A myostatin and activin decoy receptor enhances bone formation in mice.

Myostatin is a member of the bone morphogenetic protein/transforming growth factor-ß (BMP/TGFß) super-family of secreted differentiation factors. Myostatin is a negative regulator of muscle mass as shown by increased muscle mass in myostatin deficient mice. Interestingly, these mice also exhibit increased bone mass suggesting that myostatin may also play a role in regulating bone mass. To investigate the role of myostatin in bone, young adult mice were administered with either a myostatin neutralizing antibody (Mstn-mAb), a soluble myostatin decoy receptor (ActRIIB-Fc) or vehicle. While both myostatin inhibitors increased muscle mass, only ActRIIB-Fc increased bone mass. Bone volume fraction (BV/TV), as determined by microCT, was increased by 132% and 27% in the distal femur and lumbar vertebrae, respectively. Histological evaluation demonstrated that increased BV/TV in both locations was attributed to increased trabecular thickness, trabecular number and bone formation rate. Increased BV/TV resulted in enhanced vertebral maximum compressive force compared to untreated animals. The fact that ActRIIB-Fc, but not Mstn-mAb, increased bone volume suggested that this soluble decoy receptor may be binding a ligand other than myostatin, that plays a role in regulating bone mass. This was confirmed by the significant increase in BV/TV in myostatin deficient mice treated with ActRIIB-Fc. Of the other known ActRIIB-Fc ligands, BMP3 has been identified as a negative regulator of bone mass. However, BMP3 deficient mice treated with ActRIIB-Fc showed similar increases in BV/TV as wild type (WT) littermates treated with ActRIIB-Fc. This result suggests that BMP3 neutralization is not the mechanism responsible for increased bone mass. The results of this study demonstrate that ActRIIB-Fc increases both muscle and bone mass in mice. Therefore, a therapeutic that has this dual activity represents a potential approach for the treatment of frailty.

Adenoviral-mediated transfer of human BMP-6 gene accelerates healing in a rabbit ulnar osteotomy model.

This study evaluated healing of rabbit bilateral ulnar osteotomies 6 and 8 weeks after surgery in response to percutaneous injection of transgenic adenoviral (Ad) bone morphogenetic protein-6 (BMP-6) vector or green fluorescent protein vector control (Ad-GFP) administered 7 days after surgery compared to untreated osteotomy controls. The amount, composition and biomechanical properties of the healing bone repair tissue were compared among groups and to historical data for intact rabbit ulnae obtained from similar studies at the same institution. Quantitative computed tomography was used to determine area, density and mineral content of the mineralized callus in the harvested ulnae. Maximum torque, torsional stiffness, and energy absorbed to failure were determined at 1.5 degrees /s. Calcified sections of excised ulnae (5 microm) were stained with Goldner's Trichrome and Von Kossa, and evaluated for callus composition, maturity, cortical continuity, and osteotomy bridging. Radiographic assessment of bone formation indicated greater mineralized callus in the ulnae injected with Ad-hBMP-6 as early as 1 week after treatment (2 weeks after surgery) compared to untreated osteotomy ulnae (p < 0.006) and Ad-GFP treated osteotomy ulnae (p < 0.002). Quantitative computed tomography confirmed greater bone area and bone mineral content at the osteotomy at 6 weeks in Ad-BMP-6 treated osteotomy as compared to untreated osteotomy ulnae (p < 0.001) and Ad-GFP treated osteotomy ulnae (p < 0.01). Ad-BMP-6 treated osteotomy ulnae were stronger (p < 0.001 and 0.003) and stiffer (p < 0.004 and 0.003) in torsion at 6 weeks than untreated osteotomy ulnae or Ad-GFP treated osteotomy ulnae, respectively. Maximum torque, torsional stiffness, and energy absorbed to failure were greater in Ad-BMP-6 treated osteotomy ulnae compared to their respective untreated contralateral osteotomy ulnae at 8 weeks [p < 0.03]. Maximum torque and torsional stiffness in the Ad-BMP-6 treated osteotomy ulnae were not different to intact ulnae values at 6 and 8 weeks. These experiments confirm that BMP-6 can be potently osteoinductive in vivo resulting in acceleration of bone repair.

Locally delivered rhBMP-2 enhances bone ingrowth and gap healing in a canine model.

