Page 911 - Adams and Stashak's Lameness in Horses, 7th Edition

Principles of Therapy for Lameness 877

Intrasynovial injections are likely the most efficacious grade improvement in lameness at day 56 compared
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route of administration; however, the desire to treat mul- with 3% in the placebo group. At day 180, 65% were
VetBooks.ir and oral preparations. Indications for IV HA are similar ness. Clodronate has also been reported to successfully
tiple joints simultaneously has driven clinicians to use IV
still considered to have an improvement in their lame-
treat an acute, non‐weight‐bearing lameness in a horse
to those for IM PSGAGS in that IV HA reduces inflam-
mation in one or multiple joints or prevents an inflam- that was diagnosed with coffin joint effusion and bone
matory process in sport horses that are in heavy use. marrow edema of the second phalanx. Clodronate was
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Although IA administration is the most effective way to administered IM daily for 10 days at each recheck, and
deliver this drug to the joints, IA and IV administration the horse’s lameness improved.
are often concurrent. IV HA’s effect is most likely through More widespread use of bisphosphonates in horses
its anti‐inflammatory nature and not through disease‐ has created concerns regarding their use in growing
modifying effects against the progression of OA. animals and in horses that have undergone therapy prior
In a recent review of the use of HA in all facets of to sustaining a fracture. In one study examining healing
clinical and benchtop research, mention of the possibil- and functional outcome in distal radial fractures in post-
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ity of IV therapy was not made. At this time, IV use has menopausal women undergoing bisphosphonate ther-
only been evaluated in dogs and horses, and no human apy, no significant difference was noted in healing or
IV formulations exist. At this time, very little evidence‐ functional outcome between the treated and control
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based medicine has been used to evaluate IV HA other group. Other work in rabbit, dog, and sheep models,
than those listed previously. Likely, HA does have some however, have mostly shown no effect of bisphosphonate
beneficial anti‐inflammatory effect, and anecdotal effi- therapy on fracture healing or that callus size and
cacy has been noted in our practice experience. At this strength could be improved at initial stages of heal-
time, IV HA appears to be safe, but whether true benefit ing. 2,5,33,54 However, two studies noted long‐term, high‐
is noted with its use remains to be shown. dose therapy could delay healing but have no effect on
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Currently, the only labeled IV HA product on the mechanical integrity or slow long‐term callus remodeling.
market for equine is Legend (Merial Inc., Duluth, These models all used varying bisphosphonates –
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GA). Current recommendations by the manufacturer incandronate, zoledronic acid, alendronate, ibandronate,
include 40 mg intravenously weekly for three treat- and pamidronate – all of which are not currently licensed
ments. Another product, Polyglycan (Bimeda, Inc., in equine medicine.
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Oakbrook Terrace, IL), is licensed as a medical device Due to the lack of available data, off‐label use or use
and labeled for intrasynovial injection; however, it has of bisphosphonates in young, growing horses cannot be
been used off‐label for IV and IM injection. Although recommended at this time. Further studies regarding
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it has been used off‐label, when a recent study examined long‐term effect on bone density, ability of bone to heal
its IV use, significant osteophytosis was identified on after administration, and duration of action after admin-
radiography in the treatment group compared with the istration are still needed.
control group in the equine osteochondral carpal chip Current recommendations for Osphos administra-
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fragment model. 25 tion are 1.8 mg/kg by IM injection with a maximum dose
of 900 mg per horse (e.g. 900 mg dose standard for a 500‐
kg animal); recommendations to divide the dose between
a
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BISPHOSPHONATES three sites are also given (Osphos ). In a study of 146
horses, 10 horses developed mild signs of colic within the
Bisphosphonates have been used for decades to first 2 hours of treatment, but all resolved with minimal
inhibit loss of bone mass in human patients with osteo- treatment. For this reason, premedication with an
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porosis associated with age or steroid administration NSAID is not recommended and, in our experience, rarely
and for rheumatoid arthritis. Bisphosphonates inhibit required. Due to renal excretion, baseline creatinine
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osteoclast‐mediated bone resorption, a property that values are recommended prior to starting a course of bis-
may play a role in conditions such as OA and navicular phosphonates. Concurrent administration with other
bone edema/sclerosis. Three studies in horses report the nephrotoxic medications should also be avoided.
effects of the bisphosphonate tiludronate in clinical dis-
eases such as navicular disease, vertebral pain related to
OA of the thoracolumbar column, bone spavin, and TETRACYCLINES
bone loss due to cast immobilization. 13–15 All three stud-
ies reported reduced lameness, back soreness, and loss of The anti‐inflammatory effect of tetracyclines, inde-
bone with IV administration of the drug. pendent of their antimicrobial role, has been well docu-
A second FDA‐approved bisphosphonate licensed mented for multiple disease processes. 4,41,52,71 When
for treatment of navicular syndrome in horses, more recently evaluated in a rodent model of acute
clodronate (Osphos , Dechra Veterinary Products, inflammation, both minocycline and doxycycline were
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Overland Park, KS), has emerged onto the market in found to be effective through inhibition of TNF‐α and
recent years. With a similar mechanism of action to til- nitric oxide. Furthermore, and more relevant to equine
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udronate, clodronate has also been hypothesized to be practitioners, their use as disease‐modifying osteoar-
analgesic through inhibition of glutamate transport. 63 thritic drug (DMOAD) has also been established. 7,60,65,72
A recent multicenter, double‐blind, placebo‐con- When these studies were translated to in vitro work
trolled clinical trial using clodronate showed that in with equine synoviocytes, doxycycline was noted to be
horses with navicular syndrome confirmed with diag- chondroprotective through inhibition of specific matrix
nostic analgesia and radiography, 75% saw at least one metalloproteinases (MMPs) that are known to cause