Parathyroid hormone and parathyroid hormone-related protein analogs as therapies for osteoporosis

Abstract

Osteoporotic fractures result in significant morbidity and mortality. Anabolic agents reverse the negative skeletal balance that characterizes osteoporosis by stimulating osteoblast-dependent bone formation to a greater degree than osteoclast-dependent bone resorption. Parathyroid hormone (PTH) and parathyroid hormone- related protein (PTHrP) are peptide hormones, which have anabolic actions when administered intermittently. The only FDA-approved anabolic bone agent for the treatment of osteoporosis in the United States is PTH 1-34, or teriparatide, administered by daily subcutaneous injections. However, PTH 1-84 is also available in Europe. Synthetic human PTHrP 1-36 and a PTHrP 1-34 analog, BA058, have also been shown to increase lumbar spine bone density. These agents and several other PTH and PTHrP analogs, including some which are not administered as injections, continue to be investigated as potential anabolic therapies for osteoporosis.

Figure 1

Lumbar Spine and Hip Bone Mineral Density Changes in Postmenopausal Women Treated with PTHrP 1-36 400µg, 600µg or PTH 1-34 40µg. The three groups are indicated by the patterns shown in the legend within the figure. There was no significant difference in BMD change between groups at any site. Bars indicate SEM, and the * and ** symbols refer to statistical significance compared to baseline values. Lumbar spine BMD increased equivalently and significantly by day 90 in all three groups. Total hip and femoral neck BMD increased equivalently in all three groups, but was significant only for the two PTHrP(1-36) groups (p–0.05 vs baseline) at the total hip, and for the PTHrP(1-36) 400μg group at the femoral neck (p–0.05 vs baseline). Results are presented as percent change from baseline. Modified with permission from the American Society for Bone and Mineral Research [28].