Aim: The past decade, it has become evident that circadian (i.e. 24 h) rhythms within metabolically active tissues are very important for physical health. However, although shift work has been associated with osteoporosis, circadian rhythmicity has not yet been extensively studied in the field of bone research.

Methods & Results: In this study, we investigated which genes are rhythmically expressed in bone, and whether circadian disruption by means of alternating light-dark cycles affects bone turnover and structure in mice. Our results demonstrate diurnal expression patterns of clock genes (Rev-erbα, Bmal1, Per1, Per2, Cry1, Clock), as well as genes involved in osteoclastogenesis, osteoclast proliferation and function (Rankl, Opg, Ctsk) and osteocyte function (c-Fos) in bone. Alternating light-dark cycles caused a reduction in plasma levels of procollagen type 1 amino-terminal propeptide (P1NP) and tartrate-resistant acidic phosphatase (TRAP), suggestive of a reduced bone formation and bone resorption, respectively. These effects coincided with an altered trabecular bone structure and a decreased bending strength as determined by micro-CT after 16 weeks of alternating light-dark cycles. To investigate whether disruption of glucocorticoid rhythm could be an underlying mechanism by which alternating light-dark cycles affect bone health, we flattened corticosterone rhythm in mice by implanting subcutaneous corticosterone pellets. Indeed, flattening of corticosterone rhythm reduced expression of clock genes (Rev-erbα and Per1), decreased P1NP plasma levels, and affected trabecular and cortical bone structure.

Conclusion: Collectively, these results suggest that circadian rhythm is important for bone health, and that circadian disruption negatively affects bone turnover markers and bone structure. As a large part of the working population participates in shift work (e.g. almost 30% of workers in the U.S.), this justifies further research on the risk of skeletal disorders associated with circadian disturbances, as well as underlying mechanisms.