Introduction
Necrosis of the femoral condyles is an infrequently encountered cause of severe hind limb lameness in neonatal foals.1–3 Affected foals typically present with this condition at 3 to 4 weeks old,2,3 although a wide age range (2 weeks to 12 months) has been reported.1 Foals display marked lameness and joint effusion1–3 and often have difficulty standing without assistance in the late stage of the disease.1 The medial femoral condyle is predominantly affected, and in rare cases the lateral condyle is also involved.3
Most affected foals have a history of sepsis prior to development of stifle lameness.1–3 Counterintuitively, synovial fluid from affected femorotibial joints typically has a normal WBC count with mildly to moderately elevated total protein concentration.2,3 Hypotheses for the development of this condition include sepsis, trauma, or a developmental etiology.4,5 A pathogenesis similar to that of femoral head avascular necrosis in humans and small-breed dogs has been proposed by previous authors but not confirmed.1–3
Due to the rarity of this condition in foals, reports available in the current literature involve either single3 or few cases with incomplete data sets.1 The case series described here presents a larger number of cases with postmortem 3-D imaging and extensive histopathology. The objectives of the study reported here were to describe the clinical, imaging, and histopathological abnormalities associated with osteochondral necrosis of the femoral condyles in foals and to identify features suggestive of a common pathogenesis. We hypothesized that this condition is not akin to avascular necrosis as reported in dogs and humans but more likely a manifestation of osteochondrosis.
Materials and Methods
Case selection criteria
Foals that were euthanized at Scone Equine Hospital or the University of California-Davis between 2008 and 2018 with a clinical diagnosis of osteochondral necrosis of the femoral condyles for which the affected distal femurs had been collected and fixed in formalin were considered for inclusion. A clinical diagnosis of osteochondral necrosis was made on the basis of the following criteria: unilateral or bilateral lameness, effusion of the medial femorotibial joint (MFTJ) or femoropatellar joint (FPJ), radiographic abnormalities including partial or complete detachment of an osteochondral fragment from the medial femoral condyle, and synovial fluid findings for the MFTJ of the affected stifle being not compatible with conventional criteria for septic arthritis (WBCs > 20 X 103/μL, total protein concentration > 3.5 to 4 g/dL, and neutrophils > 90%).4
Medical information for each foal was retrieved from computer databases by means of searching the foal’s name or patient identification number. Information collected included signalment, clinical information (affected limb, lameness grade, and concurrent disease), available clinical pathology findings, radiographic findings, details of treatments administered, duration of hospitalization before euthanasia, and method of euthanasia. Foals were excluded if cytologic evaluation of synovial fluid from the affected MFTJ(s) had not been performed antemortem or if cytologic results were unavailable.
Postmortem CT and gross and histopathological examination of affected formalin-fixed distal femurs were performed specifically for this study.
Distal femoral specimen collection
Following postmortem examination and within 12 hours after euthanasia, the stifle joints of affected foals were disarticulated and femurs were sectioned transversely through the metaphysis, immediately proximal to the distal femoral physis. Following sectioning, the soft tissues were trimmed from the distal femoral specimens, which were subsequently fixed and stored in an adequate volume of 4% phosphate-buffered formaldehyde. In 2018, a permit was acquired from the USDA for the shipment of equine distal femoral specimens fixed in formalin from Australia to the US. Specimens were shipped from Scone, NSW, Australia to the University of California-Davis Department of Pathology, Microbiology and Immunology in formalin, packaged in accordance with International Air Transport Association regulations.
CT of distal femoral specimens
Distal femoral specimens were temporarily removed from formalin and individually imaged by use of a 16-slice helical CT scanner (LightSpeed Pro; GE Healthcare) to acquire 0.6-mm-thick transverse images using a bone algorithm in a plane approximately perpendicular to the trochlear ridges of the distal femur. The CT images were reviewed by a board-certified veterinary radiologist (MS) using the multiplanar reformat tool of a DICOM viewer (Horos; Purview). Nine regions of interest were evaluated for data collection for each condyle on the basis of location in the sagittal (cranial, middle, and caudal) and frontal (axial, central, and abaxial) planes.