The purpose of the present study was to determine if recombinant human bone morphogenetic protein-2 (rhBMP-2) enhances bone ingrowth into porous-coated implants and gap healing around the implants. In the presence of a 3-mm gap between the implant and host bone, porous-coated implants were placed bilaterally for four weeks in the proximal humeri of skeletally mature, adult male dogs. In three treatment groups, the test implant was treated with HA/TCP and rhBMP-2 in buffer at a dose of 100 microg/implant (n=5), 400 microg/implant (n=6), or 800 microg/implant (n=5) and placed in the left humerus. In these same animals, an internal control implant was treated only with HA/TCP and buffer and placed in the right humerus. These groups were compared with a previously reported external control group of seven animals in which no growth factor was delivered [J. Orthop. Res. 19 (2001) 85]. The BMP treated implants in the two lower dose groups had significantly more bone ingrowth than the external controls with the greatest effect in the 100 g/implant group (a 3.5-fold increase over the external control, p=0.008). All three dose groups had significantly more bone formation in the 3-mm gap surrounding the BMP treated implants than the external controls with the greatest effect in the 800 microg group (2.9-fold increase, p<0.001). Thus, application of rhBMP-2 to a porous-coated implant stimulated local bone ingrowth and gap healing. The enhancement of bone formation within the implant (bone ingrowth) was inversely related to dose.

rhBMP-2 injected in a calcium phosphate paste (alpha-BSM) accelerates healing in the rabbit ulnar osteotomy model.

This study evaluated the ability of recombinant human bone morphogenetic protein-2 (rhBMP-2) delivered in an injectable calcium phosphate carrier (alpha-BSM) to accelerate healing in a rabbit ulna osteotomy model compared to untreated surgical controls. Healing was assessed by radiography, histology and biomechanics. Bilateral mid-ulnar osteotomies were created in 16 skeletally mature rabbits. One limb in each animal was injected with either 0.1 mg rhBMP-2/alpha-BSM (BMP) (N=8) or buffer/alpha-BSM (BSM) (N=8). Contralateral osteotomies served as untreated surgical controls (SXCT). Gamma scintigraphy showed 75%, 45% and 5% of the initial 125I-rhBMP-2 dose was retained at the osteotomy site at 3 h, 1 week and 3 weeks. The biological activity of rhBMP-2 (alkaline phosphatase activity from bioassay) extracted from alpha-BSM incubated in vitro up to 30 days at 37 degrees C was unchanged. Radiographs demonstrated complete bridging of the BMP limbs at 4 weeks whereas none of the BSM or SXCT limbs were bridged. Post-mortem peripheral quantitative computed tomography determined mineralized callus area was 62% greater in BMP limbs compared to SXCT limbs. Torsional stiffness and strength were 63% and 103% greater in BMP limbs compared to SXCT limbs. There was no difference in torsional properties between BSM and SXCT limbs. Failure occurred outside the osteotomy in four out of seven of the BMP limbs. All BSM and SXCT limbs failed through the osteotomy. Histology showed bony bridging of the osteotomy and no residual carrier in the BMP limbs. BSM and SXCT groups showed less mature calluses composed of primarily fibrocartilaginous tissue and immature bone in the osteotomy gap. These data indicate rhBMP-2 delivered in alpha-BSM accelerated healing in a rabbit ulna osteotomy model compared to BSM and SXCT groups.

Recombinant human bone morphogenetic protein-2 enhances osteotomy healing in glucocorticoid-treated rabbits.

