Protein biomarkers in serum and urine for determining presence or absence of hip dysplasia in a canine model

Abstract

This study compares serum and urine concentrations of relevant protein biomarkers among adult dogs with or without radiographic canine hip dysplasia (CHD). Adult (≥2 years of age), client‐owned dogs (n = 74) radiographically categorized as having at least “good” hips (n = 49) or having “mild,” “moderate,” or “severe” hip dysplasia (n = 25) by the Orthopedic Foundation for Animals (OFA). Urine and serum samples were obtained from each dog at a single time‐point and processed and analyzed for relevant protein biomarkers. Urinary concentrations of CTX‐II (p < 0.001) and TIMP‐1 (p = 0.002) were significantly lower in dogs with CHD compared to dogs with no CHD. ROC curve analyses were successful in establishing a panel of four biomarkers (urinary CTX‐I and II, serum MMP‐9, and serum PIICP) with high discriminatory capability for the presence or absence of hip dysplasia in adult dogs (AUC = 0.89). Urine and serum biomarkers can distinguish adult dogs with radiographic CHD from those with no CHD with a sensitivity of 0.95 and specificity of 0.77 using ROC analysis with AUC 0.89. Clinical Significance: This finding suggests that this simple, minimally invasive diagnostic technique has potential for discriminating dysplastic dogs from dogs with normal hips, with possible translational application to humans based on similar etiopathogenesis. © 2019 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 9999:1–5, 2019.

Evaluation of Serum and Urine Biomarker Panels for Developmental Dysplasia of the Hip Prior to Onset of Secondary Osteoarthritis

“…Based on previous data for application in canine hip dysplasia 13 and DDH, 14 clinically relevant biomarkers with mechanisms related to joint health and disease were selected for testing. To measure dynamics of collagen degradation and synthesis, cross-linked C-telopeptide of type I collagen (CTX-I), and cross-linked C-telopeptide type II collagen (CTX-II), procollagen I C-terminal propeptide (PICP) and procollagen II C-terminal propeptide (PIICP) using commercially available enzyme-linked immunosorbent assays (ELISA) assays (ABclonal; Woburn, MA).…”

“…[10][11][12] Previous research has identified panels of serum and urine protein biomarkers to discriminate between dogs with healthy hips and those with hip dysplasia, prior to the onset of secondary osteoarthritis. 13 Initial data comparing individuals with DDH, prior to and following diagnosis of hip OA, and from age-matched healthy-hip controls delineated significant differences in mechanistic serum and urine biomarkers between hip-status cohorts. 14 Taken together, these data provide a foundation for development and validation of biomarker panels as a clinically applicable and cost-efficient method for screening, diagnosis, and staging for DDH to avoid misdiagnosis and improve patient outcomes.…”