For each region within this grid, assessment of the noncalcified cartilage zone, subjacent mineralized zone, and subchondral trabecular bone was performed. The noncalcified cartilage zone included superficial articular cartilage and underlying noncalcified growth cartilage.6 It has been reported that a distinct compact subchondral bone plate is not seen histologically until foals are approximately 6 months old.6 Therefore, the mineralized zone was considered to represent epiphyseal growth cartilage undergoing mineralization in the process of endochondral ossification.6 The microstructural site referred to as the ossification front was estimated to lie within the mineralized zone.6,7 The subchondral trabecular bone was easily differentiated from the mineralized zone because it was less opaque, due to the presence of marrow between bone trabeculae.6
The noncalcified cartilage zone was considered abnormal if a full-thickness defect was present or if it was separated from the mineralized zone. In foals < 2 months old, the osteochondral junction is highly porous, therefore a degree of irregularity at the boundary between cartilage and bone was expected.6,7 However, large focal radiolucent defects within the mineralized zone were considered abnormal.8 Trabecular subchondral bone was assessed for changes in opacity, with abnormalities ranging from decreased opacity (lucency) to regional loss of bone.
Gross and histopathological examination of distal femoral specimens
Distal femurs were subsequently submitted for gross and histopathological examination, concentrating on areas of interest identified on CT images. Distal condyles were examined grossly, digitally photographed, and serially sectioned with a band saw at approximately 5-mm intervals in the frontal plane to produce 4 to 7 frontal sections/condyle, with the number of sections dependent on the size of the condyle. Digital photographs were then obtained of the sectioned condyles. From each condyle, 2 to 3 of the available frontal sections were sampled for histopathological examination to correlate with areas of interest identified on CT images. Each frontal section was halved in the sagittal plane and further sagittally sectioned as needed to fit into a sample-processing cassette. For each condyle, approximately 4 sections were examined histologically in total.
Sections were decalcified in 15% formic acid for 2 to 4 days, embedded in paraffin by use of routine methods, cut at 5 µm in thickness, and stained with H&E before being reviewed by a board-certified veterinary pathologist (BGM).
Results
Signalment and clinical management
Distal femoral specimens were collected from 8 Thoroughbred foals bred on large commercial farms. This group included 5 colts and 3 fillies. One foal was born via emergency cesarean section, and no others had a history of dystocia. Seven of the 8 foals presented with 1 or more concurrent illnesses in additional to hind limb lameness, including neonatal maladjustment syndrome (n = 3), neonatal isoerythrolysis (1), and infections such as enteritis (1) and omphalitis (2). Five foals were hospitalized, and the remaining 3 foals were examined on an outpatient basis with lameness in the affected limb as the primary complaint.
Age at hospitalization or first examination ranged from time of birth (for the foal delivered by cesarean section) to 11 weeks old, with a median age of 3 days. Hind limb lameness was first observed at a median age of 10 days (range, 4 to 71 days).
Foals displayed bilateral hind limb lameness (n = 4), left hind limb lameness alone (2), and right hind limb lameness alone (2). Lameness was determined to be mild to severe in all foals, ranging from grade 2/5 (n = 1) to 5/5 (1) on the Association of American Equine Practitioners scale,9 with most foals displaying either grade 3/5 (3) or grade 4/5 (3) lameness.
Antemortem diagnosis
Hematology—Hematology data on admission to hospital or initial examination were available for 7 foals. Neutrophilia (n = 6), leukocytosis (5), and hyperfibrinogenemia (4) were the most commonly identified abnormalities in these cases.
Radiography—Radiographic reports or original radiographic images of affected stifle joints were available for review for all foals. Radiographic abnormalities were confined to the medial femoral condyle in all cases.
Four foals had a single set of radiographs taken on the day they were first evaluated for hind limb lameness. For 2 of these foals, the main radiographic abnormality was a crescent-shaped radiopaque fragment displaced from and adjacent to the medial femoral condyle (Figure 1). The predominant radiographic finding in the other 2 foals was moderate to severe subchondral bone lysis affecting the medial femoral condyle, without a displaced radiopaque fragment.
Caudolateral to craniomedial oblique (A) and caudocranial (B) radiographic views of the right stifle joint of a 9-day-old foal affected with osteochondral necrosis of the medial femoral condyle showing a thin, crescent-shaped radiopaque fragment displaced caudomedially from the medial femoral condyle (asterisk). The irregular contour of the proximal femoral trochlear ridges and patella is within normal limits for foals less than 3 months old. Lateral is to the left.
