Short-term intermittent PTH 1-34 administration enhances bone formation in SCID/Beige mice

Endocrine Journal

Ronald R. Gomes, Jr.²  Robert A. Sikes¹  Emmanuel Paul²  Arivalagan Muthusamy²  Sarah Sheehan² 

[1] Center for Translational Cancer Research, and the Laboratory for Cancer Ontogeny and Therapeutics, Department of Biological Sciences, University of Delaware, Newark, USA;Penn State College of Medicine, Department of Orthopaedics and Rehabilitation, Hershey, USA

关键词: Parathyroid hormone;    Bone turnover;    SCID/Beige mouse;    Microcomputed tomography;   

DOI  :  10.1507/endocrj.K09E-349

学科分类：内分泌与代谢学

来源: Japan Endocrine Society

【 摘 要 】

References(44)Cited-By(3)The anabolic effect of intermittent PTH on bone is variable depending on the species studied, duration/mode of administration, and location of skeletal response investigated. We tested the hypothesis low dose, short term, intermittent PTH 1-34 administration is sufficient to enhance bone formation without altering bone resorption. To test our hypothesis, mice were treated intermittently with one of three concentrations of PTH 1-34 (1 μg/kg; low, 10 μg/kg, or 20 μg/kg; high) for three weeks. The skeletal response was identified by quantifying: serum markers of bone turnover, cancellous bone parameters in distal femur, proximal tibia, and lumbar vertebrae by μCT, and number of osteoblasts and osteoclasts in distal femur. Mice receiving 20 μg/kg of PTH 1-34 demonstrated a 30% increase in serum osteocalcin, but no differences in serum calcium, type I collagen teleopeptides, or TRACP 5b. For all bones, μCT analysis suggested mice receiving 20 μg/kg of PTH 1-34 had increased cancellous bone mineral density, trabecular thickness and spacing, but decreased trabecular number. A 60% increase in the number of alkaline phosphatase positive osteoblasts in the distal femur was also observed in tissue sections; however, the number of TRAP positive osteoclasts was not different between test and control groups. While animals administered 10 μg/kg demonstrated similar trends for all bone turnover indices, such alterations were not observed in animals administered PTH 1-34 at 1 μg/kg per day. Thus, PTH 1-34, administered intermittently for three weeks at 20 μg/kg is sufficient to enhance bone formation without enhancing resorption.

【 授权许可】

Unknown