Background:Osteoclastic bone resorption markedly increases with aging, leading to osteoporosis characterized by weak and fragile bones. Mice exhibit greater bone resorption and poor bone mass when Sirt1 is removed from their osteoclasts. Here we investigated the ex vivo impacts of putative Sirt1 activators, Resveratrol (RSV), SRT2183, and SRT1720, on osteoclast formation and activity in primary mouse bone marrow cells (BMCs) derived from wild-type (WT) and osteoclast specific Sirt1 knockout (OC-Sirt1KO) mice and in the RAW264.7 mouse macrophage cell line.Results:We found that SRT2183 and SRT1720 inhibit the formation of osteoclasts and actin belts in BMCs and RAW264.7 cells, whereas RSV does not. We also observed that the OC-Sirt1KO mice exhibited less bone mineral density, and the BMCs harvested from these mice yielded more osteoclasts than BMCs harvested from littermate controls. Interestingly, both SRT2183 and SRT1720 reduced osteoclast and actin belt formation in BMCs from OC-Sirt1KO mice. SRT2183 and SRT1720 also significantly disrupted actin belts of mature osteoclasts generated from BMCs of WT mice, within 3 and 6 hours of administration, respectively. Furthermore, these compounds inhibited the resorption activity of mature osteoclasts, while RSV did not.Conclusion:Our findings suggest SRT2183 and SRT1720 impede bone resorption by disrupting actin belts of mature osteoclasts, inhibit actin belt formation, and inhibit osteoclastogenesis even in the absence of Sirt1. Thus, the mechanism of action of these compounds appears to extend beyond Sirt1 activation and possibly pave the way for potential new therapies in alleviating osteoporosis associated bone loss.
Fragility fractures are widespread in the elderly, and they have a significant influence on their quality of life by restricting autonomy, increasing disability, and shortening their lifespan. Different factors contribute to the development of fractures in fragile people. Targeting fragile people before they develop a fracture may be the most difficult problem of all, because current diagnostic technologies have limits. This paper reviews the current information on the management of fragility fractures, including risk factors, prevention, diagnosis, and the actual limitations of clinical therapy choices, as well as proposing new research questions.
Muscle weakness and atrophy are symptoms of spinal muscular atrophy (SMA), which is caused by the gradual degeneration and permanent loss of the anterior horn cells in the spinal cord (i.e., lower motor neurons) and the brain stem nuclei. Weakness can appear at any age, from before birth through maturity. The weakening is symmetric, gradual, and proximal > distal. Before the genetic basis of SMA was discovered, it was divided into clinical categories depending on the highest level of motor function obtained; however, it is now obvious that the phenotype of SMN1-associated SMA is a continuum with no distinct subgroups. Poor weight gain with growth failure, restrictive lung disease, scoliosis, and joint contractures are typical consequences with supportive care alone; however, newly accessible targeted therapy approaches are altering the illness's natural history.
Hip fractures are excruciatingly painful, necessitating lengthy hospital stays. Pain treatment options are confined in the traditional sense. Nonsteroidal Anti-Inflammatories (NSAIDs) are usually contraindicated, and opioids have adverse side effects. To yet, trials have been equivocal as to which blocks should be used and for how long. Interpatient variability is still an issue. Hip fractures remain one of the most serious injuries that occur in older people, with a mortality rate of 10% at one month, 20% at four months and 30% at one year. Many of those who recover suffer a loss in mobility and independence. Approximately half of patients who were previously functionally independent become partly dependent, while one third become totally dependent.
Bone formation in tissues without ossification properties such as muscles and connective tissues can be defined as Heterotopic Ossification (HO). It is a relevant issue for surgeons performing TMJ reconstruction with TMJ prostheses. The objective of this study was to analyze and compare previous literature findings regarding etiology, diagnosis, prophylaxis and further treatment and management of heterotopic bone formation around TMJ prostheses. Besides, a 16-year-old male clinical-case with 19-years follow-up is reported. The search strategy of this scoping review was performed in three different databases (MEDLINE, ELSEVIER and Cochrane) by three independent reviewers (NJS, GST, PHAC), the selection and analysis of the scientific articles was performed according to the following criteria: specific studies that evaluated the presence of heterotopic bone formation in TMJ prosthesis; studies on humans and reported in English language. This study provides qualitative and quantitative reviews of information regarding etiology, diagnosis, prevention, and management of HO around TMJ prostheses. Several management protocols were proposed, ranging from simple HO resection and prosthesis removal to autologous fat graft and low dose radiation therapy, with varying success rates. Nevertheless, further investigation is required to formulate a standardized prevention/management protocol to aid surgeons obtain long-term success in TMJ replacement procedures in the future.
