Disassociation of bone resorption and formation by GLP-2 A 14-day study in healthy postmenopausal women

• Published in: Bone (New York, N.Y.) N.Y.), 2007-03, Vol.40 (3), p.723-729
• Main Authors: HENRIKSEN, Dennis B, ALEXANDERSEN, Peter, HARTMANN, Bolette, ADRIAN, Charlotte L, BYRJALSEN, Inger, BONE, Henry G, HOIST, Jens J, CHRISTIANSEN, Claus
• Format: Article
• Language: English
• Subjects: Aged; Area Under Curve; Biological and medical sciences; Bone Resorption - prevention & control; Calcium - urine; Collagen Type I - blood; Collagen Type I - drug effects; Creatinine - urine; Dose-Response Relationship, Drug; Double-Blind Method; Female; Fundamental and applied biological sciences. Psychology; Glucagon-Like Peptide 2 - administration & dosage; Glucagon-Like Peptide 2 - adverse effects; Glucagon-Like Peptide 2 - pharmacokinetics; Humans; Injections, Subcutaneous; Osteocalcin - blood; Osteocalcin - drug effects; Osteogenesis - drug effects; Osteoporosis, Postmenopausal - prevention & control; Peptide Fragments - blood; Peptide Fragments - drug effects; Peptides - blood; Peptides - drug effects; Phosphates - urine; Premenopause - physiology; Procollagen - blood; Procollagen - drug effects; Skeleton and joints; Vertebrates: osteoarticular system, musculoskeletal system
• ISSN: 8756-3282; 1873-2763
• DOI: 10.1016/j.bone.2006.09.025

We have previously shown that a single subcutaneous injection of glucagon-like peptide-2 (GLP-2) at 10 p.m. in postmenopausal women results in a dose-dependent decrease in the nocturnal serum and urine concentrations of fragments derived from the degradation of the C-terminal telopeptide region of collagen type I (s-CTX and u-CTX) and u-DPD, markers of bone resorption. In contrast, bone formation, as assessed by serum osteocalcin and procollagen type I N-terminal propeptide (PINP), appeared to be unaffected by treatment with exogenous GLP-2. These effects were further investigated in a 14-day study. The aim was to demonstrate that a parenteral formulation of GLP-2 is safe and well tolerated after repeated dosing in healthy postmenopausal women for 14 days. It was further investigated whether the effects on bone turnover markers were sustained throughout the study period. The study was a double-blind placebo-controlled trial with 60 postmenopausal women and 2 different doses of GLP-2 (1.6 mg and 3.2 mg GLP-2) against a saline control. The data for bone resorption revealed a similar reduction on Day 1 and Day 14, both based on time course and AUC. There were no signs of tachyphylaxis and no serious adverse reaction. Both GLP-2 doses resulted in similar and significant (p