Pathophysiology, diagnosis and management of secondary osteoporosis

Age-related decline in sex hormones is the most frequent cause of primary osteoporosis; however, secondary causes contribute to osteoporosis in a substantial proportion of cases. These causes are diverse and often overlooked, ranging from endocrine diseases to chronic inflammatory conditions and medication use. The identification and exclusion of secondary causes of osteoporosis is crucial, because treatment typically begins by addressing the underlying condition. Investigation to exclude common secondary causes is recommended for everyone presenting with fractures indicative of osteoporosis. Advanced investigations are reserved for premenopausal individuals and those aged <50 years, and for older people in whom common risk factors, comorbidities or drugs predisposing to osteoporosis are absent. The risk of fracture can be underestimated by bone mineral density in some chronic diseases and overestimated in others. Specific adjustments can be made to the criteria in the online fracture risk FRAX calculator to provide a more accurate estimation of fracture risk in people with some forms of secondary osteoporosis. The response to conventional anti-osteoporosis treatments can be suboptimal if the underlying condition remains unrecognized and untreated. In most conditions, the evidence for antiresorptive or anabolic therapy is based on changes in bone mineral density rather than fracture. This Review covers the aetiology, pathogenesis, diagnosis and management of secondary osteoporosis, together with key areas for future research.