Spatiotemporal remodeling of bone as a reversibly adaptive biological material in Djungarian hamsters under regulated photoperiod conditions

Bone loss in humans is typically progressive and difficult to reverse, posing challenges for both pharmacological therapy and the long-term performance of bone replacement materials. Photoperiod-sensitive species such as the Djungarian hamster undergo cyclical physiological adaptations in response to seasonal light cues, providing a unique framework to investigate bone adaptation during physiologically regulated phases of bone loss under endocrine and circadian control without surgical or pharmacological intervention. Female Djungarian hamsters were maintained under long-day (LD) or short-day (SD) photoperiods to induce physiological body weight loss without surgical or pharmacological intervention. Femoral and tibial bones were analyzed across mechanical, microstructural, and cellular scales using three-point bending, high-resolution microcomputed tomography, histomorphometry, and deep-learning-based quantification of bone marrow adipocytes. Under SD conditions, bone exhibited reduced mass (p = 0.001), trabecular number (p = 0.003), cortical thickness (p = 0.009), and mechanical strength (p = 0.013), along with increased marrow adiposity (p < 0.001) and matrix erosion (p = 0.020). These changes occurred without surgical manipulation, reflecting a physiologically driven, photoperiod induced bone loss mechanism. The Djungarian hamster provides a non-invasive framework model to study bone as a physiologically regulated biological material undergoing osteoporosis-like changes. By enabling photoperiod-controlled bone remodeling, this system offers translational opportunities to study bone material adaptation and the biological environment relevant for biomaterial performance under conditions of bone loss. Moreover, this model provides a physiologically relevant platform to study age- and endocrine-associated bone loss mechanisms and to inform the development of future osteoanabolic strategies. STATEMENT OF SIGNIFICANCE: Bone loss caused by disease or disuse is typically progressive and difficult to reverse, and most experimental models rely on invasive surgical or pharmacological interventions to induce osteoporosis. In contrast, photoperiod-sensitive species such as the Djungarian hamster exhibit naturally regulated, potentially reversible skeletal adaptation. In this study, we characterize bone as a potentially reversibly adaptive biological material under controlled photoperiod conditions. Using multiscale structural, mechanical, and histological analyses, we show that short-day photoperiods induce pronounced, physiologically regulated changes in bone microarchitecture, mechanical competence, and marrow composition without surgical manipulation. Understanding how bone adapts, deteriorates, and regains function under endogenous control may inform the development of regenerative materials and therapies capable of operating within dynamically changing and compromised skeletal environments.