Page 1596 - Clinical Small Animal Internal Medicine

1534 Section 13 Diseases of Bone and Joint

Low‐impact activities (e.g., walking, cycling) have posi- can have the risk to develop adverse events that include
VetBooks.ir tive effects on human OA patients. In veterinary medi- GI disease (emesis, diarrhea, and anorexia), and subclini-
cal hyperalkaline phosphatemia and hypoproteinemia.
cine, low‐impact activities (walking, swimming) have
All COX‐selective (and nonselective) NSAIDs have
been traditionally favored over hard‐impact aerobic
activities (jumping, hard starting/running, vigorous toxicity potential. Hepatic toxicosis due to NSAID
climbing/running on irregular terrain) which can over- administration has been reported; however, all NSAIDs
stress degenerative joints. High‐impact activities may have a toxicity potential especially if a patient has under-
overstress OA joints and increase the inflammatory lying hepatic or renal disease, or thrombocytopathy.
condition of OA. Low‐impact activities are thought to Several in vivo studies using chondrocyte cell cultures or
reduce loads on an OA joint and result in less discomfort cartilage explants have reported a decrease in proteogly-
for the patient in maintaining good muscle strength/ can synthesis in those tissues incubated with selected
mass and joint function. Walking under controlled NSAIDs. It would appear to be a wiser clinical practice to
conditions (leash restraint) and/or swimming can be rec- administer NSAIDs on a PRN basis, especially for the
ommended to the owner with further instructions to patient that has only intermittent discomfort due to
eventually attempt to have the patient increase the dura- osteoarthritis.
tion of these activities gradually so long as the animal Disease‐modifying osteoarthritis agents have recently
appears to remain comfortable in doing so. To strengthen been developed for the treatment of human and veteri-
the active stabilizers (muscles and tendons) and to nary OA patients. These agents have become common-
improve the range of motion of joints in OA patients, place in the treatment of OA despite the lack of definitive
several physical rehabilitation modalities such as passive scientific studies confirming their efficacy. Most of these
and active range of motion exercises, message, deep products contain mixtures of glucosamine and chondroi-
ultrasound heat applications, and laser therapy can be tin sulfate, which supposedly enhance cartilage health
administered by certified small animal physical rehabili- by providing the necessary precursors to maintain and
tation technicians and specialists. In many OA cases, the repair cartilage. Glucosamine and chondroitin sulfate
adjunct use of physical rehabilitation can help improve reportedly have a positive effect on cartilage matrix by
patient comfort and function with very good to excellent enhancing proteoglycan production and inhibiting cata-
clinical results. bolic enzyme production or activity in OA joints. These
properties have contributed to the labeling of these
agents as “chondroprotective.” With the exception of one
Pharmacologic/Nonpharmacologic OA Agents
product which is a true pharmaceutical by definition
The primary goal in the pharmacologic management of (Adequan®, Luitpold Pharmaceuticals, FDA approved in
OA is to relieve the patient of discomfort associated horses and dogs), these agents are marketed as oral nutri-
with joint movement. Ideally, this would involve oral or tional supplements (“nutricueticals”) and not “drugs”
injectable agents with analgesic, antiinflammatory, and as such, the FDA does not require the manufacturer
and potential chondromodulating properties (disease‐ to provide efficacy data for their product. Bioavailability
modifying OA agents, DMOA). Such agents would ide- of orally ingested forms of glucosamine and chondroitin
ally biochemically block the inducible cyclooxegenase‐2 sulfate is 87% and 70% in humans and experimental ani-
(COX‐2) and lipoxygenase pathways. Several FDA‐ mals, respectively. Limited investigations have been per-
approved “COX‐selective” nonsteroidal antiinflamma- formed on the in vitro and in vivo activity of glucosamine
tory drugs (NSAIDs) have been developed for this and chondroitin sulfate separately, but products contain-
purpose (e.g., carprofen, meloxicam, firocoxib, etc.). ing both agents have become popular for treating OA
Robenaxocib is currently the only approved NSAID symptoms in humans and other animals. Synergism with
for cats in the United States. Grapiprant, a newer class of glucosamine and chondroitin sulfate has recently been
prostaglandin receptor antagonist; a non-COX pathway demonstrated histologically and with in vivo biochemical
inhibitor for the treatment of the clinical signs of OA, analysis in a rabbit OA model.
has been developed with the intent to reduce the poten- Glucosamine and chondroitin sulfate are two regular
tial of adverse events of GI. renal, and liver disease seen nutricuetical combinations used in many dietary sup-
in the small percentages of patients administered select plenets for dogs and cats. Examples of these formula-
and non-select COX-2 inhibitors. Grapiprant is specific tions are Cosequin® and Dasuquin® (similar to Cosequin®
to the blockage of Prostaglandin E2 receptor 4 (EP4); a but with the additions of with avocado/soybean
primary mediator of OA-based pain and inflammation. unsaponifiables and methylsulfonylmethane (MSM)
Although touted as a "non-NSAID" anti-inflammatory (Nutramax) and Glycoflex® (Vetri‐Science Laboratories).
and analgesic drug, OA patients administered grapiprant Although clinically noted not to have predictable