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

Serum bone-Gla protein (BGP), bone alkaline phosphatase (B-AP), and C-terminal crosslinked 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/l), 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/l; 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/l) 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.