Citation: Journal of the American Veterinary Medical Association 260, 3; 10.2460/javma.21.03.0166
For 3 foals, 2 sets of bilateral stifle radiographs were taken during hospitalization. In all 3 cases, the first set of radiographs was taken the day lameness and joint effusion were first noticed and no abnormalities were detected. Repeated radiographs of both stifle joints were taken 2 to 5 days after the first set. In all 3 of these foals, the second set of radiographs showed a crescent-shaped radiopaque fragment displaced caudomedially from the medial femoral condyle as the main abnormality.
A single foal had 2 sets of radiographs of the right stifle joint; the initial images were acquired the first day clinical signs were detected and the second set 3 days later. No abnormalities were noted on either set of radiographs.
Cytologic evaluation of synovial fluid—Synovial fluid was obtained from the MFTJ of the hind limb(s) determined to be predominantly responsible for the lameness. Specifically, synovial fluid was collected from both hind limbs in 3 of 8 foals, the left hind limb in 3 other foals, and the right hind limb in the remaining 2 foals. Cytology was performed on synovial fluid samples from all foals. Fluid was typically grossly hemorrhagic, which may have been the result of blood contamination occurring during synoviocentesis. The total WBC count ranged from 0.4 to 5.1 X 103/µL (reference range, 0 to 2 X 103/µL), with a mean of 1.9 X 103/µL. Total protein concentration ranged from 2.5 to 4.9 g/dL (reference range, < 2.0 g/dL). Synovial fluid WBC differential data were available for 10 of 11 joint samples. The mean percentage of neutrophils in these samples was 68.7% (range, 13% to 81%). The mean percentage of mononuclear cells was 21.5% (range, 4% to 55%) and of lymphocytes was 8.4% (range, 1% to 32%). The description of the cytologic findings varied, although most samples contained intact, nondegenerate neutrophils, with some activated mononuclear cells and histocytes or synoviocytes.
Synovial fluid was cultured aerobically for bacterial organisms in 3 foals, and results were positive in 1 case. Staphylococcus aureus was cultured from the synovial fluid with the highest WBC count (5.1 X 103/µL).
Treatments and euthanasia
One foal was referred to the University of California-Davis after being treated extensively by a veterinarian employed privately by the farm. This foal had developed an umbilical abscess at 9 days old and was treated with chloramphenicol (50 mg/kg, PO, q 8 h) for 12 days and amikacin (25 mg/kg, IV, q 24 h) for 9 days. At 1 month old, the foal developed a fever and left hind limb lameness. Radiographs of the left stifle joint showed that moderate lysis affected the subchondral bone of the medial femoral condyle. Antimicrobials were switched to doxycycline (10 mg/kg, PO, q 12 h) and gentamicin (6.6 mg/kg, IV, q 24 h) for 28 days. The foal remained afebrile, but the left hind limb lameness did not improve. Antimicrobials were switched again to clarithromycin (7.5 mg/kg, PO, q 12 h) and rifampin (7.5 mg/kg, PO, q 12 h) for 20 days. The left hind limb lameness remained unchanged, and the foal was referred to the University of California-Davis for arthroscopic surgery on the left stifle joint.
Arthroscopy of all 3 compartments of the left stifle joint was performed by use of standard technique and approaches.5 No gross abnormalities were detected on arthroscopic evaluation of the FPJ or the lateral femorotibial joint. The synovial fluid within the MFTJ was clear and straw colored. An extensive area of detached cartilage and soft, deformable underlying subchondral bone was observed on the axial, weight-bearing surface of the medial femoral condyle. The foal was euthanized under general anesthesia (Euthasol, 100 mg/kg, IV) due to the extensive and severe nature of the lesions and poor prognosis for future soundness.
