The importance of the circadian system & sleep for bone health

Abstract

Adequate sleep timed appropriately during the circadian night is important for numerous biological processes and systems. New evidence suggests that both sleep timing and duration may be important for optimal bone health as well. This review examines the diurnal variation of bone turnover markers (BTMs) and the importance of circadian clock genes in regulating bone mass. In addition, this review explores the evidence for a link between shift work (and its associated disturbances in sleep duration/quality and circadian alignment) and alterations in bone metabolism and bone health. Finally, we review how commonly used medications and over-the-counter substances (e.g. caffeine, melatonin) complicate the relationship between sleep and circadian disorders and bone health.

Keywords: Bone; Bone turnover; Circadian; Fracture; Sleep.

Figure 1. Bone matrix and cells with representative 24h profiles of bone cell markers

Osteoclasts (bone resorption) attach to the bone surface and secrete factors that degrade bone collagen, releasing CTX (and other breakdown products). Osteoblasts form bone matrix to fill in the resorption cavity. An important element in bone formation involves procollagen synthesis and its cleavage to form collagen, the main scaffolding for the bone matrix. When procollagen is cleaved, its terminal ends are released (P1NP, P1CP). Osteoclast and osteoblast activity are coupled, and regulated, in part, by the osteocyte. The osteocyte is a terminally differentiated osteoblast imbedded in the bone matrix that secretes proteins (such as FGF-23). Osteocytes use dendritic processes to sense mechanical loading and transmit signals to regulate the activity of other bone cells. Markers of bone turnover, such as CTX and P1NP, and the osteocyte-derived protein FGF-23 display a 24h diurnal variation (representative curves generated using data from Swanson et al [22]).

Figure 2. Conceptual framework of how circadian rhythm and sleep disturbances alter bone health

Sleep and circadian disturbances, in the form of night-shift work and/or altered sleep duration, impair bone formation, microarchitecture and strength and are associated with lower BMD through several potential mediators (ovals). Together, these changes in bone density and quality lead to an increased fracture risk. Circadian rhythm and sleep disturbances can also increase fracture risk by increasing the risk for falls, with or without sleep medications used to treat these disorders (e.g. benzodiazepines, Z-drugs like zolpidem). Age and/or sex differences may influence the circadian rhythm and sleep disturbances, mediators, and fracture risk.