Kidney Disease and Bone: Changing the Way We Look at Skeletal Health

Abstract

Purpose of review: Kidney disease imparts profound skeletal changes, and unlike many other skeletal diseases, cortical bone is predominantly impacted. Significant advances in medical imaging have led to our ability to now obtain high-resolution three-dimensional views of cortical bone. This paper overviews recent work focused on cortical bone imaging, specifically cortical porosity, in kidney disease.

Recent findings: Although a number of clinical papers have used high-resolution imaging to assess cortical bone porosity, the most impactful work involves longitudinal study designs that have assessed cortical porosity changes over time. These latter studies demonstrate dramatic increases in cortical porosity in untreated individuals and a lack of clear efficacy in reversing porosity with treatment (although data are limited). Those papers providing longitudinal assessment, both clinical and pre-clinical, reveal powerful data about cortical porosity and provide a foundation upon which future studies can build.

Keywords: CKD-MBD; Cortical bone; Cortical porosity; HR-pQCT; Imaging.

Figure 1.

Cortical porosity is the key skeletal phenotype in patients with chronic kidney disease. (A) HRpQCT provides unparalleled resolution imaging to visualize in vivo porosity. Lower limb scans typically involve the distal tibia, with scans also capturing the adjacent distal fibula which has been neglected in published papers despite it having a much thicker cortex compared to the tibia which may help in defining the cortical shell. Image courtesy of Tom Nickolas. (B) Annual percent change from baseline in volumetric BMD and bone geometry/microarchitecture by HRpQCT at the tibia (mean ± SEM). Reproduced with permission from Nickolas TL, Stein EM, Dworakowski E, Nishiyama KK, Komandah-Kosseh M, Zhang CA, et al. Rapid cortical bone loss in patients with chronic kidney disease. J Bone Miner Res. 2013;28(8):1811–20. Used with permission from John Wiley and Sons

Figure 2.

(A) 3D renderings of longitudinal distal tibia scans a CKD rat at 30 and 35 weeks of age showing notable development of cortical pores. (B). Longitudinal measures of cortical bone porosity at the distal tibia in rats that progressively develop CKD. CKD animals had increasing amounts of cortical porosity (Ct.Po, %) over the 10-week study while normal littermates had little/no porosity over the same timeframe. Data shown as a box and whisker plot and log axis to accommodate the strongly skewed distribution. *p≤0.05; **p≤0.01; ***p≤0.001; ****p≤0.0001. Reproduced with permission from McNerny EMB, Buening DT, Aref MW, Chen NX, Moe, SM, and Allen MR. Time course of rapid bone loss and cortical porosity formation observes by longitudinal uCT in a rat model of CKD. Bone. 125 (2019) 16–24. Used with permission from Elsevier.