Parathyroid hormone added to established hormone therapy: Effects on vertebral fracture and maintenance of bone mass after parathyroid hormone withdrawal

Our best pharmacologic agents for osteoporosis treatment prevent no more th an 40-60% of osteoporotic fractures in patients at highest risk. Thus, ther e is a need for agents that can further augment bone mass and reduce fractu re risk more substantially. To this end, we investigated the utility of par athyroid hormone (PTH) in combination with established hormone-replacement therapy (HRT) in women with osteoporosis, Fifty-two women who had been on H RT for at least 2 years were enrolled in this trial in which 25 were assign ed randomly to remain on HRT alone and 27 were assigned to remain on HRT an d also receive daily subcutaneous PTH(1-34) 400 U (25 mug) per day for 3 Se ars, Bone mineral density (BMD) measurements at the spine, hip, and total b ody as well as biochemical determinations of bone turnover and calcium home ostasis were obtained every 6 months. Lateral thoracic and lumbar spine X-r ays mere obtained at baseline and annually. Subjects also had measurements of bone density and biochemical indices of bone turnover 1 year after disco ntinuation of PTH, while HRT was continued. In the group receiving HRT alon e, bone density and biochemical variables of bone turnover remained stable throughout the 3-year treatment trial and 1-year follow-up. In the PTH + HR T group, biochemical variables of bone formation and resorption peaked at 6 months and subsequently remained elevated until 30 months at which time le vels were indistinguishable from baseline. Subjects in the PTH + HRT group increased bone mass by 13.4 +/- 1.4% in the spine, 4.4 +/- 1.0% in the tota l hip, and 3.7 +/- 1.4% in the total body. Bone density measurements remain ed stable 1 year after discontinuation of PTH without any significant loss H:hile women continued HRT, Biochemical variables did not change significan tly after cessation of PTH through the 1-year follow-up period, PTH + HRT r educed the percent of women who had vertebral fractures from 37.5% to 8.3% (using a 15% height reduction criterion) and from 25% to 0% (using a 20% he ight reduction criterion) compared with women receiving HRT alone (p < 0.02 for both). We conclude that ongoing HRT maintains almost all of the PTH-in duced bone mass increment for 1 year after discontinuation of PTH, Furtherm ore, PTH in combination with hormone therapy is an effective means of incre asing bone mass throughout the skeleton and specifically reducing vertebral fracture occurrence by 75-100%, compared with HRT alone.