title: Short-term, high-dose parathyroid hormone-related protein as a skeletal anabolic agent for the treatment of postmenopausal osteoporosis.
abstract: PTH-related protein (PTHrP) is homologous with PTH. PTH, an effective anabolic agent for treating osteoporosis, has been shown to stimulate both bone resorption by osteoclasts and bone formation by osteoblasts. We examined whether PTHrP might share anabolic properties in osteoporosis. A 3-month double-blind, prospective, placebo-controlled, randomized clinical trial was performed in 16 healthy postmenopausal women with osteoporosis. All received calcium and vitamin D, and all continued their prior hormone replacement therapy. One group also received daily sc PTHrP (6.56 microg/kg x d, or approximately 400 microg/d), and the other group received placebo injections. The PTHrP group displayed a 4.7% increase in lumbar spine bone mineral density (BMD) and also demonstrated an increase in osteoblastic bone formation, as assessed using serum osteocalcin measurements. In contrast, there was no increase in bone-specific alkaline phosphatase and collagen-1 propeptide or either of two markers of osteoclastic bone resorption, N-telopeptide, or deoxypyridinoline. One subject in the placebo group withdrew from the study, but there were no significant adverse events in the PTHrP group. PTHrP administered sc in high doses for only 3 months appears to be a potent anabolic agent, producing a 4.7% increase in lumbar spine BMD. This compares very favorably to available antiresorptive drugs for osteoporosis and is similar to the increases in BMD at this early time point reported for PTH. Despite the high doses, PTHrP was well tolerated. Larger clinical trials are required to confirm these results and fully assess the anabolic potential of PTHrP in osteoporosis.
authors.affiliation: Division of Endocrinology, The University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania 15213, USA.
authors.forename: Mara J
authors.initials: MJ
authors.lastname: Horwitz
authors.forename: Mary Beth
authors.initials: MB
authors.lastname: Tedesco
authors.forename: Caren
authors.initials: C
authors.lastname: Gundberg
authors.forename: Adolfo
authors.initials: A
authors.lastname: Garcia-Ocana
authors.forename: Andrew F
authors.initials: AF
authors.lastname: Stewart
mesh_terms: D015415:Biomarkers; D015519:Bone Density / Q000187:drug effects; D002118:Calcium / Q000097:blood / Q000652:urine; D004311:Double-Blind Method; D005260:Female; D005272:Femur Neck / Q000378:metabolism; D006621:Hip Joint / Q000378:metabolism; D006801:Humans; D008159:Lumbar Vertebrae / Q000378:metabolism; D008875:Middle Aged; D015663:Osteoporosis, Postmenopausal / Q000188:drug therapy*; D010281:Parathyroid Hormone / Q000008:administration & dosage* / Q000009:adverse effects; D044162:Parathyroid Hormone-Related Protein; D010349:Patient Compliance; D036361:Peptide Hormones / Q000008:administration & dosage* / Q000009:adverse effects; D010865:Pilot Projects; D011446:Prospective Studies
chemical_list: D015415:Biomarkers; C470121:PTHLH protein, human; D010281:Parathyroid Hormone; D044162:Parathyroid Hormone-Related Protein; D036361:Peptide Hormones; D002118:Calcium