Recombinant full-length parathyroid hormone (1-84)

Full-length parathyroid hormone (PTH) 1-84 is a recombinant version of human PTH. It is approved in the EU for the treatment of postmenopausal women with osteoporosis who have a high risk of fractures. Once-daily subcutaneous administration of PTH(1-84) stimulates new bone formation and increases bone mass. In the pivotal, randomised, double-blind, multicentre, 18-month TOP trial in 2532 postmenopausal women with osteoporosis, subcutaneous PTH(1-84) 100 microg/day significantly reduced the incidence of new or worsened vertebral fractures relative to placebo (primary endpoint). Moreover, the increase from baseline in bone mineral density (BMD) at the lumbar spine, total hip, femoral neck and trochanter was also significantly greater than in the placebo group. In another well designed study (PaTH; n = 238), 1 year of subcutaneous PTH(1-84) 100 microg/day followed by 1 year of alendronate 10 mg/day resulted in significantly greater increases in total spine, femoral neck and total hip BMD at 24 months compared with patients who received placebo for the second year. During the first year, PTH(1-84) in combination with alendronate was no more effective than PTH(1-84) monotherapy in terms of increasing areal lumbar spine BMD. PTH(1-84) is generally well tolerated, although patients should be monitored for elevated serum calcium.