Circulating sclerostin and estradiol levels are associated with inadequate response to bisphosphonates in postmenopausal women with osteoporosis

•Postmenopausal osteoporosis patients suffer fractures in spite of being on bisphosphonate therapy and with good adherence.•It is unknown whether estradiol and sclerostin circulating levels are associated with inadequate response to bisphosphonate therapy in this population.•Several reports showed that estrogen affect sclerostin production. We observed a nonlinear, inverted U-shaped relation between estradiol and sclerostin levels.•Our findings suggest that increased expression of sclerostin, accompanied by estrogen deficiency, can influence the response to bisphosphonate therapy.

IntroductionThe biological mechanisms associated with an inadequate response to treatment with bisphosphonates are not well known. This study investigates the association between circulating levels of sclerostin and estradiol with an inadequate clinical outcome to bisphosphonate therapy in women with postmenopausal osteoporosis.MethodsThis case-control study is based on 120 Spanish women with postmenopausal osteoporosis being treated with oral bisphosphonates. Patients were classified as adequate responders (ARs, n = 66, mean age 68.2 ± 8 years) without incident fractures during 5 years of treatment, or inadequate responders (IRs, n = 54, mean age 67 ± 9 years), with incident fractures between 1 and 5 years of treatment. Bone mineral density (DXA), structural analysis of the proximal femur and structural/fractal analysis of the distal radius were assessed. Sclerostin concentrations were measured by ELISA and 17β-estradiol levels by radioimmunoassay based on ultrasensitive methods.ResultsIn the ARs group, sclerostin serum levels were significantly lower (p = 0.02) and estradiol concentrations significantly higher (p = 0.023) than in the IRs group. A logistic regression analysis was performed, including as independent variables in the original model femoral fracture load, 25 hydroxyvitamin D, previus history of fragility fracture, sclerostin and estradiol. Only previous history of fragility fracture (OR 14.04, 95% CI 2.38–82.79, p = 0.004) and sclerostin levels (OR 1.11, 95% CI 1.02–1.20, p = 0.011), both adjusted by estradiol levels remained associated with IRs. Also, sclerostin concentrations were associated with the index of resistance to compression (IRC) in the fractal analysis of the distal radius, a parameter on bone microstructure.ConclusionsSclerostin and estradiol levels are associated with the response to bisphosphonate therapy in women with postmenopausal osteoporosis.