可能会损害应力性骨折正常愈合的过程。停用BPs后，AFFs的风险可能会降低。下肢几何形状和亚洲种族可能会增加AFFs的风险。关于特立帕肽可能促进AFFs愈合的证据并不一致。