The other 7 foals were managed medically, either following admission to Scone Equine Hospital (n = 4) or on the farm after examination and consultation with veterinarians from Scone Equine Hospital (3). Only one of the hospitalized foals had a primary complaint of lameness, secondary to suspected septic physitis of the left distal tibial growth plate. This foal had been treated on the farm with doxycycline (10 mg/kg, PO, q 12 h) for an unknown period of time. Radiographs obtained at Scone Equine Hospital confirmed left distal tibial physitis; antimicrobials were switched to chloramphenicol (50 mg/kg, PO, q 8 h) for 5 days, and phenylbutazone (2.2 mg/kg, PO, q 24 h) was also added to the treatment regimen. The lameness initially improved after 2 days of treatment, to the degree that the foal displayed no lameness at a trot, but then deteriorated again on the fifth day of treatment, coinciding with development of left MFTJ and FPJ effusion. Radiographs of the left stifle obtained on the fifth day of treatment showed a crescent-shaped radiopaque fragment displaced from the medial femoral condyle and sclerotic, collapsed underlying subchondral bone. The owners declined further treatment, and the foal was euthanized (sodium phenobarbital, 100 mg/kg, IV).
Of the other 3 hospitalized foals, 1 was born by cesarean section in the hospital, 1 was referred for colic and underwent exploratory celiotomy for a small intestinal intussusception, and 1 was referred for treatment of neonatal maladjustment syndrome, neonatal isoerythrolysis, and partial failure of passive transfer. The foal born by cesarean section was treated with fluid therapy IV, broad-spectrum antimicrobials, intranasal oxygen supplementation, and hyperimmune plasma administered IV. A nasogastric tube was placed to provide the foal with colostrum and enteral nutrition. Specific details of doses and duration of each of these treatments were not available from hospital records. The foal developed marked left hind limb lameness and effusion of the left MFTJ and FPJ at 8 days old. Radiographs of both stifles were obtained, showing crescent-shaped radiopaque fragments displaced from the medial femoral condyle bilaterally. The owners of this foal declined further treatment, and the foal was euthanized at 9 days old (sodium phenobarbital, 100 mg/kg, IV).
The foal that underwent exploratory celiotomy and reduction of a small intestinal intussusception was treated postoperatively with benzyl penicillin (22,000 U/kg, IV, q 6 h), ceftiofur (4.4 mg/kg, IV, q 12 h), flunixin meglumine (0.5 mg/kg, IV, q 24 h), omeprazole (4 mg/kg, PO, q 24 h), lactated Ringer solution (0.05 mg/kg/min, IV), dextrose (5 mg/kg/min, IV), and lidocaine (0.05 mg/kg/min, IV). Flunixin meglumine was stopped after 48 hours, and the foal was allowed short periods of nursing every 2 hours. The dextrose rate was halved, and total parenteral nutrition was added to the treatment regimen (0.025 mg/kg/min, IV). The foal developed profuse diarrhea on the fourth postoperative day. Sucralfate (20 mg/kg, PO, q 6 h) and sodium bicarbonate (PO; dose not available from clinical records) were added to the treatment regimen, and lidocaine was stopped. Intermittent right hind limb lameness at a walk was first noticed 8 days postoperatively. Radiographs of the right stifle joint obtained on the day lameness was first noticed showed a crescent-shaped osteochondral fragment displaced from the medial femoral condyle. The following day, the foal was noted to be lying down more, had to be assisted to stand, and showed consistent grade 4/5 right hind limb lameness when ambulating. The owners of this foal declined further treatment, and the foal was euthanized at 10 days old (sodium phenobarbital, 100 mg/kg, IV).
The foal that was hospitalized with neonatal maladjustment syndrome, neonatal isoerythrolysis, and partial failure of passive transfer was treated initially with IV fluids and received a blood transfusion of the mare’s washed RBCs. A nasogastric tube was placed for administration of enteral nutrition until the foal developed a coordinated suckle reflex. Specific dosages and duration of treatments were not available from hospital records. On the seventh day of hospitalization, the foal began to have difficulty standing and developed bilateral MFTJ effusion. Radiographs of both stifles were obtained on the ninth day of hospitalization and showed a large crescent-shaped radiopaque fragment displaced from the left medial femoral condyle and a similar but smaller fragment from the right medial femoral condyle. The owners of this foal declined treatment, and the foal was euthanized at 10 days old (sodium phenobarbital, 100 mg/kg, IV).
