非缺失型血红蛋白H病青少年的骨密度与Dickkopf-1

Bone Mineral Density and Dickkopf-1 in Adolescents with Non-Deletional Hemoglobin H Disease.

作者信息

Wiromrat Pattara, Rattanathongkom Aree, Laoaroon Napat, Suwannaying Kunanya, Komwilaisak Patcharee, Panamonta Ouyporn, Wongsurawat Nantaporn, Nasomyont Nat

机构信息

Section of Endocrinology, Department of Pediatrics, Faculty of Medicine, Khon Kaen University, Khon Kaen, Thailand.

出版信息

J Clin Densitom. 2023 Jul-Sep;26(3):101379. doi: 10.1016/j.jocd.2023.101379. Epub 2023 Apr 26.

DOI:10.1016/j.jocd.2023.101379

PMID:37147222

Abstract

BACKGROUND

Low bone mineral density (BMD) is prevalent in individuals with β-thalassemia and is associated with increased circulating dickkopf-1 concentration. These data are limited in α-thalassemia. Therefore, we aimed to determine the prevalence of low BMD and the association between BMD and serum dickkopf-1 in adolescents with non-deletional hemoglobin H disease, a form of α-thalassemia whose severity is comparable to β-thalassemia intermedia.

METHODOLOGY

The lumbar spine and total body BMD were measured and converted into height-adjusted z-scores. Low BMD was defined as BMD z-score ≤ -2. Participant blood was drawn for measurement of dickkopf-1 and bone turnover marker concentrations.

RESULTS

Thirty-seven participants with non-deletional hemoglobin H disease (59% female, mean age 14.6 ± 3.2 years, 86% Tanner stage ≥2, 95% regularly transfused, 16% taking prednisolone) were included. Over one year prior to the study, mean average pretransfusion hemoglobin, ferritin and 25-hydroxyvitamin D concentrations were 8.8 ± 1.0 g/dL, and 958 ± 513 and 26 ± 6 ng/mL, respectively. When participants taking prednisolone were excluded, the prevalence of low BMD at the lumbar spine and total body was 42% and 17%, respectively. BMD at both sites was correlated positively with body mass index z-score, and negatively with dickkopf-1 (all p-values <0.05). There were no correlations among dickkopf-1, 25-hydroxyvitamin D, osteocalcin and C-telopeptide of type-I collagen. Multiple regression analysis showed dickkopf-1 inversely associated with total body BMD z-score adjusting for sex, bone age, body mass index, pre-transfusion hemoglobin, 25-hydroxyvitamin D, history of delayed puberty, type of iron chelator and prednisolone use (p-value = 0.009).

CONCLUSIONS

We demonstrated a high prevalence of low BMD in adolescents with non-deletional hemoglobin H disease. Moreover, dickkopf-1 inversely associated with total body BMD suggesting it may serve as a bone biomarker in this patient population.

摘要

背景

低骨密度（BMD）在β地中海贫血患者中普遍存在，且与循环中Dickkopf-1浓度升高有关。这些数据在α地中海贫血中有限。因此，我们旨在确定非缺失型血红蛋白H病青少年中低骨密度的患病率以及骨密度与血清Dickkopf-1之间的关联，非缺失型血红蛋白H病是一种α地中海贫血，其严重程度与中间型β地中海贫血相当。

方法

测量腰椎和全身骨密度并转换为身高调整后的z评分。低骨密度定义为骨密度z评分≤-2。采集参与者血液以测量Dickkopf-1和骨转换标志物浓度。

结果

纳入37例非缺失型血红蛋白H病患者（59%为女性，平均年龄14.6±3.2岁，86% Tanner分期≥2期，95%定期输血，16%服用泼尼松龙）。在研究前一年多，平均输血前血红蛋白、铁蛋白和25-羟基维生素D浓度分别为8.8±1.0 g/dL、958±513和26±6 ng/mL。排除服用泼尼松龙的参与者后，腰椎和全身低骨密度的患病率分别为42%和17%。两个部位的骨密度均与体重指数z评分呈正相关，与Dickkopf-1呈负相关（所有p值<0.05）。Dickkopf-1、25-羟基维生素D、骨钙素和I型胶原C端肽之间无相关性。多元回归分析显示，在调整性别、骨龄、体重指数、输血前血红蛋白、25-羟基维生素D、青春期延迟史、铁螯合剂类型和泼尼松龙使用情况后，Dickkopf-1与全身骨密度z评分呈负相关（p值=0.009）。