Metabolic Influences on Skeletal Fragility: Beyond Bone Density in Fracture Risk and Recovery

Abstract

Bone fragility has traditionally been associated with osteoporosis and reduced bone mineral density; however, contemporary evidence indicates that fracture risk is influenced by a broader spectrum of metabolic, nutritional, endocrine, inflammatory, and musculoskeletal factors. The objective of this review was to analyze the metabolic determinants associated with bone fragility beyond osteoporosis and to examine their influence on fracture risk and recovery outcomes. A structured narrative review of scientific literature published in major biomedical databases was conducted, focusing on diabetes mellitus, chronic kidney disease, vitamin D deficiency, malnutrition, osteosarcopenia, endocrine dysfunction, and chronic inflammation. The findings demonstrated that these conditions contribute significantly to alterations in bone quality, remodeling capacity, muscle performance, and tissue repair, thereby increasing susceptibility to fragility fractures independently of bone mineral density measurements. Diabetes mellitus and chronic kidney disease emerged as major determinants of skeletal fragility due to their effects on collagen integrity, mineral metabolism, vascular function, and bone turnover. Nutritional deficiencies and inadequate vitamin D status were consistently associated with impaired mineralization, increased fall risk, and delayed fracture healing. Furthermore, osteosarcopenia highlighted the close biological relationship between bone and muscle health and its contribution to fracture susceptibility and functional decline. The evidence supports a multidimensional understanding of skeletal fragility that incorporates metabolic health into fracture prevention and management strategies. Expanding fracture risk assessment beyond traditional osteoporosis models may improve early identification of vulnerable individuals and facilitate more comprehensive approaches to prevention, treatment, and rehabilitation.