Effects of growth hormone (GH) replacement on bone metabolism and mineral density in adult onset of GH deficiency: Results of a double-blind placebo-controlled study with open follow-up

It is known that GH stimulates bone turnover and that GH-deficient adults have a lower bone mass than healthy controls. In order to evaluate the influences of GH replacement therapy on markers of bone turnover and on bone mineral density (BMD) in patients with adult onset GH deficiency, a double-blind placebo-controlled study of treatment with recombinant human GH (rhGH; mean dose 2.4 IU daily) in 20 patients for 6 months and an extended open study of 6 to 12 months were conducted. Eighteen patients, fourteen men and four women, with a mean age of 44 years with adult onset GH deficiency were evaluated in the study. Compared with placebo, after 6 months serum calcium (2.39+/-0.02 vs 2.32+/-0.02 mmol/l, P=0.037) and phosphate (0.97+/-0.06 vs 0.75+/-0.05 mmol/l, P=0.011) increased and the index of phosphate excretion (0.03+/-0.03 vs 0.19+/-0.02, P <0.001) decreased significantly, and there was a significant increase in the markers of bone formation (osteocalcin, 64.8+/-11.8 vs 17.4+/-1.8 ng/ml, P <0.001; procollagen type I carboxyterminal propeptide (PICP), 195.3+/-26.4 vs 124.0+/-15.5 ng/ml, P=0.026) as well as those of bone resorption (type I collagen carboxyterminal telopeptide (ICTP), 8.9+/-1.2 vs 3.3+/-0.5 ng/ml, P<0.001; urinary hydroxyproline, 0.035+/-0.006 vs 0.018+0.002 mg/ 100 ml glomerular filtration rate, P=0.009). BMD did not change during this period of time. IGF-I was significantly higher in treated patients (306.5+/-45.3 vs 88.7+/-22.5 ng/ml, P <0.001). An analysis of the data compiled from 18 patients treated with rhGH for 12 months revealed similar significant increases in serum calcium and phosphate, and the markers of bone turnover (osteocalcin, PICP, ICTP, urinary hydroxyproline). Dual energy x-ray absorptiometry (DXA)-measured BMD in the lumbar spine (1.194+/-0.058 vs 1.133+/-0.046 g/cm(2) P=0.015), femoral neck (1.009+/-0.051 vs 0.936+/-0.034 g/cm(2), P=0.004), Ward's triangle (0.881+/-0.055 vs 0.816+/-0.04 g/cm(2), P=0.019) and the trochanteric region (0.869+/-0.046 vs 0.801+/-0.033 g/cm(2), P=0.005) increased significantly linearly (compared with the individual baseline values). At 12 months, BMD in patients with low bone mass (T-score <-1.0 S.D.) increased more than in those with normal bone mass (lumbar spine 11.5 vs 2.1%, P=0.030, and femoral neck 9.7 vs 42%, P=0.055). IGF-I increased significantly in all treated patients. In conclusion, treatment of GH-deficient adults with rhGH increases bone turnover for at least 12 months. BMD in the lumbar spine and the proximal femur increases continuously in this time (open study) and the benefit is greater in patients with low bone mass. Therefore, GH-deficient patients exhibiting osteopenia or osteoporosis should be considered candidates for GH supplementation. However, long-term studies are needed to establish that the positive effects on BMD are persistent and are associated with a reduction in fracture risk.