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-termi nal 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 (0.1 25 IU/kg/week for the first month, followed by 0.25 IU/kg/week for 11 month s) and 6 months after the withdrawal of therapy. Total body bone mineral de nsity (BMD, g/cm(2)) was measured with dual energy X-ray absorptiometry (Ho logic QDR 1000/W) before, at 12 months of GH treatment and 6 months after i ts 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; ICT P: 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 afte r 3 months of GH treatment, while the maximal effect on bone formation bein g evident later (at 6(th) month). A slight decline in BGP, B-AP, T-AP and I CTP 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 +/- 0.02 7 g/cm(2), range: 0.944-1.350 g/cm(2)) was not significantly different (z-s core: +0.47 +/-0.31, NS) from that observed in healthy controls (1.065 +/- 0.008 g/cm(2), range: 1.008-1.121 g/cm(2)). CH therapy was associated with a significant reduction of mean total body BMD values (6(th) month: -1.8 +/ -0.5%, p <0.01; 12(th) month: -2.1 +/-1.0%, p <0.05 vs baseline), particula rly evident in the first six months of treatment. Six months after the with drawal of GH therapy, BGP (5.9 +/-0.5 ng/ml), B-AP (57.3 +/-7.0 IU/l) and I CTP (3.2 +/-0.1 ng/ml) levels returned similar to those recorded before tre atment, while total BMD increased (+1.5 +/-0.7, p <0.05), remaining however slightly lower than in basal conditions (-0.61 +/-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 (ear lier and greater for bone resorption); c) one-year GH therapy is associated with a reduction of total body BMD values, particularly evident in the fir st 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 G H withdrawal might be explained as consequence of persisting effects of pre vious GH stimulation on bone remodeling. ((C))2001, Editrice Kurtis.