Horses of all types of breeds and uses are susceptible to musculoskeletal diseases that result in lameness. Of all reported conditions, lameness ranks as one of the most common causes for poor performance in horses used for racing.1–3 Investigators have reported4 that lameness was ranked as the number 1 health problem affecting horses. Lameness may require veterinary treatment and care and can cause reductions in the time available for use, future athletic ability, and value. Furthermore, a permanent loss of use may be the result of severe musculoskeletal disease.
Lameness-induced pathological bone conditions include, but are not limited to, pedal osteitis, navicular disease, osteoarthritis, osteochondral fragmentation, osteochondrosis dessicans, metacarpal disease, sesamoiditis, subchondral bone disease, and fractures. Conventional treatment of lameness is generally implemented after the acute onset of clinical signs. Currently, few strategies exist to prevent development of skeletal disease or to improve or restore bone quality after injury. Tiludronate disodium, a non—nitrogen-containing biphosphonate drug, affects osteoclastic activity5–7 and has been used to prevent the resorption of bone in humans.8 Tiludronate is currently licensed for use in horses in Europe and is authorized by the FDA for compassionate use in the United States.9 Prospective clinical studies have been conducted to evaluate the use of tiludronate (1 mg/kg, IV, q 24 h for 10 days) in the treatment of navicular disease,10 arthritis in the distal portion of the tarsus,11 disuse osteopenia,12 and osteoarthritis of the thoracolumbar vertebrae,13 and results determined that the drug was efficacious.
Gallium, a trivalent semimetallic element (group IIIa), is a novel therapeutic drug that may be useful in horses for the prevention of skeletal disease or aid in the restoration of bone quality after injury. Gallium was originally used during diagnostic imaging procedures of humans with neoplasia and osteomyelitis. Gallium was found to inhibit bone resorption and thereby lower the plasma concentration of calcium.14,15 In human medicine, gallium is approved for use in the treatment of hypercalcemia of malignancy and Paget's disease. Gallium also affects osteoclastic activity by inhibiting a vacuolar-class ATPase or a surface proton pump16 while not affecting the recruitment or viability of osteoclasts. To be effective, gallium must adsorb to the cortex of bone to affect osteoclastic activity. Gallium concentrates in regions of bones undergoing increased bone metabolism such as the epiphyseal growth plate of juvenile animals and the periosteal and endosteal surfaces of bone.17,18 In addition to modulating bone resorption by osteoclasts, findings of another study18,19 indicate that gallium may have an anabolic effect on bone.
Gallium nitrate, a citrate-chelated solution, is the currently available formulation of gallium approved for use in humans; however, when administered IV, this formulation can form precipitates with calcium and phosphorous in the renal tubules and, thus, can cause nephrotoxicosis.20 To prevent nephrotoxicosis, gallium nitrate is administered IV as a constant rate infusion (5 mg/kg, q 24 h for 5 days).21 However, a similar treatment regimen is likely to be impractical when used in horses.
Gallium maltolate (tris [3-hydroxy-2 methyl-4H-pyran-4-onato] gallium [III]) is a novel preparation of gallium that may be an alternative to the use of gallium nitrate. Gallium maltolate is readily absorbed by the gastrointestinal tract, and there is less renal excretion of GaM, compared with the renal excretion of gallium nitrate.22 In humans, GaM has good oral bioavailability (25% to 57%) with linear rates of absorption and elimination after the administration of doses ranging from 100 to 500 mg.21 In addition, GaM has been investigated23,24 as a novel agent for the prevention and treatment of pneumonia caused by Rhodococcus equi in foals. Furthermore, GaM is readily absorbed and well tolerated after intragastric or oral administration in foals.23,24 The purpose of the study reported here was to determine the pharmacokinetics of GaM after intragastric administration in healthy adult horses.
Inductively coupled plasma-mass spectroscopy
Vitality Perform 14%, Nutrena, Minneapolis, Minn.
Chiral Quest, Monmouth Junction, NJ.
MILA International Inc, Erlanger, Ky.
Seastar Baseline, Seastar Chemicals Inc, Sidney, BC, Canada.
Dodel DRC 2, Perkin Elmer, Foster City, Calif.
WinNonLin Professional, version 5.0.1, Pharsight Corp, Mountain View, Calif.
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Delguste C, Amory H & Doucet M, et al. Pharmacological effects of tiludronate in horses after long-term immobilization. Bone 2007; 41:414–421.
Coudry V, Thibaud D & Riccio B, et al. Efficacy of tiludronate in the treatment of horses with signs of pain associated with osteoarthritic lesions of the thoracolumbar vertebral column. Am J Vet Res 2007; 68:329–337.
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Bernstein LR, Tanner T & Godfrey C, et al. Chemistry and pharmacokinetics of gallium maltolate, a compound with high oral gallium bioavailability. Met Based Drugs 2000; 7:33–47.
Martens RJ, Mealey K & Cohen ND, et al. Pharmacokinetics of gallium maltolate after intragastric administration in neonatal foals. Am J Vet Res 2007; 68:1041–1044.
Chaffin MK, Fajt V & Martens RJ, et al. Pharmacokinetics of an orally administered methylcellulose formulation of gallium maltolate in neonatal foals. J Vet Pharmacol Ther 2010; 33:376–382.
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