Original Article

Osteoporosis International

, Volume 23, Issue 4, pp 1235-1243

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

  • Y. E. ChungAffiliated withDepartment of Internal Medicine, Seoul Veterans Hospital
  • , S. H. LeeAffiliated withDivision of Endocrinology and Metabolism, Asan Medical Center, University of Ulsan College of Medicine
  • , S.-Y. LeeAffiliated withAsan Institute for Life Sciences
  • , S.-Y. KimAffiliated withDepartment of Orthopedic Surgery, School of Medicine, Kyungpook National University
  • , H.-H. KimAffiliated withDepartment of Cell and Developmental Biology, College of Dentistry, Seoul National University
  • , F. S. MirzaAffiliated withDivision of Endocrinology, University of Connecticut Health Center
  • , S.-K. LeeAffiliated withDivision of Endocrinology, University of Connecticut Health Center
  • , J. A. LorenzoAffiliated withDivision of Endocrinology, University of Connecticut Health Center
  • , G. S. KimAffiliated withDivision of Endocrinology and Metabolism, Asan Medical Center, University of Ulsan College of Medicine
    • , J.-M. KohAffiliated withDivision of Endocrinology and Metabolism, Asan Medical Center, University of Ulsan College of Medicine Email author 

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Abstract

Summary

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.

Introduction

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.

Methods

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.

Results

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 (γ = −0.505, p = 0.017) and control (γ = −0.410, p = 0.020) groups.

Conclusions

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.

Keywords

Bisphosphonates Bone turnover Estrogen Raloxifene Sclerostin