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J Clin Endocrinol Metab. 2003 Jun;88(6):2614-8.

The Impact of congenital, severe, untreated growth hormone (GH) deficiency on bone size and density in young adults: insights from genetic GH-releasing hormone receptor deficiency.

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  • 1Center for Endocrinology, Metabolism and Molecular Medicine, Department of Medicine, Northwestern University Medical School and Veterans Administration Chicago Health Care System, Lakeside Division, Chicago, Illinois 60611, USA.


GH and IGF-I have well recognized effects on bone elongation during development, but their importance for bone mineralization and structure during the growth phase are less well understood. Because children with GH deficiency are generally treated with GH, little detailed information exists in humans about the effects of long-term GH deficiency on bone development. The recently described syndrome of genetic GHRH receptor deficiency in Pakistan (dwarfism of Sindh) affords a unique opportunity to examine the question of GH deficiency on bone development because the affected patients have congenital, severe, isolated GH deficiency, which had never been treated because of societal reasons. We performed dual energy x-ray absorptiometry scans in four adult males (age, 23-30 yr) to address the question of bone mineralization. Areal bone mineral density (BMD) was low (mean Z scores: -3.3, -2.1, -3.7, and -1.7) in the lumbar spine, femoral neck, forearm, and total skeleton, respectively. This low areal BMD is in part caused by the small bone size in these dwarfed patients. When corrected for size, volumetric BMD (bone mineral apparent density) was normal to near normal (mean Z scores: -1.2, +0.8, and +0.8 for lumbar spine, femoral neck and total skeleton, respectively). We conclude that GH/IGF-I deficiency has relatively little impact on bone mineralization during the bone accretion phase. This is in marked contrast to their effect on bone elongation and overall bone size.

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