Analysis of Polymorphisms of the Vitamin D Receptor, Estrogen Receptor, and Collagen Iα1 Genes and Their Relationship With Height in Children With Bone Cancer

The authors' objectives were to compare height at diagnosis of children with bone tumors with that of Spanish reference children; to analyze the frequency of the genotypes for the polymorphisms of the vitamin D receptor (VDR), estrogen receptor (ER), and collagen Ialpha1 (COLIalpha1) genes in patients and in healthy controls; and to test the relationship between the genetic markers and height. PATIENTS AND METHODS: Height and weight at diagnosis were measured in 58 osteosarcoma and 36 Ewing sarcoma patients and compared with standards published for Spanish reference children according to sex and age. For the molecular analysis, genetic polymorphisms of the VDR (Fok I, Apa I, and TaqI), ER (Pvu II and XbaI), and COLIalpha1 (Msc I) genes were characterized in 72 osteosarcoma and 53 Ewing sarcomas and in a group of 143 healthy matched children. RESULTS: Osteosarcoma and Ewing sarcoma patients were significantly taller than Spanish reference children. Osteosarcoma patients showed a significantly higher frequency of the Ff genotype for the Fok I polymorphism (VDR gene) than the control group. The odds ratio for this genotype was 1.78, with an increased relative risk of 78% for heterozygous Ff carriers. Among Ewing sarcoma patients, this same genotype was significantly associated with lower height than homozygotes (FF or ff). CONCLUSIONS: Children with bone cancer are significantly taller than the reference population, which may be influenced by the genotype for the Fok I polymorphism of the VDR gene

Bone Mineral Density and Bone Metabolism In Children Treated for Bone Sarcomas

In adolescent bone sarcoma patients, bone mass acquisition is potentially compromised at a time in which it should be at a maximum. To evaluate the problem we measured bone mineral density (BMD) and serum markers of bone formation and resorption in a series of pediatric patients with bone tumors. BMD was measured by dual-energy x-ray absorptiometry, at clinical remission, for lumbar spine and the neck of the femur in 38 osteosarcoma and 25 Ewing's sarcoma patients. Mean age was 20.65 and 19.13 y respectively. Serum markers of bone metabolism were: OC, PICP, ICTP, 25-OH vit D and 1,25-(OH)(2) vit D, IGF-I, IGFBP-3 and intact PTH. Serum was sampled throughout anti-tumoral treatments and follow-up. We analyzed 85 samples from 59 osteosarcoma patients and 54 samples from 36 Ewing's sarcoma patients. Patients had decreased lumbar and femoral BMD. The decrease was more pronounced in pubertal patients compared with those who had completed pubertal development at the time of disease diagnosis. Multivariate analysis indicated that sex, age, weight and BMI were significant in lumbar BMD depletion. Weight and BMI were significant in femoral BMD depletion. Serum markers of bone formation (PICP and OC) and resorption (ICTP) were, throughout, lower than reference values. Significant alterations in other markers were also observed. Up to a third of osteosarcoma and Ewing's sarcoma patients in clinical remission had some degree of BMD deficit. The corresponding increased risk of pathologic bone fractures constitutes a reduction in future quality o

Reduced Bone Mineralization in Adolescent Survivors of Malignant Bone Tumors: Comparison of Quantitative Ultrasound and Dual-Energy X-Ray Absorptiometry

To assess bone mineralization in adolescents with bone tumors at remission using quantitative digital ultrasound (QUS) and dual-energy x-ray absorptiometry (DEXA), and to compare the bone mineralization values obtained by both methods. METHODS: Patients studied were 36 adolescents (21 boys, 15 girls) who had completed treatment of a bone tumor at the University Hospital of the University of Navarra (Pamplona, Spain). QUS was performed at the distal metaphysis of the proximal phalanxes of the last four fingers of the nondominant hand. A DBM Sonic 1200 Ultrasound densitometer was used. DEXA measurements were made at the lumbar spine (vertebrae L1-L4) using the Hologic QDR 4500 W device. Calcium and vitamin D daily intake and grade of physical activity were recorded. RESULTS: Mean age at bone mineralization determination was 19.11 years. Disease-free survival was 4.97 years. Decreased bone mineralization was observed by both methods. Bone mineralization absolute values measured by QUS and DEXA were significantly correlated. The sensitivity, specificity, diagnostic accuracy, and positive and negative predictive values of QUS for predicting osteopenia were 36.4%, 80.0%, 66.7%, 44.4%, and 74.1%, respectively. Daily vitamin D intake was below the recommended dietary allowances. CONCLUSIONS: Adolescents in remission from bone tumors have low bone mineralization determined by DEXA or QUS