Twelve RCTs (n=3,252) were included in the review.
Six trials were classified as level 1 and six as level 2. Two trials had losses to follow-up of over 20%. Only 2 trials reported adequate allocation concealment and 7 trials were double-blinded.
Postmenopausal women (8 RCTs).
One RCT (level 1) reported a significant reduction in new vertebral fractures associated with 20 microg/day (relative risk, RR 0.35, 95% confidence interval, CI: 0.22, 0.55) and 40 microg/day (RR 0.31, 95% CI: 0.19, 0.50) of hPTH (1-34), compared with placebo. Nonvertebral fractures were significantly reduced with 20 microg/day hPTH (RR 0.47, 95% CI: 0.25, 0.88). A second RCT (level 1) also reported a significant decrease in nonvertebral fractures with 40 microg/day hPTH (1-34) in comparison with 10 mg/day alendronate (4.1% versus 13.7%, p=0.042). Three other trials showed no significant differences in fractures.
Six RCTs (three level 1 and three level 2) reported that hPTH (1-34) was associated with significant increases in lumbar spine BMD, ranging from 9.7 to 10.3% with 20 microg/day and 13.7 to 14.3% with 40 microg/day, in comparison with both placebo and active comparators. Changes in femoral neck BMD were also reported, but were smaller: 2.8 to 3.9% for 20 microg/day and 4.5 to 5.1% for 40 microg/day.
Two level 1 RCTs comparing hPTH (1-34) with alendronate reported significant improvements in lumbar BMD (2 RCTs) and ultradistal radius BMD (1 RCT) in favour of hPTH.
Two level 1 RCTs showed no significant improvements in spinal or femoral neck BMD with hPTH (1-84) in comparison with placebo or alendronate.
Postmenopausal women with corticosteroid-induced osteoporosis (1 RCT).
Increases in both lumbar spine BMD (12.6%) and femoral neck BMD (5.2%) were reported for hPTH (1-34) in comparison with HRT in one level 2 trial.
Osteoporosis in men (3 RCTs).
Three RCTs (one level 1 and two level 2) showed that hPTH was associated with significant increases in lumbar spine BMD, of which two also showed an increase in femoral neck BMD. None of the trials reported data on the incidence of fractures.
Health related quality of life (1 RCT).
No significant differences in quality of life between hPTH (1-34) and placebo were found in one level 1 trial.
Back pain (3 RCTs).
One level 1 RCT reported a significant reduction in back pain for postmenopausal women taking hPTH (1-34) in comparison with placebo. A significant decrease in moderate to severe back pain was also observed for hPTH (1-34) in comparison with alendronate in the remaining 2 level 1 RCTs.
Adverse events (12 RCTs).
Nine trials of hPTH (1-34) reported post-dose hypercalcemia (282 events in 1,594 participants from 7 RCTs) and six reported transient hypercalciuria. There were no reported increases in renal stones. Differences in creatinine clearance, serum creatinine and headache frequency were either within normal ranges or were non significant in comparison with placebo. However, significant increases in the frequency of leg cramps (2 to 8%; 2 RCTs) and dizziness (3%; 1 RCT) with hPTH (1-34) were reported; these increased with higher dosages (20 to 40 microg/day). Hyperuricemia was reported in 0 to 3% of participants in 2 hPTH (1-34) trials. There were no significant differences between the intervention and control arms in terms of serious adverse events.