The objectives of this study were to evaluate the effect of chronic prednisolone treatment on osteotomy healing in rabbits and to determine whether recombinant human bone morphogenetic protein-2 (rhBMP-2) would enhance healing in the presence of chronic glucocorticoid therapy. Forty-nine skeletally mature, male rabbits were injected with either prednisolone (n = 26; 0.35 mg/kg per day, three times a week) or saline (n = 23). After a 6-week pretreatment period, bilateral ulnar osteotomies were created surgically. One osteotomy was treated with rhBMP-2 (0.2 mg/ml of rhBMP-2, 40 microg of rhBMP-2 total) delivered on an absorbable collage sponge (ACS), whereas the contralateral osteotomy remained untreated. Prednisolone or saline treatment was continued until the rabbits were killed either 6 weeks or 8 weeks after creation of the osteotomy. Osteotomy healing was evaluated by radiography, peripheral quantitative computed tomography (pQCT), torsional biomechanics, and undecalcified histology. Because we observed similar responses to both prednisolone and rhBMP-2/ACS treatment in the 6-week and 8-week cohorts, the results from these time points were combined. Serum osteocalcin and vertebral trabecular bone density were lower in the prednisolone-treated rabbits. Prednisolone treatment dramatically inhibited osteotomy healing. In the untreated ulnas, callus area and torsional strength were 25% and 55% less, respectively, in the prednisolone-treated rabbits than in the saline group (p < 0.001 for both). rhBMP-2/ACS enhanced healing in both the prednisolone- and the saline-treated groups, although the effect was larger in the prednisolone-treated rabbits. In the prednisolone-treated rabbits, callus area and torsional strength were 40% and 165% greater (p < 0.001 for both), respectively, in osteotomies treated with rhBMP-2/ACS compared with the contralateral, untreated osteotomies. Histological evaluation confirmed that osteotomy healing was inhibited by prednisolone and accelerated by rhBMP-2/ACS. In summary, a single application of rhBMP-2/ACS counteracted the inhibition of osteotomy healing caused by prednisolone exposure. These results suggest that rhBMP-2/ACS may be a useful treatment for enhancing fracture healing in patients who are undergoing chronic glucocorticoid therapy.

Recombinant human bone morphogenetic protein-2 accelerates healing in a rabbit ulnar osteotomy model.

BACKGROUND: Approximately 5% to 20% of fractures have delayed or impaired healing. Therefore, it is desirable to develop new therapies to enhance fracture-healing that can be used in conjunction with traditional treatment methods. The purpose of this study was to evaluate the ability of a single application of recombinant human bone morphogenetic protein-2 to accelerate fracture-healing in a rabbit ulnar osteotomy that heals spontaneously. METHODS: Bilateral mid-ulnar osteotomies (approximately 0.5 to 1.0 mm wide) were created in seventy-two skeletally mature male rabbits. The limbs were assigned to one of three groups: those treated with an absorbable collagen sponge containing recombinant human bone morphogenetic protein-2, those treated with an absorbable collagen sponge containing buffer, and those left untreated. In the first two groups, an 8 20-mm strip of absorbable collagen sponge containing either 40 g of recombinant human bone morphogenetic protein-2 or buffer only was wrapped around the osteotomy site. The rabbits were killed at two, three, four, or six weeks after surgery. In addition, twenty-four age-matched rabbits were used to provide data on the properties of intact limbs. The retention of recombinant human bone morphogenetic protein-2 at the osteotomy site was determined with scintigraphic imaging of (125)I-labeled recombinant human bone morphogenetic protein-2. After the rabbits were killed, the limbs were scanned with peripheral quantitative computed tomography to assess the area and mineral content of the mineralized callus. The limbs were then tested to failure in torsion, and undecalcified specimens were evaluated histologically. RESULTS: Gamma scintigraphy of (125)I-recombinant human bone morphogenetic protein-2 showed that 73% +/- 6% (mean and standard deviation) of the administered dose was initially retained at the fracture site. Approximately 37% +/- 10% of the initial dose remained at the site one week after surgery, and 8% +/- 7% remained after two weeks. The mineralized callus area was similar in all groups at two weeks, but it was 20% to 60% greater in the ulnae treated with recombinant human bone morphogenetic protein-2 than in either the ulnae treated with buffer or the untreated ulnae at three, four, and six weeks (p < 0.05). Biomechanical properties were similar in all groups at two weeks, but they were at least 80% greater in the ulnae treated with recombinant human bone morphogenetic protein-2 at three and four weeks than in either the ulnae treated with buffer (p < 0.005) or the untreated ulnae (p < 0.01). By four weeks, the biomechanical properties of the ulnae treated with recombinant human bone morphogenetic protein-2 were equivalent to those of the intact ulnae, whereas the biomechanical properties of both the ulnae treated with buffer and the untreated ulnae had reached only approximately 45% of those of the intact ulnae. At six weeks, the biomechanical properties were similar in all groups and were equivalent to those of the intact ulnae. The callus geometry and biomechanical properties of the ulnae treated with buffer were equivalent to those of the untreated ulnae at all time-points. CONCLUSIONS AND CLINICAL RELEVANCE: These findings indicate that treatment with an absorbable collagen sponge containing recombinant human bone morphogenetic protein-2 enhances healing of a long-bone osteotomy that heals spontaneously. Specifically, osteotomies treated with recombinant human bone morphogenetic protein-2 healed 33% faster than osteotomies left untreated. The results of this study provide a rationale for testing the ability of recombinant human bone morphogenetic protein-2 to accelerate healing in patients with fractures requiring open surgical management.

