TY - JOUR
T1 - Parathyroid hormone and growth hormone have additive or synergetic effect when used as intervention treatment in ovariectomized rats with established osteopenia
AU - Mosekilde, Li
AU - Tornvig, L.
AU - Thomsen, J. S.
AU - Orhii, P. B.
AU - Banu, M. J.
AU - Kalu, D. N.
N1 - Funding Information:
The authors are grateful for the excellent technical assistance of Birthe Gylling-Jørgensen, Department of Cell Biology, Institute of Anatomy, University of Aarhus. Michael Hewitt is gratefully acknowledged for his help in revising this manuscript. This study was supported in part by a grant from the NIH (No. AG13309) a university grant for osteoporosis from Procter and Gamble Pharmaceuticals (Cincinnati, OH), and a grant from the Danish Medical Research Council (No. 9503020). We thank Genentech, Inc. (South San Francisco, CA) for providing the recombinant human growth hormone (rhGH) used in this study.
PY - 2000/6
Y1 - 2000/6
N2 - The severely osteoporotic human skeleton is characterized by thin cortices and a very fragile cancellous framework. To increase the biomechanical competence of such a skeleton, powerful anabolic agents are needed. The aim of the present study was to compare the effect of parathyroid hormone (PTH), growth hormone (GH) and combination treatment with PTH and GH in an aged, rat model with established osteopenia. Furthermore, envelope- and site-specific effects of the two agents are described. Twelve-month-old virgin F344 rats were divided into six groups with 11 animals per group: (1) baseline; (2) sham-operated + solvent vehicle (s.v.) (sham); (3) ovariectomized + s.v. (ovx); (4) ovx + GH 2.5 mg/kg body weight per day; (5) ovx + PTH 80 μg/kg body weight per day; and (6) ovx + GH and PTH treatment. Group 1 were killed to establish baseline values. Groups 2 (sham) and 3 (ovx) were killed after 24 weeks. Groups 4, 5, and 6 were allowed to develop osteopenia for 16 weeks before treatment was initiated. Treatment was given for a period of 8 weeks. The effects of GH, PTH, and GH + PTH cotherapy were measured by biomechanical testing at four different skeletal sites: lumbar vertebra; femoral diaphysis; femoral neck; and distal femoral metaphysis. In addition, static histomorphometry was performed at the middiaphyseal region. Ovx induced a loss of bone strength at all sites, but this was significant only at the femoral diaphysis and distal metaphysis. GH could reverse the loss of strength at the diaphysis, but not at the metaphysis. PTH, on the other hand, reversed the loss of strength to values significantly over ovx at all four sites. At the metaphysis, PTH monotherapy increased strength to above sham levels. However, GH + PTH cotherapy showed additive or synergistic effects at the four tested sites, leading to strength values significantly over sham at all these sites. Static histomorphometry showed that GH exerted its main effect on the periosteal envelope and PTH on the endocortical envelope; for this reason, the GH + PTH combination treatment had an additive or synergistic effect. We conclude that GH and PTH have a very pronounced anabolic effect when given in cotherapy. Therefore, this treatment regime seems promising in the clinical situation for management of patients with severe, established osteoporosis. Copyright (C) 2000 Elsevier Science Inc.
AB - The severely osteoporotic human skeleton is characterized by thin cortices and a very fragile cancellous framework. To increase the biomechanical competence of such a skeleton, powerful anabolic agents are needed. The aim of the present study was to compare the effect of parathyroid hormone (PTH), growth hormone (GH) and combination treatment with PTH and GH in an aged, rat model with established osteopenia. Furthermore, envelope- and site-specific effects of the two agents are described. Twelve-month-old virgin F344 rats were divided into six groups with 11 animals per group: (1) baseline; (2) sham-operated + solvent vehicle (s.v.) (sham); (3) ovariectomized + s.v. (ovx); (4) ovx + GH 2.5 mg/kg body weight per day; (5) ovx + PTH 80 μg/kg body weight per day; and (6) ovx + GH and PTH treatment. Group 1 were killed to establish baseline values. Groups 2 (sham) and 3 (ovx) were killed after 24 weeks. Groups 4, 5, and 6 were allowed to develop osteopenia for 16 weeks before treatment was initiated. Treatment was given for a period of 8 weeks. The effects of GH, PTH, and GH + PTH cotherapy were measured by biomechanical testing at four different skeletal sites: lumbar vertebra; femoral diaphysis; femoral neck; and distal femoral metaphysis. In addition, static histomorphometry was performed at the middiaphyseal region. Ovx induced a loss of bone strength at all sites, but this was significant only at the femoral diaphysis and distal metaphysis. GH could reverse the loss of strength at the diaphysis, but not at the metaphysis. PTH, on the other hand, reversed the loss of strength to values significantly over ovx at all four sites. At the metaphysis, PTH monotherapy increased strength to above sham levels. However, GH + PTH cotherapy showed additive or synergistic effects at the four tested sites, leading to strength values significantly over sham at all these sites. Static histomorphometry showed that GH exerted its main effect on the periosteal envelope and PTH on the endocortical envelope; for this reason, the GH + PTH combination treatment had an additive or synergistic effect. We conclude that GH and PTH have a very pronounced anabolic effect when given in cotherapy. Therefore, this treatment regime seems promising in the clinical situation for management of patients with severe, established osteoporosis. Copyright (C) 2000 Elsevier Science Inc.
KW - Bone mass
KW - Bone strength
KW - Combination therapy
KW - Growth hormone (GH)
KW - Osteopenia
KW - Parathyroid hormone (PTH)
KW - Rat model
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U2 - 10.1016/S8756-3282(00)00276-3
DO - 10.1016/S8756-3282(00)00276-3
M3 - Article
C2 - 10831937
AN - SCOPUS:0034104741
VL - 26
SP - 643
EP - 651
JO - Bone
JF - Bone
SN - 8756-3282
IS - 6
ER -