Morphological characteristics of subchondral bone cysts in medial femoral condyles of adult horses as determined by computed tomography

Wade T. Walker Department of Clinical Sciences, College of Veterinary Medicine, Cornell University, Ithaca, NY 14853.

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Jesse L. Silverberg Wyss Institute for Biologically Inspired Engineering, Harvard University, Cambridge, MA 02138.

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Christopher E. Kawcak Gail Holmes Equine Orthopaedic Research Center, College of Veterinary Medicine and Biomedical Sciences, Colorado State University, Fort Collins, CO 80523.

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Bradley B. Nelson Gail Holmes Equine Orthopaedic Research Center, College of Veterinary Medicine and Biomedical Sciences, Colorado State University, Fort Collins, CO 80523.

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Lisa A. Fortier Department of Clinical Sciences, College of Veterinary Medicine, Cornell University, Ithaca, NY 14853.

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Abstract

OBJECTIVE To determine morphological characteristics of subchondral bone cysts (SBCs) in medial femoral condyles (MFCs) of adult horses with orthopedic disease.

SAMPLE CT scans of 7 MFCs with SBCs from 6 adult horses.

PROCEDURES CT was used to determine the volume, surface area, and centers of the articular cyst opening and SBC in each MFC. Cysts were ordered from smallest to largest on the basis of volume. Osseous pathological characteristics of the MFC were assessed in the frontal plane. Three-dimensional distance of displacement between the center of the articular cyst opening and center of the cyst was determined for each SBC. Cyst surface area-to-volume ratio was evaluated and compared with that of a true sphere.

RESULTS All SBCs had a defect in the subchondral bone plate at the cranial 15% to 20% of the MFC. Cyst center was located in a caudal, proximal, and abaxial direction with respect to the center of the articular cyst opening for each horse. Small- and intermediate-volume SBCs were irregular and multilobulated, whereas large-volume SBCs were smooth and discrete with a surface area-to-volume ratio approaching that of a sphere.

CONCLUSIONS AND CLINICAL RELEVANCE Consistency in morphological characteristics suggested a common etiopathogenesis for SBCs in MFCs of adult horses. Cyst enlargement may have been attributable to a biomechanical predisposition to decrease the surface area-to-volume ratio, resulting in a spherical cyst.

Abstract

OBJECTIVE To determine morphological characteristics of subchondral bone cysts (SBCs) in medial femoral condyles (MFCs) of adult horses with orthopedic disease.

SAMPLE CT scans of 7 MFCs with SBCs from 6 adult horses.

PROCEDURES CT was used to determine the volume, surface area, and centers of the articular cyst opening and SBC in each MFC. Cysts were ordered from smallest to largest on the basis of volume. Osseous pathological characteristics of the MFC were assessed in the frontal plane. Three-dimensional distance of displacement between the center of the articular cyst opening and center of the cyst was determined for each SBC. Cyst surface area-to-volume ratio was evaluated and compared with that of a true sphere.

RESULTS All SBCs had a defect in the subchondral bone plate at the cranial 15% to 20% of the MFC. Cyst center was located in a caudal, proximal, and abaxial direction with respect to the center of the articular cyst opening for each horse. Small- and intermediate-volume SBCs were irregular and multilobulated, whereas large-volume SBCs were smooth and discrete with a surface area-to-volume ratio approaching that of a sphere.

CONCLUSIONS AND CLINICAL RELEVANCE Consistency in morphological characteristics suggested a common etiopathogenesis for SBCs in MFCs of adult horses. Cyst enlargement may have been attributable to a biomechanical predisposition to decrease the surface area-to-volume ratio, resulting in a spherical cyst.

Subchondral bone cysts are commonly associated with osteoarthritis in adult horses and humans.1–4 Approximately 50% of humans with osteoarthritis of the knee joint have SBCs, as diagnosed via MRI.5,6 The etiopathogenesis of SBCs has historically been believed to be a breaching of the subchondral bone plate by synovial fluid.7,8 This belief is supported by the existence of a communication through the subchondral bone plate between the cyst and articular surface,2,8–12 also known as a cloaca. Primary bone contusion has also been suggested as an initiating cause of SBCs.1,12,13 Studies5,6,14 involving the femorotibial joint in humans have revealed a correlation between cartilage loss and SBCs. Furthermore, results of finite element analysis of the human hip joint suggest that cartilage thinning and erosions result in increases in focal stress throughout the underlying subchondral bone, theoretically supporting the role of a primary cartilage defect in the etiopathogenesis of SBCs.15

Osteochondrosis is believed to be the primary cause of SBC development in MFCs of juvenile horses because of the young age at onset and high incidence of bilateral lesions.16,17 In MFCs of adult horses, trauma and osteoarthritis are hypothesized causes of SBC formation.9,17,18 Regardless of the initiating cause, SBCs are dynamic in nature and their morphological characteristics change with time. These features have been demonstrated in longitudinal studies in rodents and humans,5,12 computational and finite element analysis models,19 and in MFCs of horses.9,18,20 Lesion identification is typically delayed until after osteoarthritis has developed, resulting in poor outcomes.21–25 A better understanding of the morphological characteristics of SBCs would potentially lead to earlier diagnosis, more effective treatments, and improved clinical outcomes.

Correlations between the presence of SBCs and abnormal clinical and imaging findings have been reported,2,5,6,9,10,21 but little is known about the initiation and subsequent progression of the lesions.12 Morphological similarities between horses and humans in cartilage and subchondral bone plates26,27 have resulted in conduction of numerous experiments involving horses for the translational study of osteoarthritis and cartilage repair.28–30 The MFC is the most common site of SBCs in horses31 and represents the most common clinical condition in horses evaluated at referral hospitals for femorotibial joint lameness.32 Unlike humans, who develop lesions at multiple loci on a given articular surface,2,5,11,21,22 SBCs in horses develop in a predictable location on the MFC and therefore have been used for understanding the development20,33 of and evaluating treatments for SBCs.4,24,34–36 In horses, experimental induction of SBCs in MFCs has been achieved through creation of a primary cartilage defect33 or penetration through the subchondral bone plate20,30 with subsequently induced repetitive trauma.

