Mechanical properties and biochemical composition of rat cortical femur and tibia after long-term treatment with biosynthetic human growth hormone

Jørgensen, Peter; Bak, Bue; Andreassen, Troels T.

doi:10.1016/8756-3282(91)90022-b

Cited by 77 publications

(34 citation statements)

References 25 publications

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“…However, the pQCT measurements of femurs in vitro revealed an unaffected cortical volumetric BMD and the measurements using Archimedes' principle showed an unchanged total femur and vertebra L6 volumetric BMD. Other studies have also shown that long-term GH treatment increases area BMD as measured by DXA (Yeh et al 1994, Ohlsson et al 1998, but the volumetric BMD (BMC/volume), as measured by Archimedes' principle or pQCT ( Jørgensen et al 1991, Andreassen et al 1995, Rosen et al 1995, is unchanged. These findings could be explained by an overestimation of the increase in BMD by DXA.…”

Section: Tablementioning

confidence: 99%

“…In old male rats, 80 days of GH treatment increased cortical bone formation mainly through increased subperiosteal bone formation (Andreassen et al 1995). In young and in old rats, GH treatment increased cortical mechanical strength, mainly as a result of an increase in bone dimensions ( Jørgensen et al 1991, Andreassen et al 1995. In primates, GH but not insulin-like growth factor (IGF)-I given to female monkeys for 7 weeks increased bone formation as measured with mineral apposition rate, and the bone formation rate (Sass et al 1997).…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

The GH secretagogues ipamorelin and GH-releasing peptide-6 increase bone mineral content in adult female rats

Svensson

Lall²,

Dickson³

et al. 2000

Journal of Endocrinology

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Growth hormone (GH) is of importance for normal bone remodelling. A recent clinical study demonstrated that MK-677, a member of a class of GH secretagogues (GHSs), increases serum concentrations of biochemical markers of bone formation and bone resorption. The aim of the present study was to investigate whether the GHSs, ipamorelin (IPA) and GH-releasing peptide-6 (GHRP-6), increase bone mineral content (BMC) in young adult female rats. Thirteen-week-old female Sprague-Dawley rats were given IPA (0·5 mg/kg per day; n=7), GHRP-6 (0·5 mg/kg per day; n=8), GH (3·5 mg/kg per day; n=7), or vehicle administered continuously s.c. via osmotic minipumps for 12 weeks. The animals were followed in vivo by dual X-ray absorptiometry (DXA) measurements every 4th week. After the animals were killed, femurs were analysed in vitro by mid-diaphyseal peripheral quantitative computed tomography (pQCT) scans. After this, excised femurs and vertebrae L6 were analysed by the use of Archimedes' principle and by determinations of ash weights. All treatments increased body weight and total tibial and vertebral BMC measured by DXA in vivo compared with vehicle-treated controls. However, total BMC corrected for the increase in body weight (total BMC:body weight ratio) was unaffected. Tibial area bone mineral density (BMD, BMC/area) was increased, but total and vertebral area BMDs were unchanged. The pQCT measurements in vitro revealed that the increase in the cortical BMC was due to an increased cross-sectional bone area, whereas the cortical volumetric BMD was unchanged. Femur and vertebra L6 volumes were increased but no effect was seen on the volumetric BMDs as measured by Archimedes' principle. Ash weight was increased by all treatments, but the mineral concentration was unchanged. We conclude that treatment of adult female rats with the GHSs ipamorelin and GHRP-6 increases BMC as measured by DXA in vivo. The results of in vitro measurements using pQCT and Archimedes' principle, in addition to ash weight determinations, show that the increases in cortical and total BMC were due to an increased growth of the bones with increased bone dimensions, whereas the volumetric BMD was unchanged.

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Section: Tablementioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

The GH secretagogues ipamorelin and GH-releasing peptide-6 increase bone mineral content in adult female rats

Svensson

Lall²,

Dickson³

et al. 2000

Journal of Endocrinology

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show abstract

“…Several studies have been performed in aged rat models [6, 7, 8, 9]. In these animal models, GH administration accelerates bone remodelling [6], increases bone mass, especially by periosteal bone apposition, increases bone strength [7, 8], and enhances fracture healing [9].…”

Section: Gh and Igf-i Administration In Animal Modelsmentioning

confidence: 99%

“…In these animal models, GH administration accelerates bone remodelling [6], increases bone mass, especially by periosteal bone apposition, increases bone strength [7, 8], and enhances fracture healing [9]. In GH-deficient rats, bone growth is reduced [10], and growth rate can be normalized by exogenous GH [11].…”

Section: Gh and Igf-i Administration In Animal Modelsmentioning

confidence: 99%

Osteoporosis and the Growth Hormone-Insulin-Like Growth Factor Axis

Geusens¹,

Boonen²

2002

Horm Res Paediatr

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Osteoporosis is the result of an imbalance between bone resorption and bone formation. Currently, mainly drugs that inhibit bone resorption are available for the treatment of osteoporosis. A new approach in the treatment of osteoporosis is the use of anabolic agents that increase bone turnover, both bone formation and resorption. Growth hormone (GH) and insulin-like growth factors (IGFs) are essential in the development and growth of the skeleton and for the maintenance of bone mass and density. We will review the evidence of GH and IGF-I in the pathophysiology and treatment of osteoporosis.

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“…Nevertheless, the delay in muscle and bone development in Hx rats affected bone geometry so severely that the structural stiffness and strength of the diaphyses were lower than normal. Only a single report of such type of effect on postyield bone strength in rats is known to us [34].…”

Section: Hypophysectomymentioning

confidence: 98%

Novel experimental effects on bone material properties and the pre- and postyield behavior of bones may be independent of bone mineralization

et al. 2005

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In this article, we summarize the results of six different tomographic/biomechanical rat studies involving hypophysectomy (Hx), ovariectomy, treatment with rhGH, olpadronate, alendronate, and toxic doses of aluminum and the development of a genetic diabetes in the eSS strain. All these conditions induced some interesting and rarely reported effects on postyield bone strength. These effects were generally related neither to the degree of mineralization or the elastic modulus of the bone tissue nor to the preyield behavior of the bones. In two particular cases (Hx, eSS), the elastic modulus of bone tissue varied independently of its degree of mineralization. These results suggest the involvement of some microstructural factor(s) of bone tissue resistance to crack progression (a postyield feature of bone behavior), rather than to crack initiation (the yield-determining factor) in the corresponding mechanism. Changes in collagen or crystal structure may play that role. These changes are relevant to the mechanism of fracture production during plastic deformation, a feature of bone strength that might be independent from mineralization. Therefore, these changes might help to explain some effects of novel treatments on bone strength unrelated to bone mineralization. This questions the belief that the remaining bone mass in metabolic osteopenias is biologically and mechanically normal.

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Mechanical properties and biochemical composition of rat cortical femur and tibia after long-term treatment with biosynthetic human growth hormone

Cited by 77 publications

References 25 publications

The GH secretagogues ipamorelin and GH-releasing peptide-6 increase bone mineral content in adult female rats

The GH secretagogues ipamorelin and GH-releasing peptide-6 increase bone mineral content in adult female rats

Osteoporosis and the Growth Hormone-Insulin-Like Growth Factor Axis

Novel experimental effects on bone material properties and the pre- and postyield behavior of bones may be independent of bone mineralization

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