The Effects of Parathyroid Hormone and Alendronate Alone or in Combination in Postmenopausal Osteoporosis

Abstract

Double-blind, placebo-controlled studies have shown that nitrogen-containing bisphosphonates that suppress bone resorption make fractures less likely in osteoporotic individuals and also increase bone mineral density (BMD). Parathyroid hormone has similar effects, but by stimulating bone formation rather than reducing resorption. This multicenter randomized trial, using a double-blind design, compared monotherapy with each of these agents alone with combination therapy. The study group included 238 postmenopausal women 55 to 85 years of age who had a T score less than -2.5 for BMD at the femoral neck, total hip, or spine and at least one risk factor for osteoporosis (age 65 or over, postmenopausal fracture, maternal history of hip fracture). Participants were assigned to receive 100 μg daily of injected full-length parathyroid hormone (1-84), 10 mg of alendronate, or both and were followed up for 12 months. All participants also received 400 IU vitamin D and 500 mg elemental calcium as calcium carbonate each day. BMD at the spine and hip was measured by dual-energy x-ray absorptiometry and quantitative computed tomography. BMD in the lumbar spine increased significantly in all treatment groups, although slightly less in patients given alendronate alone. At the other sites, BMD increased with alendronate and combination therapy. Volumetric density of trabecular bone at the spine increased markedly in all groups, but especially with parathyroid hormone alone. Volumetric density of trabecular bone at the hip increased in all groups. Cortical bone density decreased significantly with parathyroid hormone but not in patients given combination therapy. This parameter increased in patients given alendronate. N-propeptide of type I collagen, a marker of bone formation, increased in the parathyroid hormone group, as did serum C-terminal telopeptide of type I collagen, a marker of bone resorption. The C-terminal telopeptide level decreased by half after 1 month of combination therapy, and it decreased rapidly with alendronate therapy. The 8 clinical fractures were evenly distributed in all treatment groups. Serum calcium became elevated in some women given parathyroid hormone or combination therapy, but only 2 required a dose reduction for this reason. Other adverse effects were comparably frequent in all groups. Serum uric acid levels rose significantly in both the parathyroid hormone and combination therapy groups. This study gave no evidence of a synergistic response to parathyroid hormone and alendronate in osteoporotic women. The concurrent use of alendronate could limit the anabolic effects of parathyroid hormone. Longer-term data on fracture incidence are needed to determine whether and how antiresorptive drugs can best be used in conjunction with parathyroid hormone.