Sarcopenia and vitamin D deficiency in patients with Crohn’s disease: Pathological conditions that should be linked together
Sarcopenia is a prevalent condition in patients with Crohn’s disease (CD), representing an independent predictor factor for the development of major postoperative complications.
Crohn’s disease (CD) is a chronic and progressive inflammatory bowel disease (IBD) that has a high impact on a patient’s quality of life. It is well known that all segments of the gastrointestinal tract can be affected by CD, mainly the terminal ileum and colon.
Inflammation is generally segmental, asymmetrical, and transmural. Although progress has been made to achieve prolonged remission, almost half of the patients over time will develop complications (i.e., strictures, fistulas, and abscesses) that require surgical treatments. The pathogenesis of CD is not yet fully understood, however, it clearly involves multiple factors, i.e., genetic susceptibility, environmental factors, and intestinal
microflora, resulting in dysregulation of multiple and overlapping immune pathways.
In the last decades, the prevalence of CD has increased continuously worldwide, especially in the developed countries, primarily due to environmental factors, such as changes in dietary patterns and alterations in body composition. Among these, the loss of muscle mass resulting in a decrease of muscle strength, a condition named sarcopenia, is an increasingly prevalent condition in patients with CD and is a strong independent predictor factor for the appearance of major postoperative complications.
Nowadays, it is widely acknowledged that vitamin D is one of the factors involved in the proliferation, differentiation, and regeneration of muscle cells. As proof of this, alterations in vitamin D levels seem to be related to sarcopenia prevalence in several pathological conditions, including CD.
Sarcopenia in Patients with CD
In the last decade, sarcopenia has emerged as a primary factor in the nutritional assessment of patients affected by chronic inflammatory diseases, including IBD. In fact, there is evidence indicating that this syndrome impacts the course of the disease, the responsiveness to specific therapies, and the outcomes of surgery..
Sarcopenia turns out to be a widespread condition in patients with IBD, in particular CD. In a recent systematic review, it is reported that up to 60% of patients with IBD present a depletion of the muscle mass when compared with healthy subjects.
It is reported that patients with CD, affected by sarcopenia, result to be overweight or obese (a condition named “sarcopenic obesity”), rather than undernourished, at the nutritional assessment tests. This extreme variability emphasizes the need for malnutrition and sarcopenia screening in all CD patients.
In addition to malabsorption and gastrointestinal surgery, other factors may contribute to the development of sarcopenia in patients with CD, such as eventual glucocorticoid treatment and hypogonadism, and a reduced physical activity [18–20]. It should be noted that the activation of inflammatory cytokines may contribute significantly to converting
the muscle protein metabolism from synthesis to degradation.
Vitamin D and Sarcopenia
Over recent years, the potential role of vitamin D on muscle function and strength has been widely debated. At a cellular level, it is known that vitamin D acts through both genomic and nongenomic pathways.
At the nuclear level, vitamin D can regulate gene expression by interacting with Vitamin D Receptor (VDR), thus forming a heterodimeric complex of liganded VDR with Retinoid-X-receptor (RXR) and up-regulating or down-regulating target genes transcription. The non-genomic effects of Vitamin D are mediated by the activation of intracellular signal pathways through signal molecules, e.g., phospholipase C and phospholipase A2, and the production of second messengers, protein kinases, and the opening of Ca2+ and Cl− channels.
Focusing on the biological mechanisms that regulate differentiation, proliferation, and regeneration of muscle cells, it has been demonstrated that vitamin D regulates several myogenic transcription factors involved in muscle cells proliferation, e.g., insulin-like growth factor 2 and follistatin, and in muscle cells differentiation, e.g., fetal myosin, the neural cell adhesion molecule, insulin-like growth factor 1, fibroblast growth factor and myogenic differentiation protein 1.
Regarding muscle regeneration, it has been demonstrated that vitamin D promotes the initial increase of the cross-sectional area of skeletal muscle fibres, by arresting the cell cycle, and suppresses the expression of myostatin, a key factor implicated in muscular degeneration.
According to the current knowledge, vitamin D seems to mainly affect type IIA muscle cells, i.e., the “fast twitch oxidative” cells . Indeed, by using muscle biopsy, in previous works it has been shown that vitamin D deficiency is associated with type IIA muscle cells atrophy and fibrosis and, by contrast, the supplementation of vitamin D has been shown to increase the number and the diameter of type IIA muscle cells, thus increasing
Furthermore, it should be mentioned that elevated PTH may contribute to the pathogenesis of sarcopenia, given its direct effect on skeletal muscle protein metabolism and the recent demonstration that elevated PTH levels are associated with vitamin D deficiency in sarcopenia.