Development of therapeutic interventions designed to minimize expansion of SBCs requires understanding the morphological characteristics of SBCs. In horses, MFCs can be used for this purpose because of the high incidence of SBCs therein. In addition, therapeutic interventions can be evaluated in horses with experimentally induced SBCs.20,30,33 The purpose of the observational study reported here was to use quantitative, qualitative, and mathematical models and CT to comprehensively determine the morphological characteristics of SBCs in MFCs of adult horses with naturally acquired orthopedic disease.

Materials and Methods

Horses

Computed tomographic scans of 7 femorotibial joints from 6 adult horses (3 sexually intact females and 3 castrated males) with an SBC in the MFC for which no surgical intervention had been received were included in the study. Median age was 6 years (range, 3 to 7 years). Distal portions of both femurs (containing cysts 1 and 5) from 1 horse cadaver were severed at the distal diaphysis and disarticulated from the femorotibial joint. Those specimens were initially frozen and then thawed for 24 hours prior to CT scanning within a saline water bath.37 The CT scans for the other 5 horses were performed on live horses. The study protocol was approved by the Animal Care and Use Committee of Colorado State University, and owner consent was obtained prior to imaging of horses for study purposes.

CT protocol

Computed tomography was performed with a commercially available CT scanner.a Scans of the femorotibial joints of the 5 live horses were acquired with horses positioned in lateral recumbency, with the affected side down and the affected hind limb fully extended. Scans of the 2 cadaveric stifle joints were acquired in an orientation mimicking right lateral recumbency.37 A range of image acquisition settings was used for optimal clinical image quality.38 Scans were performed and reconstructed at a slice thickness of 0.8 mm and slice increment of 0.8 mm with a bone filter.

After image acquisition, unprocessed CT data were imported into a custom-written software programb,c allowing for specimen alignment, quantitative morphological analysis, and 3-D mapping. Alignment was achieved in 3 planes with a validated technique.37 Briefly, frontal and sagittal alignment was achieved cranially at the transition of the MFC and medial trochlear ridge of the femur and caudally at the most proximal aspect of the caudal portion of the MFC in perpendicular and parallel orientation, respectively. Transverse alignment was established parallel to the most distal points of the medial and lateral femoral condyles.37

Quantitative measurements of SBC morphology

Length, height, and width of MFCs were determined similarly to methods used in a previous study.37 Cyst volume was determined with a custom-made segmentation operation that created an ROI between −1,000 and 500 HUs (Figure 1). Each scan slice was evaluated in the frontal plane through the entire length of the condyle, and all pixels within the ROI, but not within the cyst, were manually removed so only the cyst proper remained. A 3-D reconstruction was generated for each cyst ROI. Volume and surface area were recorded. Subchondral bone cysts were then ordered from smallest (cyst 1) to largest (cyst 7) volume for the remainder of data analysis.

Figure 1—
Figure 1—

Selected CT images of SBCs illustrating the technique used to obtain measurements of SBCs in MFCs of adult horses. A—A frontal slice with a custom-made segmentation highlighting an ROI (cyst 6) with pixels between −1,000 and 500 HUs in yellow. B—The same image as in panel A after manual removal of all pixels that were not located within the cyst. C—A sagittal slice of the MFC with the cranial 50% sectioned into ten 5% increments derived from the length line. D—Customized CT color scale (black = −1,000 to 500 HUs, gray = 501 to 700 HUs, and red = 701 to 3,000 HUs) used to better assess cyst morphology in each slice. E—Frontal slice at the cranial 15% of the length line revealing an articular surface concavity and articular surface opening of a different cyst (cyst 1). F—Frontal slice at the cranial 25% of the MFC length line revealing an articular surface concavity and SBC (cyst 2). G—Frontal slice at the cranial 30% of the length line revealing an articular surface opening and SBC (cyst 7). H—Frontal slice at the cranial 40% of the length line revealing an intact subchondral bone plate and an SBC (cyst 7) within the subchondral trabecular bone. All frontal slices (A, B, and E to H) are oriented with the axial aspect of the MFC on the left, and the sagittal slice (C) is oriented with the cranial aspect at the top.

Citation: American Journal of Veterinary Research 77, 3; 10.2460/ajvr.77.3.265

Morphological characteristics were quantified with the surface area-to-volume ratio of each SBC plotted as a function of cyst size. These measured ratios were compared with the corresponding ratio of surface area (4π × radius2) to volume (4/3π × radius3) of a perfect sphere. In this comparison, the sphere radius was determined by measuring the SBC volume and deriving from that volume the corresponding radius. A sphere is characterized by a single radius in 3 planes, resulting in an oversimplified depiction of overall cyst geometry. Therefore, the SBC surface area-to-volume ratio was also compared with that of an ellipse, whereby the measurement of 3 separate radii in 3 planes allowed a more accurate assessment of biological variability and true SBC shape. In this situation, evaluation of a generalized 3-D cyst shape was performed by assessing the 3-D cyst radii as half of the maximal cyst length, width, and height in sagittal, transverse, and frontal planes, respectively. The 3-plane measurements of cyst radii were used to calculate the surface area-to-volume ratio for the fitted ellipse by use of the following equations39–42:

article image

in which a represents the greatest SBC radius in the sagittal plane, b represents the greatest SBC radius in the frontal plane, c represents the greatest SBC radius in the transverse plane, and p is 1.6075.

Qualitative measurement of pathological characteristics

The MFC length line derived in the sagittal plane was evenly divided into 10 frontal sections at the cranial 50% of the MFC, resulting in 5% intervals of the MFC length line (Figure 1). All 10 frontal slices were examined for each MFC with standard grayscale CT images and a customized color scale. Each slice was evaluated for the presence of a concavity in the otherwise convex curvature of the MFC, a cloaca extending from the articular surface through the subchondral bone plate, an SBC within the subchondral trabecular bone, and regions in which the subchondral bone plate was intact beneath the cyst within the subchondral trabecular bone. Data points in each frontal slice were summed to determine the most common region of pathological characteristics in the MFC and their position relative to the SBC.

