| 1. |
- Ehrnborg, Christer, 1968, et al.
(författare)
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Increased serum concentration of IGFBP-4 and IGFBP-5 in healthy adults during one month's treatment with supraphysiological doses of growth hormone.
- 2007
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Ingår i: Growth hormone & IGF research : official journal of the Growth Hormone Research Society and the International IGF Research Society. - : Elsevier BV. - 1096-6374. ; 17:3, s. 234-41
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVES: To study the effects on insulin-like growth factor binding proteins (IGFBP)-4 and -5 after one month's treatment with supraphysiological doses of growth hormone (GH) in healthy, active young adults with a normal GH-IGF-I axis. Furthermore, the possible use of IGFBP-4 and IGFBP-5 as markers of GH doping is discussed. DESIGN: Thirty healthy, physically active volunteers (15 men and 15 women), mean age 25.9 years (range 18-35), participated in this randomized, double-blind, placebo-controlled, parallel study with three groups (n=10; 5 men and 5 women in each group). The groups comprised the following: placebo, GH 0.1IU/kg/day [0.033mg/kg/day] and GH 0.2IU/kg/day [0.067mg/kg/day]. RESULTS: Baseline levels of IGFBP-4 were higher (+20%), while IGFBP-5 levels were lower (-37%) in women than in men. IGFBP-5 levels were positively correlated to age, but no significant correlation was found for IGFBP-4. In the pooled group with active GH treatment (n=20), both IGFBP-4 and IGFBP-5 levels were increased vs. the placebo group from day 14 until end of treatment [day 28, IGFBP-4 (+40%, p<0.01) and IGFBP-5 (+61%, p <0.001)]. After inclusion of serum IGF-I as a covariate in the linear regression analysis, the associations between GH treatment and the IGFBP-4 and IGFBP-5 levels were not significant. CONCLUSIONS: This study shows that the levels of IGFBP-4 and IGFBP-5 are affected by supraphysiological GH treatment given to young, healthy, physically active adults of both genders. The present study, including relatively few subjects, does not support that IGFBP-4 and IGFBP-5 can be used as IGF-I independent markers in a forthcoming method for detecting GH doping, although, further studies are needed to investigate the potential use of IGFBP-4 and IGFBP-5 as markers of GH doping.
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| 2. |
- Isaksson, Olle, 1943, et al.
(författare)
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GH and bone--experimental and clinical studies.
- 2000
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Ingår i: Endocrine journal. - 0918-8959. ; 47 Suppl
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Tidskriftsartikel (refereegranskat)abstract
- GH increases bone formation both via a direct interaction with GH receptors on osteoblasts and via locally produced IGF-I (autocrine/paracrine action). GH deficiency results in decreased bone mass in both man and laboratory animals and treatment of GHD patients with GH for several months results in increased bone mass. GH treatment also increases bone mass and the total mechanical strength of bones in rats with normal GH secretion. Because of the short duration of GH-treatment in man with normal GH secretion, the effect on bone mass is still inconclusive. The action of GH on bone metabolism in GHD adults is twofold: It stimulates both bone resorption and bone formation. A "Biphasic model" of GH action in bone remodeling has recently been proposed [1] (Fig. 2). According to this model the net effect of GH first results in a loss of bone mass, followed by a net increase in bone mass. The transition point occurs when bone formation proceeds at a higher rate than bone resorption. Taking all clinical studies of GH-treatment of GHD adults into account, it appears that the "transition point" occurs after approximately six months and that a net increase in bone mass usually is seen after 12-18 months of GH treatment. It should be emphasized that the "Biphasic model" of GH action in bone remodeling is proposed based on findings in GHD adults, and it remains to be clarified whether or not it is valid for subjects with normal GH secretion.
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| 3. |
- Ohlsson, Claes, 1965, et al.
(författare)
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Growth hormone and bone.
