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Endocrine Care: Mim Ari, Vladimir K. Bakalov, Suvimol Hill, and Carolyn A. Bondy The Effects of Growth Hormone Treatment on Bone Mineral Density and Body Composition in Girls with Turner Syndrome J Clin Endocrinol Metab 2006; 91: 4302-4305 [Abstract] [Full text] [PDF]

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Growth hormone effects on bone density and body composition in Turner syndrome

Carolyn A Bondy, Vladimir Bakalov   (19 December 2006)

E-Letter to the Editor: Effects of Growth Hormone on Bone and Body Composition in Turner Syndrome

Wolfgang Högler, Christopher T. Cowell, Institute of Endocrinology and Diabetes, The Children's Hospital at Westmead, Sydney, Australia   (12 December 2006)

Growth hormone effects on bone density and body composition in Turner syndrome 19 December 2006
Carolyn A Bondy NICHD, NIH, Vladimir Bakalov Send letter to journal: Re: Growth hormone effects on bone density and body composition in Turner syndrome bondyc{at}mail.nih.gov Carolyn A Bondy, et al.	Drs. Hogler and Cowell were concerned that our paper, Effects of Growth Hormone on Bone and Body Composition in Turner Syndrome (1) failed to cite theirs (2), which they state is “the largest published study to date, which reports both cross-sectional and two-year longitudinal effects of GH therapy.” We did not do so because their study principally investigated the effects of estrogen on bone in girls with Turner syndrome. It was not designed to evaluate GH, which was not mentioned in the title, abstract, introduction, tables or figures. The sole cross-sectional observations on GH effects in this paper were that 42 GH-treated subjects tended to be taller. No differences were found in total body or regional DXA measurements apart from a lower total body fat in those with GH therapy. The GH-treated and untreated groups were not further characterized as to exposure to GH, age or pubertal status. Our study included 39 girls on GH for at least one year with average duration of treatment of 4 years vs. 28 girls who had never received GH. Effective GH treatment is evident in that the treated group was significantly taller (Table 1). Our two groups of TS girls were very similar in average age, age range and distribution, and estrogen exposure [Table 1; moreover, bone age was used as a covariate (Table 2)]. Thus, direct comparison of actual body composition and bone density data is entirely appropriate. We were able to isolate GH effects from pubertal effects by conducting all the comparisons and analyses in groups of prepubertal girls (Table 4). Moreover, correction of BMD for body surface area is an accepted method to accommodate size differences (3-5). Hogler and Cowell apparently assumed that we referred to GH deficient children in the first sentence of the discussion, where they state we conveyed a “common misconception” and “mistaken belief”. We were in fact referring to osteopenic adults with GH deficiency reported to increase BMD when treated with GH (without increasing bone size), in studies reviewed in the cited reference. References 1. Ari M, Bakalov VK, Hill S, Bondy CA 2006 The Effects of Growth Hormone Treatment on Bone Mineral Density and Body Composition in Girls with Turner Syndrome. J Clin Endocrinol Metab 91:4302-4305 2. Hogler W, Briody J, Moore B, Garnett S, Lu PW, Cowell CT 2004 Importance of Estrogen on Bone Health in Turner Syndrome: A Cross-Sectional and Longitudinal Study Using Dual-Energy X-Ray Absorptiometry. J Clin Endocrinol Metab 89:193-199 3. Pors Nielsen S, Kolthoff N, Barenholdt O, Kristensen B, Abrahamsen B, Hermann AP, Brot C 1998 Diagnosis of osteoporosis by planar bone densitometry: can body size be disregarded? Br J Radiol 71:934-943 4. Bakalov V, Chen M, Baron J, Hanton L, Reynolds J, Stratakis C, Axelrod L, Bondy C 2003 Bone mineral density and fractures in Turner syndrome. Am J Med 115:257-262 5. Bachrach LK, Neely EK 2003 Pitfalls in the hunt for osteoporosis. Am J Med 115:322-323
E-Letter to the Editor: Effects of Growth Hormone on Bone and Body Composition in Turner Syndrome 12 December 2006
Wolfgang Högler, Pediatric Endocrinologist Department of Pediatrics, Medical University Innsbruck, Innsbruck, Austria, Christopher T. Cowell, Institute of Endocrinology and Diabetes, The Children's Hospital at Westmead, Sydney, Australia Send letter to journal: Re: E-Letter to the Editor: Effects of Growth Hormone on Bone and Body Composition in Turner Syndrome wolfgang.hoegler{at}i-med.ac.at Wolfgang Högler, et al.	