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      Effects of 3-year GH replacement therapy on bone mineral density in younger and elderly adults with adult-onset GH deficiency

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          Abstract

          Objective

          Little is known of the effects of long-term GH replacement on bone mineral content (BMC) and bone mineral density (BMD) in elderly GH-deficient (GHD) adults.

          Design/patients/methods

          In this prospective, single-center, open-label study, the effects of 3-year GH replacement were determined in 45 GHD patients >65 years and in 45 younger control GHD patients with a mean age of 39.5 ( s.e.m. 1.1) years. All patients had adult-onset disease and both groups were comparable in terms of number of anterior pituitary hormonal deficiencies, gender, body mass index, and waist:hip ratio.

          Results

          The mean maintenance dose of GH was 0.24 (0.02) mg/day in the elderly patients and 0.33 (0.02) mg/day in the younger GHD patients ( P<0.01). The 3 years of GH replacement induced a marginal effect on total body BMC and BMD, whereas femur neck and lumbar (L2–L4) spine BMC and BMD increased in both the elderly and the younger patients. The treatment response in femur neck BMC was less marked in the elderly patients ( P<0.05 vs younger group). However, this difference disappeared after correction for the lower dose of GH in the elderly patients using an analysis of covariance. There were no between-group differences in responsiveness in BMC or BMD at other skeletal locations.

          Conclusions

          This study shows that GH replacement increases lumbar (L2–L4) spine and femur neck BMD and BMC in younger as well as elderly GHD patients. This supports the notion that long-term GH replacement is also useful in elderly GHD patients.

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          Most cited references33

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          Effect of alendronate on risk of fracture in women with low bone density but without vertebral fractures: results from the Fracture Intervention Trial.

          Alendronate sodium reduces fracture risk in postmenopausal women who have vertebral fractures, but its effects on fracture risk have not been studied for women without vertebral fractures. To test the hypothesis that 4 years of alendronate would decrease the risk of clinical and vertebral fractures in women who have low bone mineral density (BMD) but no vertebral fractures. Randomized, blinded, placebo-controlled trial. Eleven community-based clinical research centers. Women aged 54 to 81 years with a femoral neck BMD of 0.68 g/cm2 or less (Hologic Inc, Waltham, Mass) but no vertebral fracture; 4432 were randomized to alendronate or placebo and 4272 (96%) completed outcome measurements at the final visit (an average of 4.2 years later). All participants reporting calcium intakes of 1000 mg/d or less received a supplement containing 500 mg of calcium and 250 IU of cholecalciferol. Subjects were randomly assigned to either placebo or 5 mg/d of alendronate sodium for 2 years followed by 10 mg/d for the remainder of the trial. Clinical fractures confirmed by x-ray reports, new vertebral deformities detected by morphometric measurements on radiographs, and BMD measured by dual x-ray absorptiometry. Alendronate increased BMD at all sites studied (P 2.5 SDs below the normal young adult mean; RH, 0.64; 95% CI, 0.50-0.82; treatment-control difference, 6.5%; number needed to treat [NNT], 15), but there was no significant reduction among those with higher BMD (RH, 1.08; 95% CI, 0.87-1.35). Alendronate decreased the risk of radiographic vertebral fractures by 44% overall (relative risk, 0.56; 95% CI, 0.39-0.80; treatment-control difference, 1.7%; NNT, 60). Alendronate did not increase the risk of gastrointestinal or other adverse effects. In women with low BMD but without vertebral fractures, 4 years of alendronate safely increased BMD and decreased the risk of first vertebral deformity. Alendronate significantly reduced the risk of clinical fractures among women with osteoporosis but not among women with higher BMD.
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            Consensus guidelines for the diagnosis and treatment of adults with GH deficiency II: a statement of the GH Research Society in association with the European Society for Pediatric Endocrinology, Lawson Wilkins Society, European Society of Endocrinology, Japan Endocrine Society, and Endocrine Society of Australia.

            Ken Ho (2007)
            The GH Research Society held a Consensus Workshop in Sydney, Australia, 2007 to incorporate the important advances in the management of GH deficiency (GHD) in adults, which have taken place since the inaugural 1997 Consensus Workshop. Two commissioned review papers, previously published Consensus Statements of the Society and key questions were circulated before the Workshop, which comprised a rigorous structure of review with breakout discussion groups. A writing group transcribed the summary group reports for drafting in a plenary forum on the last day. All participants were sent a polished draft for additional comments and gave signed approval to the final revision. Testing for GHD should be extended from hypothalamic-pituitary disease and cranial irradiation to include traumatic brain injury. Testing may indicate isolated GHD; however, idiopathic isolated GHD occurring de novo in the adult is not a recognized entity. The insulin tolerance test, combined administration of GHRH with arginine or growth hormone-releasing peptide, and glucagon are validated GH stimulation tests in the adult. A low IGF-I is a reliable diagnostic indicator of GHD in the presence of hypopituitarism, but a normal IGF-I does not rule out GHD. GH status should be reevaluated in the transition age for continued treatment to complete somatic development. Interaction of GH with other axes may influence thyroid, glucocorticoid, and sex hormone requirements. Response should be assessed clinically by monitoring biochemistry, body composition, and quality of life. There is no evidence that GH replacement increases the risk of tumor recurrence or de novo malignancy.
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              Dual-energy x-ray absorptiometry for total-body and regional bone-mineral and soft-tissue composition.

              Bone mineral density (BMD) and soft-tissue composition of the total body and major subregions were measured with dual-energy x-ray absorptiometry (DEXA). Total body scans were made in 12 young adults (6 male, 6 female) on five occasions at both a medium speed (20 min) and a fast speed (10 min). There were no significant differences in mean results or in precision errors between the two speeds. The precision errors (1 SD) for total body BMD, percent fat in soft tissue (% Fat), fat mass, and lean tissue mass were less than 0.01 g/cm2, 1.4%, 1.0 kg, and 0.8 kg, respectively. These results corresponded to a relative error of 0.8% for total body BMD and 1.5% for lean body mass. Regional BMD and soft-tissue values (arms, legs, trunk) were determined with slightly higher precision errors. Skeletal mineral was 5.8 +/- 0.5% of lean tissue mass (r = 0.96, p less than 0.001). DEXA provides precise composition analysis with a low radiation exposure (less than 0.1 microGy).

                Author and article information

                Journal
                Eur J Endocrinol
                EJE
                European Journal of Endocrinology
                BioScientifica (Bristol )
                0804-4643
                1479-683X
                February 2012
                17 November 2011
                : 166
                : 2
                : 181-189
                Affiliations
                [1]simpleDepartment of Endocrinology simpleResearch Centre for Endocrinology and Metabolism, Gröna Stråket 8, Sahlgrenska University Hospital SE-413 45, GöteborgSweden
                Author notes
                (Correspondence should be addressed to M Elbornsson; Email: mariam.elbornsson@ 123456medic.gu.se )
                Article
                EJE110886
                10.1530/EJE-11-0886
                3261573
                22106341
                e1b8185b-3f67-42c0-8992-9424fac54a2b
                © 2012 European Society of Endocrinology

                This is an Open Access article distributed under the terms of the European Journal of Endocrinology's Re-use Licence which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.

                History
                : 12 October 2011
                : 21 November 2011
                Funding
                Funded by: Swedish Research Council
                Categories
                Clinical Study

                Endocrinology & Diabetes
                Endocrinology & Diabetes

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