Homeostatic bone remodeling is a dynamic and continual process whereby skeletal mass and health are maintained by the coordinated balance of bone formation and bone resorption. The cellular components responsible for skeletal equilibrium are osteoclasts that function to degrade aged or diseased bone and osteoblasts that deposit osteoid, which subsequently mineralizes to new bone. Under normal physiologic conditions, osteoclast and osteoblast activities are tightly coupled with one another and form a functional element known as the basic multicellular unit.1 Pathologic bone disorders such as osteoporosis and skeletal neoplasms perturb finely balanced bone turnover, often favoring excessive bone resorption.2 Because mineralized bone is composed of approximately 90% type I collagen, pathologic skeletal resorption resulting from dysregulated osteoclast activity leads to proteolysis and release of type I collagen major cross-links such as deoxypyridinoline (DPD). In addition, specific collagen type I epitopes, including amino-(N-telopeptide [NTx]) and carboxy-(C-telopeptide [CTx]) terminal peptides, which hold collagen major cross-links together, also are released during bone degradation. Collectively, these cleavage products of type I collagen resulting from osteoclast activities are liberated into the bloodstream and ultimately are eliminated by the kidneys. Measurement of these bone resorption markers serves as a noninvasive method for assessing dynamic changes in bone metabolism.2–6
In humans and animals with pathologic skeletal conditions, circulating concentrations of bone resorption markers are increased.7–14 Common markers of bone resorption measured in humans with pathologic osteolytic diseases include urine NTx, urine CTx, urine DPD, serum NTx, and serum CTx.6,8,15 Although useful for supporting the diagnosis of dysregulated bone metabolism, some bone resorption markers also can be used to assess treatment responses. Bone resorption markers reflect bone metabolic changes in real time, and they have been shown in cancer patients to predict progression of skeletal metastases before radiographic changes are evident.16 In humans with skeletal metastases treated with antineoplastic or aminobisphosphonate therapies, the magnitude of reduction in bone resorption markers correlates with treatment effectiveness for reducing bone pain and tumor burden.2,10,17,18
Despite the widely documented diagnostic and therapeutic monitoring use of several urine and serum bone resorption markers in humans with skeletal metastases, comparative studies in companion animals with malignant osteolysis remain limited and incomplete.9,12,19 Although the utility of a solitary bone resorption marker, urine NTx, has been described in dogs with appendicular osteosarcoma (OSA),9,12,19 the contemporaneous examination of multiple bone resorption markers in dogs to determine differences in their ability for discriminating dogs with OSA from healthy dogs and those with orthopedic disorders has not previously been conducted. Therefore, the purpose of this study was to compare 5 bone resorption markers in 3 populations of age- and weight-matched dogs considered healthy or diagnosed with OSA or orthopedic disorders.