Avila M L, Pullenayegum E, Williams S, Shammas A, Stimec J, Sochett E, Marr K, Brandão L R
Division of Hematology/Oncology, Department of Pediatrics, The Hospital for Sick Children, University of Toronto, Toronto, M5G-1X8, ON, Canada.
Child Health Evaluative Sciences, The Hospital for Sick Children, University of Toronto, Toronto, M5G-1X8, ON, Canada.
Osteoporos Int. 2016 Apr;27(4):1547-1557. doi: 10.1007/s00198-015-3411-8. Epub 2015 Nov 16.
We studied bone mineral density (BMD) of children exposed to long-term warfarin. BMD Z-scores ≤ -2.0 were estimated to occur in less than one fifth of the patients after 10 years of warfarin exposure, and BMI and growth hormone deficiency predicted BMD changes over time. These predictors can help identify high-risk patients.
Children with chronic diseases are at increased risk of developing thrombosis, which may require long-term warfarin therapy. Warfarin could further jeopardize the bone health of a population already at risk for bone fragility. Our objective was to investigate the occurrence and timing of low bone mineral density (BMD) and the predictors that influence BMD trajectory in children receiving warfarin for >1 year.
We analyzed the results of an institutional protocol that includes dual-energy X-ray absorptiometry, with or without spinal X-rays and laboratory biomarkers, as required.
Low BMD (age, sex, race, and height-for-age-Z-score adjusted BMD Z-score ≤ -2.0) was detected in 13 % (9/70) of the patients at some point during their follow-up; these patients were more likely to have complex underlying medical conditions and low body mass index (BMI) percentile. BMD Z-scores remained within normal range in 87 % of children. Survival analysis showed that the estimated 10-year abnormal BMD-free rate for the entire group was 81 % (95 % confidence interval [CI] 69 to 93 %). Trajectory analysis revealed that BMI percentiles at baseline and growth hormone deficiency (GHD) were associated with lower BMD Z-scores at the first assessment, whereas baseline BMI percentile was the only predictor of BMD Z-score over time.
Our findings identified BMI and GHD as risk factors influencing BMD in children exposed to long-term warfarin, creating an opportunity for early detection and intervention in these patients.
我们研究了长期服用华法林儿童的骨密度(BMD)。估计在服用华法林10年后,骨密度Z值≤ -2.0的患者不到五分之一,且体重指数(BMI)和生长激素缺乏可预测骨密度随时间的变化。这些预测指标有助于识别高危患者。
患有慢性病的儿童发生血栓形成的风险增加,这可能需要长期服用华法林治疗。华法林可能会进一步损害本就有骨脆性风险人群的骨骼健康。我们的目标是调查接受华法林治疗超过1年的儿童中低骨密度(BMD)的发生情况和时间,以及影响骨密度轨迹的预测指标。
我们分析了一项机构方案的结果,该方案根据需要包括双能X线吸收法、有无脊柱X线检查以及实验室生物标志物检查。
在随访期间的某个时间点,13%(9/70)的患者检测到低骨密度(年龄、性别、种族和年龄别身高Z值校正后的骨密度Z值≤ -2.0);这些患者更有可能有复杂的基础疾病和低体重指数(BMI)百分位数。87%的儿童骨密度Z值保持在正常范围内。生存分析显示,整个组估计的10年无异常骨密度发生率为81%(95%置信区间[CI]69至93%)。轨迹分析显示,基线时的BMI百分位数和生长激素缺乏(GHD)与首次评估时较低的骨密度Z值相关,而基线BMI百分位数是随时间变化的骨密度Z值的唯一预测指标。
我们的研究结果确定BMI和GHD是影响长期服用华法林儿童骨密度的危险因素,为这些患者的早期检测和干预创造了机会。