Vitamin D in Osteosarcopenic Obesity

Abstract

Osteosarcopenic obesity is a unique clinical condition where low bone and muscle mass coexist in individuals with obesity. Alterations in adipose tissue, skeletal muscle and bone are strictly interconnected, and vitamin D plays key roles in several metabolic pathways that are involved in maintaining musculoskeletal health and glucose homeostasis. We reviewed the available literature on mechanisms underlying osteosarcopenic obesity, with a focus on the role of vitamin D in the pathogenesis and treatment of the condition. We found that, although evidence from large observational studies and pre-clinical experiments strongly supports a role of vitamin D deficiency in the pathogenesis of osteosarcopenic obesity, the common belief that vitamin D improves musculoskeletal health lacks solid clinical evidence, as trials specifically aimed at assessing the effects of vitamin D supplementation in patients with osteosarcopenic obesity are not available, and trials that investigated the role of vitamin D on muscle and bone health in other patient populations either showed no or even detrimental effects. We conclude that large observational and interventional studies including individuals with osteosarcopenic obesity representative of different sex, age and race are needed to better define the role of vitamin D in the pathogenesis and treatment of this condition.

Keywords: insulin resistance; obesity; osteopenia; osteoporosis; sarcopenia; sarcopenic obesity; vitamin D.

Figure 1

Role of endocrine and inflammatory/immune dysregulation in the pathogenesis of osteosarcopenic obesity. Red, curved arrows: negative influence; bidirectional red curved arrows indicate mutual influences perpetuating the pathogenic vicious cycle. Upward arrows indicate an increase. Causes of glucocorticoid excess include Cushing disease/syndrome, aging, sleep deprivation, stress, steroid therapy; ageing is associated with GH, IGF1 and androgen deficiency; adipose tissue dysfunction triggers low-grade chronic inflammation. See text for detailed explanation. GH, growth hormone; IGF1, insulin-like growth factor 1; TNF-α, tumor necrosis factor-alpha; IL-1, interleukin 1; IL-6, interleukin 6; CRP, C-reactive protein; PG-E2, prostaglandin E₂; LT-B4, leukotriene B4. Created with BioRender.com, accessed on 31 March 2022.

Figure 2

Potential role of vitamin D deficiency in the development of osteosarcopenic obesity. Vitamin D deficiency may reduce immune, antioxidant and anti-inflammatory capacity, is associated with multi-organ insulin resistance and altered adipogenesis, lipogenesis, lipolysis and inflammation in adipose tissue, might impair bone–skeletal muscle crosstalk and, by altering calcium–phosphorus metabolism, may impair muscle function and repair, chondrocyte maturation, bone mineralization and increase bone resorption. All these mechanisms could contribute (rightward arrow) to the development of osteosarcopenic obesity. PTH, parathyroid hormone. Upward arrow, increase; downward arrow, decrease. Created with BioRender.com, accessed on 31 March 2022.