Sonia Morales-Santana1, Adolfo Díez-Pérez2, José M Olmos3, Xavier Nogués2, Manuel Sosa4, Manuel Díaz-Curiel5, José L Pérez-Castrillón6, Ramón Pérez-Cano7, Antonio Torrijos8, Esteban Jodar9, Luis Del Rio10, José R Caeiro-Rey11, Rebeca Reyes-García12, Beatriz García-Fontana12, Jesús González-Macías3, Manuel Muñoz-Torres13. 1. 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. 2. RETICEF, Instituto de Salud Carlos III, Spain; Hospital del Mar-IMIM-UAB, Department of Internal Medicine, Barcelona, Spain. 3. RETICEF, Instituto de Salud Carlos III, Spain; Hospital Universitario Marqués Valdecilla, Department of Internal Medicine, Santander, Spain. 4. Osteoporosis Research Group. Universidad de Las Palmas de Gran Canaria. Las Palmas de Gran Canaria, Spain. 5. RETICEF, Instituto de Salud Carlos III, Spain; Fundación Jiménez Díaz, Department of Internal Medicine, Madrid, Spain. 6. RETICEF, Instituto de Salud Carlos III, Spain; Hospital Universitario Río Ortega, Department of Internal Medicine, Valladolid, Spain. 7. RETICEF, Instituto de Salud Carlos III, Spain; Hospital Virgen Macarena. Department of Internal Medicine, Sevilla, Spain. 8. RETICEF, Instituto de Salud Carlos III, Spain; Hospital La Paz, Department of Rheumatology, Madrid, Spain. 9. RETICEF, Instituto de Salud Carlos III, Spain; Hospital Universitario Quirón, Department of Endocrinology, Madrid, Spain. 10. RETICEF, Instituto de Salud Carlos III, Spain; CETIR Medical Centre, Barcelona, Spain. 11. RETICEF, Instituto de Salud Carlos III, Spain; Trabeculae, Ourense, Spain. 12. 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. 13. 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.
Abstract
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.
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.