Tiludronate infusion in the treatment of bone spavin: a double blind placebo-controlled trial.

REASONS FOR PERFORMING STUDY: Tiludronate regulates bone remodelling through a decrease of the resorptive process and should therefore ameliorate the remodelling processes active in osteoarthritis of the distal tarsal joints ('bone spavin') and alleviate pain associated with abnormal bone lysis. OBJECTIVE: To confirm the efficacy of tiludronate, administered as a single infusion at a dose of 1 mg/kg bwt, in the treatment of bone spavin in the horse. METHODS: A double blind placebo controlled trial on 108 clinical cases of bone spavin was undertaken. The lameness score of the lamest limb was assessed following distal tarsal analgesia of the contralateral limb and followed-up using the same procedure throughout the study. Bone spavin in the lamest limb was confirmed by distal tarsal analgesia and radiography. Horses were treated at Day 0 and reassessed 60 days later after controlled exercise. A second nonblinded treatment was given to unresponsive horses and all horses were re-examined at Day 120. Exercise levels were recorded at each examination. RESULTS: Eighty-seven horses completed the trial as per the protocol. The tiludronate horses were significantly less lame than the placebo horses (P = 0.0318). Horses treated at Day 60 with tiludronate showed further improvement in lameness at Day 120 (P = 0.0096 and P = 0.0034 for horses treated with tiludronate and placebo at Day 0, respectively). The only significant difference in radiographic findings between tiludronate and placebo was for presence of periarticular osteophytes (P = 0.006). CONCLUSIONS: Tiludronate treatment is proven to be effective in bone spavin in horses in association with a controlled exercise programme. CLINICAL RELEVANCE: Tiludronate in combination with controlled exercise offers an alternate medical treatment for bone spavin.

Melatonin treatment prior to the normal breeding season increases fetal number in United Kingdom sheep flocks.

Litter size determined ultrasonographically at 45-90 days after mating in eight groups of commercial sheep (n=2609) treated with slow release melatonin implants immediately prior to the natural breeding season showed a 19% treatment effect averaged over the eight groups, from 148% to 167% (P<0.01) compared with controls (n=2499). Control groups had a litter size ranging from 124% to 194% thereby representing most commercial production systems in the UK sheep industry. This is the first large scale study of slow release melatonin implants in commercial UK flocks to demonstrate a significant positive effect on litter size when used before the natural breeding season. The data indicate that increased productivity and profitability could be achieved while maintaining desirable purebred characteristics.

Diffusion of mepivacaine between adjacent synovial structures in the horse. Part 1: forelimb foot and carpus.

This paper tests the hypothesis that the local analgesic agent mepivacaine diffuses between adjacent equine synovial structures in the forelimb and with greater frequency than latex, gelatine dye or contrast media. We report the incidence of diffusion of mepivacaine between the distal interphalangeal joint (DIPJ) and navicular bursa (NB) of the forelimbs and between the intercarpal (IC) and radiocarpal (RC) joints of 31 fresh equine cadavers. The DIPJ of one forelimb and the NB of the contra lateral forelimb and the RC joint of one forelimb and the IC joint of the contra lateral forelimb were injected with mepivacaine. After flexion and extension of the joints, synovial fluid was obtained from the synovial structures adjacent to the injected synovial structures. The concentration of mepivacaine in these samples was determined using an enzyme linked immunosorbent assay. For samples obtained by dilution of synovial fluid, the concentration of mepivacaine was determined by comparing the concentrations of urea in the diluted synovial fluid and the concentration of serum urea. Mepivacaine diffused from the DIPJ to the NB or from the NB to the DIPJ in 25/25 (100%) limbs. Mepivacaine diffused from the IC to RC joints in 24/25 (96%) limbs and from the RC to IC joints in 21/25 (84%) limbs. It was detected at concentrations >0.3 mg/l in 9/25 (36%) of IC joints after RC joint injection and in 25/25 (100%) of the NB after DIPJ injection; at concentrations >100 mg/l in 2/25 (8%) of IC and RC joints and 12/25 (48%) of NB following DIPJ injection; and at concentrations >300 mg/l in 1/25 (4%) in the IC joints following RC joint injection and in 11/25 (44%) of DIPJ following NB injection. The results show greater diffusion of mepivacaine between adjacent synovial structures than assumed from previous anatomical, latex injection and contrast arthrographic studies. This study showed that commonly performed intrasynovial analgesic techniques in the forelimb of the horse are not as specific as previously reported.