The effect of recombinant human bone morphogenetic protein-2 on femoral reconstruction with an intercalary allograft in a dog model.

This study compared the effect of augmentation of allograft host bone junctions with recombinant human bone morphogenetic protein-2 (rhBMP-2) on an absorbable collagen sponge (ACS), autogenous cancellous bone graft (CBG), and a collagen sponge alone in a canine intercalary femoral defect model repaired with a frozen allograft. Outcome assessment included serial radiographs, dual energy X-ray absorptiometry scans, and gait analyses, and mechanical testing and histology of post-mortem specimens. The distal junction healed more quickly and completely with rhBMP-2 than ACS alone based on qualitative radiography and histologic evaluations. The primary tissue in the unhealed gaps in the ACS group was fibrous connective tissue. The proximal allograft host bone junction had complete bone union in the three treatment groups. There was significantly greater new bone callus formation at both junctions with rhBMP-2 than with CBG or ACS alone that resulted in increased bone density around the allograft host bone junctions. All dogs shifted their weight from the treated leg to the contralateral pelvic limb immediately after surgery. Weight bearing forces were redistributed equally between the pelvic limbs at 12 weeks after surgery with rhBMP-2, at 16 weeks after surgery with CBG, and at 24 weeks after surgery with ACS alone. Bending and compressive stiffnesses of the whole treated femora were equal to the contralateral control femora in all treatment groups, whereas torsional rigidities of the whole treated femora for the CBG and ACS groups were significantly less than the control. Both the proximal and distal junctions the treated with rhBMP-2 had torsional stiffnesses and strengths equal to intact control bones. Ultimate failure torques of the proximal junctions of the CBG group and of both junctions of the ACS group were significantly less than the BMP-treated bones. Augmentation of the allograft host bone junctions with rhBMP-2 on an ACS gave results for all parameters measured that equaled or exceeded autogenous graft in this canine intercalary femoral defect model.

Histomorphometric description of allograft bone remodeling and union in a canine segmental femoral defect model: a comparison of rhBMP-2, cancellous bone graft, and absorbable collagen sponge.

The purpose of this study was to determine the effect of recombinant human bone morphogenetic protein type 2 (rhBMP-2) on the histomorphometry of femoral allograft-host bone union and allograft remodeling. A 6 cm mid-diaphyseal femoral defect was created and filled with an allograft stabilized with an interlocking nail in 21 dogs. Dogs were randomly divided into three equal groups and the allograft-host bone junctions and the mid-diaphyses of the allografts were treated with either an absorbable collagen sponge (ACS) loaded with rhBMP-2 (BMP group), an autogenous cancellous bone graft (CBG group), or ACS loaded with buffer solution (ACS group). All dogs received daily tetracycline until sacrifice at 24 weeks to label new bone formation. Histomorphometric analyses on sections of proximal and distal allograft-host bone junctions and the mid-diaphyseal portion of allografts were performed using fluorescent and regular light microscopy. Analyses of the host bone and junctions between allograft and host bone revealed significantly greater new bone formation and larger osteon radii in the BMP group compared to CBG and ACS groups and contralateral intact bone. Porosity in CBG and ACS groups was significantly higher than in the BMP group, which had similar values to intact bone. In transverse sections of allografts, the largest pore diameters were present in the CBG group. Based on all parameters measured, significantly higher bone turnover occurred in the outer cortical area of the allograft in all groups as compared to the inner cortical and mid-cortical areas. New bone formation and osteon radius/osteon width in allografts were similar for all three groups. Higher porosity and larger pore diameters in the CBG and ACS groups suggested higher bone resorption versus formation in these groups compared to the BMP group. The results of this study reveal more balanced allograft bone resorption and bone formation in the BMP group, with greater resorptive activity in the CBG and ACS groups. However, neither rhBMP-2 nor autogenous bone graft increased allograft incorporation when compared to the negative control (ACS group).

Results of bone scintigraphy in horses used for show jumping, hunting, or eventing: 141 cases (1988-1994).

