Teriparatide [rhPTH (1-34)], But Not Strontium Ranelate, Demonstrated Bone Anabolic Efficacy in Mature, Osteopenic, Ovariectomized Rats

• Published in: Endocrinology (Philadelphia) 2011-05, Vol.152 (5), p.1767-1778
• Main Authors: Ma, Yanfei L, Zeng, Qing Q, Porras, Leah L, Harvey, Anita, Moore, Terry L, Shelbourn, Timothy L, Dalsky, Gail P, Wronski, Thomas J, Aguirre, J. Ignacio, Bryant, Henry U, Sato, Masahiko
• Format: Article
• Language: English
• Subjects: Alkaline phosphatase; Alkaline Phosphatase - genetics; Anabolic Agents - pharmacology; Animals; Biological and medical sciences; Bone and Bones - drug effects; Bone and Bones - metabolism; Bone and Bones - pathology; Bone density; Bone Density - drug effects; Bone Density Conservation Agents - pharmacology; Bone Diseases, Metabolic - blood; Bone Diseases, Metabolic - pathology; Bone Diseases, Metabolic - prevention & control; Bone growth; Bone histomorphometry; Bone loss; Bone mineral content; Bone mineral density; Bone sialoprotein; Bone strength; Cancellous bone; Cbfa-1 protein; Collagen; Collagen Type I - genetics; Core Binding Factor Alpha 1 Subunit - genetics; Diseases of the osteoarticular system; Dose-Response Relationship, Drug; Effectiveness; Estrogens; Female; Femur; Femur - drug effects; Femur - metabolism; Fundamental and applied biological sciences. Psychology; Gene expression; Gene Expression - drug effects; Genes; Humans; Integrin-Binding Sialoprotein - genetics; Lumbar Vertebrae - drug effects; Lumbar Vertebrae - metabolism; Medical sciences; Menopause; Metaphysis; Organometallic Compounds - pharmacology; Osteoblasts; Osteocalcin; Osteocalcin - blood; Osteocalcin - genetics; Osteogenesis; Osteopenia; Osteoporosis. Osteomalacia. Paget disease; Ovariectomy; Parathyroid hormone; Polymerase chain reaction; Pretreatment; Rats; Reverse Transcriptase Polymerase Chain Reaction; Strontium; Teriparatide - pharmacology; Thiophenes - pharmacology; Time Factors; Transcription factors; Vertebrae; Vertebrates: endocrinology
• ISSN: 0013-7227; 1945-7170
• DOI: 10.1210/en.2010-1112

Teriparatide, but not strontium ranelate, has bone anabolic effects in mature, osteopenic ovariectomized rats, as indicated by increased bone strength and bone formation rate. We compared teriparatide (TPTD) and strontium ranelate (SR) efficacy on bone formation activity in a mature rat model of estrogen-deficiency bone loss. Rats were ovariectomized (OVX) at age 6 months and permitted to lose bone for 2 months to establish osteopenia before initiation of treatment with TPTD (5 or 15 μg/kg · d sc) or SR (150 or 450 mg/kg · d oral gavage). After 3 wk, RT-PCR analyses of bone formation genes in the distal femur metaphysis showed significant elevation of collagen 1α2, osteocalcin, bone sialoprotein, alkaline phosphatase, and Runx2 gene expression at both TPTD doses, relative to OVX controls. SR had no significant effect on expression of these genes. TPTD treatment for 12 wk dose dependently increased lumbar vertebral (LV) and femoral midshaft bone mineral content (BMC) and bone mineral density over pretreatment and age-matched OVX controls. SR 150 increased BMC, and SR 450 increased BMC and bone mineral density of femoral midshaft and LV over OVX controls. There were significant dose-dependent TPTD increases of LV and femoral neck strength, and TPTD 15 also increased midshaft strength compared with pretreatment and age-matched OVX controls. SR did not enhance bone strength relative to pretreatment or age-matched OVX controls. Histomorphometry of the proximal tibial metaphysis showed dose-dependent effects of TPTD on trabecular area, number, width, and osteoblast surface, bone mineralizing surface, and bone formation rate relative to pretreatment and age-matched OVX controls, whereas SR had no effect on these parameters. These findings confirmed the bone anabolic efficacy of teriparatide, but not SR in mature, osteopenic, OVX rats.