Vectored morphological mapping of cysts

The 3-D quantitative topographic relationship between each cloaca and corresponding SBC was evaluated by determining the relative position of the center of the articular cyst opening and center of the cyst for each MFC. The center of the articular cyst opening and center point of the cyst were individually determined with a circle area measuring tool to determine a single approximate center locus in each of the 3 planes (Figure 2). Because MFC dimensions can vary with typical differences in body size,37 the percentage of individual 3-D displacement distance in each plane (sagittal, frontal, and transverse) over specimen dimensions (length, height, and width) for each MFC was applied to the mean length, height, and width of all MFCs rounded to the nearest 5 mm. This action normalized all distances and angles of displacement so that comparisons could be made among MFCs. To determine the principle direction of cloaca-to-cyst displacement, 3-D vectors were projected in sagittal, frontal, and transverse planes. These data were analyzed to extract the mean angle of displacement from the center of the articular cyst opening to the center of the cyst. The absolute amount of displacement from center of the articular cyst opening to the center of the cyst was determined for each SBC.d A linear regression model (with 95% confidence bounds) of the relationship between distance of displacement and size of cyst, with the y-intercept forced at 0, was used to determine the variability in displacement distance that could be attributed to the size of the SBC.

Figure 2—
Figure 2—

Selected CT images acquired in sagittal (A and D), transverse (B and E), and frontal (C and F) planes of an SBC (cyst 6) in an adult horse in which the 3-D loci of the articular surface opening center (A to C) and cyst center (D to F) have been highlighted by use of a software circle area tool. Sagittal plane images were used to determine MFC length of displacement between the articular surface opening center and the cyst center from cranial to caudal. Transverse plane images were used to determine MFC width of displacement between the articular surface opening center and the cyst center from axial to abaxial. Frontal plane images were used to determine MFC height of displacement between the articular surface opening center and the cyst center from distal to proximal.

Citation: American Journal of Veterinary Research 77, 3; 10.2460/ajvr.77.3.265

Results

The 7 MFCs from 6 adult horses had a mean length of 70 mm, mean height of 30 mm, and mean width of 45 mm when rounded to the nearest 5 mm. Characteristics of each SBC were summarized (Table 1).

Table 1—

Horse characteristics and corresponding CT measurements for 7 SBCs in the MFC, ordered from smallest to largest on the basis of cyst volume.

 Horse characteristicCyst measurements from ROIFitted ellipsoid cyst measurements from 3 plane radiiMFC measurements
SBCAge (y)SexBreedAffected hind limbVolume (mm3)Surface area (mm2)Volume (mm3)Surface area (mm2)Length (mm)Height (mm)Width (mm)
16Sexually intact femaleThoroughbredRight6.5016.704.8413.9868.2427.5442.84
25Sexually intact femaleQuarter HorseRight98.46111.21104.77110.0964.8228.8944.04
37Castrated maleArabianLeft880.66928.641,304.31595.3362.8328.739.59
46Castrated maleQuarter HorseLeft1,757.991,209.642,708.59942.6872.5529.4944.27
56Sexually intact femaleThoroughbredLeft1,901.191,497.002,152.06816.7768.7929.9944.85
63Sexually intact femaleQuarter HorseRight3,303.691,255.653,361.811,145.3562.5328.3540.63
73Castrated maleQuarter HorseRight5,035.311,827.795,570.631,529.2869.5230.5946.78

Cysts 1 and 5 were identified on different MFCs in the same horse. The approximate fitted ellipsoid measurements of cyst volume and surface area were derived from the largest diameter in sagittal, frontal, and transverse planes to create a more accurate depiction of the biological cyst morphology rather than representation as a true sphere. Medial femoral condyle measurements were averaged and rounded to the nearest 5 mm to provide a normalized value for vectored displacement measurements.

Qualitative assessment of frontal, sagittal, and 3-D reconstructions of SBCs revealed that small and intermediate-sized cysts were highly irregular while larger cysts became smooth and spherical in shape (Figure 3). The smallest SBC consisted of a subchondral bone plate defect with limited extension into the subchondral trabecular bone, whereas the majority of cyst volume in the larger SBCs was within the subchondral trabecular bone. All SBCs had an articular surface opening at the cranial 15% to 20% of the MFC in the sagittal plane. The articular surface opening extended caudally as SBCs increased in size (Figure 4). Most MFCs had a subtle concavity in the otherwise convex articular surface cranial to the cloaca, and that concavity tapered back to the typical convex shape as analysis of the MFC moved caudally. The majority of cyst volume was located caudal to the location of the articular communication. A concave but intact subchondral bone plate was present at the caudal aspect of the 3 largest SBCs between the articular surface and the cyst.

Figure 3—
Figure 3—

Selected CT images showing morphological characteristics of 7 SBCs (left to right) in the MFCs of adult horses, acquired in the frontal plane in standard grayscale (A–G; axial is to the left) and in the sagittal plane with the customized color scale in Figure 1 (H–N; cranial is at the top) and 3-D reconstructions of the SBC (O–U; viewed from the lateral aspect, with cranial on the left and distal on the bottom) in which the green line represents 10 mm. Consistent enlargement from cranial to caudal is evident as SBC size progresses. Cyst 1 is located at 15% (A), cyst 2 at 20% (B), cyst 3 at 25% (C), cyst 4 at 25% (D), cyst 5 at 30% (E), cyst 6 at 35% (F), and cyst 7 at 35% (G) of the cranial MFC length line. The 3-D reconstructions show that small SBCs are highly irregular in shape (O–R), and SBCs become more spherical and smooth (S to U) as they increase in volume.

Citation: American Journal of Veterinary Research 77, 3; 10.2460/ajvr.77.3.265

Figure 4—
Figure 4—

Number of MFCs (n = 7) from adult horses (6) with certain pathological characteristics identified via CT in the frontal plane at locations representing 5% increments advancing caudally along the MFC length line. Large cysts had an intact subchondral bone plate (SCBP) distal to the SBC. All MFCs had a cloaca at the cranial 15% to 20% of the MFC length line.

