Efficacy and Safety of Human Parathyroid Hormone-(1–84) in Increasing Bone Mineral Density in Postmenopausal Osteoporosis

Abstract

Many osteoporotic patients continue to have subnormal bone mineral density (BMD) despite treatment. Anabolic agents, including parathyroid hormone (PTH) and N-terminal fragment analogs of PTH, are able to induce large increases in bone mass and bone strength. This prospective, double-blind, placebo-controlled study evaluated 1 year of treatment with full-length recombinant human PTH (PTH-[1–84]) in postmenopausal women with osteoporosis. All participants were 50 to 75 years of age and had been postmenopausal for 5 years or longer. BMD in the lumbar spine was more than 2.5 standard deviations below the young adult mean. A total of 206 women were assigned to self-inject 50, 75, or 100 μg daily of human PTH-(1–84) or a placebo subcutaneously. All patients received calcium and vitamin D supplements. PTH treatment led to dose-related increases in BMD in the lumbar spine (Fig. 1). With the highest dose (100 μg daily), there was no tendency toward plateauing of the response. Average increases in BMD after 12 months were 3.0%, 5.1%, and 7.8%, respectively, for the 50-, 75-, and 100-μg doses. The 0.9% increase in BMD in placebo patients was not significantly greater than baseline BMD. There also was a treatment-related increase in bone area in the lumbar spine that was significant at the highest dose level. PTH treatment had a greater effect on bone mineral content than on BMD. The more severely osteoporotic women had the greatest responses to PTH treatment. Changes in BMD at the total hip and femoral neck were relatively small and inconsistent. Markers of bone remodeling such as osteocalcin were significantly increased in all PTH-treated groups after only 30 days of treatment. Serum calcium levels increased by a small but statistically significant degree in PTH-treated women. Compliance with self-injection exceeded 94% in all groups. Treatment was, in general, well tolerated. The dropout rate was 14%, noncompliance being the major cause. Only 1 patient, in the highest-dose group, withdrew because of repeated hypercalcemia. The most common adverse effect was a reaction at the injection site; it was not dose-related. Creatinine clearance tended to increase in all the PTH groups. Daily treatment with full-length PTH over 1 year led to a significant dose-related increase in lumbar spinal BMD in these postmenopausal women with osteoporosis. The treatment appears to be safe.Fig. 1: Changes in bone mineral density, bone area, and bone mineral content in the lumbar spine (L1–L4) of postmenopausal osteoporotic women treated with full-length parathyroid hormone or placebo for 1 year. Results are the mean ± standard error (n = 43–51/time point). *P <0.05 versus placebo. Reproduced with permission. J Clin Endocrinol Metab 2003;88:5212–5220. Copyright © 2003, The Endocrine Society. All rights reserved.