Palopegteriparatide is a long-acting parathyroid hormone replacement therapy for hypoparathyroidism; however, real-world data regarding its long-term efficacy and safety remain limited. We evaluated its long-term effects on symptoms, renal function, and bone metabolism in two women with chronic hypoparathyroidism who were prospectively followed for changes in serum calcium, symptoms, renal function, bone turnover markers, and bone mineral density (BMD).

The first patient, a woman in her 40s with autosomal dominant hypocalcemia type 1, successfully discontinued conventional therapy after dose titration of palopegteriparatide. Serum calcium normalized, brain fog resolved, and the annual decline in estimated glomerular filtration rate (eGFR) improved from −1.5 to −1.0 mL/min/1.73 m²/year. Bone turnover markers increased transiently after treatment initiation, accompanied by a temporary decline in BMD that subsequently stabilized.

The second patient, a woman in her 50s with idiopathic hypoparathyroidism, also discontinued conventional therapy after initiating palopegteriparatide. Serum calcium normalized, finger numbness resolved, and the annual eGFR slope improved from −1.4 to +1.2 mL/min/1.73 m²/year. BMD gradually declined during follow-up, most likely reflecting the combined effects of physiological restoration of bone remodeling and menopause.

These cases demonstrate that long-term palopegteriparatide therapy can normalize serum calcium, relieve symptoms, preserve renal function, and restore physiological bone remodeling in patients with chronic hypoparathyroidism. Because restoration of bone remodeling may transiently increase bone resorption and urinary calcium excretion during dose titration, monitoring of 24-hour urinary calcium is recommended. Periodic assessment of BMD should also be considered, particularly in postmenopausal patients and others at increased risk of bone loss. These real-world observations provide practical insights into long-term management with palopegteriparatide, particularly regarding urinary calcium monitoring and interpretation of changes in bone metabolism.