Anabolic effect of parathyroid hormone is not modified by supplementation with insulinlike growth factor I (IGF-I) or growth hormone in aged female rats fed an energy-restricted or ad libitum diet

Gunness, M.; Hock, Janet M.

doi:10.1016/8756-3282(94)00030-4

Cited by 21 publications

(4 citation statements)

References 21 publications

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“…PTH reversed aging effects on vertebra and proximal femur. Our data were largely consistent with skeletal effects reported in 15-to 24-month-old, ovary-intact virgin and multiparous, female Brown Norway, Brown-Norway/Fischer-344, and SpragueDawley rats, treated with PTH for shorter periods of 12 to 32 days (Gunness and Hock, 1995;Hock and Wood, 1995). These studies and our data show that the anabolic benefits of PTH to improve bone quality and strengthen rat bones can be induced under widely ranging conditions of treatment duration and age in both intact and ovariectomized females and intact males.…”

Section: Discussionsupporting

confidence: 80%

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Skeletal Efficacy with Parathyroid Hormone in Rats Was Not Entirely Beneficial with Long-Term Treatment

Sato

L²,

Hock³

et al. 2002

J Pharmacol Exp Ther

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We report the consequences of prolonged treatment with recombinant human parathyroid hormone (1-34) (PTH) in male and ovariectomized female rats with mature skeletons. Intact male and osteopenic, ovariectomized, female F-344 rats were evaluated after 1 year of treatment with 0, 8, or 40 g/kg/day s.c. PTH. Males and females were about 6 months of age at study initiation; females were ovariectomized (Ovx) for 5 weeks before initiation of PTH treatment. PTH did not affect the survival of either intact males or ovariectomized females. Qualitative histopathology showed expected changes associated with aging in kidneys and proximal tibiae, with no treatment-related anomalies after 1 year of PTH administration. PTH slightly increased the femoral length of ovariectomized females but not that of males. No significant differences in femoral length were observed between sham and Ovx controls. Proximal femora of the males and ovariectomized females given the high dose of 40 g/kg showed 211 and 186% greater trabecular bone area, 118 and 94% greater cortical thickness, 170 and 189% greater trabecular number, and 321 and 404% greater connectivity (node-to-node struts) compared with respective vehicle controls. Increased trabecular and endocortical surface apposition coincided with a 78 and 70% loss of marrow space for males and females treated with PTH, respectively. Biomechanical strength (ultimate load) of the femoral neck increased by 73 and 76%, respectively, in males and ovariectomized females. Cortical bone analyses of the femoral midshaft showed 105 and 72% increases in bone mineral content, 67 and 55% increases in bone mineral density, and 22 and 10% increases in crosssectional area for males and ovariectomized females, respectively, with altered shape of femora. Biomechanical analyses of the midshaft showed substantial increases in strength and stiffness but a reduction in ultimate strain, which was likely due to the altered geometry of the midshaft for PTH groups. Aging effects on strength of vertebra and femoral midshaft were reversed by PTH treatment. In summary, the 1-year treatment duration, which represents about 50% of lifetime, did not affect survival and was not associated with any treatment-related anomalies in the kidney or skeleton. PTH reversed the aging process in bones but not kidneys and substantially increased bone mass and strength to well beyond normally attained levels. However, compared with short-term studies reported previously, there seemed to be no advantages to extending PTH treatment to 12 months in rat bones.Once daily, subcutaneous administration of human PTH (1-34) stimulates new bone formation in rats, monkeys, and humans (Gasser and Jerome, 1992;Dempster et al

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Section: Discussionsupporting

confidence: 80%

“…Gunness and Hock, 1995;Hock and Wood, 1995). Nevertheless, one rat study (Neer et al, 2001;Vahle et al, 2002) detected untoward skeletal effects of PTH after nearlifetime treatment.…”

mentioning

confidence: 99%

Skeletal Efficacy with Parathyroid Hormone in Rats Was Not Entirely Beneficial with Long-Term Treatment

Sato

L²,

Hock³

et al. 2002

J Pharmacol Exp Ther

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“…Treatment with PTH and/or GH has previously been investigated (25,26) . Both studies reported the characteristic anabolic effect of PTH on bone.…”

