Growth Hormone (GH) Receptors in Clonal Osteoblast Like Cells Mediate a Mitogenic Response to GH*

Barnard, Ross; Ng, KW; Martin, T. J.; Waters, M. J.

doi:10.1210/endo-128-3-1459

Cited by 137 publications

(65 citation statements)

References 39 publications

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“…Patients were stratified by gender and by total body BMD below or above the median value. Within the GH-treated group, a greater increase in total body BMD was found in the low BMD group (P ¼ 0:02 for percentage changes from baseline and P ¼ 0:03 for actual BMD (g/cm 2 ). No differential response to GH treatment was found between males and females, nor between patients with and without previous hormone overproduction.…”

Section: Bone Mineral Density/bone Mineral Content During Therapymentioning

confidence: 90%

“…In adulthood, clinical and experimental studies have demonstrated an effect of GH and insulin-like growth factor-I (IGF-I) on bone remodelling. Growth hormone stimulates proliferation of osteoblast-like cells from trabecular bone explants (1) or osteoblast-like cell lines (2) whereas in mature osteoblasts GH stimulates markers of differentiation.…”

Section: Introductionmentioning

confidence: 99%

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Bone mineral content and bone metabolism during physiological GH treatment in GH-deficient adults--an 18-month randomised, placebo-controlled, double blinded trial

Sneppen

Hoeck

Kollerup³

et al. 2002

European Journal of Endocrinology

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Objective: To evaluate the effect of physiological adult growth hormone (GH) replacement on bones. Design: Thirty-six prospective severely growth hormone-deficient (GHD) adults (22 females and 14 males) were randomised to either 18 months of GH (0.03 mU/kg/day) or placebo treatment. Methods: Bone mineral density and content (BMD, BMC) and body composition were evaluated by dual energy X-ray absorptiometry at baseline and after 6, 12 and 18 months. Serum concentrations of insulin-like growth factor-I (IGF-I), IGF binding protein 3, osteocalcin, carboxyterminal propeptide of type I collagen, carboxyterminal crosslink telopeptide of type I collagen, amino-terminal propeptide of type III procollagen and urine pyridinolin and deoxypyridinolin were determined. Results: IGF-I levels increased from 63.2 mg/l (^10.1) to 193.6 (^25.8) mg/l (mean (^S.E.)) (P , 0:001 compared with placebo). Markers of bone turnover increased significantly from 142% to 227% of baseline values (all P , 0:001 compared with placebo). Body composition changes were an increase of lean body mass and a decrease of fat mass resulting in a reduction of percentage body fat of 21.8 (^3.8) in the GH-treated group vs an increase of 1.0 (^2.9)) in the placebo-treated group ðP ¼ 0:002Þ: Conclusions: No significant difference in BMD or BMC between the GH and placebo groups was found after 18 months. At several sites the variances of changes from baseline were significantly greater in the GH than in the placebo group, indicating an impact of the treatment. From baseline to 6 months an insignificant reduction of total BMD was seen while an increase of BMD was found from 6 to 18 months in the GH group compared with the placebo group.This placebo-controlled trial confirmed the longer term open studies on the effect on bones in patients with GHD, with an initial overrepresentation of bone resorption followed by an increase in BMD which at 18 months had reached baseline level.

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Section: Bone Mineral Density/bone Mineral Content During Therapymentioning

confidence: 90%

Section: Introductionmentioning

confidence: 99%

Bone mineral content and bone metabolism during physiological GH treatment in GH-deficient adults--an 18-month randomised, placebo-controlled, double blinded trial

Sneppen

Hoeck

Kollerup³

et al. 2002

European Journal of Endocrinology

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“…Aging is associated with decreases in growth hormone secretion and lowered serum levels of IGF-I [39], which are endocrine factors known to be anabolic for bone tissue. In fact, cultured osteoblasts show high affinity receptors and proliferative responses to each [40,41] and it is tempting to speculate that the decreased activity of the growth hormone-IGF-I axis (geriatric hyposomatotropism) might account, at least partially, for the age-related increase in bone fragility. The results of the present study support this concept and suggest that the longterm presence of IGF-I is important for skeletal integrity.…”

Section: Discussionmentioning

confidence: 99%

Factors Associated with Cortical and Trabecular Bone Loss as Quantified by Peripheral Computed Tomography (pQCT) at the Ultradistal Radius in Aging Women

