Department of Chemistry and Biochemistry, Arizona State University, Tempe, AZ 85287, USA.
Proc Natl Acad Sci U S A. 2012 Jun 19;109(25):9989-94. doi: 10.1073/pnas.1119587109. Epub 2012 May 31.
The ability to rapidly detect changes in bone mineral balance (BMB) would be of great value in the early diagnosis and evaluation of therapies for metabolic bone diseases such as osteoporosis and some cancers. However, measurements of BMB are hampered by difficulties with using biochemical markers to quantify the relative rates of bone resorption and formation and the need to wait months to years for altered BMB to produce changes in bone mineral density large enough to resolve by X-ray densitometry. We show here that, in humans, the natural abundances of Ca isotopes in urine change rapidly in response to changes in BMB. In a bed rest experiment, use of high-precision isotope ratio MS allowed the onset of bone loss to be detected in Ca isotope data after about 1 wk, long before bone mineral density has changed enough to be detectable with densitometry. The physiological basis of the relationship between Ca isotopes and BMB is sufficiently understood to allow quantitative translation of changes in Ca isotope abundances to changes in bone mineral density using a simple model. The rate of change of bone mineral density inferred from Ca isotopes is consistent with the rate observed by densitometry in long-term bed rest studies. Ca isotopic analysis provides a powerful way to monitor bone loss, potentially making it possible to diagnose metabolic bone disease and track the impact of treatments more effectively than is currently possible.
快速检测骨矿物质平衡 (BMB) 变化的能力对于代谢性骨疾病（如骨质疏松症和某些癌症）的早期诊断和治疗评估将具有重要价值。然而，BMB 的测量受到使用生化标志物定量骨吸收和形成的相对速率的困难以及需要等待数月至数年才能使 BMB 的改变导致骨矿物质密度发生足够大的变化以通过 X 射线密度测定法检测到的限制。我们在这里表明，在人类中，尿液中 Ca 同位素的天然丰度会迅速响应 BMB 的变化而变化。在卧床休息实验中，使用高精度同位素比质谱法允许在大约 1 周后，在骨矿物质密度发生足够大的变化以通过密度测定法检测到之前，在 Ca 同位素数据中检测到骨质流失的发生。Ca 同位素与 BMB 之间的关系的生理基础已经足够了解，因此可以使用简单的模型将 Ca 同位素丰度的变化定量转化为骨矿物质密度的变化。从 Ca 同位素推断的骨矿物质密度变化率与长期卧床休息研究中通过密度测定法观察到的变化率一致。Ca 同位素分析提供了一种监测骨丢失的有力方法，有可能比目前更有效地诊断代谢性骨疾病并跟踪治疗效果。
