(CSEMP028) A SYSTEMATIC REVIEW ON THE ASSOCIATION BETWEEN DENOSUMAB USE AND THE RISK OF ATYPICAL FRACTURES

Abstract:

Background: Denosumab is a RANK-ligand inhibitor that inhibits osteoclastic activity, reducing bone resorption. It is used in osteoporosis management and has been shown to improve bone mineral density and reduce the risk of fragility fractures. Atypical femoral fractures (AFF) are tensile stress fractures caused by bone remodelling suppression characterized by unique radiographic and clinical features that differ from fragility fractures. Recently, there have been reports of a relationship between denosumab use and AFFs, but the magnitude of this risk remains poorly understood.

Aim: To conduct a systematic review to determine the risk of AFF associated with denosumab use.

Methods: We systematically searched the Cochrane library, Medline, and Embase for randomized controlled trials (RCTs) and observational studies of denosumab treatment associated with AFF from database inception until October 27, 2022. Two reviewers independently extracted the data and assessed the quality of included studies using the Cochrane Risk-of-Bias (RoB 2) tool to evaluate RCTs and the Risk of Bias in Non-Randomized Studies of Interventions (ROBINS)-I tool to evaluate observational studies.

Results: A total of five RCTs, two non-randomized clinical trials, and seven observational studies met our inclusion criteria. A total of 26,811 individuals were included in these studies, of which 9223 had known malignancies. The indications for denosumab use and its dosages varied between studies. Indications included osteoporosis, giant cell tumor of bone and bone metastases. There was a low risk of bias among the RCTs and a moderate risk of bias in the observational studies examined. Overall, the observed incidence of AFFs among individuals receiving denosumab was low, varying between 0 and 4 %. The presence of important clinical heterogeneity prevented the meta-analysis of included studies.

Conclusion: The overall risk of AFF in individuals receiving denosumab is low. However, the studies retrieved were few and the populations studied included those with underlying malignancy. Further long-term studies with a focus on assessing denosumab use and AFF risk are needed.