TY - JOUR
T1 - Circulating sclerostin and estradiol levels are associated with inadequate response to bisphosphonates in postmenopausal women with osteoporosis
AU - Morales-Santana, Sonia
AU - Díez-Pérez, Adolfo
AU - Olmos, José M.
AU - Nogués, Xavier
AU - Sosa, Manuel
AU - Díaz-Curiel, Manuel
AU - Pérez-Castrillón, José L.
AU - Pérez-Cano, Ramón
AU - Torrijos, Antonio
AU - Jodar, Esteban
AU - Rio, Luis Del
AU - Caeiro-Rey, José R.
AU - Reyes-García, Rebeca
AU - García-Fontana, Beatriz
AU - González-Macías, Jesús
AU - Muñoz-Torres, Manuel
PY - 2015/12/1
Y1 - 2015/12/1
N2 - © 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.
AB - © 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.
KW - Bisphosphonates
KW - Fracture risk
KW - Inadequate responders
KW - Postmenopausal osteoporosis
KW - Sclerostin
U2 - 10.1016/j.maturitas.2015.08.007
DO - 10.1016/j.maturitas.2015.08.007
M3 - Article
SN - 0378-5122
VL - 82
SP - 402
EP - 410
JO - Maturitas
JF - Maturitas
IS - 4
ER -