Early identification helpful
Similarly, early identification of biochemical degradation in the ECM of articular cartilage that precedes morphologic damage
could lead to early and effective treatment with prevention of, or decrease in, the articular cartilage degradation of OA.
Equine veterinarians also need objective outcome parameters in assessing the results of various treatments for musculoskeletal
disease in general and joint disease in particular in the horse.
There is good potential that serum biomarkers could be an important addition to the equine veterinarian's armamentarium for
all these issues.
Human clinical trials are now specific about the recording of outcome measures. Outcome variables in OA clinical trials need
to be selected on the basis of the therapeutic objective and are a critical part of assessing the results of medication.
In a workshop of the World Health Organization and the American Academy for Orthopedic Surgeons, the methods to assess
progression of OA of the hip and knee were reviewed (Dieppe et al., 1994). In addition, the European Group for the Respect
of Ethics and Excellence in Science made recommendations on methods for registration of drugs for OA (Group for the Respect
of Ethics and Excellence in Science, 1996).
Principles of biomarkers
The terms biomarker, biochemical marker and molecular marker all have been used to describe direct or indirect indicators
of musculoskeletal turnover. These markers often are molecules that are typical products and by-products of the metabolic
process occurring within the musculoskeletal system.
Disease alterations occur between the anabolic and catabolic processes within the skeletal tissues; consequently, concentration
of biomarkers may increase or decrease. In joint disease, these molecules can be released into the synovial fluid when the
source is articular cartilage, menisci, ligament or synovial membrane. If the underlying subchondral bone is involved, molecules
from osseous tissue usually will be delivered into the bloodstream.
Biomarkers potentially can be used to clarify pathobiological processes in the joint, differentiate diagnostically between
affected and non-affected joints, distinguish the degree of degradation in articular cartilage and monitor the response to
Direct biomarkers originate principally from cartilaginous structures and provide specific information about alterations in
cartilage matrix and anabolism or catabolism.
Until now, direct biomarkers have been immunologic-based tests (ELISA or IRA), as illustrated in Figure 3. These biomarkers
can reflect anabolic processes (that often are reflective of early damage and a response from the host tissue) or catabolic
On the other hand, indirect biomarkers are not derived principally from cartilage but have the potential to influence the
metabolism of chondrocytes or the integrity of the matrix and include proteolytic enzymes and their inhibitors, growth factors,
pro-inflammatory cytokines and other molecules from non-cartilaginous sources, including MMPs, aggrecanase, TIMP, IGF-1, IL-1,
IL-6, TNFa, HA and C-reactive protein.