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This condition poses a significant global public health challenge, as osteoporotic fractures contribute substantially to morbidity, mortality, and escalating healthcare costs. Conventional treatments, such as calcium and vitamin D supplementation, often face limitations including side effects, suboptimal efficacy, and poor long-term compliance. Consequently, there is a growing impetus to explore innovative therapeutic strategies that can more effectively enhance bone regeneration and repair. Hydroxyapatite (HAp)-based bone-targeting nanosystems have emerged as a promising frontier in regenerative medicine and drug delivery for bone-related disorders, including OP. HAp, a naturally occurring mineral and a principal component of bone tissue, offers several advantages for nanosystem development: exceptional biocompatibility, chemical similarity to native bone mineral, and the capacity for controlled drug delivery to specific bone sites. These nanosystems can be engineered to optimize size, morphology, and surface functionality, enabling improved integration with bone tissue and targeted delivery of therapeutic agents. Recent advances have demonstrated that HAp-based nanosystems can facilitate personalized care, enhance drug efficacy, and reduce systemic side effects by concentrating therapeutic agents at sites of bone degeneration. Functionalization strategies, like polymer coatings, ion doping, and ligand conjugation \u2013 have expanded their potential for bone regeneration, targeted therapy, and combination treatments. This review examines the current trends, mechanisms, and future directions of HAp-based nanosystems for OP, highlighting their potential to transform clinical management and improve patient outcomes.<\/jats:p>","DOI":"10.1177\/10815589251406148","type":"journal-article","created":{"date-parts":[[2025,12,2]],"date-time":"2025-12-02T12:22:31Z","timestamp":1764678151000},"page":"407-429","update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":2,"title":["Advancements in hydroxyapatite-based nanosystems for targeting bone in osteoporosis: A review of current trends and future directions"],"prefix":"10.1177","volume":"74","author":[{"given":"Aya Mohammed","family":"Dhiaa","sequence":"first","affiliation":[{"name":"College of Pharmacy, Alnoor University, Nineveh, Iraq"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Amirali","family":"Salajegheh","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Sciences, Tehran University of Medical Sciences, Iran"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ali Fawzi","family":"Al-Hussainy","sequence":"additional","affiliation":[{"name":"College of Pharmacy, Ahl Al Bayt University, Kerbala, Iraq"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wael Waleed","family":"Mustafa","sequence":"additional","affiliation":[{"name":"Department of Pharmacology and Toxicology, Faculty of Pharmacy, Al-Turath University College, Baghdad, Iraq"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"S. 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