Endocrine Abstracts

JOINT3967

Introduction: Hypoparathyroidism is a rare disease, 75% of cases are due to thyroid or parathyroid surgery. Conventional treatment of Hypoparathyroidism with active vitamin D and calcium is associated with high pill burden and long term complications associated with high phosphate values. Replacement therapy with recombinant human parathyroid hormone (rhPTH1-84) decreased phosphate levels, however did not normalize hypercalciuria. Palopegteriparaide (TransCon PTH) is a long-acting molecule with slow release of PTH1-34, which has recently received approval from the EMA and FDA. In this one center study, we describe the effect of treatment switch from rhPTH1-84 to TransCon PTH on bone metabolism after one, three and six months of treatment.

Methods: We analyzed data from 26 patients with chronic postsurgical HypoPT (n = 23) or nonsurgical (n = 3) HypoPT during the change of treatment. Patients were predominantly women (20f/6m) with a mean age of 56±14 years (range 33-84 years). Duration of hypoPT was 16. 6 ±10 years (range 3. 9-44) and treatment with rhPTH 4. 2±1. 7 years (range1. 3-6. 5). Complications were 46% nephrocalcinosis, 11% renal insufficieny, 11% nephrolithiais, 11% Fahr’s disease, and 11% cataract. TransCon PTH was available during a compassionate-use program or used after officially becoming available in Germany starting in January 2024. Independent of the last prior rhPTH-1-84 dose, all patients were started on 18 µg of TransCon PTH and doses adapted individually. Serum values and 24 h urine were collected before treatment change and after one month, three and six months. Until now 20 patients finished the six months treatment.

Results: Six months after change from rhPTH(1-84) more patients were in the normal range for calcium and phosphate (77% vs 90%) with normalization of FGF23 metabolism (64. 2±36. 1 vs 79. 1±24. 1; P < 0. 0001). Hypercalciuria was also significantly reduced. Palopegteriparatide increased magnesium levels (0. 76±0. 07 mmol/l vs 0. 83±0. 08; P = 0. 0011) by decreasing urinary excretion of magnesium already after one-month treatment (110. 2±61. 8 mmol/day vs 100. 7±71. 8 and 97. 0±59. 2 at six months). Treatment change significantly decreased the rhPTH(1-84)-induced high bone turnover for bone alkaline phosphatase, P1NP and desoxypyridinoline/urine. Conclusions Switching treatment from rhPTH1-84 to TransCon PTH was followed by significant changes towards normalization in calcium, phosphate, and magnesium metabolism and bone turnover during the first six months of treatment.