et al. 1997

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Abstract. Peripheral quantitative computed tomography (pQCT) allows the separate determination of cortical and trabecular bone mineral density in the peripheral skeleton. This cross-sectional study was designed to examine the effects of healthy aging on pQCT measurements at the ultradistal radius. In a well-defined sample of 129 community-based women, aged 70-87 years, the differences in cortical and trabecular density over the age range were equivalent to losses of −0.41% and −0.65% per year, respectively. To investigate the mechanism of this agerelated decline, we assessed relationships between both parameters and height, weight, body mass index, dietary calcium intake, grip strength, and serum concentrations of insulin-like growth factor-I (IGF-I), calcidiol (25(OH)D 3 ), calcitriol (1,25(OH) 2 D 3 ), parathyroid hormone (PTH), and sex hormone binding globulin (SHBG). Multiple regression was used to adjust for potential confounders. Age was not significant after controlling for other covariables. Body mass index, grip strength, serum IGF-I, 25(OH)D 3 , and PTH (1-84) were found to be independent predictors of total bone density. Including (total or free) 1,25(OH) 2 D 3 did not improve the model precision. These findings provide evidence that, among other factors, the activity of the growth hormone-IGF-I-axis is of importance for skeletal integrity. Grip strength, serum IGF-I, and PTH (1-84) were discovered to be significantly related to cortical but not to trabecular density, suggesting that different mechanisms may be involved in compact and cancellous bone loss.Key words: Peripheral quantitative computed tomography (pQCT) -Age-related bone loss -Growth hormone -IGF-I.Low bone mass, as estimated by decreased bone mineral density (BMD), is an established predictor of osteoporotic fractures. Although fracture prediction by bone density is partially site-dependent [1], numerous reports have shown that fractures at all skeletal sites are significantly related to low bone mass at the distal forearm [2][3][4][5]. In all of these studies, BMD was assessed with single-photon absorptiometry. Peripheral quantitative computed tomography (pQCT) has been proposed as an adjunct to conventional densitometry [6,7]. BMD determination with pQCT at the site of the distal radius is a method of high precision and low radiation [8]. In addition, pQCT is the only noninvasive assessment of bone mineral to measure a true-dimensional density (as opposed to an areal density by standard methods) and to allow separate determination of cortical and trabecular bone density [9].Studies have indicated that bone loss in elderly women shows no evidence for an age-related leveling off [10][11][12][13]. Even at advanced ages, interventions to preserve or to enhance bone mass may therefore be an effective approach to prevention of fractures. However, the mechanisms leading to age-related bone loss remain poorly defined. Moreover, whether cortical and trabecular bone losses are mediated by differential mechanisms is virtually unknown. In the pres...

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“…We can only speculate about the possible mechanisms for these findings. The influence of GH/IGF-I on bone mineralization is well documented (16)(17)(18)(19) as it is for the influence of sex steroids (20,21). Causes for CDGP are far from clear.…”

Section: Journal Of Endocrinology (1998) 139mentioning

confidence: 99%

Bone mineral status in prepubertal children with constitutional delay of growth and puberty

Moreira-Andres¹,

Cañizo²,

Cruz

et al. 1998

European Journal of Endocrinology

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Objective: We wished to clarify whether the osteopenia reported in adult men with a history of constitutional delay of growth and puberty (CDGP) could be due to the delayed puberty or an independent predisposition to osteoporosis in this condition. Design: Short prepubertal children with CDGP and children with familial short stature (FSS) were matched for height and other auxological variables. The FSS children served as a control group. Methods: We measured spinal (L1-L4) bone mineral content (BMC) and bone mineral density (BMD) by dual energy X-ray absorptiometry (Hologic QDR 1000/w) in 56 children aged 5-11 years. All children had height below the 10th percentile for chronological age (CA), and bone age (BA) less than 10 years, 29 of them with clinical diagnosis of possible CDGP and 27 of them with FSS. The BMD standard deviation scores (SDS) relative to the values for normal height children were obtained. Results: The mean (Ϯ S.D.) spinal BMD was significantly lower in the children with CDGP than in the FSS group (0.534 Ϯ 0.059 vs 0.623 Ϯ 0.060 g/cm 2 , P < 0.001). Both groups had negative mean lumbar BMD SDS, but in the CDGP group it was significantly lower than in the FSS group as well when the SDS was based on the CA (¹1.41 Ϯ 0.61 vs ¹0.38 Ϯ 0.51, P < 0.001) and when it was related to BA (¹0.78 Ϯ 0.64 vs ¹0.17 Ϯ 0.52, P < 0.01). BMC was significantly lower in the CDGP than in the FSS group, when multiple regression analysis was performed by using scanned bone area, body weight and height, sex and BA as independent variables (P ¼ 0.0005). Conclusion:The finding of decreased mineralization in prepubertal children with CDGP before the age of puberty suggests that they may have an inherent predisposition to osteopenia.

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Growth Hormone (GH) Receptors in Clonal Osteoblast Like Cells Mediate a Mitogenic Response to GH*

Cited by 137 publications

References 39 publications

Bone mineral content and bone metabolism during physiological GH treatment in GH-deficient adults--an 18-month randomised, placebo-controlled, double blinded trial

Bone mineral content and bone metabolism during physiological GH treatment in GH-deficient adults--an 18-month randomised, placebo-controlled, double blinded trial

Factors Associated with Cortical and Trabecular Bone Loss as Quantified by Peripheral Computed Tomography (pQCT) at the Ultradistal Radius in Aging Women

Bone mineral status in prepubertal children with constitutional delay of growth and puberty

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