The Role of Circadian Rhythms in Bone Health and Metabolism

Juliana, Norsham, et al. “Effect of Circadian Rhythm Disturbance on the Human Musculoskeletal System and the Importance of Nutritional Strategies.” Nutrients, vol. 15, no. 3, 1 Feb. 2023, p. 734, https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9920183/#:~:text=3.3.,metabolism%2C%20to%20name%20a%20few.

Introduction

Bone health is influenced by various factors, including sleep, circadian rhythms, and metabolic regulation. Research indicates that circadian disturbances adversely affect bone metabolism,

leading to bone loss, lower bone density, and increased inflammation. Furthermore, sleep disturbances contribute to metabolic disorders such as type 2 diabetes mellitus (T2DM), which can negatively impact bone health.

Circadian Rhythm and Bone Metabolism  

Circadian rhythms are crucial for maintaining bone health. Animal studies have shown that alterations in clock genes occur early in conditions like osteoarthritis, indicating the role of circadian disruptions in bone disorders. Research involving rats subjected to sleep restriction revealed a significant decrease in osteoblast activity and an increase in osteoclast activity, suggesting that sleep deprivation accelerates bone resorption and hampers bone formation. Similarly, mice exposed to continuous light exhibited decreased trabecular bone volume and increased inflammation, further linking circadian disruption to bone degeneration. Human studies support these findings, showing that night shift workers have lower bone density than day workers, likely due to elevated cortisol levels and disrupted vitamin D metabolism stemming from sleep disturbances.

Circadian Disruptions and Metabolic Disorders

Shift work and circadian disruptions are associated with metabolic disorders like obesity and T2DM, which further deteriorate bone health. A study by Shan et al. found that shift work increases the risk of obesity and T2DM due to decreased energy expenditure and increased energy intake. High blood sugar levels in T2DM patients inhibit calcium absorption and bone calcification, leading to osteoporosis. In T2DM mouse models, bone density and strength were significantly reduced, alongside decreased serum osteocalcin and increased serum TRAP levels, indicating enhanced bone resorption.

The Molecular Mechanisms of Circadian Influence on Bone

Circadian rhythms are essential for bone remodeling, with studies showing diurnal variations in bone cells and markers. Knockout studies targeting clock genes in mice reveal that bone formation and resorption are regulated by circadian rhythms. For instance, osteoblast-specific Bmal1-knockout mice displayed reduced bone mass and increased osteoclast activity, highlighting the importance of clock genes in bone metabolism. Additionally, mechanical loading studies indicate that bone formation varies based on the time of day, with greater formation observed when loading aligns with the animals' natural circadian rhythms. These insights suggest potential for targeting circadian timing systems in preventing and treating bone diseases.

Clinical Implications: Chronotherapy and Nutritional Strategies  

Interventions targeting circadian mechanisms may offer new treatment avenues for bone disorders. Chronotherapy, involving medication timing to align with the body's biological clock, shows promise for enhancing the efficacy of osteoporosis treatments. By targeting clock genes, researchers can develop therapies to mitigate bone loss and prevent fractures in at-risk populations, such as night shift workers and individuals with sleep disorders.

Nutritional strategies also play a vital role in supporting bone health. Malnutrition is a significant predictor of osteoporosis and impaired healing, particularly in the elderly. A balanced diet rich in calcium, vitamin D, and anti-inflammatory foods, such as those found in the Mediterranean diet, is essential for maintaining healthy bones. Adequate calcium and vitamin D intake is crucial for preventing osteoporosis and promoting proper bone repair, as deficiencies in these nutrients are widespread globally. For instance, a diet high in calcium from dairy sources or supplements during childhood is critical for developing peak bone mass, which can reduce osteoporosis risk later in life.

Conclusion

Emerging evidence highlights the significant impact of circadian rhythms on bone health. Disrupted circadian rhythms, whether due to sleep disturbances or shift work, can lead to decreased bone formation and increased resorption, ultimately resulting in bone loss. Understanding the molecular mechanisms underlying circadian regulation of bone metabolism may lead to novel therapeutic interventions, including chronotherapy and dietary modifications, aimed at reducing osteoporosis incidence and improving overall bone health.

Work cited  

Mohd Azmi N.A.S., Juliana N., Azmani S., Mohd Effendy N., Abu I.F., Mohd Fahmi Teng N.I., Das S. Cortisol on Circadian Rhythm and Its Effect on Cardiovascular System. Int. J. Environ. Res. Public Health. 2021;18:676. doi: 10.3390/ijerph18020676.

Luo B., Zhou X., Tang Q., Yin Y., Feng G., Li S., Chen L. Circadian rhythms affect bone reconstruction by regulating bone energy metabolism. J. Transl. Med. 2021;19:410. doi: 10.1186/s12967-021-03068-x.

Mohd Azmi N.A.S., Juliana N., Mohd Fahmi Teng N.I., Azmani S., Das S., Effendy N. Consequences of Circadian Disruption in Shift Workers on Chrononutrition and their Psychosocial Well-Being. Int. J. Environ. Res. Public Health. 2020;17:2043. doi: 10.3390/ijerph17062043.

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