Page 910 - Adams and Stashak's Lameness in Horses, 7th Edition

876 Chapter 8

anecdotally, if a favorable response to IM administra- tory and degradative enzymes involved in progression of
tion occurs, it is rapid. ® OA, other studies have not measured any significant dif-
VetBooks.ir Shirley, NY) is produced from the bovine trachea and lung significant improvement in cartilage fibrillation scores
The PSGAG Adequan (Luitpold Pharmaceuticals, Inc.,
ference. When examined in the cartilage chip model,
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and is in a class of drugs that exhibits chondroprotective
was noted in the PPS treatment group, which may indicate
properties in cartilage. Pentosan polysulfate (PPS; in a its benefit is likely through its disease‐modifying effects.
sodium or calcium derivative), within a similar class of
medications, is produced from a plant source and is not Clinical Indications
licensed in the United States, but widely used in Europe
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and Australia. In the United States, compounded versions Despite lack of scientific data to support IM admin-
can be obtained for use in horses. This section focuses on istration of Adequan , some clinicians believe that it
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the use of IM PSGAG and PPS. Please refer to the chapter has a beneficial effect on certain horses. In a survey of
on IA therapy for IA use of PSGAG. over 400 equine practitioners, IM Adequan was one of
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While there has been convincing evidence of the ben- the most commonly administered medications (not in
eficial effects on cartilage, the exact mechanism of action the steroid category) in horses and was administered as
remains unknown. It has been theorized that PSGAGs a prophylactic therapy for OA. The current dosing
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form stable complexes with fibronectin and collagen fib- recommendations are 500 mg IM every 3–5 days for
3
ers and are deposited in cartilage. Studies have shown 5–7 treatments.
that PSGAGs inhibit a plethora of degradative enzymes Data is currently lacking in the benefit of IM PSGAG
that contribute to the osteoarthritic (OA) process and administration. At this time, most veterinarians that rec-
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an anti‐inflammatory role based on the inhibitory effects ommend IM Adequan do so for preventive therapy. IA
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on leukocyte migration and interleukin levels. 20,39 A bio- use has shown greater benefit and is covered in the sec-
synthetic role has also been documented in terms of its tion regarding IA therapy. PPS has consistently shown
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stimulation of HA and collagen synthesis. 53,70 greater benefit than Adequan when administered IM,
Adequan was originally intended for IA use; however, with current recommendations to administer 3 mg/kg
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alterations in the complement pathway that potentiated IM once a week for 4 weeks. 49
sub‐infective doses of Staphylococcus aureus resulted in
IM administration becoming a more popular mode of
administration. There is less clinical data for IM use of HYALURONAN
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the drug, although anecdotal reports of efficacy abound.
Reports in the literature reveal that IM administration of Hyaluronan (or hyaluronic acid, HA) is a large
a single 500‐mg dose of Adequan in horses resulted in unbranched non‐sulfated GAG composed of repeating
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therapeutic levels of the drug in antebrachiocarpal, meta- units of d‐glucuronic acid and N‐acetyl glucosamine. It
carpophalangeal, tibiotarsal, and distal interphalangeal is an integral component of synovial fluid and articular
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joints within 2 hours of injection. This was similar to a cartilage. HA actions in the synovial joint include
36
previous report examining radiolabeled IM PSGAG increasing viscosity of synovial fluid, lubricating
administration that led to measurable levels within the unloaded joints, restoring the rheologic properties of
joints of interest for up to 96 hours; concentration also synovial fluid, and most importantly, inhibiting inflam-
peaked at 2 hours after administration. When efficacy of mation. 32,55 Many of these effects appear to depend on
8
Adequan , administered IM every 4 days for seven treat- molecular size of the HA molecule administered, with
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ments, was evaluated in a full thickness cartilage defect molecular weights of 0.5–1 × 10 Da having the greatest
6
model in ponies, no significant cartilage healing was ability of decreasing inflammation. 30
noted. Furthermore, Fubini et al. reported an inability IV administration of HA is noninvasive and a route
69
of IM Adequan® to have a protective effect on methyl- that can be used to treat multiple joints. The benefits are
prednisolone‐injected joints in ponies. When PSGAG most likely due to the effects in the synovial membrane
26
(also IM every 4 days for 28 days) was used as a positive because plasma half‐life is less than an hour and is no
control in a carpal chip model evaluating the benefits of longer detectable after 3 hours. 44,57 The effects of IV
extracorporeal shockwave therapy (ESWT) after 70 days, administration may be due to the fact that the synovial
PSGAG did not improve lameness scores nor produce any membrane is highly vascularized, which may allow
disease‐modifying effects when synovial fluid and carti- greater exposure to synoviocytes than IA administration.
lage were evaluated. 24 The anti‐inflammatory effects may also be due to the
When PPS was first studied in animal models, a mul- binding characteristics of HA to CD44 receptors present
timodal effect on proteoglycan preservation and pro- on several cell types within the synovial membrane, caus-
duction and inhibition of enzymes responsible for ing an inhibition of the expression of various cytokines. 66
cartilage degradation were found. 27,29,31,51 In vitro stud- The only study to evaluate IV administration of HA
ies using equine chondrocyte monolayers and articular in the horse used an osteochondral chip model of OA.
40
cartilage explants indicate that both PSGAG and PPS Horses treated with IV HA had reduced lameness, better
stimulated proteoglycan production in cell monolayers; synovial membrane scores, significantly lower total pro-
however, no difference in production was seen with car- tein concentrations, and most importantly reduced pros-
21
tilage explants. This may suggest that common formu- taglandins in joints compared with horses receiving
lations might not be able to penetrate the extracellular saline. Interestingly, HA did not have any effects on
matrix, bind chondrocytes, and stimulate proteoglycan GAG content, synthetic rate, or morphologic scoring in
production in the live animal. While these aforemen- articular cartilage, which lends credence to the theory
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tioned studies have shown inhibition of proinflamma- that HA has mainly anti‐inflammatory effects in joints.