Bone Health in People Living with HIV: From Pathophysiology to Practical Management

As the life expectancy of people living with HIV (PLWH) continues to rise with the success of antiretroviral therapy (ART), long-term complications such as reduced bone mineral density (BMD) and osteoporosis have become increasingly prevalent. PLWH exhibit a higher risk of bone loss and fractures compared to the general population, driven by multiple factors including chronic immune activation, systemic inflammation, and ART-related toxicity. Tenofovir disoproxil fumarate is known to induce proximal renal tubular dysfunction and hypophosphatemia, contributing to reduced BMD. Tenofovir alafenamide is associated with improved renal and bone safety profiles. Recent data on integrase inhibitor-based or tenofovir-sparing regimens such as dolutegravir/lamivudine and long-acting cabotegravir plus rilpivirine suggest favorable effects on bon health. However, bone loss may still occur following ART initiation, regardless of regimen, and long-term skeletal outcomes remain under investigation. Given the increasing burden of bone disease in aging PLWH, timely assessment using dual-energy X-ray absorptiometry and fracture risk tools such as FRAX is essential. Management strategies should include lifestyle modification, calcium and vitamin D supplementation, and pharmacologic interventions including bisphosphonates or denosumab. Optimizing ART selection to minimize bone toxicity is also an important consideration. As PLWH age, bone health must be integrated into comprehensive HIV care.