M D Markel

University of Wisconsin, Madison, Madison, MS, United States

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Publications (119)265.75 Total impact

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    R M Thiede, Y Lu, M D Markel
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    ABSTRACT: The purpose of this article is to provide a broad review of the literature related to the treatment of cartilage defects and degenerated cartilage in animals with some inferences to the treatment in humans. Methods range from the insertion of osteochondral tissue or cells to the application of radio frequency or insertion of scaffolds and growth factors alone or in combination. Debridement, microfracture, radio frequency, and chondrocyte implantation are all methods normally utilized when treating smaller articular cartilage defects. Scaffolds and mosaicplasty are examples of methods to treat larger defects. This review will cover all major treatment methods currently used to treat articular cartilage defects.
    Veterinary and Comparative Orthopaedics and Traumatology 01/2012; 25(4):263-72. · 1.03 Impact Factor
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    ABSTRACT: The concept of guided growth has been used for decades in the lower extremities of children, but has not been applied to correct varus or valgus deformity in the hip, such as those that occur in children with cerebral palsy or developmental dysplasia of the hip. The purpose of this study is to determine whether guided growth techniques are effective at altering the morphology of the proximal femur in a lamb model. Ten, 2-month-old mixed-breed male lambs underwent hemiepiphyseal drilling and screw placement. Drilling occurred eccentrically (inferiorly) in an attempt to close only a portion of the growth plate. In 5 lambs, a sham surgery was performed in which the screw did not cross the proximal femoral physis. Growth was compared between groups and with the opposite hip in which no procedure was performed in both groups. Standardized radiographs were obtained preoperatively and monthly. A 3-dimensional computed tomography scan and standard histology were obtained postnecropsy. Version and neck shaft angle (NSA) was determined and recorded at the time of the index procedure with the aid of fluoroscopy. Radiographs were assessed by measurement of the NSA and the articular trochanteric distance (ATD). Results were compared by using the t test: paired 2 sample for means. The NSA and ATD were compared preoperatively and at a mean of 3.3 months after surgery. They were no significant differences preoperatively between the screw or sham group. Postoperatively, the NSA was 132 versus 143 (P=0.006) and the ATD -0.6 mm versus 10 mm (P=0.033) for the screw and sham hips, respectively. The sham group showed no statistical differences between the operative and nonoperative sides postoperatively, although the ATD trended toward a larger number on the "sham" side, possibly because of a growth stimulation effect. Screw hemiepiphysiodesis seems to alter the growth of the proximal femur in the lamb model. Further studies are ongoing and with more research this technique could be used to correct or prevent proximal femoral deformity in the growing child. Level II.
    Journal of pediatric orthopedics 01/2010; 30(7):690-4. · 1.23 Impact Factor
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    ABSTRACT: Partial-thickness articular cartilage lesions occur with knee trauma and may progress to osteoarthritis. This study evaluates the effectiveness of hyaluronic acid on cartilage healing after acute knee injury in sheep. Early administration of hyaluronic acid to an acute cartilage injury will prevent chondrocyte death and improve cartilage metabolism. Controlled laboratory study. A 10 x 10 mm partial-thickness articular cartilage lesion was created on the medial condyle of 16 adult sheep stifles (hindlimbs). Eight sheep received intra-articular hyaluronic acid injections at days 0, 8, and 15, and 8 controls received saline. Contralateral stifles were nonoperated controls. All sheep were sacrificed at 12 weeks after surgery. Synovial fluid was drawn before surgery and after euthanasia for collagen II, nitric oxide, and interleukin-1 beta analysis. The medial condyle was analyzed by gross appearance, confocal laser microscopy for cell viability, histologic analysis for cartilage morphology, and dimethylmethylene blue assay for proteoglycan. At 12 weeks, histologic analysis revealed that the hyaluronic acid group had significantly better scores than the saline group (P = .001). The hyaluronic acid group had significantly greater glycosaminoglycan content than the saline group (P = .011), and showed a trend of reduced chondrocyte death compared with the saline group (P = .07). Synovial fluid showed no significant differences between the groups in collagen II, nitric oxide, and interleukin-1 beta levels. The results demonstrated that early administration of hyaluronic acid shows a significant improvement in cartilage histologic analysis and increased glycosaminoglycan content after acute traumatic cartilage injury. Early hyaluronic acid treatment for acute partial-thickness articular cartilage lesions may decrease or delay articular degeneration.