Section: Discussionmentioning

confidence: 99%

“…Using osteoblast‐like cells, Spencer et al have shown that the mitogen effect of IGF‐I is potentiated when IGF‐I is combined with PTH(1‐34) (21) . They also administered IGF‐I and PTH (1–34) alone and in combination to rats in vivo and found that the combination of IGF‐I and PTH(1‐34) potentiated bone formation at cancellous bone surfaces. In vitro studies have shown that GH is able to stimulate local production of IGF‐I in cultured bone tissue (22–24) .…”

Section: Discussionmentioning

confidence: 99%

The Influence of Combined Parathyroid Hormone and Growth Hormone Treatment on Cortical Bone in Aged Ovariectomized Rats

Andreassen

Oxlund

2000

Journal of Bone and Mineral Research

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The influence of combined parathyroid hormone (PTH) and growth hormone (GH) treatment on bone formation and mechanical strength was investigated in femoral middiaphysial cortical bone from 20-monthold ovariectomized (OVX) rats. The animals were OVX at 10 months of age, and at 18 months they were treated daily for 56 days with PTH(1-34) alone (60 g/kg), recombinant human GH (rhGH) alone (2.7 mg/kg), or a combination of PTH(1-34) plus rhGH. Vehicle was given to OVX control rats. All animals were labeled at day 28 (calcein) and at day 49 (tetracycline) of the treatment period. PTH(1-34) alone gave rise to formation of a new zone of bone at the endocortical surface. rhGH alone caused substantial bone deposition at the periosteal surface without influencing the endocortical surface. Combined PTH(1-34) plus rhGH administration enhanced bone deposition at the periosteal surface to the same extent as that of rhGH alone. However, the combined treatment resulted in a more pronounced formation of new bone at the endocortical surface than was induced by PTH (1-34)

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The influence of growth hormone on cancellous and cortical bone of the vertebral body in aged rats

Andreassen

Melsen²,

Oxlund

1996

Journal of Bone and Mineral Research

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The influence of growth hormone administration on cancellous and cortical bone of the vertebral body in 2-year-old male rats has been investigated. All rats were injected for 80 days, then killed. Controls were given saline, and three recombinant human growth hormone (rhGH) injected groups were given either rhGH (2.7 mg/kg/day) for the first 20 or 40 days, followed by saline injection, or rhGH for all 80 days. Tetracycline labeling was performed on days 41 and 69. In all groups given rhGH, an increase in the cortical bone volume was found. In the rhGH 40-day group, single labeling corresponding to injection on day 41 was seen all around the anterior surface of the vertebral body wall (toward the abdominal cavity). In the rhGH 80-day group, double labeling was seen all around the anterior surface of the vertebral body, and a substantial increase in the mineralizing surface/total surface, mineral apposition rate, and mineralized bone formation rate was found. In the cortical bone of the anterior wall, cavities had developed in the rhGH 40- and 80-day groups. In the cancellous bone, no differences in bone volume, bone volume/total volume, or bone surface/bone volume were seen, but in the middle part of the vertebral body a decrease in the mineralizing surface/total surface was found in the rhGH 80-day group. The height of the vertebral body was not influenced by rhGH administration, whereas the transversal and midsaggital diameters were increased in the rhGH 80-day group. The compressive mechanical strength of the vertebral body specimens was increased in the rhGH 80-day group, and this increase most likely could be explained by formation and deposition of cortical bone.

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Anabolic effect of parathyroid hormone is not modified by supplementation with insulinlike growth factor I (IGF-I) or growth hormone in aged female rats fed an energy-restricted or ad libitum diet

Cited by 21 publications

References 21 publications

Skeletal Efficacy with Parathyroid Hormone in Rats Was Not Entirely Beneficial with Long-Term Treatment

Skeletal Efficacy with Parathyroid Hormone in Rats Was Not Entirely Beneficial with Long-Term Treatment

The Influence of Combined Parathyroid Hormone and Growth Hormone Treatment on Cortical Bone in Aged Ovariectomized Rats

The influence of growth hormone on cancellous and cortical bone of the vertebral body in aged rats

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