Plasma growth and differentiation factor 15 predict longitudinal changes in bone parameters in women, but not in men
Plasma growth and differentiation factor 15 predict longitudinal changes in bone parameters in women, but not in men
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血浆生长和分化因子 15 可以预测女性骨参数的纵向变化，但不能预测男性
DOI：
10.1093/gerona/glac079
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发表时间：
2022
期刊：
影响因子：
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通讯作者：
Ferrucci Luigi
中科院分区：
文献类型：
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作者：
Osawa Yusuke;Tanaka Toshiko;Semba Richard D;Fantoni Giovanna;Moaddel Ruin;Candia Juli?n;Simonsick Eleanor M;Bandinelli Stefania;Ferrucci Luigi
骨脆性会随着衰老而加重，但检测新出现的骨质减少的生物标志物尚未完全阐明。生长/分化因子 15 (GDF-15) 在多种与年龄相关的疾病中具有多效性作用，但其与骨质减少的关系尚不清楚。我们在 InCHIANTI 研究中检查了 596 名成年人（基线年龄，65-94 岁；女性，52.4%；平均随访时间，7.0 ± 3.0 年）9 年随访期间血浆 GDF-15 水平与骨参数变化率之间的关系。使用 1.3k HTS SOMAscan 测定法测量血浆 GDF-15 浓度。通过外周定量计算机断层扫描测量了右胫骨的八个骨骼参数；总骨密度、小梁骨密度、髓质加小梁骨密度、皮质骨密度、总骨面积、皮质骨面积、髓质骨面积和最小转动惯量 (mMOI)。我们运行了性别特异性线性混合效应模型，其中随机截距和斜率根据年龄、年龄平方、教育程度、体重指数、体重变化率、吸烟、久坐行为、小腿肌肉和脂肪的横截面积、25-羟基维生素 D、甲状旁腺激素、钙、糖尿病和随访时间进行了调整。我们发现，在预测女性皮质骨密度和 mMOI 的模型中，“基线 GDF-15 × 时间”存在显着关联，表明这些骨参数的下降率随着 GDF-15 的升高而增加（错误发现率<0.05）。较高的血浆 GDF-15 水平预示着女性骨骼参数的加速下降，但与男性的相关性较小。此外，还需要研究来了解这些性别差异背后的机制。
Bone fragility can progress with aging, but biomarkers to detect emerging osteopenia have not been fully elucidated. Growth/differentiation factor 15 (GDF-15) has pleiotropic roles in a broad range of age-related conditions, but its association with osteopenia is unknown. We examined the relationship between plasma GDF-15 levels and rate of change in bone parameters over 9 years of follow-up in 596 adults in the InCHIANTI study (baseline age, 65–94 years; women, 52.4%; mean follow-up, 7.0 ± 3.0 years). Plasma GDF-15 concentrations were measured using the 1.3k HTS SOMAscan assay. Eight bone parameters were measured in the right tibia by peripheral quantitative computed tomography; total bone density, trabecular bone density, medullary plus trabecular bone density, cortical bone density, total bone area, cortical bone area, medullary bone area, and minimum moment of inertia (mMOI). We ran sex-specific linear mixed-effect models with random intercepts and slopes adjusted for age, age-squared, education, body mass index, the rate of change in weight, smoking, sedentary behavior, cross-sectional areas of calf muscles and fat, 25-hydroxyvitamin D, parathyroid hormone, calcium, diabetes mellitus, and follow-up time. We found a significant association of “baseline GDF-15 × time” in models predicting cortical bone density and the mMOI in women, suggesting that the rates of decline in these bone parameters increased with higher GDF-15 (false discovery rate <0.05). Higher plasma levels GDF-15 predicted an accelerated decline in bone parameters in women, but was less associated in men. Furthermore studies are needed to understand the mechanisms underlying these sex differences.