Tag Archives: TCF3

Fanconi anemia (FA) is an inherited DNA repair disorder associated with

Fanconi anemia (FA) is an inherited DNA repair disorder associated with short stature and bone marrow failure usually requiring hematopoietic cell transplant (HCT). study included 20 FA HCT 13 Cancer HCT and 90 healthy controls age-matched Andrographolide and <18 years old at evaluation. BMD Z-scores for total body (TBMD) and lumbar spine (LBMD) were measured by dual energy x-ray absorptiometry and adjusted for height-forage Z-score (HAZ). FA HCT had lower mean TBMDHAZ Z-score (by 0.8 SD) and higher fraction with Z-score ≤ ?1 than healthy controls (42% vs. 11%). No LBMD deficits were detected. FA HCT and Cancer HCT groups did not differ significantly in TBMD or LBMD Z-scores. In FA HCT patients lower BMI and lower percent fat were associated with lower BMD. This study highlights the importance of monitoring BMD to optimize bone health in FA patients. values are from two-sample t-test or TCF3 Fisher’s exact test. Otherwise all analyses had the form of multivariate linear or logistic regression depending on the outcome and all used generalized estimating equations (GEE) with robust standard errors to account for sibling relationships within the healthy control group. Analyses testing the association between BMD Z-score and risk factors in FA Andrographolide patients were adjusted for Tanner stage. Analyses Andrographolide comparing BMD Z-score between groups were adjusted for age at study gender and Tanner stage. Height-adjusted BMD Z-scores were calculated using a method described by Zemel et al. [15]. All analyses were done using the SAS system (v. 9.3; SAS Andrographolide Institute Cary NC). values are two-sided and <0.05 is considered statistically significant except for analyses involving multiple comparisons in which value <0.0167 is considered statistically significant using a Bonferroni adjustment. RESULTS Characteristics of the study groups Table 1 shows participant characteristics. By design age and Tanner stage at DXA evaluation did not differ between the groups; all patients were 10-14 years old. At time of HCT 19 FA patients had aplastic anemia and one patient had myelodysplastic syndrome. Complementation groups included (n=13) (n=4) (n=1) (n=1) and unknown (n=1). The Cancer HCT group had a higher percentage of males compared to healthy controls; six had acute myeloid leukemia four acute lymphoblastic leukemia one chronic myelogenous leukemia one myelodysplastic syndrome and one non-Hodgkin lymphoma. Compared to the FA HCT group the Cancer HCT group was younger at HCT and had DXA scans later after HCT. The median time since HCT was 2.2 years for FA patients and 5.2 years for cancer patients. Only one FA patient received androgen treatment prior to HCT. Two FA patients had grade II-IV acute GVHD requiring systemic steroid therapy one of whom also had chronic GVHD. The incidence of acute but not chronic GVHD was higher in cancer patients than in FA patients. Table 1 Characteristics of the study groups. FA patients were the shortest of the three groups and had the lowest BMI Z-score but their percent fat and lean body mass (LBM) were similar to the other groups after adjusting for height and Tanner stage. Consistent with previous reports hypothyroidism was common among FA patients (30% in FA vs. 0% in healthy controls) although not as common as in cancer patients (54%). All patients with hypothyroidism were euthyroid (normal free T4 and TSH) on thyroid hormone replacement at the time of evaluation. A significant proportion of those FA patients who were in the pubertal age had hypergonadotropic hypogonadism (20% in FA vs. 0% in healthy controls). The mean levels of sex hormones (estradiol and testosterone) however did not differ between the groups. Bone mineral density in FA children vs. healthy controls As shown in Table 2 FA patients had significantly lower TBMD Z-scores and LBMD Z-scores compared to healthy controls and a higher proportion of FA patients had TBMD and LBMD Z-scores ≤ ?1 compared to healthy controls. However after adjusting for height-for-age Z-score (HAZ) only the differences in TBMD Z-scores remained significant. FA patients had mean TBMDHAZ Z-score -0.8 compared to 0.01 in healthy controls. Also a higher proportion of FA patients had TBMDHAZ Z-score ≤ ?1 compared to healthy controls (42% vs. 11%). Adjusting for age at study gender and Tanner stage did not change the statistical significance of any of these differences (Fig. 1). Six FA patients were on growth hormone treatment at the time of DXA evaluation. Their BMD.