    The American journal of sports medicine 09/2009; 37(12):2323-7. · 3.61 Impact Factor
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    ABSTRACT: Repetitive bone injury and development of stress fracture is a common problem in humans and animals. The Thoroughbred racehorse is a model in which adaptive failure and associated development of stress fracture is common. We performed a histologic study of the distal end of the third metacarpal bone in two groups of horses: young Thoroughbreds that were actively racing (n = 10) and a group of non-athletic horses (n = 8). The purpose of this study was to determine whether development of articular microcracks was associated with specific alterations to subchondral plate osteocytes. Morphometric measurements were made in five regions of the joint surface: lateral condyle, lateral condylar groove, sagittal ridge, medial condylar groove, and medial condyle. The following variables were quantified: hyaline cartilage width; calcified cartilage width; the number of tidemarks; microcrack density at the articular surface; blood vessel density entering articular cartilage; the presence of atypical bone matrix in the subchondral plate; bone volume fraction; and osteocyte density. Adaptation of articular cartilage was similar in both groups of horses. Vascularization of articular cartilage was increased in the group of non-athletic horses. Microcracks, which typically had an oblique orientation to the joint surface, were co-localized with blood vessels, and resorption spaces. Microcracking was increased in the condylar grooves of athletic horses compared with the other joint regions and was also increased compared with the condylar groove regions of non-athletic horses. Coalescence of microcracks also led to development of an intracortical articular condylar stress fracture in some joints and targeted remodeling of affected subchondral plate. The subchondral plate of the condyles in athletic horses was sclerotic, and contained atypically stained bone matrix with increased numbers of osteocytes with atypical morphology. However, osteocyte numbers were not significantly different between groups. We conclude that differences in site-specific microdamage accumulation and associated targeted remodeling between athletic and non-athletic horses are much greater than differences in subchondral osteocyte morphology. However, the presence of atypical subchondral bone matrix in athletic horses was associated with extensive osteocyte loss. Although osteocyte mechanotransduction is considered important for functional adaptation, in this model, adaptation is likely regulated by multiple mechanotransduction pathways.
    Journal of Anatomy 01/2009; 213(6):706-17. · 2.36 Impact Factor
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    ABSTRACT: To compare the efficacy of recombinant human bone morphogenetic protein-2 (rhBMP-2)/calcium phosphate (CP) to autogenous cancellous bone graft (CBG) and to no treatment on bone healing, in surgically induced osteotomies and ostectomies of the accessory metatarsal bones in an equine model. Experimental. Adult horses (n=9). Segmental ostectomies of the second metatarsal bone (MT2) and osteotomies of the fourth metatarsal bone (MT4) were performed bilaterally in 9 horses. There were a total of 35 defects (1 MT4 was previously fractured) created and supplemented randomly either with no treatment (untreated control), rhBMP-2/CP cement, or matrix (CPC or CPM), or CBG. Radiography was performed every 2 weeks until study endpoint at 12 weeks. After euthanasia, bone healing was evaluated using radiography, mechanical testing, and histology. Data were analyzed with ANOVA followed by the Duncan's Multiple Range Test or nonparametric analyses. At 12 weeks, radiographic scores for union were significantly greater for the rhBMP-2 (P<.0001) and CBG (P=.004) groups compared with the untreated control group, for both MT2 ostectomies and MT4 osteotomies. The rhBMP-2 treated MT2 had greater maximum torque to failure in torsion than CBG and control limbs at 12 weeks (P=.011). Histologic analysis demonstrated increased bone formation and more mature bone at the ostectomy site for MT2 in the rhBMP-2 and CBG groups compared with the untreated control group. Injection of rhBMP-2/CP into surgically induced ostectomies and osteotomies of the accessory metatarsal bones might accelerate early bone healing in the horse. RhBMP-2/CP may be as effective if not superior to CBG as an adjuvant treatment to accelerate healing of bone defects.
