Bisphosphonate treatment reduces fracture risk in women with postmenopausal osteoporosis. However, some patients have an inadequate response to treatment. Estradiol and sclerostin play an important role in bone metabolism. Sclerostin is an endogenous inhibitor of osteoblastic activity and estrogen deficiency increases osteoclast activity and bone resorption.
We examined the influence of both measures on fracture incidence in postmenopausal osteoporosis in 120 women on bisphosphonate therapy. Patients were classified in adequate responders (AR, n=66) without incident fractures during 5 years of treatment and inadequate responders (IR, n=54), with incident fractures between 1 and 5 years of treatment. Several variables were measured; anthropometric, biochemical, bone mineral density (DXA), structural analysis of the proximal femur and structural/fractal analysis of the distal radius. Circulating sclerostin concentrations were measured by ELISA and 17β-estradiol levels by RIA based on ultrasensitive methods.
In AR group, sclerostin serum levels were significantly lower (P=0.02) and estradiol concentrations significantly higher (P=0.023) than IR group. In a logistic regression model the independent predictors of inadequate response were: previous history of fragility fracture (OR 11.27, 95% CI 1.8867.34, P=0.008) and sclerostin levels (OR 1.11, 95% CI 1.021.20, P=0.011). Estradiol levels were protective (OR 0.93, 95% CI 0.861.01, P=.09). We observed a nonlinear, inverted U-shaped relation between estradiol and sclerostin levels. Lower sclerostin levels were found at both low and high estradiol levels.
In conclusion, sclerostin and estradiol circulating levels are related to inadequate response to treatment with bisphosphonates in women with postmenopausal osteoporosis.
17 May 2014 - 20 May 2014