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Bone Abstracts (2014) 3 PP92 | DOI: 10.1530/boneabs.3.PP92

Bone development/growth and fracture repair

Effect of subcutaneous recombinant human parathyroid hormone, rhPTH(1--84), on skeletal dynamics in hypoparathyroidism: findings from the 24-week replace and 8-week relay phase III clinical trials

John P Bilezikian1, Gerard Maruani2, Jeffrey Rothman3, Bart L Clarke4, Michael Mannstadt5, Tamara Vokes6, Hjalmar Lagast7 & Dolores M Shoback8


1Columbia University, New York, New York, USA; 2Hôpital Européen Georges-Pompidou, Assistance Publique-Hôpitaux de Paris, Paris, France; 3Staten Island University Hospital, Staten Island, New York, New York, USA; 4Mayo Clinic, Rochester, Minnesota, USA; 5Harvard Medical School, Massachusetts General Hospital, Boston, Massachusetts, USA; 6University of Chicago Medicine, Chicago, Illinois, USA; 7NPS Pharmaceuticals, Inc., Bedminster, New Jersey, USA; 8University of California, San Francisco, San Francisco, California, USA.

Hypoparathyroidism results in low bone turnover and increased bone mineral density (BMD). Replacing deficient PTH with rhPTH(1–84) has the potential to correct these skeletal abnormalities. To investigate the effect of rhPTH(1–84) on BMD and bone turnover markers (BTMs), data from two studies were assessed.

REPLACE, a double-blind, multicenter, placebo-controlled study, randomized 134 patients with hypoparathyroidism to receive once-daily rhPTH(1–84) (50 μg initially, increased to 75, then 100 μg if needed) or placebo. In RELAY, a dose-blind, multicenter study, 47 patients with hypoparathyroidism were randomized to receive 25 or 50 μg/day rhPTH(1–84). Twenty-one patients in RELAY (enrolled after 4-week washout) were previously treated in REPLACE. In both studies, BTMs (bone-specific alkaline phosphatase (BSAP), carboxy-terminal telopeptide of type 1 collagen (CTX), osteocalcin (OCN), and aminoterminal propeptide of type 1 collagen (P1NP)) were assessed at baseline and at weeks 8 (RELAY) and 24 (REPLACE). BMD was assessed in REPLACE.

In REPLACE, treatment with rhPTH(1–84) significantly increased all BTMs from low-normal baseline values to significantly higher levels at week 24 (Table 1) compared with placebo (P≤0.001). In RELAY, all BTMs increased with both rhPTH(1–84) doses at week 8 (Table), with no significant differences between doses for any marker. In REPLACE, BMD decreased toward normal in patients receiving rhPTH(1–84) at lumbar spine, total hip, femoral neck, and distal one-third radius. rhPTH(1–84) was generally well tolerated in both studies.

Patients with hypoparathyroidism with low bone turnover and high BMD respond to rhPTH(1–84) in 8 weeks. BTMs reflect restoration of turnover toward normal, and BMD also returns toward normal.

Table 1 BTMs: change from baseline with rhPTH(1–84) (mean±S.D.).
BSAP (μg/l)CTX (pg/ml)P1NP (μg/l)OCN (μg/l)
REPLACE20.5 (18.1)798.4 (648.0)299.5 (234.6)25.9 (27.7)
RELAY 25 μg0.66 (3.8)79.5 (239.6)13.7 (38.5)0.27 (2.7)
RELAY 50 μg0.08 (4.3)92.7 (141.6)22.0 (39.6)1.4 (2.9)

Volume 3

European Calcified Tissue Society Congress 2014

Prague, Czech Republic
17 May 2014 - 20 May 2014

European Calcified Tissue Society 

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