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Daily treatment of aged ovariectomized rats with human parathyroid hormone (1-84) for 12 months reverses bone loss and enhances trabecular and cortical bone strength.
Calcif Tissue Int. 2006 Oct; 79(4):262-72.CT

Abstract

Most studies that have investigated the anabolic effects of parathyroid hormone (1-84) (PTH) or PTH fragments on the skeleton of ovariectomized (OVX) rats have evaluated the short-term effects of high-dose PTH(1-34) in young animals. This study used densitometry, histomorphometry, and biomechanical testing to evaluate the effects of 12-month daily treatment with low-dose PTH (15 or 30 microg/kg) in rats that were 10 months old at baseline, 4 months after OVX. Bone mineral density (BMD) and bone strength were reduced substantially in control OVX rats. The 15 microg/kg dose of PTH restored BMD to levels similar to those in sham animals within 6 months at the lumbar spine, distal and central femur, and whole body and maintained the BMD gain from 6 to 12 months. The 30 microg/kg dose produced greater effects. Both PTH doses normalized the trabecular bone volume-to-total volume ratio (BV/TV) at lumbar vertebra 3 but not at the proximal tibia (where baseline BV/TV was very low), solely by increasing trabecular thickness. PTH dose-dependently increased bone formation by increasing the mineralizing surface, but only the 30 microg/kg dose increased resorption. PTH increased cortical BMD, area, and thickness, primarily by increasing endocortical bone formation, and restored all measures of bone strength to levels similar to those in sham animals at all skeletal sites. PTH increased bone mass safely; there was no osteoid accumulation, mineralization defect, or marrow fibrosis and there were no abnormal cells. Thus, long-term PTH therapy normalized bone strength in the aged OVX rat, a model of postmenopausal osteoporosis, through increased bone turnover and enhanced formation of both trabecular and cortical bone.

Authors+Show Affiliations

NPS Pharmaceuticals, 383 Colorow Drive, Salt Lake City, UT 84108, USA. jfox@npsp.comNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article

Language

eng

PubMed ID

16969596

Citation

Fox, J, et al. "Daily Treatment of Aged Ovariectomized Rats With Human Parathyroid Hormone (1-84) for 12 Months Reverses Bone Loss and Enhances Trabecular and Cortical Bone Strength." Calcified Tissue International, vol. 79, no. 4, 2006, pp. 262-72.
Fox J, Miller MA, Newman MK, et al. Daily treatment of aged ovariectomized rats with human parathyroid hormone (1-84) for 12 months reverses bone loss and enhances trabecular and cortical bone strength. Calcif Tissue Int. 2006;79(4):262-72.
Fox, J., Miller, M. A., Newman, M. K., Metcalfe, A. F., Turner, C. H., Recker, R. R., & Smith, S. Y. (2006). Daily treatment of aged ovariectomized rats with human parathyroid hormone (1-84) for 12 months reverses bone loss and enhances trabecular and cortical bone strength. Calcified Tissue International, 79(4), 262-72.
Fox J, et al. Daily Treatment of Aged Ovariectomized Rats With Human Parathyroid Hormone (1-84) for 12 Months Reverses Bone Loss and Enhances Trabecular and Cortical Bone Strength. Calcif Tissue Int. 2006;79(4):262-72. PubMed PMID: 16969596.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Daily treatment of aged ovariectomized rats with human parathyroid hormone (1-84) for 12 months reverses bone loss and enhances trabecular and cortical bone strength. AU - Fox,J, AU - Miller,M A, AU - Newman,M K, AU - Metcalfe,A F, AU - Turner,C H, AU - Recker,R R, AU - Smith,S Y, Y1 - 2006/09/11/ PY - 2006/04/10/received PY - 2006/07/10/accepted PY - 2006/9/14/pubmed PY - 2006/12/29/medline PY - 2006/9/14/entrez SP - 262 EP - 72 JF - Calcified tissue international JO - Calcif. Tissue Int. VL - 79 IS - 4 N2 - Most studies that have investigated the anabolic effects of parathyroid hormone (1-84) (PTH) or PTH fragments on the skeleton of ovariectomized (OVX) rats have evaluated the short-term effects of high-dose PTH(1-34) in young animals. This study used densitometry, histomorphometry, and biomechanical testing to evaluate the effects of 12-month daily treatment with low-dose PTH (15 or 30 microg/kg) in rats that were 10 months old at baseline, 4 months after OVX. Bone mineral density (BMD) and bone strength were reduced substantially in control OVX rats. The 15 microg/kg dose of PTH restored BMD to levels similar to those in sham animals within 6 months at the lumbar spine, distal and central femur, and whole body and maintained the BMD gain from 6 to 12 months. The 30 microg/kg dose produced greater effects. Both PTH doses normalized the trabecular bone volume-to-total volume ratio (BV/TV) at lumbar vertebra 3 but not at the proximal tibia (where baseline BV/TV was very low), solely by increasing trabecular thickness. PTH dose-dependently increased bone formation by increasing the mineralizing surface, but only the 30 microg/kg dose increased resorption. PTH increased cortical BMD, area, and thickness, primarily by increasing endocortical bone formation, and restored all measures of bone strength to levels similar to those in sham animals at all skeletal sites. PTH increased bone mass safely; there was no osteoid accumulation, mineralization defect, or marrow fibrosis and there were no abnormal cells. Thus, long-term PTH therapy normalized bone strength in the aged OVX rat, a model of postmenopausal osteoporosis, through increased bone turnover and enhanced formation of both trabecular and cortical bone. SN - 0171-967X UR - https://www.unboundmedicine.com/medline/citation/16969596/Daily_treatment_of_aged_ovariectomized_rats_with_human_parathyroid_hormone__1_84__for_12_months_reverses_bone_loss_and_enhances_trabecular_and_cortical_bone_strength_ L2 - https://dx.doi.org/10.1007/s00223-006-0108-1 DB - PRIME DP - Unbound Medicine ER -