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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. |
- Johannsson, Gudmundur, 1960, et al.
(författare)
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Low dose dehydroepiandrosterone affects behavior in hypopituitary androgen-deficient women: a placebo-controlled trial.
- 2002
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Ingår i: The Journal of clinical endocrinology and metabolism. - : The Endocrine Society. - 0021-972X .- 1945-7197. ; 87:5, s. 2046-52
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Tidskriftsartikel (refereegranskat)abstract
- Thirty-eight women, aged 25-65 yr, with androgen deficiency due to hypopituitarism were treated with oral dehydroepiandrosterone (DHEA; 30 mg/d if <45 yr of age and 20 mg if > or =45 yr of age) for 6 months in a randomized, placebo-controlled, double blind study, followed by a 6-month open treatment period. The administration of DHEA raised the serum levels of DHEAS to normal age-related reference ranges and increased androstenedione and T to subnormal levels. Androgen effects on skin and/or pubic and/or axillary hair were observed in 84% (32 of 38) of the women after all received 6 months of DHEA treatment. No such effects were observed after the placebo treatment. These effects after 6 months were correlated with the serum levels of DHEAS (r = 0.37; P = 0.03), androstenedione (r = 0.42; P = 0.01), and T (r = 0.37; P = 0.03). The percentages of partners who reported improved alertness, stamina, and initiative by their spouses were 70%, 64%, and 55%, respectively, in the DHEA group and 11%, 6%, and 11%, respectively, in the placebo group (P < 0.05). According to the partners, sexual relations tended to improve compared with placebo (P = 0.06). After 6 months of treatment, increased sexual interest or activity was reported by 50% of the women taking 30 mg DHEA, by none taking 20 mg DHEA, and by two women taking placebo (P = NS). Compared with levels after placebo administration, high density lipoprotein cholesterol and apolipoprotein A-1 levels decreased after DHEA. Serum concentrations of IGF-I, serum markers of bone metabolism, and bone density did not change. In conclusion, oral administration of a low dose of DHEA to adult hypopituitary women induced androgen effects on skin and axillary and pubic hair as well as changes in behavior, with only minor effects on metabolism.
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| 4. |
- Landin-Wilhelmsen, Kerstin, 1952, et al.
(författare)
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Calcaneal ultrasound measurements are determined by age and physical activity. Studies in two Swedish random population samples.
- 2000
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Ingår i: Journal of internal medicine. - 0954-6820. ; 247:2, s. 269-78
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Tidskriftsartikel (refereegranskat)abstract
- AIM: To present reference values and correlations with body composition, blood variables and lifestyle factors. SUBJECTS: Two random population samples from Göteborg, Sweden, one comprising 184 men and 455 women aged 25-64 years (MONICA) and the other 860 women aged 55-82 years (BEDA) were studied. METHODS: Calcaneal ultrasound measurement (LUNAR Achilles) and bioimpedance were measured. Smoking habits, coffee consumption, physical activity, psychological stress, education and marital status, as well as blood lipids, blood pressure, and fractures were studied. RESULTS: Broadband ultrasound attenuation and stiffness were higher in men than in women (P < 0. 001), but speed of sound did not differ between sexes. Speed of sound, broadband ultrasound attenuation and stiffness decreased with age (P < 0.001). In both sexes speed of sound, broadband ultrasound attenuation and stiffness correlated positively to body size variables, and negatively with smoking in women after adjustment for age. Speed of sound, broadband ultrasound attenuation and stiffness were positively related to physical activity in both sexes, and these relationships were the only ones that remained in multivariate analyses in addition to age (negative). Osteoporotic fractures increased with age. Speed of sound, broadband ultrasound attenuation and stiffness were lower amongst women with osteoporotic fractures. CONCLUSION: Speed of sound, broadband ultrasound attenuation and stiffness decreased with age and increased with physical activity, but body weight and height were not correlated in multivariate analyses. Osteoporotic fractures increased with age and were associated with lower calcaneal ultrasound values.
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| 5. |
- Landin-Wilhelmsen, Kerstin, 1952, et al.
(författare)
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Growth hormone increases bone mineral content in postmenopausal osteoporosis: a randomized placebo-controlled trial.
- 2003
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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. ; 18:3, s. 393-405
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Tidskriftsartikel (refereegranskat)abstract
- Eighty osteoporotic, postmenopausal women, 50-70 years of age, with ongoing estrogen therapy (HRT), were randomized to recombinant human growth hormone (GH), 1.0 U or 2.5 U/day, subcutaneous, versus placebo. This study was double-blinded and lasted for 18 months. The placebo group then stopped the injections, but both GH groups continued for a total of 3 years with GH and followed for 5 years. Calcium (750 mg) and vitamin D (400 U) were given to all patients. Bone mineral density and bone mineral content were measured with DXA. At 18 months, when the double-blind phase was terminated, total body bone mineral content was highest in the GH 2.5 U group (p = 0.04 vs. placebo). At 3 years, when GH was discontinued, total body and femoral neck bone mineral content had increased in both GH-treated groups (NS between groups). At 4-year follow-up, total body and lumbar spine bone mineral content increased 5% and 14%, respectively, for GH 2.5 U (p = 0.01 and p = 0.0006 vs. placebo). Femoral neck bone mineral density increased 5% and bone mineral content 13% for GH 2.5 U (p = 0.01 vs. GH 1.0 U). At 5-year follow-up, no differences in bone mineral density or bone mineral content were seen between groups. Bone markers showed increased turnover. Three fractures occurred in the GH 1.0 U group. No subjects dropped out. Side effects were rare. In conclusion, bone mineral content increased to 14% with GH treatment on top of HRT and calcium/vitamin D in postmenopausal women with osteoporosis. There seems to be a delayed, extended, and dose-dependent effect of GH on bone. Thus, GH could be used as an anabolic agent in osteoporosis.
