Physiology Modifiers in Joint Disease Reviewed (AAEP 2011)

Drugs are known to help cure certain ailments, but we don't often consider how exactly they promote healing when administered to horses. Physiology modifiers (drugs that are either present naturally within the body or that mimic chemicals reacting within the body), in particular, influence the cells within the musculoskeletal system. At the 2011 American Association of Equine Practitioners convention, held Nov. 18-22 in San Antonio, Texas, Chris E. Kawcak, DVM, PhD, Dipl. ACVS, ACVSMR (Veterinary Sports Medicine and Rehabilitation), of Colorado State University, presented a discussion of the mechanisms and effects of some of the most commonly used physiology modifiers--hyaluronan, polysulfated glycosaminoglycans, and bisphosphonates--in equine joint disease treatment.

Hyaluronan Kawcak began the presentation discussing hyaluronan. This chemical, found within the body, interacts with the CD44 receptor, which mediates cell-cell and cell-matrix interactions "to modulate cell proliferation, migration, and gene expression." Study results indicate this interaction might influence variability--specifically, that the mass (molecular weight, MW) of hyaluronan administered within a joint might alter its effects. For instance, most studies show that high MW hyaluronan decreases inflammation when it binds to CD44, yet low and medium density hyaluronan might actually increase inflammation.

According to Kawcak, researchers have also shown that administering intra-articular hyaluronan can decrease pain and have disease-modifying effects such as decreased cartilage fibrillation (the softening and grooving of joint surface cartilage) within the joint. Veterinarians have used hyaluronan primarily in combination with corticosteroids in the joint. Intravenously administered hyaluronan has produced symptom-modifying effects. A study of oral preparation of hyaluronan in yearlings with hock osteochondritis dissecans resulted in decreased joint effusion (swelling).

Polysulfated glycosaminoglycans (PSGAGs) In laboratory conditions (in vitro) PSGAGs stimulate proteoglycan and collagen synthesis and decrease prostaglandin E2 (an inflammatory mediator) production. However, in vivo (in the animal) effects have been variable: In a study of an osteochondral defect model of the middle carpal (knee) joint, PSGAGs had no effect relative to the controls, while in another study using a carpal chip model of osteoarthritis (OA) PSGAGs decreased synovial effusion, subintimal fibrosis, and synovial membrane vascularity (all indicators of synovial inflammation).

In a survey clinicians reported PSGAG was better than hyaluronan for treating subacute (very early stage) disease; they believed the opposite was the case for acute OA.

Bisphosphonates Bone deposition and resorption are held in balance in normal healthy bone; osteoclasts remove bone and osteoblasts lay down new bone. However, bone resorption is common with orthopedic disease, said Kawcak. Bone edema (fluid within the tissue space) can lead to subchondral bone lysis (loss of the bone beneath the cartilage). Stopping this lysis is the principle behind using bisphosphonates such as tiludronate in treating orthopedic disease.

Bisphosphonates inhibit osteoclastic activity and have anti-inflammatory effects. Several studies showed possible benefits in the horse, including reduced bone loss in horses with lower limb casts, reduced lameness scores in horses with navicular disease, and improved dorsal (topline) flexibility in horses with articular lesions of the spine. Veterinarians have raised some concerns about using bisphosphonates in young horses undergoing substantial bone remodeling; however, the drugs have been used to treat human epiphysitis (inflammation of the growth plate in children). Kawcak also noted that osteonecrosis (bone death caused by poor blood supply to the area) of the jaw bone has been seen in humans following long-term use.

After discussing these physiology modifiers, Kawcak concluded that they show promise in managing ongoing equine conditions such as joint disease.

About the Author

Christy Corp-Minamiji, DVM

Christy Corp-Minamiji, DVM, practices large animal medicine in Northern California, with particular interests in equine wound management and geriatric equine care. She and her husband have three children, and she writes fiction and creative nonfiction in her spare time.

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