Abstract
Low bone mass is emerging as a frequent and debilitating morbidity in Thalassemia (thal). The TCRN conducted a cross-sectional observational study to determine the prevalence and factors contributing to bone disease among North American thal patients (pts). Spinal (L1-L4) Bone Mineral Density (BMD) Z- and T-score measurements by DXA (Hologic 4500 and Delphi models) were read centrally. Each subject’s weight, height, hematologic, endocrine and genetic parameters, iron chelation and transfusion regimens, dietary calcium intake, history of fractures and bone pain, self-reported physical activity and bone turnover markers were assessed. BMD was measured in 302 pts: 207 Thal Major (TM), 37 Thal Intermedia (TI), 35 Beta E, 7 Hemoglobin H disease (HbH), 2 homozygous alpha (α) and 14 HbH/Constant Spring (HbH/CS). Among all diagnostic groups, the prevalence of low bone mass (LBM; Z/T <-2), reduced bone mass (RBM; Z/T -2 to -1) and normal bone mass (NBM; Z/T >-1) was 52%, 27% and 21%, respectively. LBM prevalence was 55% in TM, 53% in TI, 51% in Beta E, 0% in HbH, 50% in α and 43% in HbH/CS. RBM prevalence was 26% in TM, 22% in TI, 31% in Beta E, 71% in HbH, 50% in α and 29% in HbH/CS. Pt groups aged: 6–11 yrs, 11–20 yrs, 20+ yrs had Z/T-scores mean±SD[n] were: −1.32±0.82[51], −1.73±1.08[77] and −2.43±1.14[174], respectively. Z/T-scores were significantly lower among older pts (p<.001) and significantly higher among heavier pts after controlling for Tanner stage. Mean age-adjusted Z/T-scores of thal diagnostic groups and their slopes vs. age did not differ significantly although the samples of some groups were small. Among TM and TI pts, those with genotype β°/β° tended to have lower age- and weight-adjusted Z/T-scores (mean [95% CI]: −2.25 [−2.65 to −1.86], n=39). Less than 1% had hypoparathyroidism, 4% vit D deficiency, 8.5% diabetes mellitus, 8.5% hypothyroidism and 11.5% growth hormone deficiency (GHD). Only GHD was significantly correlated with decreased Z/T-scores after controlling for age and diagnosis. Urinary N-telopeptide (NTx) is elevated across all three age groups (median[IQR] mM BCE/mM creatinine: 664[456–930], 302[90–624], 69[34–124]), respectively. Preliminary analysis of bone turnover markers in a subset of subjects (n=114) suggests that NTx, urinary or serum was a significant independent predictor of spine Z/T-scores controlled for age and age-adjusted weight. There was no relationship between Z/T-score and serum osteocalcin. This large and comprehensive study of thal bone disease has demonstrated that decreased bone mass occurs with high frequency, worsens with age, is affected by weight and GHD and is associated with elevated NTx, i.e. increased bone resorption. Future studies are needed to identify efficacious long-term therapies to improve thal bone disease.
Serumβ-Catenin Levels Associated with the Ratio of RANKL/OPG in Patients with Postmenopausal Osteoporosis
