Modulation of Bone Turnover Markers with Dipeptidyl Deptidase-4: Interplay in Bone Health

Understanding the structure, development, and maintenance of bone is crucial to the assessment of bone health and interpretation of clinical outcomes. Bone turnover markers released during bone remodeling have been extensively investigated in osteoporosis studies. These markers include bone formation markers, which are involved in osteogenesis, and bone resorption markers, which break down the bone structure. Although these markers complement bone mineral density results, their clinical use faces challenges because of fluctuations related to factors such as age, gender, and circadian rhythms, as well as analytical variability. Dipeptidyl peptidase-4 (DPP-4) is a ubiquitous exopeptidase that regulates the functions of various proteins. It is present in bound and free form and circulates freely in the extracellular space. It regulates glucose metabolism, cell migration and differentiation, oxidative stress, inflammation, cellular signaling, and the immune system. It also plays an important role in collagen metabolism due to its presence in osteocytes, osteoclasts, and osteoblasts. The substrates of DPP-4, like gastrointestinal peptides, incretins, and neuropeptides, influence bone homeostasis as well via modulation of bone markers. This review explores bone turnover markers in relation to DPP-4 to better understand their role in bone metabolism concerning osteoporosis.