OBJECTIVE: To determine anatomic patterns and clinical importance of increased radiopharmaceutical uptake in bones of horses used for show jumping, hunting, and eventing. DESIGN: Retrospective study. ANIMALS: 141 horses evaluated because of lameness. PROCEDURE: Medical records were reviewed, and information on results of physical examination, radiography, and scintigraphy were obtained. Scintigrams were evaluated to identify areas of increased radio-pharmaceutical uptake. RESULTS: 834 areas of increased radiopharmaceutical uptake were identified. Scintigraphy of the vertebral column was performed in 78 horses, and 50 had areas of increased radiopharmaceutical uptake involving the spinous processes. Scintigraphy of the proximal phalanx of the forelimb was performed in 88 horses. Similarly, scintigraphy of the proximal phalanx of the hind limb was performed in 99 horses, and scintigrams of 374 proximal phalanges were available for review. One hundred fifty-five scintigrams had areas of increased radiopharmaceutical uptake. Scintigraphy of the tarsal joint was performed in 99 horses, and scintigrams of 198 joints were available for review. Eighty-five had areas of increased radiopharmaceutical uptake. Overall, 214 of 834 areas of increased radiopharmaceutical uptake were definitively associated with lameness. CLINICAL IMPLICATIONS: Results of this study suggest that jumping creates unique stresses on the bones of horses. The distinctive patterns of increased radiopharmaceutical uptake identified in this study suggest that horses used for jumping may have a predilection to develop orthopedic disease at specific sites distinct from those in racehorses.

Computed tomographic evaluation of comminuted middle phalangeal fractures in the horse.

Comminuted fractures of the middle phalanx have been well described in the horse. Choice of treatment, surgical planning and prognosis have traditionally been based upon evaluation of radiographs. However, the complex nature of comminuted fractures makes radiographic interpretation difficult. Computed tomography (CT) allows the production of cross-sectional images with spatial separation of structures which are superimposed on survey radiographs. This allows accurate assessment of the number and direction of fracture lines within the bone. In this paper we report the use of CT in the evaluation of 6 comminuted middle phalangeal fractures. Computed tomography is potentially useful in deciding the type of treatment, surgical planning and determining the prognosis.

The role of computed tomography in evaluation of subchondral osseous lesions in seven horses with chronic synovitis.

Seven horses with severe, persistent lameness of sudden onset were evaluated with scintigraphy and/or computed tomography. The lameness was localised to the front fetlock joint in 2 horses and to the tibiotarsal joint in 5 horses. Five of the horses had a history of intra-articular injections of the involved joint prior to presentation. All horses had effusion of the affected joint and were positive to flexion tests. Intraarticular anaesthesia eliminated or improved the lameness in 4 cases and a nerve conduction block proximal to the affected joint improved the lameness in another. Cytology examination of fluid from affected joints identified normal joint fluid (one horse) or elevations in nucleated cell counts of 0.9 x 10(9)/l-36.8 x 10(9)/l and total protein 20-42 g/l (6 horses). The joint fluid of 2 of these horses cultured positive for bacteria. Initial radiographs were either normal (4 cases) or the changes seen were not sufficient to explain the degree of lameness. In the 6 cases where scintigraphy was performed, intense focal isotope uptake was found in the suspected region, which corresponded to the proximal portion of the first phalanx (2 cases), distal tibia (2 cases), or talus (3 cases). Computed tomography (CT) was performed because occult fracture or osteomyelitis was suspected; and knowledge of the precise anatomical location of the lesion was considered necessary to assess the need for surgery and to plan the surgical approach. Hypodense focal lesions with hyperdense haloes were found in the subchondral bone deep to the sagittal groove of the first phalanx (P1) (2 cases) in the cochlea of the distal tibia (2 cases), and in the intertrochlear portion of the talus (3 cases). Communication between the lesion and the joint space was demonstrated by CT in 5 cases. Post mortem examination of one case revealed synovitis and a chronic bone abscess (Brodie's abscess) communicating with the joint space.

Primary closure of equine laryngotomy incisions: a review of 42 cases.

Laryngotomy incisions for either staphylectomy, ventriculectomy, cordectomy, resection of the palatopharyngeal arch, or subepiglottal cyst removal, were closed primarily in 42 horses. Incisional complications were subcutaneous emphysema (11 horses, 26%), incisional discharge (4 horses, 10%), postoperative fever (4 horses, 10%), incisional abscessation (3 horses, 7%), incisional seroma (2 horses, 5%), and subcutaneous edema (2 horses, 5%). Incisional complications were identified in 22 horses, but only 8 horses (19%) required intervention for incisional healing to occur. Factors such as preoperative and postoperative administration of antibiotics or nonsteroid anti-inflammatory drugs, use of antibiotic lavage or drains, type of suture material and suture pattern, were not significantly associated with incisional complications. Horses with incisional complications had significantly shorter mean surgical time (P = .011) than horses without incisional complications. Surgical experience was associated with fewer complications (P = .018), but had no significant effect on the frequency of complications requiring intervention. Results of this study indicate that equine laryngotomy incisions can be closed primarily and that most will heal without need for further surgical intervention.

