Static histomorphometry parameters can identify bone turnover status in children and adults with chronic kidney disease.

Introduction: Tetracycline labeling for bone biopsy facilitates quantification of the pace of new bone production. As tetracycline labeling needs to be done prior to biopsy, it cannot be used to assess bone turnover in patients presenting with fractures, yet knowing turnover rate in patients experiencing fractures - especially in those with chronic kidney disease (CKD) - may guide appropriate medical therapy after surgical repair. Therefore, we sought to determine the diagnostic accuracy of static markers of bone turnover relative to tetracycline labeling in a pediatric and adult cohort of patients with chronic kidney disease (CKD) undergoing iliac crest biopsy with histomorphometry.

Methods: We evaluated two cohorts, one of 147 children and young adults ages 18±10 and another of 151 adults ages 49±13 who had undergone iliac crest biopsy with tetracycline labeling for clinical indications of CKD-mineral and bone disorders. We used bone formation rate relative to bone surface (BFR/BS) based on double tetracycline labeling as our gold standard marker of bone turnover. A blinded investigator used light microscopy without fluorescence to measure static bone turnover parameters. We compared the area under the ROC curve (AUC), sensitivity, and specificity of each static parameter with low and high bone turnover based on BFR/BS.

Results: In the pediatric and adult cohorts, 35 (24 %) and 70 (46 %) had low bone turnover, respectively, and 18 (12 %) and 30 (20 %) had high bone turnover, respectively. The static parameters with the greatest AUCs for low and high turnover were osteoblast surface/bone surface (Ob.S/BS), osteoclast surface/bone surface (Oc.S/BS), eroded surface/bone surface (ES/BS), osteoid surface/bone surface (OS/BS), osteoid volume/bone volume (OV/BV), and osteoid thickness (O.Th.) in both cohorts. Ob.S/BS had the highest AUC for low and high turnover in the pediatric cohort (0.8204 and 0.8678, respectively) whereas Oc.S/BS had the highest AUC for low turnover (0.8325) and ES/BS had the highest AUC for high turnover (0.7360) in the adult cohort.

Discussion: Static measures of histomorphometry that do not rely on tetracycline bone labeling can identify low and high bone turnover in children and adults with CKD with moderate to high accuracy. This approach may allow assessment of bone turnover in the setting of clinical fractures where clinicians may have access to bone tissue but where tetracycline labeling is not available.