Department of Endocrinology, St. Bartholomews Hospital (W.M.D., P.V.C., K.T.M., K.A.M., C.C.-H., M.O.S., J.P.M.), London, EC1A 7BE United Kingdom; Department of Pediatric Endocrinology, Birmingham Childrens Hospital (N.J.S.), Birmingham, B4 6NH United Kingdom; Department of Pediatric Endocrinology, John Radcliffe Hospital (D.B.D.), Oxford, OX3 9DU United Kingdom; and Department of Pediatric Endocrinology, Royal Victoria Infirmary (T.D.C.), Newcastle, NE1 4LP United Kingdom
Address correspondence to: W. M. Drake, M.D., St. Bartholomews Hospital, Department of Endocrinology, West Smithfield, London, EC1A 7BE, United Kingdom. E-mail: w.m.drake{at}qmul.ac.uk.
To the editor:
Cowell and Högler, in response to our recent report of the consequences of cessation of GH therapy on bone mineral accretion at the completion of linear growth in adolescent GH-deficient patients (1), highlight a number of important points in relation to the assessment of bone mass in this patient group. They are entirely correct to point out that growth is an important determinant of bone mineral content (BMC) and spinal bone mineral density (BMD); and that areal BMD will increase simply by virtue of an increased vertebral diameter, irrespective of the volumetric BMD. In retrospect, we should have included the height data in the manuscript, but we can now report that there was no difference in height between the start and conclusion of the 12-month study in either group (162.1 ± 11.6 cm at baseline; 162.4 ± 11.6 cm at 12 months in the GH continuers vs. 162.4 ± 10.8 cm at baseline; 162.3 ± 11.0 cm at 12 months in the GH discontinuers, all SD).
They go on to raise the issue of the possible influence of discrepant stages of pubertal development on the accretion of bone mass. Again, the point is well taken, but we would refer them back to Patients and Methods in which we state that there was no difference in the length of time between the onset of puberty, either spontaneous or induced, to inclusion in the study. Clearly, in a study of this nature with a range of etiologies of GH deficiency, the timing of onset of puberty will partly depend on the presence of coexistent gonadotropin deficiency. Hence, to highlight the different numbers of patients in each group with spontaneous puberty is to ignore the message that the duration of exposure to sex steroids was the same in each group.
With respect to the statistical implications of the inclusion/exclusion of outliers, we have no explanation for the unexpected, dramatic changes in BMC observed in two of the patients who discontinued GH. On the advice of an expert statistician, the patient with a large decline in BMC was excluded from part of the analyses to avoid the possibility that his/her inclusion might lead to an exaggeration of the effects of continuation of GH on bone mineral accretion and bias our hypothesis. On a general note, we elected to display the totality of the BMC data (see Fig. 2), partly for transparency, but also to illustrate the point that group data may hide the clinically important message that some patients are closer to peak bone mass than others at the time of completion of linear growth. Hence, although median BMC increased by 6.1% in those patients who continued GH, in reality there exist patients for whom continuation of GH beyond the completion of growth may have no benefit in terms of attainment of peak bone mass (see Fig. 2). It is our expectation that this preliminary report will provide the catalyst for future, larger studies that examine this issue, together with the important question of whether a "sabbatical" from GH therapy once linear growth is complete, followed by recommencement at a later stage, has any adverse consequences for the attainment of peak bone mass.
Last, we would strongly caution against the extrapolation of normative data derived from a single densitometer manufacturer to results from a multicenter study of limited size.
Received May 23, 2003.
References
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