Modeling the Clockwork of Bone: A Narrative Review of Experimental Approaches to Circadian Rhythm in Bone Metabolism

Circadian rhythms are fundamental regulators of bone remodeling, orchestrating the co-ordinated actions of osteoblasts, osteocytes, and osteoclasts. Recent studies have high-lighted how core clock genes, such as Bmal1, Clock, Per1/2, and Cry1/2, exhibit rhythmic expression in bone tissue and modulate key markers of bone formation and resorption. Disruptions in circadian regulations, whether caused by environmental factors or genetic alterations, have been linked to osteoporosis, impaired fracture healing, and increased risk of bone fragility. This review provides a comprehensive evaluation of current experi-mental models used to study circadian regulation in skeletal biology, including in vivo, ex vivo, and in vitro approaches. We summarize their respective advantages and limitations and outline the molecular and cellular markers employed to assess circadian function in bone cells. We also discuss the emerging co-culture models and human-relevant plat-forms, for their potential to bridge the gaps between mechanistic research and transla-tional applications. By comparing model characteristics and highlighting integrated re-search strategies, this review aims to advance circadian bone research and inform future investigations into potential temporal aspects of skeletal health.