Increased risk of osteoporosis and femoral neck fractures in patients with familial Mediterranean fever—a large retrospective cohort study

Objectives: The direct impact of inflammatory conditions and their therapy with corticosteroids contribute to an increased risk of osteoporosis with associated fractures. Familial Mediterranean fever (FMF) is an autoinflammatory disorder not commonly treated with corticosteroids. Evidence regarding FMF association with osteoporosis and femur fractures is anecdotal. We aimed to evaluate the incidence and risk of osteoporosis and femoral neck fracture in FMF patients compared with the general population. Methods: A retrospective cohort study using the electronic database of Clalit Health Services of all FMF patients first diagnosed between 2000 and 2016 and controls was conducted including age- and sex-matched controls in a 1:1 ratio. Follow-up continued until the first diagnosis of osteoporosis or fracture. Risk for these conditions was compared using univariate and multivariate Cox regression models. Results: A total of 9769 FMF patients were followed for a median period of 12.5 years. Of these, 304 FMF patients were diagnosed with osteoporosis compared with 191 controls, resulting in an incidence rate (per 10 000 persons-years) of 28.8 and 17.8, respectively, and a crude hazard ratio of 1.62 (95% CI 1.35, 1.93; P < 0.001). Patients were diagnosed with osteoporosis at a considerably younger age than controls [60.1 (S.D. 12.4) vs 62.5 (S.D. 11.0) years; P ¼ 0.028]. A total of 56 FMF patients were diagnosed with femoral neck fracture compared with 35 controls, resulting in an incidence rate of 5.3 and 3.3, respectively, and a crude HR of 1.60 (95% CI 1.05, 2.44; P < 0.05). Conclusion: FMF patients are at increased risk for osteoporosis and consequently femur fracture. Our findings emphasize the importance of considering bone health in the management of FMF patients.