Hypoparathyroidism results in low bone turnover and increased bone mineral density (BMD). Replacing deficient PTH with rhPTH(184) has the potential to correct these skeletal abnormalities. To investigate the effect of rhPTH(184) 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(184) (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(184). 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(184) 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(184) doses at week 8 (Table), with no significant differences between doses for any marker. In REPLACE, BMD decreased toward normal in patients receiving rhPTH(184) at lumbar spine, total hip, femoral neck, and distal one-third radius. rhPTH(184) was generally well tolerated in both studies.
Patients with hypoparathyroidism with low bone turnover and high BMD respond to rhPTH(184) in 8 weeks. BTMs reflect restoration of turnover toward normal, and BMD also returns toward normal.
|BSAP (μg/l)||CTX (pg/ml)||P1NP (μg/l)||OCN (μg/l)|
|REPLACE||20.5 (18.1)||798.4 (648.0)||299.5 (234.6)||25.9 (27.7)|
|RELAY 25 μg||0.66 (3.8)||79.5 (239.6)||13.7 (38.5)||0.27 (2.7)|
|RELAY 50 μg||0.08 (4.3)||92.7 (141.6)||22.0 (39.6)||1.4 (2.9)|
17 May 2014 - 20 May 2014