CONTEXT: Human recombinant (rh)PTH(1-84) was recently approved for the treatment of refractory hypoparathyroidism, based upon a short-term phase 3 clinical trial. Long-term data are needed, because no time limit was placed on the treatment period. OBJECTIVE: We studied the effect of long-term rhPTH(1-84) treatment in hypoparathyroidism for up to 6 years. DESIGN: Prospective open-label study. SETTING: Referral center. PATIENTS: A total of 33 subjects with hypoparathyroidism. INTERVENTIONS: rhPTH(1-84) treatment was initiated at a starting dose of 100 μg every other day for 6 years. Due to the availability of new dosages during the 6-year time period of the study, the dose could be and was adjusted for most patients to a daily dosing regimen. MAIN OUTCOME MEASURES: Supplemental calcium and vitamin D requirements, serum and urinary calcium (monthly for 6 mo and then biannually), serum phosphorus, bone turnover markers, and bone mineral density (BMD) biannually. RESULTS: Treatment with rhPTH(1-84) progressively reduced supplemental calcium requirements over 6 years by 53% (P < .0001) and 1,25-dihydroxyvitamin D requirements by 67% (P < .0001). Sixteen subjects (48%) were able to eliminate 1,25-dihydroxyvitamin D supplementation completely. Serum calcium concentration remained stable, and urinary calcium excretion fell. Lumbar spine BMD increased (3.8 ± 1%, P = .004) as did total hip BMD (2.4 ± 1%, P = .02), whereas femoral neck BMD remained stable and the distal one third radius decreased (-4.4 ±1%, P < .0001). Bone turnover markers increased significantly, reaching a 3-fold peak above baseline values at 1 year and subsequently declining but remaining higher than pretreatment values. Hypercalcemia was uncommon (12 episodes over 6 y; 2.5% of all values). CONCLUSIONS: Long-term, continuous therapy of hypoparathyroidism for 6 years with rhPTH(1-84) is associated with reductions in supplemental calcium and calcitriol requirements, stable serum calcium concentration, and reduced urinary calcium excretion. The safety profile remains good. These data represent the longest experience with the therapeutic use of PTH for any condition and demonstrate its long-term efficacy and safety in hypoparathyroidism.
CONTEXT: Human recombinant (rh)PTH(1-84) was recently approved for the treatment of refractory hypoparathyroidism, based upon a short-term phase 3 clinical trial. Long-term data are needed, because no time limit was placed on the treatment period. OBJECTIVE: We studied the effect of long-term rhPTH(1-84) treatment in hypoparathyroidism for up to 6 years. DESIGN: Prospective open-label study. SETTING: Referral center. PATIENTS: A total of 33 subjects with hypoparathyroidism. INTERVENTIONS:rhPTH(1-84) treatment was initiated at a starting dose of 100 μg every other day for 6 years. Due to the availability of new dosages during the 6-year time period of the study, the dose could be and was adjusted for most patients to a daily dosing regimen. MAIN OUTCOME MEASURES: Supplemental calcium and vitamin D requirements, serum and urinary calcium (monthly for 6 mo and then biannually), serum phosphorus, bone turnover markers, and bone mineral density (BMD) biannually. RESULTS: Treatment with rhPTH(1-84) progressively reduced supplemental calcium requirements over 6 years by 53% (P < .0001) and 1,25-dihydroxyvitamin D requirements by 67% (P < .0001). Sixteen subjects (48%) were able to eliminate 1,25-dihydroxyvitamin D supplementation completely. Serum calcium concentration remained stable, and urinary calcium excretion fell. Lumbar spine BMD increased (3.8 ± 1%, P = .004) as did total hip BMD (2.4 ± 1%, P = .02), whereas femoral neck BMD remained stable and the distal one third radius decreased (-4.4 ±1%, P < .0001). Bone turnover markers increased significantly, reaching a 3-fold peak above baseline values at 1 year and subsequently declining but remaining higher than pretreatment values. Hypercalcemia was uncommon (12 episodes over 6 y; 2.5% of all values). CONCLUSIONS: Long-term, continuous therapy of hypoparathyroidism for 6 years with rhPTH(1-84) is associated with reductions in supplemental calcium and calcitriol requirements, stable serum calcium concentration, and reduced urinary calcium excretion. The safety profile remains good. These data represent the longest experience with the therapeutic use of PTH for any condition and demonstrate its long-term efficacy and safety in hypoparathyroidism.
Authors: John P Bilezikian; Aliya Khan; John T Potts; Maria Luisa Brandi; Bart L Clarke; Dolores Shoback; Harald Jüppner; Pierre D'Amour; John Fox; Lars Rejnmark; Leif Mosekilde; Mishaela R Rubin; David Dempster; Rachel Gafni; Michael T Collins; Jim Sliney; James Sanders Journal: J Bone Miner Res Date: 2011-10 Impact factor: 6.741
Authors: Natalie E Cusano; Mishaela R Rubin; Donald J McMahon; Chiyuan Zhang; Rebecca Ives; Amanda Tulley; James Sliney; Serge C Cremers; John P Bilezikian Journal: J Clin Endocrinol Metab Date: 2012-11-15 Impact factor: 5.958
Authors: Karen K Winer; Ninet Sinaii; James Reynolds; Donna Peterson; Karen Dowdy; Gordon B Cutler Journal: J Clin Endocrinol Metab Date: 2010-04-14 Impact factor: 5.958
Authors: Karen K Winer; Bo Zhang; Joseph A Shrader; Donna Peterson; Michaele Smith; Paul S Albert; Gordon B Cutler Journal: J Clin Endocrinol Metab Date: 2011-11-16 Impact factor: 5.958
Authors: Natalie E Cusano; Laura Anderson; Mishaela R Rubin; Barbara C Silva; Aline G Costa; Dinaz Irani; James Sliney; John P Bilezikian Journal: J Clin Endocrinol Metab Date: 2013-09-13 Impact factor: 5.958
Authors: Karen K Winer; Andrea Kelly; Alicia Johns; Bo Zhang; Karen Dowdy; Lauren Kim; James C Reynolds; Paul S Albert; Gordon B Cutler Journal: J Pediatr Date: 2018-12 Impact factor: 4.406
Authors: Mishaela R Rubin; Hua Zhou; Natalie E Cusano; Rukshana Majeed; Beatriz Omeragic; Maximo Gomez; Thomas L Nickolas; David W Dempster; John P Bilezikian Journal: J Bone Miner Res Date: 2018-08-16 Impact factor: 6.741
Authors: Natalie E Cusano; Mishaela R Rubin; John M Williams; Sanchita Agarwal; Gaia Tabacco; Donovan Tay; Rukshana Majeed; Beatriz Omeragic; John P Bilezikian Journal: J Bone Miner Res Date: 2020-03-26 Impact factor: 6.741