In vivo studies of hydroxyapatite for bone remodeling, regeneration, and replacement: A bibliometric analysis (2015–2025) and systematic review

<ns7:p>Background Critical bone defects necessitate the use of biocompatible, osteoconductive, and long-term remodeling-facilitating replacement materials for effective bone restoration. Hydroxyapatite (HAp) has emerged as a leading candidate owing to its resemblance to natural bone minerals; however, its gradual resorption properties and mechanical vulnerability have necessitated the development of novel formulations. Objective This study examines the existing in vivo evidence on the use of hydroxyapatite (HAp) as a bone substitute material, highlighting the impact of structural and compositional modifications on regeneration and osseointegration outcomes while mapping the global research landscape through bibliometric analysis. Methods A bibliometric analysis was conducted using the Scopus database (2015–2025) and visualized using VOSviewer software. Eligible articles (n = 1,682) were analyzed for publication trends, authorship networks, institutional and country collaborations, and keyword co-occurrence. Key bibliometric indicators included the number of publications per year, citation patterns, and thematic clusters related to in vivo hydroxyapatite research. Results Publications on in vivo hydroxyapatite research showed an overall upward trend, peaking in 2021, with 186 articles. China (704 articles), the United States (245), and India (118) were the most prolific contributors, with strong collaborative networks extending across Asia, Europe, and North America. Keyword mapping revealed frequent associations between “hydroxyapatite,” “osseointegration,” “bone remodeling,” “biomechanics,” and “titanium implants,” reflecting the dominance of studies on scaffolds, polymer composites, ionic doping, and coating. Conclusion This bibliometric analysis highlights that in vivo investigations consistently demonstrate hydroxyapatite, particularly in its nano, composite, or ion-doped forms, as an effective bone substitute material. Beyond confirming its osteoconductive and osseointegrative roles, this study underscores critical translational challenges, including the synchronization of resorption and remodeling, nanoparticle safety, and methodological standardization. Mapping global trends provides practical insights for researchers and the industry to prioritize biomaterial innovations that accelerate the clinical translation of HAp-based bone substitutes.</ns7:p>