Risk of bone overstimulation in long-term PTH(1-34) therapy for hypoparathyroidism

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OBJECTIVE: PTH(1-34), used off-label, effectively controls serum calcium in patients with chronic hypoparathyroidism inadequately managed by standard-of-care therapy. PTH(1-34) also strongly stimulates bone remodeling and often raises bone turnover markers above normal levels. This study aimed to visually assess the risk of excessive bone stimulation associated with prolonged PTH(1-34) replacement therapy. DESIGN: An observational study (N°20201026100318) was conducted in adults with chronic hypoparathyroidism treated with PTH(1-34) for over 2 years at 3 referral centers. METHODS: Patients underwent whole-body 99mTc-methylenediphosphonate scintigraphy, biochemical evaluation, and bone mineral density assessment. The primary endpoint was the proportion of patients with pathological increases in bone tracer uptake. RESULTS: Forty-one patients received a mean daily dose of 29.9 µg [Q1; Q3 22.5; 39.9] of PTH(1-34) for a duration of 57 months [40; 70], representing an exposure of 218.3 patient-years. Median age at imaging was 44 years [30; 55]; 31 (75.6%) were women. Pathological bone uptake was observed in 25 (61%) patients despite serum calcium predominantly in the target therapeutic values. Osteoarticular pain did not differentiate affected individuals. These patients had higher weight-adjusted PTH(1-34) doses (0.44 µg/kg [0.32; 0.56] vs 0.34 µg/kg [0.24;0.40], P = .045), elevated bone remodeling markers, lower serum magnesium, and increased urinary calcium excretion. A score combining serum C-telopeptides of collagen I, osteocalcin, and magnesium correctly classified 97% of patients (95% CI: 91%-100%). CONCLUSION: Long-term PTH(1-34) therapy in chronic hypoparathyroidism is frequently associated with excessive bone remodeling despite adequate calcemic control. Careful monitoring is therefore essential, especially in patients with elevated bone remodeling markers and hypomagnesemia.

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