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Effects of Growth Hormone Replacement on Parathyroid Hormone Sensitivity and Bone Mineral Metabolism

Departments of Diabetes and Endocrinology and Department of Clinical Chemistry (B.H.D., W.D.F.), Royal Liverpool University Hospital, Liverpool, United Kingdom L7 8XP

Address all correspondence and requests for reprints to: Dr. A. M. Ahmad, Link 7-C, Department of Diabetes and Endocrinology, Royal Liverpool University Hospital, Prescot Street, Liverpool, United Kingdom L7 8XP. E-mail: draahmad{at}yahoo.com.

Adult GH deficiency (AGHD) is associated with reduced bone mineral density, and decreased end-organ sensitivity to the effects of PTH has been suggested as a possible underlying mechanism. We investigated the effects of GH replacement (GHR) on PTH circulating activity and its association with phosphocalcium metabolism and bone turnover in 16 (8 men and 8 women) AGHD patients. Half-hourly blood and 3 hourly urine sampling was performed on each patient over a 24-h period before GHR and then after 1, 3, 6, and 12 months of GHR. GH was commenced at a dose of 0.5 IU/d and was titrated to achieve and maintain an IGF-I SD score within 2 SD of the age-related reference range.

The target IGF-I SD score was achieved within 3 months and was maintained at 12 months after GHR in all patients. Our results demonstrated a significant decrease in serum PTH at all visits after GHR compared with baseline values (P < 0.001), with a concomitant increase in nephrogenous cAMP excretion at 1 (P < 0.001) and 3 (P < 0.05) months and increases in serum calcium (P < 0.001), serum phosphate (P < 0.001), 1,25-dihydroxyvitamin D₃ (P < 0.001), type I collagen C-telopeptide (a bone resorption marker; P < 0.001), and procollagen type I amino-terminal propeptide (a bone formation marker; P < 0.001). Simultaneously, we observed a significant decrease in urinary calcium excretion (P < 0.001) and an increase in maximum tubular phosphate reabsorption (P < 0.001). Together these results suggest increased end-organ responsiveness to the effects of circulating PTH resulting in increased bone turnover and reduced calcium excretion. Significant circadian rhythms were observed for serum PTH, phosphate, type I collagen C-telopeptide, and procollagen type I amino-terminal propeptide before and after GHR. However, sustained PTH secretion was observed between 1400–2200 h, with a reduced nocturnal rise in untreated AGHD patients, whereas PTH secretion decreased significantly between 1400–2200 h (P < 0.001), with a significant increase in nocturnal PTH secretion (P < 0.001) after 12 months of GHR.

Our results demonstrate that GH may have a regulatory role in bone mineral metabolism, and our data provide a possible underlying mechanism for the development of osteoporosis in AGHD patients. The changes observed after GHR may further explain the beneficial effects of GHR on bone mineral density that have consistently been reported.

This work was supported in part by the Research and Development Department of the Royal Liverpool and Broadgreen University Hospital Trust.

Abbreviations: AGHD, Adult GH deficiency: BMD, bone mineral density; CTX, type I collagen C-telopeptide; CV, coefficient of variance; 1,25(OH)₂D₃, 1,25-dihydroxyvitamin D₃; GFR, glomerular filtration rate; GHR, GH replacement; MESOR, midline estimate statistic of rhythm; NcAMP, nephrogenous cAMP; PcAMP, plasma cAMP; PINP, procollagen type I amino-terminal propeptide; SDS, SD score; TmPO₄/GFR, tubular phosphate reabsorption.

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