Citation: American Journal of Veterinary Research 77, 3; 10.2460/ajvr.77.3.265

All articular surface openings were located at a similar point on the MFC and passed along a similar trajectory, approximately perpendicular to the articular surface. Centers of the articular surface openings were located at the cranial 15% to 20% of the MFC length line in the sagittal plane, distal 32% to 52% of the MFC height line in the frontal plane, and axial 37% to 47% of the MFC width line in the transverse plane for all SBCs. In sagittal, transverse, and frontal planes, all SBCs were located caudal, abaxial, and proximal to the corresponding articular surface openings, respectively. Mean vectored angle of displacement for all SBCs was 52°, 24°, and 71° to the x-axis in sagittal, transverse, and frontal planes, respectively (Figure 5). As cyst size increased, distance of displacement between the articular surface opening and the cyst also increased for each MFC (Figure 6). Linear regression revealed that approximately two-thirds of variability in the amount of articular surface opening-to-cyst displacement could be attributed to the ultimate size of the defect (R2 = 0.68), whereas the remaining variability was likely from uncontrolled biological and experimental factors. Actual measurements of the SBC surface area-to-volume ratio agreed favorably with the surface area-to-volume ratio of a sphere with an equivalent cyst volume as well as with the fitted ellipsoidal surface area-to-volume ratio that approximated the overall cyst shape. When the percentage difference between the actual surface area-to-volume ratio and that of a sphere was calculated, intermediate-sized cysts had the largest deviations.

Figure 5—
Figure 5—

Three-dimensional plot of the vectored displacement from the articular surface opening center to the SBC center with an overlay CT 3-D reconstruction of an orthopedically normal MFC (A) and plots of articular surface opening-to-cyst displacement in sagittal (B), frontal (C), and transverse (D) planes. The black line in panel A represents the mean 3-D vectored displacement in each plane for all 7 SBCs represented in Figure 4. All articular openings were at the cranial 15% to 20% of the MFC. In panels B through D, angle of displacement was calculated with the point of the articular surface opening center normalized for all cysts. Mean angle of displacement from the articular surface opening center to the cyst center was identified at a 52° angle from craniodistal to caudoproximal in the sagittal plane, at a 71° angle from axiodistal to abaxioproximal in the frontal plane, and at a 24° angle from cranioaxial to caudoabaxial in the transverse plane.

Citation: American Journal of Veterinary Research 77, 3; 10.2460/ajvr.77.3.265

Figure 6—
Figure 6—

Distance of displacement from articular surface opening center to cyst center (A), surface area-to-volume ratio (B), and percentage difference from a sphere in surface area-to- volume ratio (C) for each of the 7 SBCs in Figure 4, with cysts ranked in size from smallest (1) to largest (7). A—The distance of displacement from articular surface opening center to cyst center increases as the cyst volume increases. B—The surface area-to-volume ratios of the calculated fitted approximate ellipsoid cyst shape based on 3 plane radii (triangles), a perfect sphere of the same volume (circles), and actual cyst ratio (squares) were compared. The exceptional correlation in surface area-to-volume ratio of a sphere and the fitted approximate ellipsoid calculation suggested that all cysts had the greater surface structure of a sphere. C—The percentage difference of surface area-to-volume ratio of a perfect sphere with an equivalent volume to each respective cyst (squares) compared with actual surface area-to-volume ratio of each cyst (singular arc) shows that intermediate-sized cysts (3 to 5) had considerably increased surface area-to-volume ratios. Given the determined overall spherical shape of SBCs, the greater surface area-to-volume ratio for intermediate-sized cysts could have been attributed to heterogeneity within the body of the cyst.

Citation: American Journal of Veterinary Research 77, 3; 10.2460/ajvr.77.3.265

Discussion

Although the morphological characteristics of SBCs reportedly change with time,5,9,12,20 no reports exist of the use of qualitative and quantitative methods to evaluate such characteristics. The present study involving SBCs in MFCs of adult horses revealed a consistent site of articular communication and a 3-D vectored angle of displacement from the articular surface opening to the SBC center for each MFC. All MFCs examined had an articular opening (ie, cloaca) at the cranial 15% to 20% of the length line in sagittal plane CT scans (Figure 4). The 3-D centers for the loci of articular surface openings were consistent for all cysts, particularly in the sagittal plane. The smallest SBC consisted solely of a cloaca and a small cyst volume, whereas SBCs with large volumes had large articular surface openings.

The qualitative results of the study reported here suggested that SBCs in MFCs of adult horses could have a common etiopathogenesis. Identification of an articular surface opening with limited subchondral trabecular bone lysis for 1 cyst (cyst 1) and detection of a cloaca at the cranial 15% to 20% of the MFC for all cysts suggested that SBCs first developed at the cranial aspect of the MFC with a breach in the subchondral bone plate.

This breach could have been a result of subchondral bone plate collapse secondary to microscopic damage in the subchondral trabecular bone or a primary disruption in the subchondral bone plate. The displacement and qualitative morphological data suggested that cyst expansion occurred primarily in a caudal direction within the subchondral trabecular bone, leaving an intact subchondral bone plate (Figure 4). Large SBCs had an intact but concave subchondral bone plate caudally, suggesting that cloaca expansion was caused by collapse of the subchondral bone plate after progression of the cyst within the subchondral trabecular bone. However, this possible explanation for SBC cyst initiation and expansion in MFCs of adult horses is based on 1-time measurement of a small number of specimens and therefore needs to be validated by a longitudinal study in which the morphological progression of SBCs is monitored over time.

A subtle concavity was recognized cranial or adjacent to cloaca formation in all MFCs in the present study (Figure 4). Such a concavity has been recognized in horses with and without SBCs that undergo intensive exercise.37 The articular irregularity is believed to represent a normal morphological characteristic of the MFC, to be a result of osteochondrosis, or to be due to bone remodeling caused by repetitive trauma.37 Although the clinical importance of the identified articular irregularity is unclear, finite element analysis of the human hip joint has revealed that even partial thinning of cartilage results in peak stress within the subchondral bone plate and trabecular bone.15 The identified articular irregularity could result in disparate joint loading, potentially leading to maladaptive bone remodeling and formation of a subchondral bone plate, microfracture. Repetitively induced trauma at the site of microfracture could permit the breach of synovial fluid through the subchondral bone plate, leading to cloaca formation and progression of SBCs.

