Background: Musculoskeletal disorders (MSDs) involve muscles, nerves, tendons, joints, cartilage, and spinal discs. These conditions can be triggered by both the work environment and the type of work performed, factors that, in some cases, can also exacerbate pre-existing conditions. This systematic review aims to provide an overview of the impact that different work-related activities have on the musculoskeletal system. Methods: A global search of publications was conducted using the following international bibliographic web databases: PubMed and Web of Science. The search strategies combined terms for musculoskeletal disorders and workers. In addition, a meta-analysis was conducted to estimate the prevalence of MSDs within the healthcare sector. Results: A total of 10,805 non-duplicated articles were identified, and finally, 32 studies were reviewed in this article. Once the literature search was completed, occupational figures were categorized into healthcare, farming, industrial, and computer sectors. In the healthcare sector, the prevalence estimate for degenerative diseases of the lumbar spine was 21% (497 out of 2547 physicians and dentists) (95% CI, 17–26%), while for osteoarthritis of the hand, it was 37% (382 out of 1013 dentists) (95% CI, 23–51%). Conclusions: Musculoskeletal disorders significantly impair workers’ quality of life, especially in healthcare sector. These conditions are also associated with high costs for employers, such as absenteeism, lost productivity, and increased costs for healthcare, disability, and workers’ compensation.

The aging of the world population is closely associated with an increased prevalence of musculoskeletal disorders, such as osteoporosis, sarcopenia, and osteoarthritis, due to common genetic, endocrine, and mechanical risk factors. These conditions are characterized by degeneration of bone, muscle, and cartilage tissue, resulting in an increased risk of fractures and reduced mobility. Importantly, a crucial role in the pathophysiology of these diseases has been proposed for cellular senescence, a state of irreversible cell cycle arrest induced by factors such as DNA damage, telomere shortening, and mitochondrial dysfunction. In addition, senescent cells secrete pro-inflammatory molecules, called senescence-associated secretory phenotype (SASP), which can alter tissue homeostasis and promote disease progression. Undoubtedly, targeting senescent cells and their secretory profiles could promote the development of integrated strategies, including regular exercise and a balanced diet or the use of senolytics and senomorphs, to improve the quality of life of the aging population. Therefore, our review aimed to highlight the role of cellular senescence in age-related musculoskeletal diseases, summarizing the main underlying mechanisms and potential anti-senescence strategies for the treatment of osteoporosis, sarcopenia, and osteoarthritis.

The vitamin D receptor (VDR) regulates bone development and calcium homeostasis, suggesting a central role in musculoskeletal diseases such as osteoporosis (OP). Several studies have examined the contribution of VDR polymorphisms and epigenetic signatures in bone metabolism and OP risk, with sometimes inconclusive results. Our study aimed to explore the association between genetic variability, expression and the methylation pattern of VDR with the risk of OP in a cohort of Caucasian patients. Genomic DNA from 139 OP, 54 osteopenic (Ope) and 73 healthy (CTR) subjects were used for genotyping the rs731236 (TaqI), rs2228570 (FokI) and rs11568820 (Cdx2) polymorphisms of the VDR gene by an allelic discrimination assay. Quantitative real-time polymerase chain reaction (qRT-PCR) analysis of VDR expression levels and pyrosequencing analysis of a VDR promoter CpG island were carried out in a subcohort (25 OP and 25 CTR) of subjects. Data obtained showed a significantly higher OP risk for rs11568820 G/A and A/A genotypes (p = 0.05). qRT-PCR revealed lower VDR gene expression levels in the OP group compared to CTR subjects (p = 0.0009), also associated with both the rs11568820 A/A genotype (p = 0.03) and femoral fragility fractures (p = 0.05). No association was found between the methylation pattern of the region analyzed of the VDR promoter and its expression levels. Our results identify a significative association between Cdx2 rs11568820 polymorphism and OP risk. In addition, the VDR transcriptomic profile suggests a putative interconnection with OP progression, providing a useful tool to stratify OP phenotype and fragility fracture risk.

