A global deficiency in vitamin D is now widely prevalent. Extensive scientific research has provided compelling evidence of the detrimental effects of vitamin D deficiency on the skeletal system. Furthermore, vitamin D supplementation not only helps prevent bone fractures but may also slow the progression of various conditions, such as diabetes, autoimmune disorders, and cardiovascular disease. Achieving optimal circulating vitamin D levels can be challenging, particularly in certain clinical scenarios. Moreover, the effect of vitamin D supplementation varies depending on factors such as body weight, pregnancy status, absorption capacity, metabolic rate, and renal function. This review aims to explore which vitamin D formulations are most effective in specific clinical contexts where reaching adequate vitamin D levels may not be straightforward.

Due to their widespread prevalence and the aging global population, metabolic syndrome (MetS) and osteoporosis represent significant public health challenges. Clinical interest in MetS is currently primarily focused on cardiovascular risks. However, emerging evidence indicates that metabolic conditions may also adversely affect bone health. Each component of MetS—especially glucose metabolism impairment, central obesity, and endocrine factors—impacts bones in distinct ways, creating a complex network of interactions that influences skeletal health. These metabolic disturbances can lead to changes in bone remodeling, potentially resulting in alterations to bone mineral density and microarchitectural structure and an increased risk of fractures. Regarding uncertain and controversial pieces of evidence about the effect of MetS on bone health, this narrative review discusses and summarizes the current research on the association of MetS and its components with bone metabolism, bone quantity (based on bone mineral density, or BMD), bone quality (based on trabecular bone score, or TBS), and fracture risk.

Vitamin D is involved in immune regulation through effects on innate and adaptive immune responses mediated by vitamin D receptor activation within immune cells. Experimental and translational studies support its role in promoting regulatory T-cell activity, modulating Th1/Th17 responses, and influencing autoantibody production. At the population level, low serum 25-hydroxyvitamin D concentrations are consistently associated with an increased risk of autoimmune diseases, including autoimmune thyroid disorders such as Hashimoto’s thyroiditis (HT) and Graves’ disease (GD), suggesting a potential preventive association. In contrast, clinical evidence from interventional studies in patients with established disease is heterogeneous. Although vitamin D supplementation has been associated with reductions in thyroid autoantibody titers in some studies—particularly in patients with HT and baseline vitamin D deficiency—consistent effects on thyroid function, disease progression, or relapse prevention have not been demonstrated. Overall, current evidence supports vitamin D deficiency as a potentially modifiable risk marker rather than a confirmed disease-modifying therapeutic target in autoimmune thyroid diseases, highlighting the need for further studies focused on clinically meaningful outcomes.

Background: Incretin-based therapies (IBTs), including glucagon-like peptide-1 receptor agonists (GLP-1 RAs) and dual glucose-dependent insulinotropic polypeptide/glucagon-like peptide-1 receptor agonists (GIP/GLP-1 RAs), have transformed the management of obesity and type 2 diabetes mellitus (T2DM). Although these agents provide substantial metabolic and cardiometabolic benefits, their effects on skeletal muscle, particularly in older adults at increased risk of sarcopenia and functional decline, remain incompletely understood. Methods: This narrative review synthesizes evidence from randomized controlled trials (RCTs) and observational studies evaluating the effects of semaglutide and tirzepatide on skeletal muscle mass (SMM), muscle quality, strength, and physical performance. Current evidence on nutritional and exercise strategies aimed at preserving skeletal muscle during IBT was also reviewed. Results: Both semaglutide and tirzepatide induce substantial weight loss accompanied by reductions in lean body mass (LBM). However, current evidence indicates that LBM loss is generally proportional to the magnitude of weight loss and should not be interpreted as a direct surrogate for skeletal muscle loss or drug-induced myotoxicity. Tirzepatide appears to improve skeletal muscle composition by reducing muscle fat infiltration (MFI), whereas semaglutide shows more heterogeneous effects on muscle strength and physical performance, particularly in older or frail individuals. Emerging evidence highlights the importance of muscle quality, nutritional adequacy, and resistance exercise as key determinants of muscle preservation, although functional outcomes and data in older adults remain limited. Conclusions: The effects of incretin-based therapies (IBTs) on skeletal muscle are multifactorial and influenced by age, baseline muscle reserve, nutritional status, and physical activity. Preserving skeletal muscle health should be considered an integral component of obesity management through individualized nutritional care, adequate protein intake, resistance exercise, and regular functional assessment. Future research should prioritize the standardized evaluation of muscle quality and function and determine whether targeted nutritional interventions can improve the quality of weight loss and support healthy aging during IBT.