Effects of 12-month GH treatment on bone metabolism and bone mineral density in adults with adult-onset GH deficiency

Serum bone-GIa protein (BGP), bone alkaline phosphatase (B-AP), and C-terminal cross-linked telopeptide of type I collagen (ICTP) levels were evaluated in 18 adults with acquired GH deficiency (GHD, 14 males and 4 females, age range: 25-59 yr) before, at 3, 6, 9 and 12 months of rec-GH treatment (0.125 IU/kg/week for the first month, followed by 0.25 IU/kg/week for 11 months) and 6 months after the withdrawal of therapy. Total body bone mineral density (BMD, g/cm2) was measured with dual energy X-ray absorptiometry (Hologic QDR 1000/W) before, at 12 months of GH treatment and 6 months after its withdrawal. Before treatment, BGP (mean±SE: 5.1±0.4 ng/ml), B-AP (59.4±6.5 IU/I), ICTP (3.1±0.3 ng/ml) levels of patients were similar to in healthy controls (BGP: 5.4±0.1 ng/ml; B-AP: 58.2±2.0 IU/I; ICTP: 4.1±0.3 ng/ml). GH treatment caused a significant increase of BGP, B-AP, ICTP levels, the maximal stimulation of bone resorption, occurring after 3 months of GH treatment, while the maximal effect on bone formation being evident later (at 6th month). A slight decline in BGP, B-AP, T-AP and ICTP levels occurred at 9-12 months of therapy, although the values remained significantly higher than in basal conditions and with respect to healthy controls. Before treatment, mean total body BMD of patients (1.110±0.027 g/cm2, range: 0.944-1.350 g/cm2) was not significantly different (z-score: +0.47±0.31, NS) from that observed in healthy controls (1.065±0.008 g/cm2, range: 1.008-1.121 g/cm2). GH therapy was associated with a significant reduction of mean total body BMD values (6th month: -1.8±0.5%, p<0.01; 12th month: -2.1±1.0%, p<0.05 vs baseline), particularly evident in the first six months of treatment. Six months after the withdrawal of GH therapy, BGP (5.9±0.5 ng/ml), B-AP (57.3±7.0 IU/I) and ICTP (3.2±0.1 ng/ml) levels returned similar to those recorded before treatment, while total BMD increased (+1.5±0.7, p<0.05), remaining however slightly lower than in basal conditions (-0.6±1.2, NS). In conclusion, our study shows that: a) acquired GHD in adulthood is associated with both normal bone formation/resorption indexes and normal total body BMD; b) GH therapy causes a significant rise of bone formation/resorption markers (earlier and greater for bone resorption); c) one-year GH therapy is associated with a reduction of total body BMD values, particularly evident in the first 6 months of treatment; d) the effects of GH therapy on bone turnover are transient, being completely reverted six months after the withdrawal of GH therapy; e) the increase of total body BMD (up to baseline values) after GH withdrawal might be explained as consequence of persisting effects of previous GH stimulation on bone remodeling.