Effect of parathyroid hormone (1-34) on fractures and bone mineral densityin postmenopausal women with osteoporosis.

Background: Once-daily injections of parathyroid hormone or its amino-termi nal fragments increase bone formation and bone mass without causing hyperca lcemia, but their effects on fractures are unknown. Methods: We randomly assigned 1637 postmenopausal women with prior vertebra l fractures to receive 20 or 40 mug of parathyroid hormone (1-34) or placeb o, administered subcutaneously by the women daily. We obtained vertebral ra diographs at base line and at the end of the study (median duration of obse rvation, 21 months) and performed serial measurements of bone mass by dual- energy x-ray absorptiometry. Results: New vertebral fractures occurred in 14 percent of the women in the placebo group and in 5 percent and 4 percent, respectively, of the women i n the 20-mug and 40-mug parathyroid hormone groups; the respective relative risks of fracture in the 20-mug and 40-mug groups, as compared with the pl acebo group, were 0.35 and 0.31 (95 percent confidence intervals, 0.22 to 0 .55 and 0.19 to 0.50). New nonvertebral fragility fractures occurred in 6 p ercent of the women in the placebo group and in 3 percent of those in each parathyroid hormone group (relative risk, 0.47 and 0.46, respectively [95 p ercent confidence intervals, 0.25 to 0.88 and 0.25 to 0.86]). As compared w ith placebo, the 20-mug and 40-mug doses of parathyroid hormone increased b one mineral density by 9 and 13 more percentage points in the lumbar spine and by 3 and 6 more percentage points in the femoral neck; the 40-mug dose decreased bone mineral density at the shaft of the radius by 2 more percent age points. Both doses increased total-body bone mineral by 2 to 4 more per centage points than did placebo. Parathyroid hormone had only minor side ef fects (occasional nausea and headache). Conclusions: Treatment of postmenopausal osteoporosis with parathyroid horm one (1-34) decreases the risk of vertebral and nonvertebral fractures; incr eases vertebral, femoral, and total-body bone mineral density; and is well tolerated. The 40-mug dose increased bone mineral density more than the 20- mug dose but had similar effects on the risk of fracture and was more likel y to have side effects. (N Engl J Med 2001;344:1434-41.) Copyright (C) 2001 Massachusetts Medical Society.