Subchondral bone cysts of the MFC in horses develop in a predictable location,31 suggesting a common etiopathogenesis. Computed tomographic imaging in the present study revealed a consistent locus of articular surface opening for all SBCs, particularly in the sagittal plane (Figure 5). The small disparities in articular surface opening center loci were likely attributable to expansion of the articular surface opening as the cysts enlarged rather than to a different site of initiation. Results of histologic studies10,12 involving SBCs of the MFC indicate that mechanical trauma at the point of load bearing likely results in microfractures, leading to osseous resorptive activity and cyst formation. The SBC articular surface opening for each MFC in the present study was located at the same ROI that would be loaded had the femorotibial joint been maximally extended.43 Focal increases in femorotibial pressures occur when the joint is maximally extended in orthopedically normal horses43,44 and in the presence of pathological change,45,46 suggesting that repetitive trauma to the cranial aspect of the MFC as the limb strikes the ground in maximal extension47 is an initiating cause of SBCs in adult horses.

The amount of articular surface opening-to-cyst displacement generally increased in the present study as cyst size increased, suggesting that expansion of SBCs was dynamic and did not occur around a single fixed epicenter (Figure 6). Angle of displacement from the center of the articular surface opening to the cyst center was measured in each plane, and displacement occurred in a cranial to caudal, distal to proximal, and slightly axial to abaxial direction for all SCBs evaluated. Displacement in the sagittal plane was most profound from a cranial to caudal direction. Vectored displacement findings were consistent within all SBCs and likely represented the direction and amplitude of the articular forces that existed when the limb struck the ground in extension.47 These results can contribute to the development of a finite element analysis model to elucidate the hinge and rotational elements of the medial aspect of the femorotibial joint in horses.

Morphological characteristics changed dramatically as cyst volume enlarged in the present study. Smaller and intermediate-sized SBCs were highly irregular and multilobulated (Figure 3), whereas larger cysts were more spherical and had a sclerotic rim. Similar clinical morphological descriptions of SBCs have been published2,9,11,21,22,31; however, no correlation with disease severity has been established. By integrating biophysical principles with the observed morphological patterns, a mathematical and morphological correlation can be made. In particular, the finding that SBCs became more spherical as they increased in size suggested that 2 competing mechanisms were involved: one that acted to minimize the surface area of the defect and another that maximized its volume. Investigations of the properties of fluids, membranes, and other plastically deforming objects have revealed that the competition of these forces drives objects to become spherical.48 In these examples, surface tension forces typically serve as a mediator, and thus, we argue by analogy that the morphological evolution of SBCs may be driven by an effective surface tension that arises from the interplay among mechanical loading, forces at the fluid-bone interface within the joint, and bone remodeling. Findings of the study reported here indicated that effective surface tension may be related to bone remodeling and a mechanical impetus for osteoclastic activation to create more spherical SBCs.

In the present study, intermediate-sized cysts had extensive intralesional trabecular struts that disappeared as the cysts became larger, smooth, and spherical. The presence of intralesional trabecular struts within intermediate-sized cysts resulted in a honeycomb appearance with small ellipsoid cavities coalescing at multiple points similar to a cluster of grapes (Figure 3). In a finite element analysis of surface tension within a fluid pressurized bone cyst, an increase in fluid pressure resulted in stress shielding and decrease in strain energy to the surrounding trabecular bone.19 The outcome was net bone resorption and enlargement of morphologically irregular cysts. Further modeling that incorporated bone adaptation in response to cell death resulted in a large spheroid cyst with a sclerotic rim.19 Although the exact method of cyst volume expansion is poorly understood, findings of the present study suggested a predilection for decreasing the surface area-to-volume ratio, leading to a spherical shape as cyst size increased. Those findings indicated that SBCs in MFCs of adult horses were potentially initiated with an articular surface opening, developed an irregular multilobulated shape, and finally became a large spherical cyst with sclerotic margins. The newly proposed effective surface tension hypothesis for cyst progression is based on the interplay of mechanical loading, fluid-solid forces within the joint, and bone remodeling. This hypothesis is in its infancy and thus deserves much scrutiny. A combination of longitudinal observational and experimental studies would help to elucidate the details of SBC progression.

Identification of a consistent site of articular communication of SBCs in MFCs and therefore a possible site of initiation7,8 could allow additional investigation of subclinical cyst development before SBCs are readily detectable on caudocranial radiographic views. A flexed 20° craniolateral-to-caudomedial oblique projection49 can be used to highlight the cranial 15% to 20% of the MFC where the SBC cloaca is found. In the authors’ hospitals, this projection has been successfully used in the diagnosis of subclinical SBCs in the MFCs of horses that cannot be identified on other projections. Early diagnosis could allow for timely monitoring and rehabilitation before irreversible cyst enlargement and development of advanced degenerative disease ensues. Furthermore, if SBC enlargement is a result of effective surface tension forces at the interface between fluid and bone and an overall predisposition to decrease the surface area-to-volume ratio, then an effort to surgically obliterate any fluid within the cyst cavity may be appropriate. This can be accomplished by packing the surgically debrided cyst with a sealed cancellous bone graft or synthetic bone substitute.4

Unlike a sphere, the closed analytic expression for the surface area of an ellipsoid does not exist39; however, an empirical approximation of ellipsoid surface area proposed by Knud Thomsen results in a relative error of 1.061%.39–42 This approximation has therefore been used extensively in multiple biological studies39–42 to investigate the effects of surface area-to-volume ratios of organisms and tumors. Subchondral bone cysts in the present study were believed to have been caused by repetitive trauma to the cranial aspect of the MFC when the affected limb struck the ground in full extension. Subchondral bone cysts in juvenile horses or at other anatomic regions potentially have a different primary etiopathogenesis.

