Site-specific fracture risk in chronic hypoparathyroidism: systematic review and meta-analysis

Chronic hypoparathyroidism (HypoPT) is characterized by sustained parathyroid hormone (PTH) deficiency, leading to reduced bone turnover, increased bone mineral density (BMD), and altered skeletal microarchitecture. Despite preserved or elevated BMD, fracture risk in HypoPT remains controversial. We conducted a systematic review and meta-analysis to assess site-specific fracture risk and the influence of disease duration in patients with chronic HypoPT. Fifteen observational studies, including 13,563 HypoPT subjects and 137,245 controls, were analyzed. HypoPT subjects had a significantly higher risk of vertebral fractures (VFs) than controls (OR 1.88, 95% CI 1.23-2.88), with the excess risk confined to individuals with non-surgical disease (OR 3.05, 95% CI 1.68-5.54). No significant difference between HypoPT and controls were observed in non-vertebral (OR 1.01 (95% CI 0.83, 1.22) or hip fractures (OR 0.81, 95% CI 0.63-1.04). Meta-regression analyses demonstrated that longer median disease duration was associated with higher fracture prevalence at non-vertebral and hip sites. These findings support a site-specific pattern of skeletal fragility, characterized by increased vertebral vulnerability, particularly in non-surgical HypoPT, alongside relative protection at cortical-predominant sites. Fracture risk in HypoPT appears to evolve over time and to become evident during long-term follow-up. Longitudinal, site-directed fracture assessment should be considered in clinical practice.