The effect of reversible left recurrent laryngeal neuropathy on the metabolic cost of locomotion and peak aerobic power in thoroughbred racehorses.

The effect of left recurrent laryngeal neuropathy (LRLN) on the metabolic cost of locomotion (MCL) and peak aerobic power (VO2peak) was evaluated in four trained Thoroughbred racehorses. Oxygen consumption (VO2), carbon dioxide production (VCO2), venous lactate concentrations (LAC), and heart rate (HR) were measured during a treadmill exercise test (TET). Each horse performed the exercise test four times, alternating between normal upper airway function and reversibly induced LRLN. Subcutaneous infusion of 2% mepivicaine, a local anesthetic, into the region were the left recurrent laryngeal nerve passes caudal to the cricoid cartilage was used to induce LRLN. The induction of LRLN did not alter the relationship between VO2 and treadmill speed at exercise intensities where VO2 was less than VO2peak (< 9 m/sec). However, a 15.3% reduction in VO2peak (Normal = 165.3 +/- 3.4, LRLN = 140.0 +/- 3.2 mL/kg/min +/- SE, P < .001) occurred at higher treadmill speeds in horses with induced LRLN. A significant group (Normal v LRLN) by treadmill speed effect was found for LAC and R only at treadmill speeds where VO2 = VO2peak. Peak lactate (LACpeak) did not change after the induction of LRLN. The relationship between HR and treadmill speed increased in horses with induced LRLN at exercise intensities where VO2 < VO2peak. Peak heart rate (HRpeak) remained unchanged. Performance as indicated by the maximum number of speed intervals completed (STEPmax) decreased 7% in horses with induced LRLN (Normal = 9.1 +/- 0.04, LRLN = 8.5 +/- 0.2 minutes +/- SE, P < .04). A comparison of paired exercise test measurements showed no evidence of a training effect, or decreased performance caused by a learned response, over the course of the experiment.(ABSTRACT TRUNCATED AT 250 WORDS)

Pulmonary edema associated with transient airway obstruction in three horses.

Pulmonary edema associated with transient airway obstruction was detected in 3 horses. The cause of obstruction was different in each horse, but after relief of the obstruction, clinical signs and radiographic abnormalities were indicative of pulmonary edema. In 2 of the 3 horses, pink frothy fluid was evident in the airways. The horses were treated with furosemide, nasal insufflation of O2, anti-inflammatory agents, and anti-biotics. Of the 3 horses examined, 1 horse died acutely, 1 horse recovered fully, and 1 developed pleuritis and was subsequently euthanatized.

Scintigraphic identification of skeletal muscle damage in horses 24 hours after strenuous exercise.

The uptake of the bone-seeking radiopharmaceutical 99mTc-MDP by damaged skeletal muscle in horses is evaluated. Twenty-four hours following strenuous exercise, 109 racehorses with a history of inadequate athletic performance and subtle lameness were imaged using scintigraphic techniques. Ten horses (9.2 per cent) demonstrated abnormal uptake of the radioisotope within skeletal muscles. A muscle biopsy from one of these horses confirmed that the muscles with increased scintigraphic activity had histologic evidence of rhabdomyolysis. This technique allows localisation and relative quantification of muscle damage and is a valuable aid in the evaluation of the athletic horse.

Treadmill exercise testing. Treadmill installation and training protocols used for clinical evaluations of equine athletes.

The use of motorized treadmills has made it possible to evaluate equine poor performance with sophisticated diagnostic techniques during peak exercise. Treadmill exercise tests currently being used for clinical evaluations include treadmill gait analysis, dynamic hoof balancing, endoscopic evaluation of upper airway function, and exercise performance profiling. Large motorized treadmills (1 to 1.5 m in width and 4 to 5 m in length) are best suited for clinical evaluations. Ideally, the treadmill should be installed in-ground using a pit. This type of installation results in the tread surface being at the same level as the surrounding floor. A standard protocol should always be used to train horses to exercise on a treadmill. Training should be designed to introduce the horse to procedures required for a specific clinical evaluation gradually.

