Abstract

Abstract Background and Aims A full histomorphometric analysis of a transiliac bone biopsy with prior tetracycline labeling remains the gold standard to diagnose renal osteodystrophy. Bone turnover is primarly evaluated by the dynamic parameter bone formation rate, calculated from the incorporation of tetracycline in bone. In cases of failed tetracycline labels, however, an evaluation of bone turnover based on static parameters is warranted. This study investigates the diagnostic accuracy of static histomorphometric parameters for the diagnosis of high and low bone turnover. Method Bone biopsies with prior tetracycline labeling of sufficient quality for a full histomorpometric analysis were included (n = 205). Mean age of participants was 56±13 years, 67% were men, and 22% had diabetes mellitus. Diagnostic accuracy of static histomorphometric parameters for bone turnover was evaluated by area under the receiver operator characteristics curve (AUC) statistics, against the full set of static and dynamic histomorphometric parameters. The cohort was randomly split to allow calculation of optimal diagnostic cutoffs in an exploration cohort (n=105), with subsequent validation in a separate subset of patients (n=100). Results All histomorphometric parameters were significantly different across categories of low (24%), normal (60%), and high (16%) bone turnover (p < 0.01), and all were significant predictors of both high and low bone turnover (Figure 1). Calculated optimal cutoffs and their sensitivities and specificities in the validation cohort are shown in Table 1. Diagnostic accuracy was very good for high turnover, as the combination of presence of fibrosis with ObPm>5.4%, OcPm>1.5%, and OAr>2.4% provided a correct diagnosis in 94% of patients, with positive (PPV) and negative (NPV) predictive values of 80% and 96%, respectively. Using the same predefined combination, an accuracy of 80% was achieved for low turnover (no fibrosis, ObPm≤1.9% OcPm≤0.9% and OAr≤1.6%), with a PPV of 71% and a NPV of 82%. Conclusion Static histomorphometric parameters provide an acceptable alternative for the diagnosis of high and low bone turnover. In the absence of successful tetracycline labeling, the proposed cutoffs may provide a suitable alternative for the evaluation of bone turnover in renal osteodystrophy.

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