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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

Department of Endocrinology (W.M.D., P.V.C., K.T.M., K.A.M., C.C.-H., M.O.S., J.P.M.), St. Bartholomew’s Hospital, London EC1A 7BE, United Kingdom; Department of Paediatric Endocrinology (N.J.S.), Birmingham Children’s Hospital, Birmingham B4 6NH, United Kingdom; Department of Paediatric Endocrinology (D.B.D.), John Radcliffe Hospital, Oxford OX3 9DU, United Kingdom; and Department of Paediatric Endocrinology (T.D.C.), Royal Victoria Infirmary, Newcastle NE1 4LP, United Kingdom

Address all correspondence and requests for reprints to: Dr. W. M. Drake, Department of Endocrinology, St. Bartholomew’s Hospital, London EC1A 7BE, United Kingdom. E-mail: w.m.drake{at}qmul.ac.uk.

In many countries, treatment of childhood-onset GH deficiency (GHD) with GH ceases when linear growth is complete. Peak bone mass occurs several years after the completion of linear growth. Given that GH has important anabolic actions on bone, discontinuation of GH therapy at the completion of linear growth may have adverse consequences for the attainment of peak bone mass in adolescent GHD patients. In this United Kingdom multicenter study, 24 adolescents (13 males, mean age 17.0 ± 1.4 yr, SD) with severe GHD were randomized to discontinue or continue GH (0.35 IU/kg·wk) at the completion of linear growth. Whole body bone mineral content (BMC) and lumbar spine bone mineral density were assessed by dual-energy x-ray absorptiometry at baseline and then at 6-month intervals for 1 yr. Markers of bone remodeling (serum bone-specific alkaline phosphatase and urinary deoxypyridinoline) were measured at the same time points. In patients who continued GH (GH+), median BMC increased by 3.8% (interquartile range, 2.6, 5.9, P < 0.001) at 6 months; and by 6.0% (3.7–9.1, P < 0.001) at 12 months. In patients who discontinued GH (GH-) median BMC was unchanged at 6 and 12 months (+1.9%, -0.4–4.2, P = 0.9; and +2.4%, 0.4–4.9, P = 0.5, respectively, median, interquartile range). The differences in median change in BMC between the two groups at 6 and 12 months was marginally significant (P = 0.085 and 0.074, respectively). Mean lumbar spine bone mineral density increased by 4.7 (95% confidence interval, 1.0, 8.2) at 12 months in patients continuing GH (P = 0.01), but the mean change was not statistically significant change in patients who discontinued GH [+2.7% (95% confidence interval, -0.8, +6.2)]. These preliminary data suggest that, in adolescent patients with severe GHD, discontinuation of GH at completion of growth may limit the attainment of peak bone mass in this patient group. This may predispose to clinically significant osteopenia in later adult life.

This work was supported by an unrestricted grant from Pharmacia Corporation to the Department of Endocrinology for its work on GH and growth factors.

Abbreviations: BAP, Bone-specific alkaline phosphatase; BMC, bone mineral content; BMD, bone mineral density; CI, confidence interval; CO, childhood onset; DpD, deoxypyridinoline; GHD, GH deficiency; LS, lumbar spine; PBM, peak bone mass; rh, recombinant human.

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