title: Effects of 12 months rec-GH therapy on bone and collagen turnover and bone mineral density in GH deficient children with thalassaemia major.
abstract: Children suffering from thalassaemia major are reported to have growth delay and bone alterations even when well transfused and chelated. In the present study we evaluated bone and collagen turnover (bone Gla-protein, BGP; carboxyterminal telopeptide of type I collagen, ICTP; aminoterminal propeptide of type III procollagen, PIIINP, respectively) and bone mineral density (BMD) in 5 pre-pubertal GH deficient thalassaemic children before and during rec-GH treatment (0.6 IU/kg/week). Data were compared with those recorded in an age- and sex-matched control group. Before treatment, serum BGP and ICTP levels were significantly lower (p<0.0001) in children with thalassaemia (9.3+/-0.7 ng/ml and 5.3+/-0.5 ng/ml, respectively) than in healthy controls (18.9+/-0.9 ng/ml and 14.4+/-0.6 ng/ml, respectively), while serum PIIINP levels did not significantly differ in the two groups (6.7+/-0.7 ng/ml vs 6.7+/-0.7 ng/ml). Mean lumbar BMD values of patients (0.62+/-0.05 g/cm2) were significantly lower (p<0.05) than those recorded in healthy controls (0.78+/-0.01 g/cm2), while femoral BMD values were similar in the two groups (patients: 0.70+/-0.08 g/cm2 vs controls: 0.74+/-0.01 g/cm2). One-year GH therapy significantly increased height velocity (from 2.3+/-0.2 cm/year to 6.1+/-0.4 cm/yr, p<0.0001) and IGF-I levels (from 61.6+/-15.4 to 342+/-38.5 ng/ml, p<0.005). Serum BGP (basal: 9.3+/-0.7 ng/ml, 6th month: 10.8+/-0.6 ng/ml, 12th month: 14.9+/-1.4 ng/ml), ICTP (basal: 5.3+/-0.5 ng/ml, 6th month: 7.9+/-0.8 ng/ml, 12th month: 10.9+/-1.7 ng/ml) and PIIINP levels (basal: 6.7+/-0.7 ng/ml, 6th month: 9.9+/-1.0 ng/ml, 12th month: 9.6+/-1.4 ng/ml) significantly increased (p<0.05), while no significant effects were observed on lumbar and femoral BMD values. Although the GH-induced stimulation of bone turnover markedly increased BGP (+60%) and ICTP (+105%) levels, one-year GH therapy was not sufficient to completely normalize these parameters, which remained significantly lower than in healthy controls. In conclusion, our study shows that pre-pubertal GH deficient children with thalassaemia major have reduced bone turnover (both bone formation and resorption) and lumbar BMD values, thus indicating that bone metabolism should be monitored and improved even in well-transfused patients. One-year GH treatment is able to increase, but not normalize, bone turnover, this effect being insufficient to improve BMD values. More prolonged periods of GH therapy are probably requested to positively affect both bone turnover and BMD values in GH deficient thalassaemic patients, as occurs in children and adults with GH deficiency.
authors.affiliation: Divisione Malattie Metaboliche III, Istituto Auxologico Italiano, IRCCS, Piancavallo (VB), Milano. sartorio@auxologico.it
authors.forename: A
authors.initials: A
authors.lastname: Sartorio
authors.forename: G
authors.initials: G
authors.lastname: Conte
authors.forename: A
authors.initials: A
authors.lastname: Conti
authors.forename: A
authors.initials: A
authors.lastname: Masala
authors.forename: S
authors.initials: S
authors.lastname: Alagna
authors.forename: P
authors.initials: P
authors.lastname: Rovasio
authors.forename: G
authors.initials: G
authors.lastname: Faglia
mesh_terms: D000293:Adolescent; D015519:Bone Density / Q000187:drug effects*; D016723:Bone Remodeling / Q000187:drug effects*; D002648:Child; D003094:Collagen / Q000378:metabolism*; D024042:Collagen Type I; D013006:Growth Hormone / Q000008:administration & dosage / Q000172:deficiency* / Q000627:therapeutic use*; D006801:Humans; D008297:Male; D015675:Osteocalcin / Q000097:blood; D010446:Peptide Fragments / Q000097:blood; D010455:Peptides; D011347:Procollagen / Q000097:blood; D011994:Recombinant Proteins / Q000627:therapeutic use; D013789:Thalassemia / Q000097:blood / Q000150:complications*; D013997:Time Factors
chemical_list: D024042:Collagen Type I; D010446:Peptide Fragments; D010455:Peptides; D011347:Procollagen; D011994:Recombinant Proteins; C052929:collagen type I trimeric cross-linked peptide; C041876:procollagen Type III-N-terminal peptide; D015675:Osteocalcin; D013006:Growth Hormone; D003094:Collagen