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Osteoporosis is characterized by an alteration of bone microstructure with a decreased bone mineral density, leading to the incidence of fragility fractures. Around 200 million people are affected by osteoporosis, representing a major health burden worldwide. Several factors are involved in the pathogenesis of osteoporosis. Today, altered intestinal homeostasis is being investigated as a potential additional risk factor for reduced bone health and, therefore, as a novel potential therapeutic target. The intestinal microflora influences osteoclasts’ activity by regulating the serum levels of IGF-1, while also acting on the intestinal absorption of calcium. It is therefore not surprising that gut dysbiosis impacts bone health. Microbiota alterations affect the OPG/RANKL pathway in osteoclasts, and are correlated with reduced bone strength and quality. In this context, it has been hypothesized that dietary supplements, prebiotics, and probiotics contribute to the intestinal microecological balance that is important for bone health. The aim of the present comprehensive review is to describe the state of the art on the role of dietary supplements and probiotics as therapeutic agents for bone health regulation and osteoporosis, through gut microbiota modulation.

Neuromuscular diseases (NMDs) are inherited or acquired conditions affecting skeletal muscles, motor nerves, or neuromuscular junctions. Most of them are characterized by a progressive damage of muscle fibers with reduced muscle strength, disability, and poor health-related quality of life of affected patients. In this scenario, skeletal health is usually compromised as a consequence of modified bone–muscle cross-talk including biomechanical and bio-humoral issues, resulting in increased risk of bone fragility and fractures. In addition, NMD patients frequently face nutritional issues, including malnutrition due to feeding disorders and swallowing problems that might affect bone health. Moreover, in these patients, low levels of physical activity or immobility are common and might lead to overweight or obesity that can also interfere with bone strength features. Also, vitamin D deficiency could play a critical role both in the pathogenesis and in the clinical scenario of many NMDs, suggesting that its correction could be useful in maintaining or enhancing bone health, especially in the early phases of NMDs. Last but not least, specific disease-modifying drugs, available for some NMDs, are frequently burdened with adverse effects on bone tissue. For example, glucocorticoid therapy, standard of care for many muscular dystrophies, prolongs long-term survival in treated patients; nevertheless, high dose and/or chronic use of these drugs are a common cause of secondary osteoporosis. This review addresses the current state of knowledge about the factors that play a role in determining bone alterations reported in NMDs, how these factors can modify the biological pathways underlying bone health, and which are the available interventions to manage bone involvement in patients affected by NMDs. Considering the complexity of care of these patients, an interdisciplinary and multimodal management strategy based on both pharmacological and non-pharmacological interventions is recommended, particularly targeting musculoskeletal issues that are closely related to functional independence as well as social implications.

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