Two foals were each examined on 1 occasion at Scone Equine Hospital for lameness. In each case, a provisional diagnosis of osteochondral necrosis of the medial femoral condyle(s) was made on the basis of stifle radiography and synovial fluid cytology. In these 2 cases, hospitalization for further treatment was offered but declined on the basis of economic considerations. Both foals were discharged with instructions for stall confinement and administration of an NSAID (meloxicam, 0.6 mg/kg, PO, q 12 h) for 7 days. Both foals were euthanized on the farm: one foal 7 days after examination and the other foal 16 days after examination. In both cases, euthanasia was carried out by veterinarians employed privately by the farm using sodium phenobarbital (100 mg/kg, IV) on humane grounds due to progression in severity of hind limb lameness.
The last foal included in this study was examined on the farm at 9 days old for an 18-cm longitudinal skin laceration on the medial aspect of the left gaskin region. The foal was anesthetized with ketamine and diazepam following sedation with xylazine. The wound was sutured following clipping and aseptic preparation of surrounding skin, and the foal was subsequently hand-recovered from general anesthesia. A 3-day course of procaine penicillin IM, gentamicin IV, and meloxicam PO was prescribed (exact doses were not available from records). The foal was reexamined 4 days later for right hind limb lameness and effusion of the right MFTJ and FPJ. Radiographs of the right stifle were taken, and synoviocentesis of the right MFTJ was performed. The synovial fluid appeared grossly normal and was not evaluated further. The right MFTJ was injected with 200 mg of gentamicin, and a 7-day course of doxycycline PO plus an additional 3 days of meloxicam PO were prescribed. The right hind limb lameness initially improved after 2 days of this treatment, but the foal was again lame at the walk 3 days later. Synoviocentesis of the right MFTJ was repeated the day after the course of doxycycline was completed, and the synovial fluid was found to have an elevated total protein concentration and neutrophil percentage, but the WBC count was within normal limits. The foal was euthanized on the farm at 14 days old (sodium phenobarbital, 100mg/kg, IV) due to deteriorating lameness.
Postmortem findings and collection of distal femurs
The foal that had been euthanized at the University of California-Davis underwent a complete gross postmortem examination. The articular cartilage of the left medial femoral condyle had fragmented, and the subchondral bone was hemorrhagic. There was an approximately 5-cm-diameter abscess with a thick capsule within the musculature of the left abdominal wall, and fluid aspirated from the abscess yielded a pure growth of Salmonella enteriditis on bacterial culture.
The 4 foals that were hospitalized for treatment at Scone Equine Hospital underwent an abbreviated postmortem examination of both stifles within 12 hours after euthanasia. The hind limbs of the 3 foals that were treated and euthanized on the farm were disarticulated at the coxofemoral joint following euthanasia and transported to the referral equine hospital for a similar abbreviated postmortem examination. In 5 of 7 foals, gross abnormalities were noted bilaterally; in 1 foal, only the left stifle joint was affected; and in 1 foal, only the right stifle joint was affected. Abnormalities common to all affected stifle joints included a large volume of synovial fluid in the medial femorotibial and femoropatellar joints, as well as detachment of the articular epiphyseal cartilage complex (AECC) from the axial aspect of the medial femoral condyle and pale tan to gray discoloration of the underlying condylar epiphyseal bone.
Following the abbreviated postmortem examination, affected distal femurs were collected and stored in formalin as previously described. Preserved femoral specimens from 7 foals were shipped from Australia to California specifically for inclusion in this study.
Postmortem CT
Computed tomography was performed postmortem on bilateral distal femurs for 5 of 8 foals. For the remaining 3 foals, only the distal femur that was considered clinically affected was available.
The most common abnormalities were lysis of the trabecular bone and detachment of the noncalcified cartilage zone, noted in 13 of 14 medial femoral condyles (Figure 2). These changes were typically most severe at the caudoaxial aspect of the medial femoral condyle in a weight-bearing area, with this site being involved in all cases. The caudal central and middle axial areas were involved in 12 of the 13 assessed condyles; other areas were less frequently affected.
Computed tomographic images of the right stifle joint of a 9-day-old foal affected with osteochondral necrosis of the medial femoral condyle reformatted into sagittal (A), transverse (B), and frontal (C) planes. There is a cartilage flap displaced caudomedially from the medial femoral condyle and mild irregular sclerosis in the compact subchondral bone. Lateral is to the right.
