Diagnostic Accuracy of Bone Turnover Markers in Patients With CKD: A Systematic Review and Meta-Analysis

Abnormal bone turnover in chronic kidney disease (CKD) increases fracture risk and influences treatment response, making accurate assessment essential. Although bone histomorphometry is the diagnostic gold standard, its invasiveness limits routine use. This study evaluated the diagnostic accuracy of noninvasive bone turnover markers-tartrate-resistant acid phosphatase 5b (TRAP5b), bone-specific alkaline phosphatase (BALP), and procollagen type I N-terminal propeptide (PINP)-compared with parathyroid hormone (PTH) for detecting high or low bone turnover in CKD.

A systematic review and meta-analysis of observational studies.

Adult patients with CKD (all stages).

Studies were included if they compared serum bone turnover markers to bone histomorphometry.

Two reviewers independently extracted study characteristics, population details, assay types, cutoff thresholds, sensitivity, specificity, and area under the ROC curve (AUC).

A meta-analysis using random-effects models pooled AUCs for detecting high and low bone turnover per marker including intact PTH. Subgroup analyses assessed assay types (mass-based vs activity-based BALP, intact vs total PINP) and CKD stages.

Eight studies were included with 6 studies providing AUC data for pooling. Intact PINP and BALP (mass assay) demonstrated the highest accuracy for identifying high bone turnover, whereas intact PTH showed only moderate discriminatory performance. For low turnover, TRAP5b, BALP, and intact PINP displayed comparable accuracy, while total PINP and PTH were less reliable. Reported diagnostic thresholds varied but generally yielded sensitivities of 50%-90% and specificities of 60%-95%. One study suggested that combining bone turnover markers, such as PINP with BALP or TRAP5b, may further enhance diagnostic discrimination.

Limited representation of non-hemodialysis populations, small sample sizes, and lack of standardized methods to determine thresholds.

TRAP5b, BALP, and intact PINP demonstrated moderate diagnostic accuracy and may support treatment decisions in CKD when bone biopsy is not feasible. (PROSPERO: CRD420251003120).