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BACKGROUND Glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptide-2 (GLP-2) are gut hormones secreted in response to food ingestion, and they have been suggested to regulate bone turnover. In humans, exogenous GIP and GLP-2 acutely inhibit bone resorption as measured by circulating levels of carboxy-terminal type 1 collagen crosslinks (CTX). OBJECTIVE The objective was to study the individual and combined acute effects of GIP and GLP-2 on bone turnover in postmenopausal women during nighttime - a period of increased bone resorption. METHODS Using a randomized, placebo-controlled, double-blinded, crossover design, each participant (n = 9) received on four separate study days: GIP, GLP-2, GIP+GLP-2, and placebo (saline) as subcutaneous injections at bedtime. Main outcomes were levels of CTX and procollagen type 1 N-terminal propeptide (P1NP). RESULTS Compared with placebo, GIP and GLP-2 alone significantly inhibited bone resorption (measured by CTX). GIP rapidly reduced CTX levels in the period from 45 to 120 minutes after injection, while GLP-2 had a more delayed effect with reduced CTX levels in the period from 120 to 240 minutes after injection. Combining GIP and GLP-2 showed complementary effects resulting in a sustained inhibition of CTX with reduced levels from 45 to 240 minutes after injection. Furthermore, GIP acutely increased bone formation (measured by P1NP). CONCLUSION Both GIP and GLP-2 reduced CTX during the night and had complementary effects when combined.