Citation: Journal of the American Veterinary Medical Association 260, 3; 10.2460/javma.21.03.0166
Medial femoral condylar abnormalities were found to be bilateral in all 5 foals for which both distal femurs were available. This included 2 foals that were considered to be unilaterally affected either clinically or according to radiographs.
Abnormalities noted in the lateral femoral condyles were much less severe. Mild contour irregularity of the mineralization zone at the caudoaxial aspect of the lateral condyle was present in 12 of the 13 femurs and was considered a normal variation. In 3 femurs, focal lucency suggestive of lysis was noted in the trabecular bone at the caudal abaxial aspect of the lateral femoral condyle.
Gross and histopathological abnormalities of distal femurs
A total of 13 medial femoral condyles in 8 foals were examined grossly and histologically. In 5 foals, both the left and right medial condyles were examined. In 1 foal only the left medial condyle was examined, as no abnormalities of the right medial condyle were identified on CT images. The lateral condyle was examined in addition to the medial condyle uniaxially in 3 foals to investigate areas of trabecular subchondral bone lysis apparent on CT images.
Gross abnormalities included detachment of the AECC (13/13 medial condyles), a demarcation between normal and ischemic trabecular subchondral bone (12/13), and deformation of the normally smooth, circumscribed contour of the medial femoral condyle (10/13; Figure 3).
Photographs of a caudal view (A), cranial view (B), and sections (C) of the medial femoral condyle of the right distal femur shown in Figure 1 showing detachment of growth cartilage, a demarcation between normal and ischemic subchondral bone (dashed lines in panel C), and degenerative deformation of the subchondral-epiphyseal bone. Degenerative deformation refers to separation of a region of ischemic or necrotic subchondral bone from the epiphysis, resulting in deformation of the normally smooth, circumscribed contour of the medial femoral condyle.
Citation: Journal of the American Veterinary Medical Association 260, 3; 10.2460/javma.21.03.0166
Detachment, degeneration, and necrosis of the AECC was a histopathological finding common to all foals and was observed in all 13 examined medial condyles (Figure 4). One or more of the following histopathological abnormalities related to ischemia were found in all foals: ischemic cartilage canals within the AECC (11/13 medial condyles), partial subchondral bone ischemia characterized by regional absence of hematopoietic cells with continued presence of adipose tissue and spongiosa (11/13), and subchondral bone necrosis with or without direct evidence of infarctions (11/13). Chronic changes including bone lysis and bone production (modeling) and subchondral granulation tissue and fibrin deposition were each seen in 11 of 13 medial condyles.
Low-power (A) and high-power (B through D) photomicrographs of the right medial femoral condylar epiphysis shown in Figures 1 and 3. The growth cartilage (I) is separated from the immediately underlying necrotic subchondral bone (II) via a fracture through primary trabeculae of the articular epiphyseal cartilage complex (arrowheads). The deeper subchondral bone (III) is affected by multifocal to coalescing osteomyelitis (accumulation of neutrophils and fibrin; not visible at 20X magnification). A region of granulation tissue is present at the junction of II and III (not visible at 20X magnification). The encircled cartilage canals in panel A are shown in panels B and C, highlighting neutrophilic infiltration (arrows). Subpanel D shows osteoclasts (arrowheads) acting on a spicule of trabecular bone (asterisks). Regions of fibrin deposition and osteonecrosis (interrupted line in panel A) and dense neutrophilic infiltration (dashed line) are highlighted. H&E stain; bar = 1 mm in panel A, 170 μm in panel B, 43 μm in panel C, and 54 μm in panel D.
Citation: Journal of the American Veterinary Medical Association 260, 3; 10.2460/javma.21.03.0166
One or more histologic findings associated with acute inflammation were found in 7 of 8 foals. These included fibrinosuppurative synovitis and arthritis (8/13 medial condyles), polymorphonuclear cells in cartilage canals (acute septic canals; 6/13), and suppurative osteomyelitis (5/13; Figure 4). Only 1 foal had no evidence of osteomyelitis, synovitis and arthritis, or polymorphonuclear cells in the cartilage canals.
Epiphyseal venous thrombosis was an uncommon finding, identified in only 2 of 13 medial condyles. Only 1 foal had evidence of osteomyelitis in the metaphysis and ischemic cartilage canals in the physis.
