Effects of growth hormone administration on bone mineral metabolism, PTH sensitivity and PTH secretory rhythm in postmenopausal women with established osteoporosis.
BACKGROUND
Growth hormone (GH) replacement improves target organ sensitivity to PTH, PTH circadian rhythm, calcium and phosphate metabolism, bone turnover, and BMD in adult GH-deficient (AGHD) patients. In postmenopausal women with established osteoporosis, GH and insulin like growth factor-1 (IGF-1) concentrations are low, and administration of GH has been shown to increase bone turnover and BMD, but the mechanisms remain unclear. We studied the effects of GH administration on PTH sensitivity, PTH circadian rhythm, and bone mineral metabolism in postmenopausal women with established osteoporosis.


METHODS
Fourteen postmenopausal women with osteoporosis were compared with 14 healthy premenopausal controls at baseline that then received GH for a period of 12 mo. Patients were hospitalized for 24 h before and 1, 3, 6, and 12 mo after GH administration and half-hourly blood and 3-h urine samples were collected. PTH, calcium (Ca), phosphate (PO(4)), nephrogenous cyclic AMP (NcAMP), beta C-telopeptide of type 1 collagen (betaCTX), procollagen type I amino-terminal propeptide (PINP), and 1,25-dihydroxyvitamin D [1,25(OH)(2)D] were measured. Circadian rhythm analysis was performed using Chronolab 3.0 and Student's t-test and general linear model ANOVAs for repeated measures were used where appropriate.


RESULTS
IGF-1 concentration was significantly lower in the women with established osteoporosis compared with controls (101.5 +/- 8.9 versus 140.9 +/- 10.8 mug/liter; p < 0.05) and increased significantly after 1, 3, 6, and 12 mo of GH administration (p < 0.001). Twenty-four-hour mean PTH concentration was higher in the osteoporotic women (5.4 +/- 0.1 pM) than in healthy controls (4.4 +/- 0.1 pM, p < 0.001) and decreased after 1 (5.2 +/- 0.1 pM, p < 0.001), 3 (5.0 +/- 0.1 pM, p < 0.001), 6 (4.7 +/- 0.1 pM, p < 0.001), and 12 mo (4.9 +/- 0.1 pM, p < 0.05) of GH administration compared with baseline. NcAMP was significantly lower in osteoporotic women (17.2 +/- 1.2 nM glomerular filtration rate [GFR]) compared with controls (21.4 +/- 1.4 nM GFR, p < 0.05) and increased after 1 (24.2 +/- 2.5 nM GFR, p < 0.05), 3 (27.3 +/- 1.5 nM GFR, p < 0.001), and 6 mo (32.4 +/- 2.5 nM GFR, p < 0.001) compared with baseline. PTH secretion was characterized by two peaks in premenopausal women and was altered in postmenopausal women with a sustained increase in PTH concentration. GH administration also restored a normal PTH secretory pattern in the osteoporotic women. The 24-h mean adjusted serum calcium (ACa) concentration increased at 1 and 3 mo (p < 0.001) and PO(4) at 1, 3, 6, and 12 mo (p < 0.001). 1,25(OH)(2)D concentration increased after 3, 6, and 12 mo of GH (p < 0.05). An increase in urine Ca excretion was observed at 3 and 6 mo (p < 0.05), and the renal threshold for maximum tubular phosphate reabsorption rate (TmPO4/GFR) increased after 1, 3, 6, and 12 mo (p < 0.05). betaCTX concentration increased progressively from 0.74 +/- 0.07 mug/liter at baseline to 0.83 +/- 0.07 mug/liter (p < 0.05) at 1 mo and 1.07 +/- 0.09 mug/liter (p < 0.01) at 3 mo, with no further increase at 6 or 12 mo. PINP concentration increased progressively from baseline (60 +/- 5 mug/liter) to 6 mo (126 +/- 11 mug/liter, p < 0.001), with no further increase at 12 mo. The percentage increase in PINP concentration was significantly higher than betaCTX (p < 0.05).


CONCLUSIONS
Our study shows that GH has a regulatory role in bone mineral metabolism. GH administration to postmenopausal osteoporotic women improves target organ sensitivity to PTH and bone mineral metabolism and alters PTH secretory pattern with greater increases in bone formation than resorption. These changes, resulting in a net positive bone balance, may partly explain the mechanism causing the increase in BMD after long-term administration of GH in postmenopausal women with osteoporosis shown in previous studies and proposes a further component in the development of age-related postmenopausal osteoporosis.
Department of Diabetes and Endocrinology, Royal Liverpool University Hospital, Liverpool, United Kingdom.
Franklin
F
Joseph
Aftab M
AM
Ahmad
Mazhar
M
Ul-Haq
Brian H
BH
Durham
Pauline
P
Whittingham
William D
WD
Fraser
Jiten P
JP
Vora
D001842:Bone and Bones / Q000378:metabolism*; D002118:Calcium / Q000097:blood; D002940:Circadian Rhythm; D003094:Collagen / Q000097:blood; D000242:Cyclic AMP / Q000097:blood; D005260:Female; D013006:Growth Hormone / Q000008:administration & dosage*; D006801:Humans; D007334:Insulin-Like Growth Factor I / Q000378:metabolism; D008875:Middle Aged; D008903:Minerals / Q000378:metabolism*; D010281:Parathyroid Hormone / Q000378:metabolism / Q000502:physiology*; D014807:Vitamin D / Q000031:analogs & derivatives / Q000097:blood
D008903:Minerals; D010281:Parathyroid Hormone; D014807:Vitamin D; C097949:1,25-dihydroxyvitamin D; D007334:Insulin-Like Growth Factor I; D013006:Growth Hormone; D003094:Collagen; D000242:Cyclic AMP; D002118:Calcium