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The Effect of Cessation of Growth Hormone (GH) Therapy on Bone Mineral Accretion in GH-Deficient Adolescents at the Completion of Linear Growth

Institute of Endocrinology and Diabetes, The Children’s Hospital at Westmead, Westmead, New South Wales 2145, Australia

Address correspondence to: Christopher T. Cowell, M.D., The Children’s Hospital at Westmead, Pediatric Endocrinologist, Corner Hawkesbury Road and Hainsworth Street, Westmead, 2145 Australia. E-mail: chrisc{at}chw.edu.au.

To the editor:

Drake et al. (1) demonstrate an increase in whole body bone mineral content (BMC) and lumbar spine bone mineral density (BMD) in adolescents with GH deficiency who continued GH for 12 months at the completion of linear growth (GH+ group). Final height was defined as a height velocity less than 2 cm/yr. No significant increases in either BMC or lumbar spine BMD over 12 months were detected in the GH-deficient adolescents who did not receive GH (GH- group). Additionally, no significant differences were found between the groups at 6 and 12 months, possibly because the study was not adequately powered to detect group differences given the heterogeneity of response, especially in the GH- group for BMC.

There are issues with interpretation of this study’s results that would be helped by presenting raw data for BMC and height. Both BMC and lumbar spine BMD are dependent on growth. Thus, to interpret their data, it is imperative to know whether height changed in either group. We have calculated from our normative data (2, 3) the effect of a 1-cm change in height on whole body BMC for average-stature adolescents aged 17–18 yr. This age group corresponds to the mean age of 17 yr in their study. BMC increases approximately 60 gm/cm and 52 gm/cm in males and females, respectively, which is equivalent to a 2.1 and 2.2% increase per centimeter, respectively. Thus, the percentage change found in the study of Drake et al. could be explained by growth, and furthermore, the BMC percentage difference between the two groups after 12 months could be explained by a difference in height gain.

There are two outliers for BMC change in the GH- group, one individual gaining approximately 27% BMC over 12 months and the other losing approximately 25%. Although the latter individual is excluded from some analyses, there is no adequate explanation for such major change in either individual. BMC increases of 25–30% over 12 months do occur during the peak BMC accretion of puberty (4) but are highly improbable at completion of growth. The inclusion of either outlier in their analyses will significantly increase the variability of their summary statistics.

The authors do not comment on the impact of puberty in the two groups. Spontaneous puberty occurred in five of 12 individuals in the GH- group, compared with eight of 12 in the GH+ group. Could the low frequency of spontaneous puberty in the GH- group have attenuated their increase in BMC and lumbar spine BMD?

Received May 23, 2003.

References

1. Drake WM, Carroll PV, Maher KT, Metcalfe KA, Camacho-Hubner C, Shaw NJ, Dunger DB, Cheetham TD, Savage MO, Monson JP 2003 The effect of cessation of growth hormone (GH) therapy on bone mineral accretion in GH-deficient adolescents at the completion of linear growth. J Clin Endocrinol Metab 88:1658–1663[Abstract/Free Full Text]
2. Ogle GD, Allen JR, Humphries IR, Lu PW, Briody JN, Morley K, Howman-Giles R, Cowell CT 1995 Body-composition assessment by dual-energy x-ray absorptiometry in subjects aged 4–26 y. Am J Clin Nutr 61:746–753[Abstract/Free Full Text]
3. Högler W, Briody J, Woodhead H, Chan A, Cowell CT 2003 The importance of lean mass in the interpretation of total body densitometry in children and adolescents. J Pediatr 143:1–8[Medline]
4. Bailey DA, McKay HA, Mirwald RL, Crocker PR, Faulkner RA 1999 A six-year longitudinal study of the relationship of physical activity to bone mineral accrual in growing children: the University of Saskatchewan Bone Mineral Accrual Study. J Bone Miner Res 14:1672–1679[CrossRef][Medline]

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