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Sequential effects of chronic human PTH (1-84) treatment of estrogen-deficiency osteopenia in the rat.
J Bone Miner Res. 1996 Apr; 11(4):430-9.JB

Abstract

Although daily injections of parathyroid hormone (PTH) can rapidly reverse estrogen-deficiency bone loss in rats, PTH treatment of osteoporotic humans has to date produced more modest increases in bone mass. To explore the reasons for this important difference, we evaluated the dose- and time-dependence of human PTH 1-84 treatment effects on bone mass and biochemical markers of bone metabolism in rats with estrogen-deficiency bone loss. The highest doses of PTH increased spinal, femoral, and total skeletal mass to supra-normal levels and stimulated cortical endosteal bone formation. Spine and whole skeleton mass and density increased rapidly at first, but then increased more slowly; the rate of change decreased significantly (p < 0.01) during continued treatment with the highest doses of PTH. The effects of PTH treatment on biochemical markers also were both dose-dependent and time-dependent. Serum osteocalcin, a marker of osteoblast function, increased with the highest doses of PTH (p < 0.001), but reached an early plateau and later returned toward baseline. Urinary excretion of pyridinolines, a marker of osteoclast function, increased in a time-dependent fashion throughout treatment (p < 0.001). Serum 1,25(OH)2 vitamin D levels increased in a dose-related fashion, but then decreased toward control levels despite continued treatment. We demonstrate that both osteoblast and osteoclast function are increased during daily PTH therapy in the rat. The pattern of response depends on both the dose of PTH and the duration of therapy. These dose- and time-related effects should be taken into account when designing experimental PTH treatments for osteoporosis, and they deserve intensive study.

Authors+Show Affiliations

Department of Medicine, Massachusetts General Hospital, Harvard Medical School, Boston, USA.No affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article

Language

eng

PubMed ID

8992873

Citation

Mitlak, B H., et al. "Sequential Effects of Chronic Human PTH (1-84) Treatment of Estrogen-deficiency Osteopenia in the Rat." Journal of Bone and Mineral Research : the Official Journal of the American Society for Bone and Mineral Research, vol. 11, no. 4, 1996, pp. 430-9.
Mitlak BH, Burdette-Miller P, Schoenfeld D, et al. Sequential effects of chronic human PTH (1-84) treatment of estrogen-deficiency osteopenia in the rat. J Bone Miner Res. 1996;11(4):430-9.
Mitlak, B. H., Burdette-Miller, P., Schoenfeld, D., & Neer, R. M. (1996). Sequential effects of chronic human PTH (1-84) treatment of estrogen-deficiency osteopenia in the rat. Journal of Bone and Mineral Research : the Official Journal of the American Society for Bone and Mineral Research, 11(4), 430-9.
Mitlak BH, et al. Sequential Effects of Chronic Human PTH (1-84) Treatment of Estrogen-deficiency Osteopenia in the Rat. J Bone Miner Res. 1996;11(4):430-9. PubMed PMID: 8992873.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Sequential effects of chronic human PTH (1-84) treatment of estrogen-deficiency osteopenia in the rat. AU - Mitlak,B H, AU - Burdette-Miller,P, AU - Schoenfeld,D, AU - Neer,R M, PY - 1996/4/1/pubmed PY - 1996/4/1/medline PY - 1996/4/1/entrez SP - 430 EP - 9 JF - Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research JO - J Bone Miner Res VL - 11 IS - 4 N2 - Although daily injections of parathyroid hormone (PTH) can rapidly reverse estrogen-deficiency bone loss in rats, PTH treatment of osteoporotic humans has to date produced more modest increases in bone mass. To explore the reasons for this important difference, we evaluated the dose- and time-dependence of human PTH 1-84 treatment effects on bone mass and biochemical markers of bone metabolism in rats with estrogen-deficiency bone loss. The highest doses of PTH increased spinal, femoral, and total skeletal mass to supra-normal levels and stimulated cortical endosteal bone formation. Spine and whole skeleton mass and density increased rapidly at first, but then increased more slowly; the rate of change decreased significantly (p < 0.01) during continued treatment with the highest doses of PTH. The effects of PTH treatment on biochemical markers also were both dose-dependent and time-dependent. Serum osteocalcin, a marker of osteoblast function, increased with the highest doses of PTH (p < 0.001), but reached an early plateau and later returned toward baseline. Urinary excretion of pyridinolines, a marker of osteoclast function, increased in a time-dependent fashion throughout treatment (p < 0.001). Serum 1,25(OH)2 vitamin D levels increased in a dose-related fashion, but then decreased toward control levels despite continued treatment. We demonstrate that both osteoblast and osteoclast function are increased during daily PTH therapy in the rat. The pattern of response depends on both the dose of PTH and the duration of therapy. These dose- and time-related effects should be taken into account when designing experimental PTH treatments for osteoporosis, and they deserve intensive study. SN - 0884-0431 UR - https://www.unboundmedicine.com/medline/citation/8992873/Sequential_effects_of_chronic_human_PTH__1_84__treatment_of_estrogen_deficiency_osteopenia_in_the_rat_ L2 - https://doi.org/10.1002/jbmr.5650110403 DB - PRIME DP - Unbound Medicine ER -