The most common abnormalities in lateral femoral condyles were partial subchondral bone ischemia characterized by regional absence of hematopoietic cells with continued presence of adipose tissue and spongiosa (3/3 lateral condyles), ischemic cartilage canals (2/3), and subchondral trabecular bone lysis and production (2/3). No inflammatory histologic features were found in any lateral femoral condyle.
No evidence of retained growth cartilage (ie, osteochondrosis manifesta)10 or bacteria was seen in any sample.
Discussion
All foals included in this case series were euthanized with a presumptive diagnosis of osteochondral necrosis of the femoral condyles. The majority of foals were concurrently diagnosed with a focus of infection remote to the affected stifle or neonatal maladjustment syndrome. Osteochondral necrosis affected the medial femoral condyle in all cases (8/8 foals) and was often bilateral (5/8). The most common CT abnormalities were lysis of the trabecular bone and detachment of the noncalcified cartilage. Lysis was most severe at the caudal aspect of the medial femoral condyle, where the distal femoral epiphyseal growth cartilage is thickest.11 In all cases, synovial fluid cytology from affected MFTJs was either within normal limits or consistent with mild inflammation. Most foals (7/8) had histopathological evidence of septic changes in the affected distal femoral epiphysis. Bacteria may reach the epiphysis by either direct extension from an adjacent soft tissue infection or more likely via a hematogenous route from the perichondral plexus or metaphyseal vessels supplying the ossification front.12 Our initial hypothesis of an osteochondrosis-like disease process was rejected, as histologic examination demonstrated that the bone lesions resulted from an osteolytic process with associated inflammation rather than delayed ossification, as expected in the definition of osteochondrosis manifesta.10 The term osteochondrosis has replaced the antiquated term osteochondritis because the osteochondrosis lesion does not have an inflammatory pathogenesis.13 Clearly, the lesions described in these foals were inflammatory.
The results of the present study differed from previous reports1,3 describing osteochondral necrosis of the femoral condyles in neonatal foals in that histologic evidence of septic processes (osteomyelitis, arthritis and synovitis, or septic cartilage canals) was often present. The fact that bilateral lesions were found in more than half of the foals included in this study further supported the theory of a septic (hematogenous) origin. Histologic evidence of bacteria was not observed in any section, but this does not preclude an infectious etiology, as it is often challenging to detect pathogens in the histopathological examination of bone.14 Due to their larger size and more common presence, neutrophils were used as a criterion for identification of septic canals in the absence of bacteria.8,14,15
Bacterial septicemia is considered the most likely mechanism by which bacteria may contaminate the cartilage canals, followed by an influx of inflammatory cells and formation of fibrinous or bacterial emboli, causing epiphyseal vascular disruption.16–18 Ischemia and subsequent osteochondral necrosis result in collapse of the subchondral bone and detachment of epiphyseal growth cartilage.19–21 Septic arthritis could also theoretically seed the epiphyseal osteochondral unit with bacteria,15 although this is considered less likely as antemortem cytologic findings were not consistent with septic arthritis in any foal of the present study.
In neonatal foals older than 15 days, the distal femoral epiphysis is supplied by the epiphyseal nutrient artery and perichondral arteries.22,23 Small gaps in the endothelium of blood vessels in the cartilage canals24 may allow bacteria to adhere and trigger inflammation-mediated disruption of endothelium, promoting a hypercoagulable state and vascular occlusion.25 Bacteria may also migrate through endothelial gaps and subsequently colonize epiphyseal growth cartilage or bone.21,26 It has been previously demonstrated in chickens and pigs that bacterial binding occurs in cartilage canals leading to occlusion of the vessels either by bacteria27 or fibrin thrombi.28,29 The outcome of occlusion of the blood supply to the distal femoral epiphysis may be chondronecrosis, osteochondral necrosis, or both, depending on the level at which the epiphyseal vasculature is interrupted and which vessels are involved.15,30
One of the most common sites of epiphyseal infections in foals is the distal femur.4,31 Regression of cartilage canals is slower in the growth cartilage of the distal femur than other sites including the distal talus, which renders the femoral condyles susceptible to hematogenous osteomyelitis for a longer period of time.32 Our data supported previous studies31,33 that found osteomyelitis more commonly affects the medial femoral condyle than the lateral. It is of note that in the present study, the most severe CT abnormalities were typically located at the caudal aspect of the medial femoral condyle. This finding may also have been related to the specific density of vessels rendering this region more vulnerable to hematogenous osteomyelitis. In foals younger than 65 days, the growth cartilage is consistently thicker in the caudal aspect of the medial compared to the lateral femoral condyle.11 Increased cartilage thickness has been linked with a higher number of cartilage canal vessels in developing equine bones including the distal femur.22,32,34 As a result, increased growth cartilage vascular density in the medial compared to the lateral femoral condyle may provide greater opportunity for hematogenous bacterial invasion.
