title: Circulating sclerostin and estradiol levels are associated with inadequate response to bisphosphonates in postmenopausal women with osteoporosis.
abstract: BACKGROUND
  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.
authors.affiliation: Metabolic Bone Unit, Endocrinology Division (RETICEF), Hospital Universitario San Cecilio, Instituto de Investigación Biosanitaria (ibs.GRANADA), Granada, Spain; RETICEF, Instituto de Salud Carlos III, Spain; Proteomic Research Service, Hospital Universitario San Cecilio, Instituto de Investigación Biosanitaria de Granada (ibs.GRANADA), Granada, Spain.
authors.forename: Sonia
authors.initials: S
authors.lastname: Morales-Santana
authors.affiliation: RETICEF, Instituto de Salud Carlos III, Spain; Hospital del Mar-IMIM-UAB, Department of Internal Medicine, Barcelona, Spain.
authors.forename: Adolfo
authors.initials: A
authors.lastname: Díez-Pérez
authors.affiliation: RETICEF, Instituto de Salud Carlos III, Spain; Hospital Universitario Marqués Valdecilla, Department of Internal Medicine, Santander, Spain.
authors.forename: José M
authors.initials: JM
authors.lastname: Olmos
authors.affiliation: RETICEF, Instituto de Salud Carlos III, Spain; Hospital del Mar-IMIM-UAB, Department of Internal Medicine, Barcelona, Spain.
authors.forename: Xavier
authors.initials: X
authors.lastname: Nogués
authors.affiliation: Osteoporosis Research Group. Universidad de Las Palmas de Gran Canaria. Las Palmas de Gran Canaria, Spain.
authors.forename: Manuel
authors.initials: M
authors.lastname: Sosa
authors.affiliation: RETICEF, Instituto de Salud Carlos III, Spain; Fundación Jiménez Díaz, Department of Internal Medicine, Madrid, Spain.
authors.forename: Manuel
authors.initials: M
authors.lastname: Díaz-Curiel
authors.affiliation: RETICEF, Instituto de Salud Carlos III, Spain; Hospital Universitario Río Ortega, Department of Internal Medicine, Valladolid, Spain.
authors.forename: José L
authors.initials: JL
authors.lastname: Pérez-Castrillón
authors.affiliation: RETICEF, Instituto de Salud Carlos III, Spain; Hospital Virgen Macarena. Department of Internal Medicine, Sevilla, Spain.
authors.forename: Ramón
authors.initials: R
authors.lastname: Pérez-Cano
authors.affiliation: RETICEF, Instituto de Salud Carlos III, Spain; Hospital La Paz, Department of Rheumatology, Madrid, Spain.
authors.forename: Antonio
authors.initials: A
authors.lastname: Torrijos
authors.affiliation: RETICEF, Instituto de Salud Carlos III, Spain; Hospital Universitario Quirón, Department of Endocrinology, Madrid, Spain.
authors.forename: Esteban
authors.initials: E
authors.lastname: Jodar
authors.affiliation: RETICEF, Instituto de Salud Carlos III, Spain; CETIR Medical Centre, Barcelona, Spain.
authors.forename: Luis Del
authors.initials: LD
authors.lastname: Rio
authors.affiliation: RETICEF, Instituto de Salud Carlos III, Spain; Trabeculae, Ourense, Spain.
authors.forename: José R
authors.initials: JR
authors.lastname: Caeiro-Rey
authors.affiliation: Metabolic Bone Unit, Endocrinology Division (RETICEF), Hospital Universitario San Cecilio, Instituto de Investigación Biosanitaria (ibs.GRANADA), Granada, Spain; RETICEF, Instituto de Salud Carlos III, Spain.
authors.forename: Rebeca
authors.initials: R
authors.lastname: Reyes-García
authors.affiliation: Metabolic Bone Unit, Endocrinology Division (RETICEF), Hospital Universitario San Cecilio, Instituto de Investigación Biosanitaria (ibs.GRANADA), Granada, Spain; RETICEF, Instituto de Salud Carlos III, Spain.
authors.forename: Beatriz
authors.initials: B
authors.lastname: García-Fontana
authors.affiliation: RETICEF, Instituto de Salud Carlos III, Spain; Hospital Universitario Marqués Valdecilla, Department of Internal Medicine, Santander, Spain.
authors.forename: Jesús
authors.initials: J
authors.lastname: González-Macías
authors.affiliation: Metabolic Bone Unit, Endocrinology Division (RETICEF), Hospital Universitario San Cecilio, Instituto de Investigación Biosanitaria (ibs.GRANADA), Granada, Spain; RETICEF, Instituto de Salud Carlos III, Spain. Electronic address: mmt@mamuto.es.
authors.forename: Manuel
authors.initials: M
authors.lastname: Muñoz-Torres
mesh_terms: D048868:Adaptor Proteins, Signal Transducing; D000368:Aged; D015519:Bone Density; D050071:Bone Density Conservation Agents / Q000627:therapeutic use*; D019485:Bone Morphogenetic Proteins / Q000097:blood*; D016022:Case-Control Studies; D004164:Diphosphonates / Q000627:therapeutic use*; D004958:Estradiol / Q000097:blood*; D005260:Female; D005819:Genetic Markers; D006801:Humans; D015994:Incidence; D008875:Middle Aged; D015663:Osteoporosis, Postmenopausal / Q000097:blood / Q000188:drug therapy*; D058866:Osteoporotic Fractures / Q000453:epidemiology* / Q000517:prevention & control; D017698:Postmenopause; D016896:Treatment Outcome
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D050071:Bone Density Conservation Agents; D019485:Bone Morphogenetic Proteins; D004164:Diphosphonates; D005819:Genetic Markers; C422903:SOST protein, human; D004958:Estradiol
keywords: Bisphosphonates; Fracture risk; Inadequate responders; Postmenopausal osteoporosis; Sclerostin