The present study had several limitations. The small number of MFCs used may not have allowed representation of the entire breadth of morphological characteristics of SBCs of the MFC and prevented robust statistical analysis. Acquisition of femorotibial CT scans from live horses is only available at a few institutions because of a limited ability to fit the hind limb of a horse into most standard CT bores. Findings were further constrained by the strict inclusion criteria to exclude SBCs in adult horses that had previously received surgical intervention. Horses > 3 years of age were chosen in an effort to evaluate SBCs that might have developed as a result of repetitive trauma. The age at which each SBC had developed was unknown for all horses, and the 2 cysts with the largest volumes were identified in 3-year-old horses. Osteochondrosis could not be ruled out as the primary cause of any SBC, despite inclusion of only adult horses. Disease severity was derived on the basis of SBC volume rather than lameness or degenerative disease within the joint. The presence of SBCs in humans with osteoarthritis is not strongly associated with degree of pain,50 making the correlation between size and disease severity in the present study potentially inappropriate. The study was also observational in design, involving CT scans of 7 MFCs in 6 horses with clinical orthopedic disease. Longitudinal evaluation of horses with experimentally induced or naturally developing SBCs is necessary to identify mechanisms underlying the initiation and progression of SBCs in adult horses.

In the study reported here, an articular communication with the SBC was identified at the cranial aspect of each MFC evaluated. Displacement from the cloacal center to cyst center occurred in a predictable 3-D direction. Distance of that displacement increased as the cyst volume increased, suggesting that the progression of SBCs was dynamic and had not taken place around a single locus. Cyst initiation was believed to have occurred with an articular surface opening and while expansion took place within the subchondral trabecular bone. Secondary collapse of the subchondral bone plate was believed to have resulted in articular surface opening expansion. Small and intermediate-sized SBCs were highly irregular in shape, with a large surface area-to-volume ratio. As volume increased, cysts became more homogenous with smooth spherical boundaries, resulting in a decreased surface area-to-volume ratio. The mechanism of SBC progression in affected horses was not identified; however, findings suggested that a predilection existed to decrease the overall surface area-to-volume ratio similar to that of a sphere. Longitudinal studies are needed to determine the sequence of events leading to SBC formation and expansion in adult horses.

Acknowledgments

Supported in part by a research grant through the American Quarter Horse Association (CEK).

Presented in abstract form at the American College of Veterinary Surgeons Annual Symposium, San Diego, October 2014.

The authors thank Margaret Goodale for help with generation of figures.

ABBREVIATIONS

HU

Hounsfield unit

MFC

Medial femoral condyle

ROI

Region of interest

SBC

Subchondral bone cyst

Footnotes

a.

Gemini TF Big Bore 16-slice scanner, Philips Medical Systems, Amsterdam, The Netherlands.

b.

OsteoApp, Orthopaedic Research Center, College of Veterinary Medicine and Biomedical Sciences, Colorado State University, Fort Collins, Colo.

c.

IDL, version 5.4, Research Systems Inc, Boulder, Colo.

d.

MATLAB, Mathworks, Natick, Mass.

References

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  • 2. Resnick D, Nixayama G, Coutts RD. Subchondral cysts (geodes) in arthritis disorders: pathologic and radiographic appearance of the hip joint. AJR Am J Roentgenol 1977; 128: 799806.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 3. McErlain DD, Appleton CTG, Litchfield RB, et al. Study of subchondral bone adaptations in a rodent surgical model of OA using in vivo micro-computed tomography. Osteoarthritis Cartilage 2008; 16: 458469.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 4. Ortved KF, Nixon AJ, Mohammed HO, et al. Treatment of subchondral cystic lesions of the medial femoral condyle of mature horses with growth factor enhanced chondrocyte grafts: a retrospective study in 49 cases. Equine Vet J 2012; 44: 606613.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 5. Raynauld J, Martel-Pelletier J, Berthiaume MJ, et al. Correlation between bone lesion changes and cartilage volume loss in patients with osteoarthritis of the knee as assessed by quantitative magnetic resonance imaging over a 24-month period. Ann Rheum Dis 2008; 67: 683688.

    • Search Google Scholar
    • Export Citation
  • 6. Tanamas SK, Wluka AE, Pelletier J, et al. The association between subchondral bone cysts and tibial cartilage volume and risk of joint replacement in people with knee osteoarthritis: a longitudinal study. Arthritis Res Ther 2010; 12: R58.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 7. Freund E. The pathological significance of intra-articular pressure. Edinburgh Med J 1940; 47: 192203.

  • 8. Landells JW. The bone cysts of osteoarthritis. J Bone Joint Surg Br 1953; 35: 643649.

  • 9. Jeffcott LB, Kold SE. Clinical and radiological aspects of stifle bone cysts in the horse. Equine Vet J 1982; 14: 4046.

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  • 11. Reilingh ML, Blankevoort L, van Eekeren ICM, et al. Morphological analysis of subchondral talar cysts on microCT. Knee Surg Sports Traumatol Arthrosc 2013; 21: 14091417.

    • Crossref
    • Search Google Scholar
    • Export Citation
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    • Crossref
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    • Crossref
    • Search Google Scholar
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    • Crossref
    • Search Google Scholar
    • Export Citation
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    • Search Google Scholar
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    • Search Google Scholar
    • Export Citation
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    • Crossref
    • Search Google Scholar
    • Export Citation
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    • Search Google Scholar
    • Export Citation
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    • Crossref
    • Search Google Scholar
    • Export Citation
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    • Crossref
    • Search Google Scholar
    • Export Citation
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    • Search Google Scholar
    • Export Citation
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    • Export Citation
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    • Search Google Scholar
    • Export Citation
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    • Search Google Scholar
    • Export Citation
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  • Figure 1—

