Roland Kocijan1, Christian Muschitz, Astrid Fahrleitner-Pammer, Karin Amrein, Peter Pietschmann, Judith Haschka, Sebastian Dinu, Stylianos Kapiotis, Heinrich Resch. 1. Medical Department II (R.K., C.M., J.H., H.R.), St Vincent Hospital, The VINFORCE Study Group, Academic Teaching Hospital of Medical University of Vienna, 1060 Vienna, Austria; Department of Pathophysiology and Allergy Research (P.P.), Center for Pathophysiology, Infectiology, and Immunology, Medical University of Vienna, 1090 Vienna, Austria; Central Laboratory (S.D., S.K.) St. Vincent Group, 1060 Vienna, Austria; and Department of Internal Medicine (A.F.-P., K.A.), Division of Endocrinology and Metabolism, Medical University of Graz, 8036 Graz, Austria.
Abstract
CONTEXT: There are no specific biochemical bone markers available for osteogenesis imperfecta (OI), and the role of sclerostin as a key regulator of bone formation in OI is unknown. OBJECTIVES: We aimed to evaluate the role of sclerostin and its association with bone turnover markers as well as body composition parameters in adult patients with different types of OI. DESIGN, SETTING, AND PARTICIPANTS: This was a case-control study in 27 adult patients and 50 healthy age- and gender-matched controls. MAIN OUTCOME MEASURES: Serum sclerostin levels and bone turnover markers including serum osteocalcin, amino terminal propeptide of type I procollagen, and CrossLaps as well as body composition parameters were determined in mild OI stage I (OI-I) and moderate-severe OI stages III-IV (OI-III-IV), according to Sillence classification. Data were compared with healthy controls. RESULTS: Sclerostin levels were significantly lower in OI-I (19.9 ± 10.9 pmol/L; P < .001) and OI-III-IV (13.3 ± 10.0 pmol/L; P < .001) compared with healthy adults (45.3 ± 14.9 pmol/L), even after adjustment for age, sex, bone mineral content, and body mass index. CrossLaps and PTH were significantly lower in OI-I (0.197 ± 0.15 ng/L; P = .007 and 33.7 ± 19.1 pg/L; P = .033, respectively) and OI-III-IV (0.221 ± 0.18 ng/L; P = .039, and 27.9 ± 14.7 pg/L; P = .001, respectively) than in healthy controls (0.322 ± 0.15 ng/L and 45.0 ± 16.6 pg/L). Amino-terminal propeptide of type I procollagen was below the reference range for OI-I and OI-III-IV. Patients with OI were shorter and lighter and had a decreased bone mineral content (P < .001) but similar fat distribution and lean body mass, compared with controls. Serum sclerostin levels were not related to any bone marker except osteocalcin, the number of prevalent fractures, or body composition readings. CONCLUSION: Decreased sclerostin levels in OI might reflect a down-regulation or negative feedback mechanism to prevent further bone loss.
CONTEXT: There are no specific biochemical bone markers available for osteogenesis imperfecta (OI), and the role of sclerostin as a key regulator of bone formation in OI is unknown. OBJECTIVES: We aimed to evaluate the role of sclerostin and its association with bone turnover markers as well as body composition parameters in adult patients with different types of OI. DESIGN, SETTING, AND PARTICIPANTS: This was a case-control study in 27 adult patients and 50 healthy age- and gender-matched controls. MAIN OUTCOME MEASURES: Serum sclerostin levels and bone turnover markers including serum osteocalcin, amino terminal propeptide of type I procollagen, and CrossLaps as well as body composition parameters were determined in mild OI stage I (OI-I) and moderate-severe OI stages III-IV (OI-III-IV), according to Sillence classification. Data were compared with healthy controls. RESULTS:Sclerostin levels were significantly lower in OI-I (19.9 ± 10.9 pmol/L; P < .001) and OI-III-IV (13.3 ± 10.0 pmol/L; P < .001) compared with healthy adults (45.3 ± 14.9 pmol/L), even after adjustment for age, sex, bone mineral content, and body mass index. CrossLaps and PTH were significantly lower in OI-I (0.197 ± 0.15 ng/L; P = .007 and 33.7 ± 19.1 pg/L; P = .033, respectively) and OI-III-IV (0.221 ± 0.18 ng/L; P = .039, and 27.9 ± 14.7 pg/L; P = .001, respectively) than in healthy controls (0.322 ± 0.15 ng/L and 45.0 ± 16.6 pg/L). Amino-terminal propeptide of type I procollagen was below the reference range for OI-I and OI-III-IV. Patients with OI were shorter and lighter and had a decreased bone mineral content (P < .001) but similar fat distribution and lean body mass, compared with controls. Serum sclerostin levels were not related to any bone marker except osteocalcin, the number of prevalent fractures, or body composition readings. CONCLUSION: Decreased sclerostin levels in OI might reflect a down-regulation or negative feedback mechanism to prevent further bone loss.
Authors: Fabian Plachel; Ursula Renner; Roland Kocijan; Christian Muschitz; Fritz Lomoschitz; Heinrich Resch Journal: Wien Med Wochenschr Date: 2015-07-21
Authors: Matthias Mähr; Stéphane Blouin; Martina Behanova; Barbara M Misof; Francis H Glorieux; Jochen Zwerina; Frank Rauch; Markus A Hartmann; Nadja Fratzl-Zelman Journal: Int J Mol Sci Date: 2021-04-26 Impact factor: 5.923