The use of high-speed treadmills for lameness and hoof balance evaluations in the horse.

Examination for lameness remains the most important component of the clinical evaluation for poor performance. Although conventional examinations can be used to diagnose many causes of lameness, treadmill video gait analysis and dynamic hoof balance evaluations have proved to be useful not only for evaluating lameness but also for maintenance of long-term soundness. Treadmill lameness evaluations offer a major advantage compared to conventional evaluations because of the stationary position of the exercising horse relative to the people performing the examination. Lameness is suspected if asymmetric motion is observed or asymmetric sounds of the feet contacting the tread surface are heard during the treadmill evaluation. Localization of lameness to the front or hind legs is the first step in the treadmill gait analysis protocol. In trotting and pacing horses, asymmetric movements associated with foreleg lameness generally are confined to the front end. In contrast to the pacing gait, asymmetric movements associated with hindlimb lameness can involve both the front and rear of the horse at the trot. The evaluation is continued to determine which side of the horse is abnormal. Viewed from the front, horses with primary forelimb lameness appear to have an asymmetric downward rotation of the torso, head, and neck away from the stiffer lame front leg toward the flexed normal leg as it contacts the tread surface. The lame hind leg can appear to be stiff relative to the opposite normal leg. This results in uneven side-to-side oscillations of the pelvis rotating away from the abnormal stiff-appearing hind leg toward the normal, flexed hind leg as it contacts the tread surface. Both front- and hind-leg lamenesses cause dissociation of the normal foot-fall sequence, resulting in the alteration of the normal two beat gait at the trot or the pace to a three-beat gait. The final step of the lameness examination involves the use of diagnostic regional anesthesia to determine the anatomic location of the lameness. Treadmill video gait analysis can be used to evaluate differences in the horse's gait before and after each anesthetic block. Optimal foot balance during exercise is critical for long-term maintenance of musculoskeletal soundness. Combining slow-motion video gait analysis with treadmill exercise provides an excellent method for evaluating hoof balance at a variety of speeds. Optimal hoof balance can be achieved by using the technique of successive trimming and re-evaluation. The principles of hoof balancing include establishing dorsopalmar or dorsoplantar hoof balance.(ABSTRACT TRUNCATED AT 400 WORDS)

Comparison of yearling, two-year-old and adult Thoroughbreds using a standardised exercise test.

The purpose of this study was to compare exercise measurements in yearling, two-year-old and adult Thoroughbreds using a standardised treadmill incremental exercise test. Peak oxygen consumption (VO2 peak: 128.0 +/- 2.1, 140.0 +/- 2.1, 163.7 +/- 3.4; ml/kg/min +/- se, P less than 0.05), peak packed cell volume (PCV peak: 0.50 +/- 0.01, 0.58 +/- 0.01, 0.64 +/- 0.01 litres/litre +/- se, P less than 0.05) and the maximum number of steps completed in the exercise test (STEPmax: 7.7 +/- 0.1, 8.1 +/- 0.1, 8.6 +/- 0.1; steps +/- se, P less than 0.05) increased with age and degree of physical activity. Peak venous lactate concentration (LACpeak: 21.3 +/- 1.5, 19.5 +/- 1.7, 14.4 +/- 1.7; mmol/litre +/- se, P less than 0.05) and peak respiratory exchange ratio (Rpeak) were significantly higher in both groups of younger horses compared to the adult racehorses. Peak heart rate (HRpeak: 230 +/- 2, 231 +/- 3, 229 +/- 3; beats/min +/- se) did not change with age or training. The rate of change of VO2 between steps in the exercise test (VO2trans) was significantly lower in the adult racehorses at the highest exercise intensities. The slopes of the linear approximation between R (LinR bx), the natural log transformation of venous lactate concentration (LogLAC bx), and heart rate (HR bx) with velocity were significantly lower in the trained adult racehorses. The slope of venous lactate concentration normalised to per cent VO2peak (LogLAC per cent bx) was significantly lower and R breakpoint (R brkpt) normalised to per cent VO2peak was significantly higher in the trained adult racehorses. There was a more rapid decrease in venous lactate and a more rapid return to initial R values in the adult horses relative to the younger, untrained horses. No significant age or training effects were found in the remainder of the post exercise measurements. These results indicate that aerobic power and exercise capacity increased with age and training. Anaerobic power was already well developed even at a young age.