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| 6. |
- 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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| 7. |
- Svensson, Johan, 1964, et al.
(författare)
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Effects of seven years of GH-replacement therapy on insulin sensitivity in GH-deficient adults.
- 2002
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Ingår i: The Journal of clinical endocrinology and metabolism. - 0021-972X. ; 87:5, s. 2121-7
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Tidskriftsartikel (refereegranskat)abstract
- The few trials in GH-deficient (GHD) adults that have investigated the long-term effects of GH-replacement therapy on insulin sensitivity have shown conflicting results. In this study, insulin sensitivity was determined using the hyperinsulinemic, euglycemic clamp technique in 11 GHD adults at baseline and after 6 months, 1 yr, 2 yr, and 7 yr of GH-replacement therapy. Furthermore, insulin sensitivity in the GHD patients was compared with that in 11 matched control subjects at baseline and with that in 11 other matched controls at study end. The mean initial GH dose was 1.10 mg/d. The dose was gradually lowered; and after 7 yr, the mean dose was 0.61 mg/d. A sustained reduction in body fat and a sustained increase in fat-free mass were observed. Serum high-density lipoprotein-cholesterol (HDL-C) increased, and serum low-density lipoprotein-cholesterol (LDL-C) decreased, after 7 yr of treatment. Fasting blood glucose was transiently increased during the first year of GH replacement. The glucose infusion rate/body weight (GIR/BW), as measured using the hyperinsulinemic, euglycemic clamp technique, was unaltered during GH-replacement therapy. The comparisons with the control subjects revealed that GIR/BW in the GHD patients was 45% of that in the control subjects at baseline; whereas, at study end, the GIR/BW was 71% of that in the control subjects (P = 0.06 vs. baseline). This could suggest that GH-replacement therapy may prevent the age-related decline in insulin sensitivity in GHD patients.
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| 8. |
- Svensson, Johan, 1964, et al.
(författare)
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Malignant disease and cardiovascular morbidity in hypopituitary adults with or without growth hormone replacement therapy.
- 2004
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Ingår i: The Journal of clinical endocrinology and metabolism. - : The Endocrine Society. - 0021-972X .- 1945-7197. ; 89:7, s. 3306-12
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Tidskriftsartikel (refereegranskat)abstract
- A retrospective comparison was performed between 1411 hypopituitary adults without GH replacement [mean age, 56.9 (sd 18.6) yr] and the normal population in terms of fatal and nonfatal morbidity. A similar prospective comparison was then made in 289 hypopituitary patients on long-term GH replacement [mean age, 47.6 (sd 14.8) yr; mean duration of GH treatment, 60 months].In the 1411 hypopituitary patients without GH replacement, overall mortality (P < 0.001), and the rates of myocardial infarctions (P < 0.01), cerebrovascular events (P < 0.001), and malignancies (P < 0.001) were increased compared with the normal population. Colorectal cancer was the most common malignancy in this cohort (P < 0.001 vs. the background population). In the 289 hypopituitary patients on GH replacement, overall mortality and the rate of malignancies were similar to the normal population. In the hypopituitary adults on GH therapy, the rate of myocardial infarctions was lower than that in the background population (P < 0.05), and there was a tendency toward an increased rate of cerebrovascular events.In conclusion, overall mortality and the rate of myocardial infarctions were increased in hypopituitary patients without GH replacement. An increased rate of malignancies was observed in the hypopituitary adults without GH therapy, with a predominance of colorectal cancer. GH replacement appeared to provide protection from myocardial infarctions. The rate of cerebrovascular events tended to be increased also in hypopituitary adults on GH therapy.
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| 9. |
- 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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| 10. |
- Svensson, Johan, 1964, et al.
(författare)
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Three-years of growth hormone (GH) replacement therapy in GH-deficient adults: effects on quality of life, patient-reported outcomes and healthcare consumption.
- 2004
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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. ; 14:3, s. 207-15
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE: The objective was to investigate the effects of 3 years of growth hormone (GH) replacement therapy in GH deficient (GHD) patients in Sweden. DESIGN AND PATIENTS: An open label study in 237 adults with GHD (116 men and 121 women), consecutively enrolled in KIMS (Pfizer's international metabolic database) in Sweden. MEASUREMENTS: QoL and healthcare consumption were determined using questionnaires [QoL-assessment of GHD in Adults (QoL-AGHDA), the psychological general well-being (PGWB) index and the patient life situation form (PLSF)]. RESULTS: The mean starting dose of GH was 0.13 mg/day and the mean maintenance dose was 0.37 mg/day. The mean insulin-like growth factor I (IGF-I) SD score increased from -1.92 at baseline to 0.38 after 3 years. There was a sustained increase in QoL as measured by the QoL-AGHDA and PGWB questionnaires. The number of doctor visits and the number of days in hospital were reduced after 3 years of GH replacement. The number of days of sickleave decreased during the first 2 years of treatment, but returned towards baseline values after 3 years. Leisure-time physical activity and satisfaction with physical activity increased. CONCLUSION: Three years of GH replacement therapy induced a sustained improvement in QoL. Healthcare consumption was reduced, although the reduction in the number of days of sickleave was not statistically significant after 3 years of treatment.
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