Long-term treatment with raloxifene, but not bisphosphonates, reduces circulating sclerostin levels in postmenopausal women

We determined whether suppression of sclerostin levels by estrogen treatment was mediated by anti-resorptive effect. Raloxifene, but not bisphosphonates, suppressed circulating sclerostin concentration, suggesting that sclerostin may mediate the action of estrogen on bone metabolism, independently of their anti-resorptive effects. Circulating sclerostin concentrations are higher in postmenopausal than in premenopausal women, and estrogen treatment suppresses sclerostin levels in both men and women. We determined whether anti-resorptives may suppress the circulating sclerostin levels. We conducted a retrospective observational study. Eighty postmenopausal women were treated with raloxifene for 19.4 +/- 7.7 months (n = 16), bisphosphonates for 19.2 +/- 6.7 months (n = 32), or were untreated (n = 32) for 17.1 +/- 4.6 months. Plasma sclerostin concentrations were measured before and after treatment. Plasma sclerostin levels after treatment were significantly lower in the raloxifene than in the control group (55.8 +/- 23.4 pmol/l vs. 92.1 +/- 50.4 pmol/l, p = 0.046), but were similar between the bisphosphonate and control groups. Relative to baseline, raloxifene treatment markedly reduced plasma sclerostin concentration (-40.7 +/- 22.8%, p < 0.001), with respect to both control (-7.5 +/- 29.1%) and bisphosphonate (-3.1 +/- 35.2%) groups. Changes in bone-specific alkaline phosphatase and osteocalcin levels showed reverse associations with sclerostin concentration changes in the raloxifene (gamma = -0.505, p = 0.017) and control (gamma = -0.410, p = 0.020) groups. Raloxifene, but not bisphosphonates, significantly suppressed circulating sclerostin concentration, suggesting that sclerostin may mediate the action of estrogen on bone metabolism, independently of their anti-resorptive effects.