Artificial intelligence, explainable deep learning, and generative models for osteoporosis and bone disease prediction: a systematic review and future research roadmap.

Osteoporosis is a major global health burden, with considerable morbidity, mortality, and healthcare costs. Artificial intelligence (AI) has opened new avenues for osteoporosis screening, bone mineral density quantification, fracture-risk prediction, and clinical decision support, but progress remains fragmented across machine learning, deep learning, explainable AI (XAI), generative models, and multimodal learning. This systematic review brings these strands together and identifies priority research needs for AI-based osteoporosis prediction. Following the PRISMA 2020 statement, studies were identified from Scopus and Google Scholar, published between January 2020 and the final search date of 30 June 2026, with two reviewers screening independently and resolving disagreements by consensus. Design-related risk-of-bias indicators, such as retrospective vs. prospective design, validation strategy, and reference standard, were recorded for every study; a full PROBAST, QUADAS-2, and Newcastle-Ottawa Scale appraisal is planned but not yet complete. Fifty-eight studies met the inclusion criteria and were synthesized narratively and descriptively, without formal meta-analysis, given substantial heterogeneity. Findings spanned five themes: classical machine learning, deep learning for imaging, explainable AI, generative models, and multimodal learning. Deep learning achieved strong predictive accuracy (AUC 0.82-0.96), XAI improved clinical interpretability, generative models helped offset data scarcity, and multimodal approaches boosted performance by combining imaging and clinical data. Key gaps remain, including limited external validation, heavy reliance on retrospective data, poor generalisability, and limited regulatory readiness. Building on these findings, this review proposes MXGNet, a multimodal, explainable, generative framework incorporating privacy-preserving federated learning, intended to guide development of robust, interpretable, clinically deployable AI tools for osteoporosis prediction.