It is uncommon for epiphyseal osteomyelitis to occur in the absence of purulent changes in the synovia of the adjacent joint.33 In fact, the incidence of septic arthritis adjacent to the site of epiphyseal osteomyelitis is 70% to 80% in retrospective studies.31,35 Experimentally, it has been demonstrated that IA injection of bacteria may result in bacterial colonization and subsequent fibrin occlusion of cartilage canals, with cartilage canal necrosis occurring 14 days postinjection.29 Antemortem synovial fluid cytologic findings were not consistent with septic arthritis36,37 in any foal of the present study, despite cartilage detachment permitting extensive communication between inflamed osteochondral tissues and the synovial fluid. Theoretically, it is possible that a higher synovial WBC count and neutrophil percentage could be present earlier in the disease process (ie, before clinical signs of lameness and joint effusion prompt arthrocentesis),38 in which case our inclusion criteria may have effectively excluded acute stages of disease progression. However, if osteochondral necrosis were preceded by septic arthritis, the reason for apparent resolution of cytologic parameters indicative of synovial infection in the face of static (or more often, worsening) clinical signs is unknown.
Nonseptic causes of cartilage deformation in foals including trauma and osteochondrosis were considered during our investigation. Trauma may have played a role in the development or exacerbation of these lesions, but trauma alone does not explain the presence of suppurative osteomyelitis or septic cartilage canals. Furthermore, a traumatic incident would not be expected to produce bilateral lesions as observed in most foals included in the present study. Recently, it has been reported that septic arthritis, physitis, and osteomyelitis may lead to osteochondrosis in juvenile horses.15 The definition of osteochondrosis manifesta requires evidence of delayed ossification,10 which was not detected histologically in any of the study foals. However, lesions typical of osteochondrosis latens (ie, subclinical osteochondrosis) were seen, including ischemic cartilage canals, multinucleated osteoclasts, and fibrovascular granulation tissue39 within subjacent bone. It is possible that evidence of ossification delay (ie, osteochondrosis manifesta) may have been present but was obliterated or obscured by fracturing and necrosis at the osteochondral junction. Additionally, micro-CT has higher spatial resolution than conventional CT40 and may have been a preferable digital imaging technique to guide histologic slices for the detection of focal areas of delayed ossification.
The main limitation of the study reported here was the lack of clinical data for some foals. The proposed pathogenesis of osteochondral necrosis of the femoral condyles assumes bacterial septicemia as the means by which the epiphysis is exposed to bacteria. All hospitalized foals in our case series had at least 1 recognized risk factor for the development of bacterial septicemia41,42; unfortunately, neither blood cultures nor sepsis scores were available for any foal. The 3 foals that were not hospitalized may also have had systemic or localized disease predisposing them to septicemia, but records were insufficient to confirm. Therefore, the assumption of bacterial septicemia remains speculative, especially for the 3 foals that were examined on an outpatient basis for lameness and for which available clinical details were limited.
Consistent with previous reports, the prognosis for osteochondral necrosis of the femoral condyles in neonatal foals appears to be poor. However, the foals of the present study all had severe deformity of the distal femoral epiphysis and progressive lameness. It is possible that milder cases may go undetected until horses are radiographed as yearlings in the case of commercial Thoroughbred operations. Clinicians should recognize that normal synovial fluid cytologic findings do not eliminate the possibility of adjacent osteomyelitis, even when extensive communication exists between inflamed subchondral bone and the synovial environment. Osteochondral necrosis of the femoral condyles is likely a sequela of bacterial septicemia in neonatal foals, although further studies are needed to establish causality.
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