Urea as a measure of dilution of equine synovial fluid.

This paper tests the hypothesis that serum and synovial urea concentrations are similar and that urea concentration can be used as an accurate marker for synovial fluid dilution in normal equine joints. Serum and synovial fluid urea concentrations were compared in 42 horses and were equivalent for individual horses (P<0.0001). Mean +/- s.e. serum concentration was 6.1+/-0.552 mmol/l and synovial concentration 6.0+/-0.459 mmol/l. The normal range for synovial urea concentration was determined as 2.5-7.7 mmol/l. The synovial urea concentration from different synovial structures in individual horses were compared and were equivalent (P = 0.002). Known dilutions of synovial fluid with saline were made. The actual and expected synovial urea concentrations were compared and were equivalent (P<0.001). An accurate method of calculating synovial fluid dilution has been determined.

Diffusion of mepivacaine between adjacent synovial structures in the horse. Part 2: tarsus and stifle.

This paper tests the hypothesis that the local analgesic agent mepivacaine diffuses between adjacent equine synovial structures in the hindlimb and with greater frequency than latex, gelatine dye or contrast media. We report the incidence of diffusion of mepivacaine between the tarsometatarsal, centrodistal and tarsocrural joints, and the 3 synovial compartments of the stifle in 33 fresh equine cadavers. The tarsometatarsal joint and one synovial compartment of the stifle in the left limb and the centrodistal joint and a different synovial compartment of the stifle in the right limbs were injected with mepivacaine. Following flexion and extension of the limb, synovial fluid was aspirated from the noninjected centrodistal and tarsometatarsal joints and the tarsocrural joints of the hock and the noninjected compartments of the stifle. Concentrations of mepivacaine in these samples were assayed using an enzyme linked immunosorbent assay. For samples obtained by dilution of synovial fluid the concentration of mepivacaine was determined by comparing the concentration of urea in the diluted synovial fluid and the concentrations of the serum urea. Mepivacaine was detected in 25/25 (100%) adjacent tarsometatarsal and centrodistal joints after diffusion in both directions, in 23/25 (92%) of tarsocrural joints after diffusion from tarsometatarsal joints and in 22/25 (88%) tarsocrural joints after diffusion from centrodistal joints in the hocks. Diffusion from the femoropatellar to medial and lateral femorotibial joints and between the medial and lateral femorotibial joints in both directions were 20/20 (100%). Diffusion from the lateral femorotibial to the femoropatellar joint was 18/20 (90%) and from the medial femorotibial to femoropatellar joints 17/20 (85%). Mepivacaine was detected at concentrations >0.3 mg/l in a proportion of samples ranging from 15/25 (60%) in the tarsocrural joint following tarsometatarsal joint injection to 18/20 (90%) in the lateral femorotibial joint after femoropatellar joint injection. At mepivacaine concentrations >100 mg/l, detection ranged from 3/20 (15%) in the lateral femorotibial joint from the medial femorotibial joint to 19/25 (76%) in the centrodistal joint from the tarsometatarsal joint. At mepivacaine concentrations >300 mg/l, detection ranged from 1/25 (4%) in the tarsocrural joint from the tarsometatarsal joint to 16/25 (64%) in the from centrodistal joint the tarsometatarsal joint. The results show greater diffusion of mepivacaine between these adjacent synovial structures than assumed from previous anatomical, latex injection and contrast arthrographic studies. Therefore, commonly performed intrasynovial local analgesic techniques in the hindlimb of the horse are not as specific as first thought.