Abstract 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.
Fischler et al. (Wed,) studied this question.