A Comparison of Five Different Bone Resorption Markers in Osteosarcoma‐Bearing Dogs, Normal Dogs, and Dogs with Orthopedic Diseases

Abstract

Background: Various bone resorption markers in humans are useful for supporting the diagnosis of malignant skeletal pathology, with certain bone resorption markers appearing to be more discriminatory for detecting cancer-induced osteolysis than others. Canine osteosarcoma (OSA) is characterized by focal bone destruction, but a systematic investigation for determining which bone resorption marker best supports the diagnosis of OSA in dogs has not been reported.Hypothesis: Dogs with OSA will have increased concentrations of bone resorption markers compared with healthy dogs and dogs with orthopedic disorders. Differences will exist among various bone resorption markers for their ability to support the diagnosis of malignant osteolysis in dogs with OSA.Animals: Single time point, cross-sectional, cohort study including dogs with OSA (n 5 20) or orthopedic disorders (n 5 20) and healthy dogs (n 5 22).Methods: Basal concentrations of urine and serum N-telopeptide (NTx), urine and serum C-telopeptide (CTx), and urine deoxypyridinoline (DPD) were compared among all 3 groups.Results: Compared with healthy dogs and dogs with orthopedic disorders, urine NTx, serum NTx, and serum CTx concentrations were significantly increased in dogs with OSA. For urine NTx and serum NTx, the calculated lower and upper 95% confidence limits in dogs with OSA did not overlap with dogs diagnosed with orthopedic disorders or healthy dogs.Conclusions and clinical importance: Of the markers evaluated in this study, urine NTx and serum NTx appear to be the most discriminatory resorption markers supporting the diagnosis of focal malignant osteolysis in dogs with OSA.

Bone Resorption Markers and Dual‐EnergyX‐Ray Absorptiometry in Dogs with Avascular Necrosis, Degenerative Joint Disease, and Trauma of the Coxofemoral Joint

“…Indeed, serum NTx correlated with densitometric measurements and was elevated in our population of dogs with avascular necrosis. These values were also outside the normal range previously reported in normal dogs and dogs with orthopedic diseases . Although this is the first study we are aware of reporting serum NTx concentrations in dogs with avascular necrosis, previous reports have proposed bone markers as useful tools for early detection and monitoring of nonneoplastic bone conditions, such as facture healing and osteomyelitis , 37‐39 .…”

“…Serum ICTP concentrations indicate the presence of carboxy‐terminal telopeptide of type I collagen detected by radio‐immunoassay, whereas we measured the concentrations of NTx of type I collagen, by enzyme‐linked immune‐sorbent assay (ELISA). We selected this technique because we previously found that serum NTx was more discriminatory than the detection of C‐telopeptide in dogs with or without resorptive bone disease . Markers showing large changes in response to disease processes or treatment also tend to show substantial biologic variability .…”

“…Urine samples were immediately centrifuged at 4°C at 1500 rpm for 10 minutes and the supernatant was collected and stored at −80°C in 2 mL polypropylene cryovials until analysis. Urine NTx concentrations were measured with a commercial ELISA kit (Osteomark NTx Urine, Wampole Laboratories, Princeton, NJ), previously validated in dogs . Excretion of urine NTx was corrected for creatinine and expressed as nanomoles (nM) of bone collagen equivalent (BCE)/millimole (mM) of urine creatinine.…”

“…Whole blood samples were centrifuged for 10 minutes at 2000 rpm, and serum was separated and stored at −80°C in 2 mL polypropylene cryovials until analysis. Serum NTx concentrations were measured with a commercial ELISA kit (Osteomark NTx Serum, Wampole Laboratories), previously validated for use in the dog . Serum NTx concentrations were expressed as nM of BCE.…”

“…This body of evidence prompted investigations of these markers in dogs with osteosarcoma, to monitor the progression of disease and evaluate new therapies . In this population, urine NTx and serum NTx appeared more discriminatory than urine Dpd as well as urine CTx and serum CTx in supporting the diagnosis of focal malignant osteolysis . However, the diagnostic value of these markers in dogs with nonmalignant resorptive bone disease remains unclear.…”