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      Growth hormone effects on cortical bone dimensions in young adults with childhood-onset growth hormone deficiency

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          Abstract

          Summary

          Growth hormone (GH) treatment in young adults with childhood-onset GH deficiency has beneficial effects on bone mass. The present study shows that cortical bone dimensions also benefit from GH treatment, with endosteal expansion and increased cortical thickness leading to improved bone strength.

          Introduction

          In young adults with childhood-onset growth hormone deficiency (CO GHD), GH treatment after final height is reached has been shown to have beneficial effects on spine and hip bone mineral density. The objective of the study was to evaluate the influence of GH on cortical bone dimensions.

          Methods

          Patients ( n = 160; mean age, 21.2 years; 63% males) with CO GHD were randomised 2:1 to GH or no treatment for 24 months. Cortical bone dimensions were evaluated by digital x-ray radiogrammetry of the metacarpal bones every 6 months.

          Results

          After 24 months, cortical thickness was increased compared with the controls (6.43%, CI 3.34 to 9.61%; p = 0.0001) and metacarpal index (MCI) (6.14%, CI 3.95 to 8.38%; p < 0.0001), while the endosteal diameter decreased (−4.64%, CI −7.15 to −2.05; p < 0.001). Total bone width did not change significantly (0.68%, CI −1.17 to 2.57%; not significant (NS)). A gender effect was seen on bone width ( p < 0.0001), endosteal diameter ( p < 0.01) and cortical thickness ( p < 0.01), but not with MCI (NS).

          Conclusions

          Cortical bone reacts promptly to reinstitution of GH beyond the attainment of final height by increasing the cortical thickness through endosteal bone growth. This leads to a higher peak bone mass and may reduce the risk of cortical bone fragility later in life.

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          Most cited references30

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          Pathogenesis of bone fragility in women and men.

          Ego Seeman (2002)
          There is no one cause of bone fragility; genetic and environmental factors play a part in development of smaller bones, fewer or thinner trabeculae, and thin cortices, all of which result in low peak bone density. Material and structural strength is maintained in early adulthood by remodelling; the focal replacement of old with new bone. However, as age advances less new bone is formed than resorbed in each site remodelled, producing bone loss and structural damage. In women, menopause-related oestrogen deficiency increases remodelling, and at each remodelled site more bone is resorbed and less is formed, accelerating bone loss and causing trabecular thinning and disconnection, cortical thinning and porosity. There is no equivalent midlife event in men, though reduced bone formation and subsequent trabecular and cortical thinning do result in bone loss. Hypogonadism contributes to bone loss in 20-30% of elderly men, and in both sexes hyperparathyroidism secondary to calcium malabsorption increases remodelling, worsening the cortical thinning and porosity and predisposing to hip fractures. Concurrent bone formation on the outer (periosteal) cortical bone surface during ageing partly compensates for bone loss and is greater in men than in women, so internal bone loss is better offset in men. More women than men sustain fractures because their smaller skeleton incurs greater architectural damage and adapts less effectively by periosteal bone formation. The structural basis of bone fragility is determined before birth, takes root during growth, and gains full expression during ageing in both sexes.
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            Consensus Guidelines for the Diagnosis and Treatment of Adults with Growth Hormone Deficiency: Summary Statement of the Growth Hormone Research Society Workshop on Adult Growth Hormone Deficiency

            ; (1998)
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              Growth hormone (GH) dose-response in young adults with childhood-onset GH deficiency: a two-year, multicenter, multiple-dose, placebo-controlled study.

              GH replacement therapy has been shown to improve abnormalities in body composition, bone mineral density (BMD), lipid profile, and other changes resulting from GH deficiency (GHD) in adults. There is, however, need to determine appropriate dosing in young adults who were treated for GHD as children, to bridge the interval between childhood (in which relatively high doses are used) and older adulthood (in which only lower doses are tolerated). This multicenter, randomized, double-blind, placebo-controlled study compares the safety and efficacy of two doses of GH (25 and 12.5 microg/kg.d) with placebo, maintained for 2 yr, in adults with GHD who were treated as children and were off GH for at least 1 yr (mean, 5.6 yr). The 64 treated subjects were less than 35 yr of age (mean, 23.8 yr) and had maximum serum GH responses, on retesting less than 5 microg/liter (mean, 0.7 micro g/liter). At baseline, 22% had spine BMD below -2 SD, 59% were overweight or obese, and 45% had serum total cholesterol more than 200 mg/dl. A significant dose response was seen for percent increase in spine BMD at 24 months (mean of 1.3%, 3.3%, and 5.2% in the placebo, 12.5-, and 25- microg/kg.d groups, respectively, P = 0.018). Both GH-treated groups had similar changes in body composition at 6 months (decreased fat mass, increased lean mass); however, some gains were subsequently lost in the lower dose group. A significant decrease in low-density lipoprotein cholesterol was seen only in the higher GH dose group. Significant changes were not observed in quality of life and echocardiographic measures. The groups were similar with regard to adverse events and laboratory measurements, except for a higher incidence of edema in the GH-treated groups. We conclude that this dose-response study confirms the benefits of GH-replacement therapy in GHD adults and indicates that, to achieve treatment goals in younger adults, higher doses may be needed than those generally used in older adults.
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                Author and article information

                Contributors
                +45-3862-2290 , +45-3862-3640 , hyld@dadlnet.dk
                Journal
                Osteoporos Int
                Osteoporos Int
                Osteoporosis International
                Springer-Verlag (London )
                0937-941X
                1433-2965
                29 November 2011
                29 November 2011
                August 2012
                : 23
                : 8
                : 2219-2226
                Affiliations
                [1 ]Department of Endocrinology (541), Hvidovre University Hospital, DK-2650 Hvidovre, Denmark
                [2 ]Department of Endocrinology and Diabetes, University College London Hospitals, London, UK
                [3 ]2nd Department of Medicine, Semmelweis University, Budapest, Hungary
                [4 ]Children’s Hospital, University of Leipzig, Leipzig, Germany
                [5 ]Service d’Endocrinologie et des Maladies de la Reproduction, and Centre de Référence des Maladies Endocriniennes Rares de la Croissance, Assistance-Publique Hôpitaux de Paris, Hôpital de Bicêtre, University Paris-Sud, Le Kremlin-Bicêtre, France
                [6 ]Department of Endocrinology and Diabetes, Royal Children’s Hospital, Parkville, VIC Australia
                [7 ]GHT Medical Affairs, Global Marketing, Novo Nordisk, Bagsvaerd, Denmark
                Article
                1854
                10.1007/s00198-011-1854-0
                3406313
                22124576
                494630a3-7e3c-4fb1-9490-c8c8a77b8904
                © The Author(s) 2011
                History
                : 11 August 2011
                : 26 October 2011
                Categories
                Original Article
                Custom metadata
                © International Osteoporosis Foundation and National Osteoporosis Foundation 2012

                Orthopedics
                growth hormone treatment,growth hormone deficiency,metacarpal index,cortical bone,bone strength

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