    Selected CT images of SBCs illustrating the technique used to obtain measurements of SBCs in MFCs of adult horses. A—A frontal slice with a custom-made segmentation highlighting an ROI (cyst 6) with pixels between −1,000 and 500 HUs in yellow. B—The same image as in panel A after manual removal of all pixels that were not located within the cyst. C—A sagittal slice of the MFC with the cranial 50% sectioned into ten 5% increments derived from the length line. D—Customized CT color scale (black = −1,000 to 500 HUs, gray = 501 to 700 HUs, and red = 701 to 3,000 HUs) used to better assess cyst morphology in each slice. E—Frontal slice at the cranial 15% of the length line revealing an articular surface concavity and articular surface opening of a different cyst (cyst 1). F—Frontal slice at the cranial 25% of the MFC length line revealing an articular surface concavity and SBC (cyst 2). G—Frontal slice at the cranial 30% of the length line revealing an articular surface opening and SBC (cyst 7). H—Frontal slice at the cranial 40% of the length line revealing an intact subchondral bone plate and an SBC (cyst 7) within the subchondral trabecular bone. All frontal slices (A, B, and E to H) are oriented with the axial aspect of the MFC on the left, and the sagittal slice (C) is oriented with the cranial aspect at the top.

  • Figure 2—

    Selected CT images acquired in sagittal (A and D), transverse (B and E), and frontal (C and F) planes of an SBC (cyst 6) in an adult horse in which the 3-D loci of the articular surface opening center (A to C) and cyst center (D to F) have been highlighted by use of a software circle area tool. Sagittal plane images were used to determine MFC length of displacement between the articular surface opening center and the cyst center from cranial to caudal. Transverse plane images were used to determine MFC width of displacement between the articular surface opening center and the cyst center from axial to abaxial. Frontal plane images were used to determine MFC height of displacement between the articular surface opening center and the cyst center from distal to proximal.

  • Figure 3—

    Selected CT images showing morphological characteristics of 7 SBCs (left to right) in the MFCs of adult horses, acquired in the frontal plane in standard grayscale (A–G; axial is to the left) and in the sagittal plane with the customized color scale in Figure 1 (H–N; cranial is at the top) and 3-D reconstructions of the SBC (O–U; viewed from the lateral aspect, with cranial on the left and distal on the bottom) in which the green line represents 10 mm. Consistent enlargement from cranial to caudal is evident as SBC size progresses. Cyst 1 is located at 15% (A), cyst 2 at 20% (B), cyst 3 at 25% (C), cyst 4 at 25% (D), cyst 5 at 30% (E), cyst 6 at 35% (F), and cyst 7 at 35% (G) of the cranial MFC length line. The 3-D reconstructions show that small SBCs are highly irregular in shape (O–R), and SBCs become more spherical and smooth (S to U) as they increase in volume.

  • Figure 4—

    Number of MFCs (n = 7) from adult horses (6) with certain pathological characteristics identified via CT in the frontal plane at locations representing 5% increments advancing caudally along the MFC length line. Large cysts had an intact subchondral bone plate (SCBP) distal to the SBC. All MFCs had a cloaca at the cranial 15% to 20% of the MFC length line.

  • Figure 5—

    Three-dimensional plot of the vectored displacement from the articular surface opening center to the SBC center with an overlay CT 3-D reconstruction of an orthopedically normal MFC (A) and plots of articular surface opening-to-cyst displacement in sagittal (B), frontal (C), and transverse (D) planes. The black line in panel A represents the mean 3-D vectored displacement in each plane for all 7 SBCs represented in Figure 4. All articular openings were at the cranial 15% to 20% of the MFC. In panels B through D, angle of displacement was calculated with the point of the articular surface opening center normalized for all cysts. Mean angle of displacement from the articular surface opening center to the cyst center was identified at a 52° angle from craniodistal to caudoproximal in the sagittal plane, at a 71° angle from axiodistal to abaxioproximal in the frontal plane, and at a 24° angle from cranioaxial to caudoabaxial in the transverse plane.

  • Figure 6—

    Distance of displacement from articular surface opening center to cyst center (A), surface area-to-volume ratio (B), and percentage difference from a sphere in surface area-to- volume ratio (C) for each of the 7 SBCs in Figure 4, with cysts ranked in size from smallest (1) to largest (7). A—The distance of displacement from articular surface opening center to cyst center increases as the cyst volume increases. B—The surface area-to-volume ratios of the calculated fitted approximate ellipsoid cyst shape based on 3 plane radii (triangles), a perfect sphere of the same volume (circles), and actual cyst ratio (squares) were compared. The exceptional correlation in surface area-to-volume ratio of a sphere and the fitted approximate ellipsoid calculation suggested that all cysts had the greater surface structure of a sphere. C—The percentage difference of surface area-to-volume ratio of a perfect sphere with an equivalent volume to each respective cyst (squares) compared with actual surface area-to-volume ratio of each cyst (singular arc) shows that intermediate-sized cysts (3 to 5) had considerably increased surface area-to-volume ratios. Given the determined overall spherical shape of SBCs, the greater surface area-to-volume ratio for intermediate-sized cysts could have been attributed to heterogeneity within the body of the cyst.

  • 1. Ondrouch AS. Cyst formation in osteoarthritis. J Bone Joint Surg Br 1963; 45: 755760.

  • 2. Resnick D, Nixayama G, Coutts RD. Subchondral cysts (geodes) in arthritis disorders: pathologic and radiographic appearance of the hip joint. AJR Am J Roentgenol 1977; 128: 799806.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 3. McErlain DD, Appleton CTG, Litchfield RB, et al. Study of subchondral bone adaptations in a rodent surgical model of OA using in vivo micro-computed tomography. Osteoarthritis Cartilage 2008; 16: 458469.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 4. Ortved KF, Nixon AJ, Mohammed HO, et al. Treatment of subchondral cystic lesions of the medial femoral condyle of mature horses with growth factor enhanced chondrocyte grafts: a retrospective study in 49 cases. Equine Vet J 2012; 44: 606613.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 5. Raynauld J, Martel-Pelletier J, Berthiaume MJ, et al. Correlation between bone lesion changes and cartilage volume loss in patients with osteoarthritis of the knee as assessed by quantitative magnetic resonance imaging over a 24-month period. Ann Rheum Dis 2008; 67: 683688.