Clusterin (CLU) is a secreted heterodimeric glycoprotein expressed in all organism fluids as well as in the intracellular matrix that plays key roles in several pathological processes. Its recent involvement in muscle degeneration of osteoporotic patients led to investigation of the role of CLU in bone metabolism, given the biochemical and biomechanical crosstalk of the bone–muscle unit. Quantitative real time-polymerase chain reaction (qRT-PCR) analysis of CLU expression was performed in both osteoblasts and Peripheral Blood Mononuclear Cells (PBMCs) from osteoporotic patients (OP) and healthy individuals (CTR). Furthermore, immunohistochemical analysis on femoral head tissues and enzyme-linked immunosorbent assay (ELISA) in plasma samples were performed to investigate CLU expression pattern. Finally, genotyping of CLU rs11136000 polymorphism has also been performed by qRT-PCR assays to explore a possible association with CLU expression levels. Data obtained showed a significantly increased expression level of secreted CLU isoform in PBMCs and osteoblasts from OP patients. Immunohistochemical analysis confirms the increased expression of CLU in OP patients, both in osteocytes and osteoblasts, while plasma analysis reveals a statistically significant decrease of CLU levels. Unfortunately, no functional association between CLU expression levels and the presence of CLU rs11136000 polymorphism in OP patients was found. These data suggest a potential role played by CLU as a potential biomarker for the diagnosis and prognosis of OP progression.

Background/Objectives: Cellular aging represents a crucial element in the progression of musculoskeletal diseases, contributing to muscle atrophy, functional decline, and alterations in bone turnover, which promote fragility fractures. However, knowledge about expression patterns of factors potentially involved in aging and senescence at the tissue level remains limited. Our pilot study aimed to characterize the expression profile of cell cycle regulators, factors released by aged cells, and sirtuin 1 (SIRT1) in the muscle tissue of 26 elderly patients undergoing hip arthroplasty, including 13 with low-energy fracture and 13 with osteoarthritis (OA). Methods: The mRNA expression levels of cyclin-dependent kinase inhibitor 1A (CDKN1A), cyclin-dependent kinase inhibitor 1B (CDKN1B), cyclin-dependent kinase inhibitor 2A (CDKN2A), p53, tumor necrosis factor alpha (TNF-α), interleukin-1 beta (IL-1β), interleukin-6 (IL-6), interleukin-15 (IL-15), chemokine (C-C motif) ligand 2 (CCL2), chemokine (C-C motif) ligand 3 (CCL3), growth differentiation factor 15 (GDF15), and SIRT1 were evaluated in muscle tissue by qRT-PCR. In addition, immunohistochemistry and Western blotting analysis were conducted to measure the protein levels of SIRT1. Results: A marked muscle atrophy was observed in fractured patients compared to the OA group, in association with an up-regulation of cell cycle regulators and factors released by the aged cells. The expression of matrix metallopeptidase 3 (MMP3), plasminogen activator inhibitor 1 (PAI-1), and fas cell surface death receptor (FAS) was also investigated, although no significant differences were observed between the two experimental groups. Notably, SIRT1 expression was significantly higher in OA patients, confirming its role in maintaining muscle health during aging. Conclusions: Further studies will be needed to clarify the role of SIRT1 in the senescence characteristic of age-related musculoskeletal disorders, counteracting the muscle atrophy that predisposes to fragility fractures.

Phosphate accounts for about 0.6% of body weight at birth and about 1% of body weight in adults. This anion is essential for the performance of many essential human cellular processes, including energy metabolism and cell signaling; it is also a key component of the phospholipid bilayer and nucleic acids structure. In addition, phosphate is responsible for maintaining acid-base balance within the cells, functioning of the nervous system and preserving bone integrity. Normal serum phosphate levels change throughout life, varying from the neonatal period, through adolescence, and stabilizing at adult values by the end of puberty. Serum phosphate homeostasis is maintained through dietary intake, intra- and intercellular shifts, and excretion/absorption/reabsorption processes mediated by Fibroblast Growth Factor 23, parathyroid hormone, and 1,25-(OH)₂D₃. Within this homeostatic network, dietary sources and current population-based intake data highlight a widespread oversupply in modern diets that can influence chronic disease outcomes. Ultimately, alterations in serum phosphate concentrations lead to numerous pathological conditions, both congenital and acquired. These conditions may involve either hypo- or hyperphosphatemia, each characterized by a wide spectrum of clinical manifestations, some of which primarily affect the musculoskeletal system. Starting from this evidence, the primary purpose of this review is to examine the phosphate-related pathological conditions from biological-molecular and clinical perspectives, while also considering targeted nutritional and clinical strategies for managing phosphate balance. Algorithms for management and differential diagnosis are also considered, thus providing a recent overview of a medical field that is becoming increasingly important for clinicians.