Hiller Ruth G G, Patecki Margret, Neunaber Claudia, Reifenrath Janin, Kielstein Jan T, Kielstein Heike
Institute for Pathology, University Hospital Halle (Saale), Magdeburger Straße 14, 06112, Halle (Saale), Germany.
Department of Nephrology and Hypertension, Hannover Medical School, Hannover, Germany.
BMC Nephrol. 2017 Apr 13;18(1):134. doi: 10.1186/s12882-017-0550-5.
Patients with an impaired renal function show a high incidence of bone and mineral disturbances. These 'chronic kidney disease - mineral and bone disorders' (CKD-MBD) range from high turnover osteoporosis to adynamic bone disease. Currently, the histomorphometric analysis of a bone biopsy taken from the iliac crest is viewed as the gold standard for CKD-MBD subtype differentiation. However, the clinical relevance of such a biopsy is questionable since iliac crest fractures are an extremely rare finding. Therefore, we aimed to elucidate if the histomorphometric parameter 'trabecular bone volume (BV/TV)' from the iliac crest is representative for other biopsy locations. We chose two skeletal sites of higher fracture risk for testing, namely, the tibial bone and the lumbar spine, to examine if the current gold standard of bone biopsy is indeed golden.
Bone biopsies were taken from 12 embalmed body donors at the iliac crest, the proximal tibia, and the lumbar vertebral body, respectively. Masson-Goldner stained sections of methyl methacrylate embedded biopsies were used for trabecular bone volume calculation. Furthermore, exemplary μ-computed tomography (XtremeCT) scans with subsequent analysis were performed.
Median values of trabecular bone volume were comparable between all body donors with median (interquartile range, IQR) 18.3% (10.9-22.9%) at the iliac crest, 21.5% (9.5-40.1%) at the proximal tibia, and 16.3% (11.4-25.0%) at the lumbar spine. However, single values showed extensive intra-individual variation, which were also confirmed by XtremeCT imaging.
Distinct intra-individual heterogeneity of trabecular bone volume elucidate why a bone biopsy from one site does not necessarily predict patient relevant endpoints like hip or spine fractures. Physicians interpreting bone biopsy results should know this limitation of the current gold standard for CKD-MBD diagnostic, especially, when systemic therapeutic decisions should be based on it.
肾功能受损患者的骨与矿物质紊乱发生率较高。这些“慢性肾脏病 - 矿物质和骨异常”(CKD - MBD)范围从高转换型骨质疏松到骨动力不足性骨病。目前,取自髂嵴的骨活检组织形态计量学分析被视为CKD - MBD亚型分化的金标准。然而,由于髂嵴骨折极为罕见,这种活检的临床相关性值得怀疑。因此,我们旨在阐明来自髂嵴的组织形态计量学参数“小梁骨体积(BV/TV)”是否代表其他活检部位。我们选择了两个骨折风险较高的骨骼部位进行测试,即胫骨和腰椎,以检验当前骨活检的金标准是否真的名副其实。
分别从12名尸体供体的髂嵴、胫骨近端和腰椎椎体获取骨活检样本。使用甲基丙烯酸甲酯包埋活检样本的马松 - 戈德纳染色切片来计算小梁骨体积。此外,还进行了示例性的μ - 计算机断层扫描(XtremeCT)并随后进行分析。
所有尸体供体的小梁骨体积中位数具有可比性,髂嵴处中位数(四分位间距,IQR)为18.3%(10.9 - 22.9%),胫骨近端为21.5%(9.5 - 40.1%),腰椎为16.3%(11.4 - 25.0%)。然而,单个值显示出个体内的广泛差异,这也通过XtremeCT成像得到证实。
小梁骨体积明显的个体内异质性解释了为什么从一个部位进行的骨活检不一定能预测与患者相关的终点事件,如髋部或脊柱骨折。解读骨活检结果的医生应该了解CKD - MBD诊断当前金标准的这一局限性,特别是在应基于此做出系统性治疗决策时。