- 1998
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Ingår i: Endocrine reviews. - 0163-769X. ; 19:1, s. 55-79
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Tidskriftsartikel (refereegranskat)abstract
- It is well known that GH is important in the regulation of longitudinal bone growth. Its role in the regulation of bone metabolism in man has not been understood until recently. Several in vivo and in vitro studies have demonstrated that GH is important in the regulation of both bone formation and bone resorption. In Figure 9 a simplified model for the cellular effects of GH in the regulation of bone remodeling is presented (Fig. 9). GH increases bone formation in two ways: via a direct interaction with GHRs on osteoblasts and via an induction of endocrine and autocrine/paracrine IGF-I. It is difficult to say how much of the GH effect is mediated by IGFs and how much is IGF-independent. GH treatment also results in increased bone resorption. It is still unknown whether osteoclasts express functional GHRs, but recent in vitro studies indicate that GH regulates osteoclast formation in bone marrow cultures. Possible modulations of the GH/IGF axis by glucocorticoids and estrogens are also included in Fig. 9. GH deficiency results in a decreased bone mass in both man and experimental animals. Long-term treatment (> 18 months) of GHD patients with GH results in an increased bone mass. GH treatment also increases bone mass and the total mechanical strength of bones in rats with a normal GH secretion. Recent clinical studies demonstrate that GH treatment of patients with normal GH secretion increases biochemical markers for both bone formation and bone resorption. Because of the short duration of GH treatment in man with normal GH secretion, the effect on bone mass is still inconclusive. Interestingly, GH treatment to GHD adults initially results in increased bone resorption with an increased number of bone-remodeling units and more newly produced unmineralized bone, resulting in an apparent low or unchanged bone mass. However, GH treatment for more than 18 months gives increased bone formation and bone mineralization of newly produced bone and a concomitant increase in bone mass as determined with DEXA. Thus, the action of GH on bone metabolism in GHD adults is 2-fold: it stimulates both bone resorption and bone formation. We therefore propose "the biphasic model" of GH action in bone remodeling (Fig. 10). According to this model, GH initially increases bone resorption with a concomitant bone loss that is followed by a phase of increased bone formation. After the moment when bone formation is stimulated more than bone resorption (transition point), bone mass is increased. However, a net gain of bone mass caused by GH may take some time as the initial decrease in bone mass must first be replaced (Fig. 10). When all clinical studies of GH treatment of GHD adults are taken into account, it appears that the "transition point" occurs after approximately 6 months and that a net increase of bone mass will be seen after 12-18 months of GH treatment. It should be emphasized that the biphasic model of GH action in bone remodeling is based on findings in GHD adults. It remains to be clarified whether or not it is valid for subjects with normal GH secretion. A treatment intended to increase the effects of GH/IGF-I axis on bone metabolism might include: 1) GH, 2) IGF, 3) other hormones/factors increasing the local IGF-I production in bone, and 4) GH-releasing factors. Other hormones/growth factors increasing local IGF may be important but are not discussed in this article. IGF-I has been shown to increase bone mass in animal models and biochemical markers in humans. However, no effect on bone mass has yet been presented in humans. Because the financial cost for GH treatment is high it has been suggested that GH-releasing factors might be used to stimulate the GH/IGF-I axis. The advantage of GH-releasing factors over GH is that some of them can be administered orally and that they may induce a more physiological GH secretion. (ABSTRACT TRUNCATED)
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| 4. |
- Svensson, Johan, 1964, et al.
(författare)
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Effects of growth hormone and its secretagogues on bone.
- 2001
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Ingår i: Endocrine. - 0969-711X. ; 14:1, s. 63-6
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Tidskriftsartikel (refereegranskat)abstract
- The growth hormone (GH)/insulin-like growth factor-1 axis is not only of importance for linear body growth during childhood, but it is also one of the major determinants of adult bone mass. Studies show that GH treatment increases bone mass in rodents as well as in adult GH-deficient humans, but the effect of GH treatment on bone mass in healthy humans has so far not been impressive. Recently, a new class of GH secretagogues (GHSs) has been developed. In humans, GHS treatment affects biochemical markers of bone turnover and increases growth velocity in selected short children with or without GH deficiency. In rodents, GHS treatment increase bone mineral content, but it has not yet been shown that GHS treatment can affect bone mass in adult humans.
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| 5. |
- Svensson, Johan, 1964, et al.
(författare)
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The GH secretagogues ipamorelin and GH-releasing peptide-6 increase bone mineral content in adult female rats.
- 2000
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Ingår i: The Journal of endocrinology. - : Bioscientifica. - 0022-0795 .- 1479-6805. ; 165:3, s. 569-77
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Tidskriftsartikel (refereegranskat)abstract
- 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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| 6. |
- Svensson, Johan, 1964, et al.
(författare)
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Treatment with the oral growth hormone secretagogue MK-677 increases markers of bone formation and bone resorption in obese young males.
- 1998
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Ingår i: Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research. - 0884-0431. ; 13:7, s. 1158-66
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Tidskriftsartikel (refereegranskat)abstract
- The effect of 2 months of treatment with the oral growth hormone (GH) secretagogue MK-677 on markers of bone metabolism was determined in healthy obese male subjects. This was a randomized, double-blind, parallel, placebo-controlled study. Twenty-four healthy obese males, 19-49 years of age, with body mass index > 30 kg/m2 were treated with MK-677 (25 mg/day; n = 12) or placebo (n = 12) for 8 weeks. MK-677 increased markers of bone formation; a 23% increase in the carboxy-terminal propeptide of type I procollagen levels and a 28% increase in procollagen III peptide levels were seen with as little as 2 weeks of MK-677 treatment (p < 0.01 and p = 0.001 vs. placebo, respectively) while a 15% increase in serum levels of osteocalcin was not detected until 8 weeks of treatment (p < 0.01 vs. placebo). Markers of bone resorption were induced within 2 weeks of treatment with MK-677; serum levels of the carboxy-terminal cross-linked telopeptide of type I collagen were increased 26% at 8 weeks (p = 0.001 vs. placebo), and urine hydroxyproline/creatinine and calcium/creatinine ratios at 8 weeks were increased by 23% (p < 0.05 vs. placebo) and 46% (p < 0.05 vs placebo), respectively, MK-677 increased serum insulin-like growth factor binding protein-5 (IGFBP-5) by 43-44% after 2-8 weeks of treatment (p < 0.01 vs. placebo). Serum IGFBP-4 was increased by 25% after 2 weeks of treatment (p < 0.001 vs. placebo) but no significant change from baseline was observed after 8 weeks of treatment. Plasma interleukin-6 was not significantly changed by active treatment. In conclusion, short-term treatment of healthy obese male volunteers with the GH secretagogue MK-677 increases markers of both bone resorption and formation. Large increases in serum levels of IGF-1 and IGFBP-5 and a transient increase in serum IGFBP-4 were found. Future long-term studies are needed to investigate if prolonged treatment with MK-677 increases bone mass.
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