Sartorio A, Conte G, Conti A, Masala A, Alagna S, Rovasio P, Faglia G
Divisione Malattie Metaboliche III, Istituto Auxologico Italiano, IRCCS, Piancavallo (VB), Milano.
J Endocrinol Invest. 2000 Jun;23(6):356-61. doi: 10.1007/BF03343738.
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.
据报道，重度地中海贫血患儿即使输血和螯合治疗情况良好，仍会出现生长发育迟缓及骨骼改变。在本研究中，我们评估了5例青春期前生长激素缺乏的地中海贫血患儿在接受重组生长激素（rec-GH）治疗前及治疗期间（0.6 IU/kg/周）的骨和胶原蛋白转换情况（分别为骨钙素、BGP；I型胶原羧基末端肽、ICTP；III型前胶原氨基末端前肽、PIIINP）以及骨密度（BMD）。将数据与年龄和性别匹配的对照组记录的数据进行比较。治疗前，地中海贫血患儿的血清BGP和ICTP水平（分别为9.3±0.7 ng/ml和5.3±0.5 ng/ml）显著低于健康对照组（分别为18.9±0.9 ng/ml和14.4±0.6 ng/ml）（p<0.0001），而两组血清PIIINP水平无显著差异（6.7±0.7 ng/ml对6.7±0.7 ng/ml）。患者的平均腰椎BMD值（0.62±0.05 g/cm²）显著低于健康对照组记录的值（0.78±0.01 g/cm²）（p<0.05），而两组股骨BMD值相似（患者：0.70±0.08 g/cm²对对照组：0.74±0.01 g/cm²）。一年的生长激素治疗显著提高了身高增长速度（从2.3±0.2 cm/年增至6.1±0.4 cm/年，p<0.0001）和胰岛素样生长因子-I（IGF-I）水平（从61.6±15.4增至342±38.5 ng/ml，p<0.005）。血清BGP（基础值：9.3±0.7 ng/ml，第6个月：10.8±0.6 ng/ml，第12个月：14.9±1.4 ng/ml）、ICTP（基础值：5.3±0.5 ng/ml，第6个月：7.9±0.8 ng/ml，第12个月：10.9±1.7 ng/ml）和PIIINP水平（基础值：6.7±0.7 ng/ml，第6个月：9.9±1.0 ng/ml，第12个月：9.6±1.4 ng/ml）显著升高（p<0.05），而对腰椎和股骨BMD值未观察到显著影响。尽管生长激素诱导的骨转换刺激显著提高了BGP（+60%）和ICTP（+105%）水平，但一年的生长激素治疗不足以使这些参数完全正常化，其仍显著低于健康对照组。总之，我们的研究表明，青春期前生长激素缺乏的重度地中海贫血患儿骨转换（包括骨形成和骨吸收）及腰椎BMD值降低，这表明即使是输血情况良好的患者，也应监测并改善骨代谢。一年的生长激素治疗能够增加但不能使骨转换正常化，这种效果不足以改善BMD值。可能需要更长时间的生长激素治疗才能对生长激素缺乏的地中海贫血患者的骨转换和BMD值产生积极影响，就像生长激素缺乏的儿童和成人那样。
