Pagliarosi et al. explored the emerging genetic alterations associated with Gorham-Stout disease, a rare osteolytic disorder with unknown etiology. By integrating available genetic and molecular data, the authors discussed the potential involvement of angiogenic, lymphangiogenic, and osteoclastogenic pathways in progressive bone loss. Their review provides a mechanistic framework for future functional studies and highlights the relevance of molecular genetics in deciphering ultra-rare bone diseases.In the work of Schembri and Formosa, a focus was performed on the identification of osteoporosis genes using family-based studies. They reviewed the evidence showing how rare, high-impact variants segregating within families can uncover novel genetic determinants that may be missed by population-based genome-wide association studies. Their work reinforces the translational potential of genetic profiling for risk stratification and personalized approaches to osteoporosis prevention and management.In the work of Wang et al. diabetic sarcopenia was investigated using a proteomic strategy, revealing that dysregulation of autophagy-and apoptosis-related pathways contributes to muscle deterioration in diabetes.Although focused on muscle, their findings are highly relevant to skeletal biology, as these same molecular programs influence osteoblast and osteoclast survival and activity. This study highlights how omics-based profiling can identify shared molecular determinants of musculoskeletal decline and opens new perspectives for integrated therapeutic strategies targeting both muscle and bone in metabolic disease. Zhou et al. reviewed the association between single nucleotide polymorphisms and susceptibility to osteomyelitis and prosthetic joint infection. Their analysis showed how host genetic variation influences immune responses, inflammatory pathways, and infection risk in skeletal tissues. These findings underscore the relevance of molecular genetics for patient stratification and for developing personalized strategies in orthopedic surgery and infection prevention.The studies included in this Research Topic demonstrated how genetic and molecular discoveries are increasingly translated into clinical contexts. From rare skeletal disorders to complex conditions such as osteoporosis, the integration of omics technologies, and epigenetic research is reshaping diagnostic and therapeutic paradigms. These contributions highlight the potential of molecular profiling to support precision medicine, enabling earlier diagnosis, refined risk assessment, and the identification of novel therapeutic targets.
Rossi et al. (Tue,) studied this question.