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

Sonia Morales-Santana, Adolfo Díez-Pérez, José M. Olmos, Xavier Nogués, Manuel Sosa, Manuel Díaz-Curiel, José L. Pérez-Castrillón, Ramón Pérez-Cano, Antonio Torrijos, Esteban Jodar, Luis Del Rio, José R. Caeiro-Rey, Rebeca Reyes-García, Beatriz García-Fontana, Jesús González-Macías, Manuel Muñoz-Torres

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5 Citations (Scopus)

Abstract

© 2015 Elsevier Ireland Ltd. All rights reserved. Introduction The 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. Methods This 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. Results In 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. Conclusions Sclerostin and estradiol levels are associated with the response to bisphosphonate therapy in women with postmenopausal osteoporosis.
Original languageEnglish
Pages (from-to)402-410
JournalMaturitas
Volume82
Issue number4
DOIs
Publication statusPublished - 1 Dec 2015

Keywords

  • Bisphosphonates
  • Fracture risk
  • Inadequate responders
  • Postmenopausal osteoporosis
  • Sclerostin

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