Given that an increased ROS production is one of the main mechanisms related to bone and muscle modifications after SCI, all these results suggest a potential role of H2S treatment in SCI-related bone loss. Parathyroid Hormone Parathyroid hormone (PTH) is a well-known player in calcium metabolism. available to date. The development of multidisciplinary recommendations is required for a proper clinical management of SCI patients. strong class=”kwd-title” Keywords: spinal cord injury, bone, muscle, bone loss, osteoporosis, sarcopenia, rehabilitation Introduction Spinal cord injuries (SCIs) encompass a spectrum of conditions associated with modifications in the function of both central and peripheral nervous systems. Due to the crucial role of the spinal cord in linking the brain with the body, these alterations may lead to dramatic consequences in terms of motor, sensitive, and visceral controls (1). A complex variety of biological Dicoumarol pathways arising in both bone and muscle tissues plays a clinically relevant role in SCIs. Hence, these patients experience important changes in the bones (e.g., osteoporosis) that cause Dicoumarol a significantly increased risk of fractures, even after minor traumas (e.g., transferring or sitting) (2, 3). These clinical conditions lead to further immobilization of the patient, increased spasticity, pressure ulcers, and in general worsened disability (3). Bone tissue loss after SCIs starts rapidly and grows in the first 2 years after the injury (4). In chronic SCIs, the skeleton of the lower third of the femur and upper third of the tibia may be subjected to 70% of decreased mineral density (5, 6). Muscle modifications further increase the patients’ fragility because they lead to immobilization, increased fracture risk, pressure sores, thrombosis, overpressure, chronic pain, and psychosocial issues (7). The loss of mass in the muscles below the SCI is Dicoumarol usually remarkable, reaching up to 40% in the first 2 years after the injury (8). Regrettably, despite muscle atrophy is usually macroscopically more evident than osteoporosis, this phenomenon is usually often underestimated (7). In this scenario, understanding the biological Dicoumarol interplay of the bone and muscle tissues is crucial for proper clinical management of SCIs. Here, we sought to provide a comprehensive portrait of the potentials and limitations of the various treatment options available (or proposed) to date for both osteoporosis and muscle atrophy occurring after SCIs. Pharmacological Approaches to Bone Alterations The use of single, combination, or sequential therapy protocols in the management of bone alterations in SCI is usually a matter of controversy. After the achievement of clinical benefits, the discontinuation of osteoanabolic treatments could result in a rapid loss of the newly gained bone (9C12). For this reason, clinicians are recommended to promptly start other anti-resorptive therapies after osteoanabolic interventions discontinuation. At present, there are no widely adopted guidelines about the most reliable pharmacological strategy. Bisphosphonates Bisphosphonates are the most used class of drugs in the prevention and treatment of osteoporosis (13). Several studies have assessed the efficacy of these anti-resorptive drugs in acute and chronic SCIs. A meta-analysis provided circumstantial evidence to suggest that the early administration of bisphosphonates can reduce SCI-related osteoporosis (13). It should be taken into account, however, that this hypothesis is usually biased by the small sample size of the few clinical trials available to date (14). Moreover, despite many groups showed that bisphosphonates may be particularly effective at the hip level, only a few information is currently available on their role at the distal third of the femur and/or at the proximal Rabbit polyclonal to LOXL1 third of the tibia. A recent, non-randomized study around the yearly administration of zoledronic acid failed to show an improvement in the bone mass density (BMD) at this level, being associated, on the contrary, with a reduction in bone mass (15). Therefore, several doubts exist about the efficacy and the safety profile of bisphosphonates in patients with SCI. Due to these issues, at the.