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Osteoporosis, a prevalent ailment worldwide, compromises bone strength and resilience, particularly afflicting the elderly population. This condition significantly heightens susceptibility to fractures even from trivial incidents, such as minor falls or impacts. A major challenge in diagnosing osteoporosis is the absence of discernible symptoms, allowing osteoporosis to remain undetected until the occurrence of a fracture event. Early symptom detection and swift diagnosis are critical for preventing severe issues related to bone diseases. Assessing bone turnover markers aids in identifying, diagnosing, and monitoring these conditions, guiding treatment decisions. However, conventional techniques for measuring bone mineral density are costly, time-consuming, and require specialized expertise. The integration of sensor technologies into medical practices has transformed how we monitor, diagnose, and treat various health conditions, including bone health and orthopedics. This review aims to provide a comprehensive overview of the current state of sensor technologies used in bone, covering their integration with bone tissue, various applications, recent advancements, challenges, and future directions. [ABSTRACT FROM AUTHOR]

Osteogenesis imperfecta (OI) is a genetic disorder characterized by bone fragility, low bone mass, fractures, and extraskeletal manifestations. Since OI is commonly caused by single-nucleotide mutation(s) in the COL1A1 or COL1A2 genes encoding type I collagens, we developed a genome-editing strategy to correct a Col1a2 mutation in an OIM mouse model resembling a severe dominant form of human type III OI. Using a recombinant adeno-associated virus (rAAV), we delivered CRISPR-Cas9 to bone-forming osteoblast-lineage cells in the skeleton. Homology-directed repair (HDR)-mediated gene editing efficiency in these cells was improved when CRISPR-Cas9 was coupled with a donor AAV vector containing a promoterless partial mouse Col1a2 complementary DNA sequence. This approach effectively reversed the dysregulation of osteogenic differentiation by a Col1a2 mutation in vitro . Furthermore, systemic administration of dual rAAVs in OIM mice lowered bone matrix turnover rates by reducing osteoblast and osteoclast development while improving the cellular network of mechano-sensing osteocytes embedded in the bone matrix. This strategy significantly improved bone architecture/mass/mineralization, skeletal deformities, grip strength, and spontaneous fractures. Our study is the first demonstration that HDR-mediated gene editing via AAV-mediated delivery effectively corrects a collagen mutation in OI osteoblasts and reverses skeletal phenotypes in OIM mice., Competing Interests: Y.-S.Y., S.C., J.X., G.G., and J.-H.S. have submitted a patent application concerning the methodology described in this study. G.G. and J.-H.S. are scientific cofounders of AAVAA Therapeutics and hold equity in this company. G.G. is also a scientific cofounder of Adrenas Therapeutics, Voyager Therapeutics, and Aspa Therapeutics and holds equity in these companies. G.G. is an inventor on patents with potential royalties licensed to Adrenas Therapeutics, Voyager Therapeutics, Aspa Therapeutics, and other biopharmaceutical companies., (© 2023 The Author(s).)

Improper activity of bone-resorbing osteoclasts results in low bone density and deterioration of bone structure, which increase the risk of fractures. Anti-resorptive therapies targeting osteoclasts have proven effective in preserving bone mass, but these therapeutic agents lead to defective new bone formation and numerous potential side effects. In this study, we demonstrate that recombinant adeno-associated virus, serotype 9 (rAAV9) can deliver to osteoclasts an artificial microRNA (amiR) that silences expression of key osteoclast regulators, RANK (receptor activator for nuclear factor κB) and cathepsin K (rAAV9. amiR-rank , rAAV9. amiR-ctsk ), to prevent bone loss in osteoporosis. As rAAV9 is highly effective for the transduction of osteoclasts, systemic administration of rAAV9 carrying amiR-rank or amiR-ctsk results in a significant increase of bone mass in mice. Furthermore, the bone-targeting peptide motif (Asp) 14 or (AspSerSer) 6 was grafted onto the AAV9-VP2 capsid protein, resulting in significant reduction of transgene expression in non-bone peripheral organs. Finally, systemic delivery of bone-targeting rAAV9. amiR-ctsk counteracts bone loss and improves bone mechanical properties in mouse models of postmenopausal and senile osteoporosis. Collectively, inhibition of osteoclast-mediated bone resorption via bone-targeting rAAV9-mediated silencing of ctsk is a promising gene therapy that can preserve bone formation and mitigate osteoporosis, while limiting adverse off-target effects., (© 2020 The Author(s).)