title: Long-term treatment with raloxifene, but not bisphosphonates, reduces circulating sclerostin levels in postmenopausal women.
abstract: 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.
  
  
  BACKGROUND
  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.
authors.affiliation: Department of Internal Medicine, Seoul Veterans Hospital, Seoul, South Korea.
authors.forename: Y E
authors.initials: YE
authors.lastname: Chung
authors.forename: S H
authors.initials: SH
authors.lastname: Lee
authors.forename: S-Y
authors.initials: SY
authors.lastname: Lee
authors.forename: S-Y
authors.initials: SY
authors.lastname: Kim
authors.forename: H-H
authors.initials: HH
authors.lastname: Kim
authors.forename: F S
authors.initials: FS
authors.lastname: Mirza
authors.forename: S-K
authors.initials: SK
authors.lastname: Lee
authors.forename: J A
authors.initials: JA
authors.lastname: Lorenzo
authors.forename: G S
authors.initials: GS
authors.lastname: Kim
authors.forename: J-M
authors.initials: JM
authors.lastname: Koh
mesh_terms: D048868:Adaptor Proteins, Signal Transducing; D000368:Aged; D000469:Alkaline Phosphatase / Q000097:blood; D015415:Biomarkers / Q000097:blood; D015519:Bone Density / Q000187:drug effects; D050071:Bone Density Conservation Agents / Q000008:administration & dosage / Q000494:pharmacology* / Q000627:therapeutic use; D019485:Bone Morphogenetic Proteins / Q000097:blood / Q000187:drug effects*; D004164:Diphosphonates / Q000008:administration & dosage / Q000494:pharmacology* / Q000627:therapeutic use; D004334:Drug Administration Schedule; D005260:Female; D005819:Genetic Markers / Q000187:drug effects*; D006801:Humans; D008875:Middle Aged; D015675:Osteocalcin / Q000097:blood; D015663:Osteoporosis, Postmenopausal / Q000097:blood* / Q000188:drug therapy / Q000503:physiopathology; D020849:Raloxifene Hydrochloride / Q000008:administration & dosage / Q000494:pharmacology* / Q000627:therapeutic use; D012189:Retrospective Studies; D020845:Selective Estrogen Receptor Modulators / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D015415:Biomarkers; D050071:Bone Density Conservation Agents; D019485:Bone Morphogenetic Proteins; D004164:Diphosphonates; D005819:Genetic Markers; C422903:SOST protein, human; D020845:Selective Estrogen Receptor Modulators; D015675:Osteocalcin; D020849:Raloxifene Hydrochloride; D000469:Alkaline Phosphatase