Bone turnover marker rhythmicity: implications for osteoporosis treatment and fracture healing

Bone turnover is a dynamic process with markers of bone turnover displaying varying degrees of rhythmicity. The objective of this narrative review was to synthesize current evidence on the regulation of bone turnover marker (BTM) rhythmicity and to evaluate how these rhythms may influence clinically relevant outcomes in osteoporosis treatment and fracture healing. Structured literature searches were conducted in PubMed to identify studies that examined BTM rhythmicity, intrinsic versus extrinsic factors that influence this rhythmicity, and timing effects of osteoporosis medications and fracture-related healing to inform this narrative review. The reviewed evidence demonstrates that markers of bone resorption exhibit robust diurnal rhythms, whereas bone formation markers show lower-amplitude and more variable oscillations. These rhythms are primarily circadian driven and influenced by environmental factors (e.g. fasting) and have important implications for accurate use and interpretation when used clinically and in research. Clinical and preclinical studies further indicate that the administration time of some osteoporosis medications can influence efficacy and safety, with certain anabolic and antiresorptive agents showing differences in biochemical or structural responses depending on administration time, while others appear timing insensitive or remain unstudied. Emerging experimental data suggest that fracture healing may also display rhythmicity and be differentially impacted by the timing of interventions.

This review summarizes how bone turnover marker levels vary across the day and night and how this rhythmicity may influence the effects of some medications, with implications for optimal use of these markers in clinical practice and research to improve osteoporosis treatment and potentially fracture healing.