Routine assessment of the skeleton's response to disease and injury traditionally has consisted of plain-film radiography supplemented with advanced imaging techniques, such as computed tomography, magnetic resonance imaging, nuclear scintigraphy, and bone densitometry. Although these techniques provide increased sensitivity as compared with radiography, they still are limited by the fact that they can only document the net results of past skeletal activity. In contrast, serum and urinary biomarkers of bone formation and resorption provide near real-time information about bone cell activity. In this review, I describe the scientific rationale behind the use of these markers in humans and detail the efforts that have been made to adapt this technology to veterinary medicine and animal research. Commercial assay kits that are applicable to different animal species are described, and the potential limitations of the technology are discussed. The goal of this review is to provide clinical pathologists and researchers with the information needed to decide whether the use of bone markers is likely to be helpful and to select the most appropriate marker (or panel of markers) to answer a particular question.

Bone metastasis is a common untreatable complication associated with prostate cancer. Metastatic cells seed in skeletal sites under active turnover containing dense marrow cellularity. We hypothesized that differences in these skeletal-specific processes are among the critical factors that facilitate the preferential localization of metastatic prostate cancer in bone. To test this, athymic mice were administered PTH to induce bone turnover and increase marrow cellularity daily 1 wk before and after intracardiac inoculation of luciferase-tagged PC-3 cells. Tumor localization was monitored by bioluminescence imaging weekly for 5 wk. At the time of tumor inoculation, PTH-treated mice demonstrated significant increases in serum levels of bone turnover markers such as osteocalcin and tartrate-resistant acid phosphatase 5b and in the number of tartrate-resistant acid phosphatase-positive osteoclasts per millimeter of bone when compared with the other groups. Likewise, PTH treatment stimulated a qualitative increase in marrow cellular proliferation as determined by 5-bromo-2'-deoxyuridine immunostaining. Skeletal metastases formed in the hind limb and craniofacial regions of young mice with no difference between groups. In adult mice, however, bioluminescent signals in the hind limb and craniofacial regions were 3-fold higher in PTH-treated mice vs. controls. Fluorochrome labeling revealed increased bone formation activity in trabecular bone adjacent to tumors. When zoledronic acid, a nitrogen-containing bisphosphonate that inhibits osteoclast-mediated bone resorption, was administered concurrently with PTH, a significant reduction in the incidence of bone tumors was observed. Overall, these studies provide new evidence that skeletal sites rich in marrow cellularity under active turnover offer a more congenial microenvironment to facilitate cancer localization in the skeleton.

Although the anatomy of the ovine stifle joint is similar to that of the human knee joint, a number of unique features were identified. These included the presence of the tendon of the m. extensor digitorum longus on the craniolateral aspect of the stifle joint, the absence of a cranial meniscofemoral ligament (ligament of Humphrey) in the caudal joint space, and attachment of the patellar tendon to the cranial pole of the patella (rather than to the distal pole, as in humans). The implications of these differences are discussed with reference to the suitability of the ovine stifle as a surgical model for the human knee joint.

Results suggested that a single intra-articular injection of autologous platelets resulted in significant improvements at 12 weeks in dogs with osteoarthritis involving a single joint.

Particulate wear debris can induce the release of bone-resorbing cytokines from cultured macrophages and fibroblasts in vitro, and these mediators are believed to be the cause of the periprosthetic bone resorption which leads to aseptic loosening in vivo. Much less is known about the effects of particulate debris on the growth and metabolism of osteoblastic cells. We exposed two human osteoblast-like cell lines (SaOS-2 and MG-63) to particulate cobalt, chromium and cobalt-chromium alloy at concentrations of 0, 0.01, 0.1 and 1.0 mg/ml. Cobalt was toxic to both cell lines and inhibited the production of type-I collagen, osteocalcin and alkaline phosphatase. Chromium and cobalt-chromium were well tolerated by both cell lines, producing no cytotoxicity and no inhibition of type-I collagen synthesis. At the highest concentration tested (1.0 mg/ml), however, chromium inhibited alkaline phosphatase activity, and both chromium and cobalt-chromium alloy inhibited osteocalcin expression. Our results clearly show that particulate metal debris can modulate the growth and metabolism of osteoblastic cells in vitro. Reduced osteoblastic activity at the bone-implant interface may be an important mechanism by which particulate wear debris influences the pathogenesis of aseptic loosening in vivo.