Reduction of nocturnal rise in bone resorption by subcutaneous GLP-2

Abstract

We have previously shown that a subcutaneous injection of glucagon-like peptide-2 (GLP-2) at 9 a.m. in fasting postmenopausal women results in a dose-dependent decrease in the serum concentration of fragments derived from the degradation of the C-terminal telopeptide region of collagen type I (s-CTX), a marker of bone resorption. In contrast, GLP-2 was found to have a neutral effect on bone formation, as assessed by serum osteocalcin. Since increased s-CTX levels are normally observed at night, we conducted bedtime studies in healthy postmenopausal women. The objective was to study the effect of GLP-2 injection on bone turnover given at bedtime. A total of 81 postmenopausal women were included in two randomised placebo-controlled studies. In conclusion, we found a dose-related reduction of s-CTX after injection of GLP-2 (P < 0.05) and osteocalcin levels was increased as compared to placebo (P = 0.07) by the treatment, suggestive of a stimulative effect on bone formation. An area under the curve (AUC0-10 h) analysis for s-CTX after GLP-2 injection confirmed the dose-related decrease as compared to placebo (P < 0.05).