Page 923 - Adams and Stashak's Lameness in Horses, 7th Edition
P. 923

Principles of Therapy for Lameness  889


             Table 8.2.  Commonly used hyaluronan preparations.
  VetBooks.ir  Trade name            Concentration   Manufacturer  Molecular weight   How packaged  Current recommended

                                                                                                dose (mg) per joint
                                     (mg/mL)
                                                                (Daltons)
                                                                      a
              Hyvisc                 11           Boehringer    2.1 × 10 6     2‐mL syringe     22
                                                  Ingelheim
              HY‐50                  17           Dechra        7.5 × 10 5     3‐mL syringe     51
              Hyalovet               10           Boehringer    5–7.3 × 10 5   2‐mL syringe or vial  20
                                                  Ingelheim
              Legend b               10           Merial Inc.   3 × 10 5       2‐mL vial        20

              HyCoat (used IA)       5            Neogen        >1.0 × 10 6    10‐mL vial       30
              MAP‐5 (used IA at this dose)  10.3 (2 mL)  Bioniche  7.5 × 10 5  2‐ or 10‐mL vial  20
                                     5 (10 mL)

             a  Manufacturer’s reported molecular weight.
             b  Marketed for IV and IA use.

             high molecular weight HA. There was no significant dif-  One speculation includes the presence of unknown drug
             ference in HA molecular weight between synovial fluid   interactions; however, further evaluation of the combi-
             from normal joints and those with chronic injury.   nation of HA and TA is warranted. At this time there is
             Table 8.2 lists commonly used HA products, their molec-  minimal clinical evidence to support combining HA and
             ular weights, and current recommended dosages.      TA in horses.
               HA can be expensive for owners, and therefore, use
             in joints with advanced disease may yield less satisfying
             results compared with joints with incipient disease. This   IA POLYSULFATED GLYCOSAMINOGLYCANS
             is consistent with human medicine, where people with
             less severe joint disease demonstrate greater improve-  Polysulfated glycosaminoglycans (PSGAGs) princi-
             ment to IA HA compared with those with more advanced   pally comprise chondroitin sulfate, a GAG found in the
             radiographic changes. 114                           aggregating proteoglycan of cartilage. It is a semisyn-
                                                                 thetic preparation from bovine trachea and is reported
                                                                 to have chondroprotective and anti‐inflammatory prop-
             CORTICOSTEROID AND HA COMBINATIONS                  erties as well as the ability to induce articular cartilage
                                                                 matrix synthesis and minimize matrix degradation.
                                                                                                             110
               The combination of HA and steroids to treat inflam-
             mation intrasynovially is commonplace. 15,26,74  Synergistic   Mechanism of Action
             effects have been reported in human patients, and simi-
             lar effects have been seen in vitro in horses. 75,119  Many   The exact mechanism of action remains unclear. The
             clinicians believe that the combination allows a smaller   drug most commonly is administered intramuscularly as
             dose of CS to be administered with the HA, although   IA administration was initially associated with joint
             further clinical studies are needed to determine efficacy   infections due to a reduction in complement activity in
             of combinations. The combination of HA and CS is also   the joint. IA administration is now most commonly
             thought to provide a longer clinical effect than either   combined with 125–250  mg of amikacin to deter any
             injection alone, especially in high‐motion joints.  infection, and this practice appears to be effective.
               A recent open‐label multicenter clinical trial involv-  Many in vitro studies mimic the IA administration of
             ing 80 horses with clinical joint disease found that the   PSGAGs because it is unlikely that concentrations
             IA combination of 12‐mg TA and 20‐mg HA was associ-  injected intramuscularly can translate to similarly ele-
             ated with a lower short‐term success rate (64.1%) com-  vated concentrations in the joint fluid. In vitro studies
             pared with 12‐mg  TA alone (87.8%).  In this study,   and in vivo IA administration have revealed a significant
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             short‐term success was defined as greater than or equal   ability of the drug to decrease lameness, modify OA
             to a 2‐grade reduction in lameness (0–5 scale) 3 weeks   through reducing bone remodeling, promote synthesis
             after injection. Furthermore, this reduction in short‐  of endogenous HA, and inhibit mediators of inflamma-
             term success rate for the combination treatment group   tion, specifically PGE  production. Additionally, it has
                                                                                    2
             was associated with advanced age (≥13 years).  This   been found to reduce the levels of MMPs that rise in
             same study revealed no significant difference in medium‐  response to production of IL‐1β. 20,49,52  Most recently, IA
             term outcome (3 months’ posttreatment), with approxi-  PSGAGs were compared with HA in an osteochondral
             mately 50% of horses returning to their previous level   chip fragment model. While HA significantly reduced
             of exercise regardless of treatment group. The reason for   fibrillation of the cartilage, PSGAGs were demonstrated
             the difference in the observed outcome is unknown.    to reduce joint effusion and reduce synovial membrane
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