Enneman A W, Swart K M A, Zillikens M C, van Dijk S C, van Wijngaarden J P, Brouwer-Brolsma E M, Dhonukshe-Rutten R A M, Hofman A, Rivadeneira F, van der Cammen T J M, Lips P, de Groot C P G M, Uitterlinden A G, van Meurs J B J, van Schoor N M, van der Velde N
Department of Internal Medicine, Erasmus MC, University Medical Centre Rotterdam, P.O. Box 2040, 3000 CA Rotterdam, The Netherlands.
Department of Epidemiology and Biostatistics, EMGO Institute for Health and Care Research, VU University Medical Center, Van der Boechorststraat 7, 1081 BT Amsterdam, The Netherlands.
Bone. 2014 Jun;63:141-6. doi: 10.1016/j.bone.2014.03.002. Epub 2014 Mar 12.
High plasma homocysteine levels have been associated with incident osteoporotic fractures, but the mechanisms underlying this association are still unknown. It has been hypothesized that homocysteine might interfere with collagen cross-linking in bone, thereby weakening bone structure. Therefore, we wanted to investigate whether plasma homocysteine levels are associated with bone quality parameters, rather than with bone mineral density.
Cross-sectional data of the B-PROOF study (n=1227) and of two cohorts of the Rotterdam Study (RS-I (n=2850) and RS-II (n=2023)) were used. Data on bone mineral density of the femoral neck and lumbar spine were obtained in these participants using dual-energy X-ray assessment (DXA). In addition, participants of B-PROOF and RS-I underwent quantitative ultrasound measurement of the calcaneus, as a marker for bone quality. Multiple linear regression analysis was used to investigate the associations between natural-log transformed plasma levels of homocysteine and bone mineral density or ultrasound parameters.
Natural-log transformed homocysteine levels were inversely associated with femoral neck bone mineral density in the two cohorts of the Rotterdam Study (B=-0.025, p=0.004 and B=-0.024, p=0.024). In B-PROOF, no association was found. Pooled data analysis showed significant associations between homocysteine and bone mineral density at both femoral neck (B=-0.032, p=0.010) and lumbar spine (B=-0.098, p=0.021). Higher natural-log transformed homocysteine levels associated significantly with lower bone ultrasound attenuation in B-PROOF (B=-3.7, p=0.009) and speed of sound in both B-PROOF (B=-8.9, p=0.001) and RS-I (B=-14.5, p=0.003), indicating lower bone quality. Pooled analysis confirmed the association between homocysteine and SOS (B=-13.1, p=0.016). Results from ANCOVA-analysis indicate that differences in SOS and BUA between participants having a plasma homocysteine level above or below median correspond to 0.14 and 0.09 SD, respectively.
In this study, plasma levels of homocysteine were significantly inversely associated with both bone ultrasound parameters and with bone mineral density. However, the size of the associations seems to be of limited clinical relevance and may therefore not explain the previously observed association between plasma homocysteine and osteoporotic fracture incidence.
高血浆同型半胱氨酸水平与骨质疏松性骨折的发生有关，但其潜在机制仍不清楚。据推测，同型半胱氨酸可能会干扰骨中的胶原交联，从而削弱骨结构。因此，我们想研究血浆同型半胱氨酸水平是否与骨质量参数相关，而非与骨密度相关。
使用了B-PROOF研究（n = 1227）以及鹿特丹研究的两个队列（RS-I（n = 2850）和RS-II（n = 2023））的横断面数据。通过双能X线评估（DXA）获取这些参与者股骨颈和腰椎的骨密度数据。此外，B-PROOF和RS-I的参与者接受了跟骨定量超声测量，作为骨质量的标志物。采用多元线性回归分析来研究同型半胱氨酸自然对数转换后的血浆水平与骨密度或超声参数之间的关联。
在鹿特丹研究的两个队列中，同型半胱氨酸自然对数转换后的水平与股骨颈骨密度呈负相关（β=-0.025，p = 0.004；β=-0.024，p = 0.024）。在B-PROOF研究中未发现关联。汇总数据分析显示，同型半胱氨酸与股骨颈（β=-0.032，p = 0.010）和腰椎（β=-0.098，p = 0.021）的骨密度均存在显著关联。在B-PROOF研究中，同型半胱氨酸自然对数转换后的水平越高，与较低的骨超声衰减显著相关（β=-3.7，p = 0.009），在B-PROOF研究（β=-8.9，p = 0.001）和RS-I研究（β=-14.5，p = 0.003）中均与声速显著相关，表明骨质量较低。汇总分析证实了同型半胱氨酸与声速之间的关联（β=-13.1，p = 0.016）。协方差分析结果表明，血浆同型半胱氨酸水平高于或低于中位数的参与者之间，声速和宽带超声衰减的差异分别相当于0.14和0.09个标准差。
在本研究中，血浆同型半胱氨酸水平与骨超声参数和骨密度均显著负相关。然而，这种关联的程度似乎在临床方面相关性有限，因此可能无法解释先前观察到的血浆同型半胱氨酸与骨质疏松性骨折发生率之间的关联。
