Arikoski P, Komulainen J, Riikonen P, Voutilainen R, Knip M, Kröger H
Department of Pediatrics, Kuopio University Hospital, Finland.
J Clin Endocrinol Metab. 1999 Sep;84(9):3174-81. doi: 10.1210/jcem.84.9.5968.
In the present study, longitudinal changes in bone mineral density, bone turnover, and bone hormonal metabolism were evaluated in newly diagnosed children with cancer. Lumbar spine (L2-L4) and femoral neck bone mineral densities (grams per cm2) were measured by dual energy x-ray absorptiometry in 28 children (age, 2.9-16.0 yr; median, 8.0 yr; 10 acute lymphoblastic leukemias, 18 solid tumors) at diagnosis and after a 1-yr follow-up. Apparent volumetric density (grams per cm3) was calculated to minimize the effect of bone size on BMD. Serum levels of osteocalcin (OC), type I collagen carboxyl-terminal propeptide (PICP), and type I collagen carboxyl-terminal telopeptide were measured serially during the study. Serum 25-hydroxyvitamin D, 1,25-dihydroxyvitamin D, insulin-like growth factor I (IGF-I), and IGF-binding protein-3 were analyzed at diagnosis and at 1-yr follow-up. A significant decrease in femoral bone mineral density and apparent volumetric density was observed during the year after diagnosis [(mean (SD), -10.1% (8.8%) and -11.3% (8.1%) respectively; P < 0.01], whereas age- and sex-matched controls showed annual increments of +5.4% (7.7%; P < 0.01) and +0.7% (5.7%; P = NS) respectively. The markers of bone formation (PICP and OC) were significantly decreased at diagnosis. By the end of the follow-up, PICP and OC were normalized, whereas the marker of bone resorption (type I collagen carboxyl-terminal telopeptide) was significantly increased. Reduced levels of 25-hydroxyvitamin D, 1,25-dihydroxyvitamin D, and IGF-binding protein-3 were observed during the study. To conclude, increased bone resorption and impaired development of femoral bone density were observed in children with cancer during chemotherapy. Deficient accumulation of bone mass may lead to impaired development of peak bone mass and predispose children with cancer to increased risk of osteoporosis and diminished skeletal resistance to fractures later in life.
在本研究中,对新诊断的癌症患儿的骨矿物质密度、骨转换和骨激素代谢的纵向变化进行了评估。采用双能X线吸收法测量了28例患儿(年龄2.9 - 16.0岁;中位数8.0岁;10例急性淋巴细胞白血病,18例实体瘤)诊断时及1年随访后的腰椎(L2 - L4)和股骨颈骨矿物质密度(克/平方厘米)。计算表观体积密度(克/立方厘米)以尽量减少骨大小对骨密度的影响。在研究期间连续测量血清骨钙素(OC)、I型胶原羧基末端前肽(PICP)和I型胶原羧基末端端肽水平。在诊断时及1年随访时分析血清25 - 羟基维生素D、1,25 - 二羟基维生素D、胰岛素样生长因子I(IGF - I)和IGF结合蛋白 - 3。诊断后1年内观察到股骨骨矿物质密度和表观体积密度显著降低[(均值(标准差),分别为 - 10.1%(8.8%)和 - 11.3%(8.1%);P < 0.01],而年龄和性别匹配的对照组分别显示年增加量为 + 5.4%(7.7%;P < 0.01)和 + 0.7%(5.7%;P = 无显著性差异)。骨形成标志物(PICP和OC)在诊断时显著降低。随访结束时,PICP和OC恢复正常,而骨吸收标志物(I型胶原羧基末端端肽)显著增加。在研究期间观察到25 - 羟基维生素D、1,25 - 二羟基维生素D和IGF结合蛋白 - 3水平降低。总之,化疗期间癌症患儿出现骨吸收增加和股骨骨密度发育受损。骨量积累不足可能导致峰值骨量发育受损,并使癌症患儿在以后的生活中患骨质疏松症的风险增加,骨骼抗骨折能力下降。