Ari et al (1) reported on effects of growth hormone (GH) on bone and body composition, as assessed by phalangeal radiography and dual energy x-ray absorptiometry (DXA), in a cross-sectional study of girls with Turner syndrome (TS). The authors claim there is little previous similar information. However, in their literature search, they must have missed the largest published study to date (2), which reports both cross-sectional and two-year longitudinal effects of GH therapy. The cross-sectional results in this study showed no difference between GH-treated (n = 42) and untreated patients (n = 41) in size-corrected bone parameters assessed by DXA. Similar to Ari et al.’s study, the only difference was a tendency for the GH-treated group to be taller (+0.39 SDs, P = 0.085) and lower in percentage body fat (22.8 vs. 30.7%, P = 0.004). After two years of GH therapy, no change in volumetric BMD (g/cm3) at the lumbar spine or femoral neck, and no positive effect on size-corrected total body bone mass could be observed. Other issues related to analysis of DXA results need to be clarified. Their report (1) would have benefited from the use of SD-Scores for bone variables, as the study population spans a large age range and normative data are available for both techniques used. In addition, there is a tremendous effect of puberty (or estrogen supplementation) on bone (2) in TS. This effect obscures the results of the mixed prepubertal/pubertal study population in the study. A comparison of the prepubertal and pubertal subjects would be advisable. The GH effects that the authors report on body composition have previously been demonstrated in a number of studies in TS girls (2-5), idiopathic short stature (ISS) and growth hormone deficiency (GHD) (6). In our own studies, the two-year changes during GH treatment in body fat percentage were -2.37, -0.27 and -5.94% in TS (n = 17), ISS (n = 42) and GHD (n = 13), respectively. The respective SD changes in lean mass were +0.58, +0.46, +0.87 SD. Again, the changes are different if broken down into prepubertal and pubertal subjects. The authors quote the common misconception that bone mineral density in GH-deficient individuals is reduced and restored with GH repletion. This mistaken belief arose at a time when the effect of body size on DXA variables was unappreciated. Short individuals like GHD patients have low DXA SD-scores simply as a result of short stature. A number of size- adjustments have been proposed to overcome this limitation. More recent studies clearly show that bone mass and density are not reduced in children with GHD or ISS once appropriate size-corrections are made (6) or when using the more accurate 3-dimensional pQCT device (7). There are GH-related changes in bone geometry, but not density. Unfortunately, there is no consensus on which size-adjustments should be used for DXA variables in children. However, correction of BMD for body surface area, as used by the authors has limitations. First, BMD (g/cm2) already represents a size-corrected variable: the three- dimensional bone mass (BMC, g) corrected by the two-dimensional bone area (cm2). This means that only one dimension (e.g., height or depth, cm) is missing in the correction. Additional size correction by an additional area (body surface area, m2) appears inappropriate. Second, body surface area may not be a suitable variable in the frequently overweight (2), short Turner syndrome females. Despite all of these limitations, we agree with the authors that GH has little effect on cortical or trabecular bone mass, as assessed by DXA. References 1. Ari M, Bakalov VK, Hill S, Bondy CA. 2006. The effects of growth hormone treatment on bone mineral density and body composition in girls with turner syndrome. J Clin Endocrinol Metab 91:4302-4305 2. Högler W, Briody J, Moore B, Garnett S, Lu PW, Cowell CT. 2004. Importance of Estrogen on Bone Health in Turner syndrome: A Cross-sectional and Longitudinal Study using Dual-Energy X-Ray Absorptiometry. J Clin Endocrinol Metab 89:193-199 3. Shaw NJ, Rehan VK, Husain S, Marshall T, Smith CS. 1997. Bone mineral density in Turner's syndrome--a longitudinal study. Clin Endocrinol (Oxf) 47:367-370 4. Leger J, Carel C, Legrand I, Paulsen A, Hassan M, Czernichow P. 1994. Magnetic resonance imaging evaluation of adipose tissue and muscle tissue mass in children with growth hormone (GH) deficiency, Turner's syndrome, and intrauterine growth retardation during the first year of treatment with GH. J Clin Endocrinol Metab 78:904-909 5. Gravholt CH, Naeraa RW, Brixen K, Kastrup KW, Mosekilde L, Jorgensen JO, Christiansen JS. 2002. Short-term growth hormone treatment in girls with Turner syndrome decreases fat mass and insulin sensitivity: a randomized, double-blind, placebo-controlled, crossover study. Pediatrics 110:889-896 6. Högler W, Briody J, Moore B, Lu PW, Cowell CT. 2005. Effect of growth hormone therapy and puberty on bone and body composition in children with idiopathic short stature and growth hormone deficiency. Bone 37:642-650 7. Schweizer R, Martin DD, Schwarze CP, Binder G, Georgiadou A, Ihle J, Ranke MB. 2003. Cortical Bone Density Is Normal in Prepubertal Children with Growth Hormone (GH) Deficiency, but Initially Decreases during GH Replacement due to Early Bone Remodeling. J Clin Endocrinol Metab 88:5266-5272