    • Search Google Scholar
    • Export Citation
  • 6. Tanamas SK, Wluka AE, Pelletier J, et al. The association between subchondral bone cysts and tibial cartilage volume and risk of joint replacement in people with knee osteoarthritis: a longitudinal study. Arthritis Res Ther 2010; 12: R58.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 7. Freund E. The pathological significance of intra-articular pressure. Edinburgh Med J 1940; 47: 192203.

  • 8. Landells JW. The bone cysts of osteoarthritis. J Bone Joint Surg Br 1953; 35: 643649.

  • 9. Jeffcott LB, Kold SE. Clinical and radiological aspects of stifle bone cysts in the horse. Equine Vet J 1982; 14: 4046.

  • 10. Jeffcott LB, Kold SE. Aspects of the pathology of stifle bone cysts in the horse. Equine Vet J 1983; 15: 304311.

  • 11. Reilingh ML, Blankevoort L, van Eekeren ICM, et al. Morphological analysis of subchondral talar cysts on microCT. Knee Surg Sports Traumatol Arthrosc 2013; 21: 14091417.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 12. McErlain DD, Ulici V, Darling M, et al. An in vivo investigation of the initiation and progression of subchondral cysts in a rodent model of secondary osteoarthritis. Arthritis Res Ther 2012; 14: R26.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 13. Rhaney K, Lamb DW. The cysts of osteoarthritis of the hip; a radiological and pathological study. J Bone Joint Surg Br 1955; 37: 663675.

    • Search Google Scholar
    • Export Citation
  • 14. Marra MD, Crema MD, Chung MR. et al. MRI features of cystic lesions around the knee. Knee 2008; 15: 423438.

  • 15. Durr HR, Martin H, Pellengahr C, et al. The cause of subchondral bone cysts in osteoarthrosis: a finite element analysis. Acta Orthop Scand 2004; 75: 554558.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 16. McIlwraith CW. Subchondral cystic lesions (osteochondrosis) in the horse. Compend Contin Educ Pract Vet 1982; 4: S394S404.

  • 17. Baxter GM. Subchondral cystic lesions in horses. In: McIlwraith CW, Trotter GW, eds. Joint disease in the horse. Philadelphia: WB Saunders Co, 1996;384397.

    • Search Google Scholar
    • Export Citation
  • 18. Verschooten F, De Moor A. Subchondral cystic and related lesions affecting the equine pedal bone and stifle. Equine Vet J 1982; 14: 4754.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 19. Cox LGE, Lagemaat MW, van Donkelaar CC, et al. The role of pressurized fluid in subchondral bone cyst growth. Bone 2011; 49: 762768.

  • 20. Ray CS, Baxter GM, McIlwraith CW, et al. Development of subchondral cystic lesions after articular cartilage and subchondral bone damage in young horses. Equine Vet J 1996; 28: 225232.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 21. Robinson DE, Winson IG, Harries WJ, et al. Arthroscopic treatment of osteochondral lesions of the talus. J Bone Joint Surg Br 2003; 85: 989993.

    • Search Google Scholar
    • Export Citation
  • 22. Kolker D, Murray M, Wilson M. Osteochondral defects of the talus treated with autologous bone grafting. J Bone Joint Surg Br 2004; 86: 521526.

    • Search Google Scholar
    • Export Citation
  • 23. Smith MA, Walmsley JP, Phillips TJ, et al. Effect of age at presentation on outcome following arthroscopic debridement of subchondral cystic lesions of the medial femoral condyle: 85 horses (1993–2003). Equine Vet J 2005; 37: 175180.

    • Search Google Scholar
    • Export Citation
  • 24. Wallis TW, Goodrich LR, McIlwraith CW, et al. Arthroscopic injection of corticosteroids into the fibrous tissue of subchondral cystic lesions of the medial femoral condyle in horses: a retrospective study of 52 cases (2001–2006). Equine Vet J 2008; 40: 461467.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 25. Hendrix SM, Baxter GM, McIlwraith CW, et al. Concurrent or sequential development of medial meniscal and subchondral cystic lesions within the medial femorotibial joint in horses (1996–2006). Equine Vet J 2010; 42: 59.

    • Search Google Scholar
    • Export Citation
  • 26. Frisbie DD, Cross MW, McIlwraith CW. A comparative study of articular cartilage thickness in the stifle of animal species used in human pre-clinical studies, compared with articular cartilage thickness in the human knee. Vet Comp Orthop Traumatol 2006; 19: 142146.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 27. Chevrier A, Kouao ASM, Picard G, et al. Interspecies comparison of subchondral bone properties important for cartilage repair. J Orthop Res 2015; 33: 6370.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 28. Nixon AJ, Fortier LA, Williams J, et al. Enhanced repair of extensive articular defects by insulin-like growth factor-I-laden fibrin composites. J Orthop Res 1999; 17: 475487.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 29. Fortier LA, Balkman CE, Sandell LJ, et al. Insulin-like growth factor-I gene expression patterns during spontaneous repair of acute articular cartilage injury. J Orthop Res 2001; 19: 720728.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 30. Frisbie DD, Kisiday JD, Kawcak CE, et al. Evaluation of adipose-derived stromal vascular fraction or bone marrow-derived mesenchymal stem cells for treatment of osteoarthritis. J Orthop Res 2009; 27: 16751680.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 31. von Rechenberg B, McIlwraith CW, Auer JA. Cystic bone lesions in horses and humans: a comparative review. Vet Comp Orthop Traumatol 1998; 11: 818.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 32. Jefcott LB, Kold SE. Stifle lameness in the horse: a survey of 86 referred cases. Equine Vet J 1982; 14: 3139.

  • 33. Kold SE, Hickman J. An experimental study of the healing process of equine chondral and osteochondral defects. Equine Vet J 1986; 18: 1824.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 34. White NA, McIlwraith CW, Allen D. Curettage of subchondral bone cysts in medial femoral condyles of the horse. Equine Vet J Suppl 1988; 6: 120124.

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