Intravenous regional limb perfusion (IVRLP) with tiludronate is a commonly used treatment for distal limb orthopedic disease in horses, but doses and protocols are anecdotal. IVRLP exposes articular cartilage within the perfused area to tiludronate, raising concerns about safety of this treatment, as high tiludronate concentrations (≥19mg/L) were harmful for cartilage in vitro. This is the first study to evaluate synovial fluid tiludronate concentrations following IVRLP to determine safety for articular cartilage in horses. Synovial fluid cytology variables and tiludronate concentrations were evaluated in the navicular bursa, coffin and fetlock joints following IVRLP of one front limb with low dose (0.5mg, n=6) or high dose (50mg, n=6) tiludronate. The contralateral limb was perfused with saline as a control. Synovial fluid samples were taken 1 week prior and 30 minutes following IVRLP from all structures and 24 hours post-perfusion from coffin and fetlock joints. Synovial fluid tiludronate concentrations were lower in
limbs perfused with 0.5mg in all synovial structures (metacarpophalangeal joint = 3.7 ± 1.5 mg/L, distal interphalangeal joint = 16.3 ± 1.9 mg/L, navicular bursa = 6.0 ± 1.9 mg/L) than in limbs perfused with 50 mg (metacarpophalangeal joint = 0.04 ± 0.02 mg/L, distal interphalangeal joint = 0.12 ± 0.06 mg/L, navicular bursa = 0.08 ± 0.03 mg/L) at tourniquet release. Only limbs perfused with 50mg had tiludronate detectable in synovial fluid 24 hours post-perfusion. There were no significant differences in synovial fluid cytology variables between samples from limbs perfused with saline vs. tiludronate. Thus, perfusion with tiludronate at doses used did not cause synovial inflammation in comparison to saline control limbs. Cytology variables did increase over time in both treated and control limbs, suggesting that IVRLP and/or synovial fluid sample acquisition stimulates an inflammatory response within synovial structures. Doses of 0.5mg or 50mg of tiludronate given via IVRLP resulted in synovial fluid concentrations that can be considered safe for articular cartilage based on previous in-vitro data. Tiludronate concentrations in bone should be explored to determine safety for bone and possible treatment efficacy for orthopaedic diseases of the distal equine limb.