Incidence of Atypical Femur Fractures in Cancer Patients: The MD Anderson Cancer Center Experience

Abstract

Atypical femoral fractures (AFFs) are rare adverse events attributed to bisphosphonate (BP) use. Few cases of AFF in cancer have been described; the aim of this study is to identify the incidence and risk factors for AFF in a large cancer center. This retrospective study was conducted at the MD Anderson Cancer Center. The incidence rate of AFF among BP users was calculated from January 1, 2004 through December 31, 2013. The control group (n = 51) included 2 or 3 patients on BPs matched for age (≤1 year) and gender. Logistic regression analysis was used to assess the relationship between clinical characteristics and AFF. Twenty-three AFF cases were identified radiographically among 10,587 BP users, the total BP exposure was 53,789 months (4482 years), and the incidence of AFF in BP users was 0.05 cases per 100,000 person-years. Meanwhile, among 300,553 patients who did not receive BPs there were 2 cases of AFF as compared with the 23 cases noted above. The odds ratio (OR) of having AFF in BP users was 355.58 times higher (95% CI, 84.1 to 1501.4, p < 0.0001) than the risk in non-BP users. The OR of having AFF in alendronate users was 5.54 times greater (OR 5.54 [95% CI, 1.60 to 19.112, p = 0.007]) than the odds of having AFF among other BP users. Patients who were on zoledronic acid (ZOL) had smaller odds of developing AFF compared with other BP users in this matched case control sample. AFFs are rare, serious adverse events that occur in patients with cancer who receive BP therapy. Patients with cancer who receive BPs for prior osteoporosis therapy or for metastatic cancer are at higher risk of AFF. © 2016 American Society for Bone and Mineral Research.

Atypical femoral fractures and current management

“…AFFs have long been regarded as a new type of osteoporotic fractures. However, emerging sporadic evidence indicated that AFFs also occurred in patients receiving higher doses of BPs with more frequent intravenous injections (e.g., at a monthly dose of 4 mg zoledronate) for skeletal malignancies, such as bone metastasis and myeloma, supporting the long-standing opinion that severely decreased bone turnover due to either chronic or higher-dose BP exposure might be the underlying mechanism of AFFs [19] , [21] , [22] . A retrospective study by Puhaindran et al [21] indentified four patients with AFFs in 327 patients receiving at least 24 doses of intravenous BPs for cancer therapy.…”

“…However, it is still unknown whether this association can be attributed to the pathologically specific effect of alendronate on bone or can simply be a result of variation in the prescription rate of different types of BPs. Regardless of these epidemiological differences, all BPs used for treating OP are required to be prescribed with caution as these are associated with an increased risk for AFF, according to the Food and Drug Administration as well as the European Union [19] .…”

MANAGEMENT OF ENDOCRINE DISEASE: Atypical femoral fractures: risks and benefits of long-term treatment of osteoporosis with anti-resorptive therapy

“…Although both patients received anti-resorptives at much greater doses than those of osteoporosis patients, the two patients may have had osteoporosis before starting anti-resorptive therapy. More recently a larger review [10] of cancer patients on bisphosphonate therapy concluded that such patients were at higher risk for AFF than cancer patients not on bisphosphonates. However, from this review and earlier reports of AFF in patients not on bisphosphonates [9], it is not possible to know if such some of these patients had osteoporosis.…”

Case of atypical femoral fractures that mimicked the typical imaging findings of prostate cancer‐induced bone metastasis

“…AFFs are categorized as incomplete or complete fractures and can often progress from incomplete to complete . The incidence of AFFs in cancer patients is 0.05 per 100 000 cases per year, with an odds ratio of 300 (patients administered with BRIs vs patients not administered BRIs) . The incidence of AFF increases when BRIs are administered for longer periods …”