Letter to the Editor: Possible Decrease in GIP Levels May Explain Increased Plasma Dipeptidyl Peptidase-4 Activity-Associated Osteoporosis

We read with great interest the Early Release article in the Journal of Clinical Endocrinology & Metabolism (August 2015) with the title of “Plasma DPP4 activities are associated with osteoporosis in postmenopausal women with normal glucose tolerance” by Zheng et al (1). The authors prepared an outstanding study in the field of bone metabolism on the topic of dipeptidyl peptidase-4 (DPP4) activities and osteoporosis. However, the article raises some important points about this effect. The authors mentioned that increased DPP4 activities are associated with osteoporosis, regardless of decrease in the active fasting glucagon-like peptide-1 level. Gastric inhibitory polypeptide (GIP) is released from the K cells of the upper intestine, and secreted GIP is rapidly inactivated by DPP-4 (2). Bollag et al (3) reported that GIP receptors are present in bone and osteoblast-like cells, and collagen type 1 expression and alkaline phosphatase activity in osteoblastic-like cells are increased by GIP. Intermittent injection of GIP significantly increased bone mineral density in ovariectomized rats (4). Zhong et al (5) demonstrated the presence of GIP receptors in osteoclasts, in which GIP seems to suppress bone resorption and the resorptive activity of mature osteoclasts. Using GIP receptor knockout mice, Xie et al (6) demonstrated a reduction in bone formation, deteriorated bone microstructure, and biomechanical properties and an increase in bone resorption with a low bone mass. On the other hand, GIP-overexpressing transgenic mice caused elevated bone density (7). We would like to emphasize that increased DPP4 activity-induced GIP reduction may have a role in increased DPP4-associated osteoporosis. In this study, the authors did not report any information about the GIP levels. We think that it would be more reasonable if the authors add the data of the above-mentioned suggestions, which would strengthen their study. Finally, we would like to congratulate Zheng et al (1) on their outstanding study. The authors chose not to comment on this letter. Disclosure Summary: The authors have nothing to disclose. dipeptidyl peptidase-4 gastric inhibitory polypeptide.