    Veterinary Surgery 11/2008; 37(7):648-55. · 1.24 Impact Factor
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    ABSTRACT: To compare the biomechanical properties of cervical arthroplasty to a ventral slot procedure and pin-polymethylmethacrylate (pin-PMMA) fixation. Fresh cadaveric cervical (C2-T1) spines from 6 large dogs. Four spinal conditions were studied in each spinal specimen: intact, disk arthroplasty, ventral slot, and fixation with smooth pin-PMMA at C5-C6 intervertebral space. Axial compression, torsion, flexion-extension, and lateral bending moments were sequentially tested on each specimen for the 4 spinal conditions. Data from the C3-C4, C4-C5, C5-C6, and C6-C7 vertebral motion units (VMUs) were compared among treatments. In axial compression and torsion, the ventral slot procedure allowed significantly less motion than intact, pin-PMMA, and arthroplasty groups at C5-C6. In lateral bending and flexion-extension, pin-PMMA had the least motion of C5-C6, followed by the arthroplasty group, intact spine, and ventral slot, all of which were significantly different from each other. Overall, the artificial disk was better able to mimic the behavior of the intact specimens compared with the ventral slot and pin-PMMA, producing similar displacements in axial compression and rotation in torsion, but more limited motion than intact in flexion-extension and in lateral bending. Cervical spine specimens with an implanted prosthesis have biomechanical behaviors more similar to an intact spine compared with spinal specimens with ventral slot and pin-PMMA procedures. Cervical arthroplasty may then preserve some of the motion in the affected area after neural decompression while providing distraction. Cervical arthroplasty should be further investigated in vivo to determine if it is a viable alternative to the ventral slot or pin-PMMA procedures for surgical treatment of cervical diseases in dogs and in particular for treatment of disk-associated caudal cervical spondylomyelopathy.
    Veterinary Surgery 01/2008; 36(8):729-41. · 1.24 Impact Factor
  • R B Edwards, Y Lu, B J Cole, P Muir, M D Markel
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    ABSTRACT: To compare a radiofrequency energy (RFE) prototype probe to mechanical debridement (MD) and a commercially available RFE system used for chondroplasty in the treatment of an experimentally created partial thickness cartilage lesion in horses. The study design was experimental, randomized complete block, n=8, using fifteen mature ponies. Grade 2 to 3 cartilage lesions were prepared in both patellae. After 10 months duration, the injuries were used to study the effects of MD, a commercially available bipolar RFE device (CoVac 50; ArthroCare Corporation) and a prototype monopolar RFE device (Smith & Nephew Endoscopy). Six months after treatment the patellae were examined for chondrocyte viability and cartilage structure. Mean depth of cell death was significantly different among groups (controls, MD <prototype<CoVac 50) (P<0.05). Total histologic scores did not demonstrate any significant differences among the controls, MD and prototype RFE groups, which were all better than the CoVac 50 scores (P<0.05). There was a trend for the prototype RFE probe treated regions to have better surface structural characteristics than MD (P=0.11). Cartilage thickness was greater for the prototype RFE group than all other groups, and was the thinnest for the CoVac 50 group (P<0.05). When thermal chondroplasty is performed with a power-controlled prototype RFE probe, there is a better surface smoothing effect compared to MD, which causes less chondrocyte death and has the potential to maintain thicker cartilage compared to the commercially available RFE system.
    Veterinary and Comparative Orthopaedics and Traumatology 01/2008; 21(1):41-8. · 1.03 Impact Factor
  • Y Lu, M L Meyer, J J Bogdanske, M D Markel
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    ABSTRACT: To determine the thermal effects of monopolar radiofrequency energy (mRFE) on bovine articular cartilage when it was moved at different speeds and using varying application forces. Thirty-six fresh osteochondral sections divided into two groups (18 sections/group) were used in this study. The first group was tested at three speed rates of mRFE probe (1 mm/sec, 5 mm/sec and 10 mm/sec) at a constant force (50 g) applied to the probe tip. In the second group, three application forces of the probe tip were tested (25 g, 50 g and 75 g) at a constant speed (5 mm/sec) (n = 6/test). All tests were performed using a custom-built jig to control the mRFE (Vulcan EAS) probe during a 20-mm pass on each section. After treatment, viability of osteochondral sections was determined by confocal laser microscopy (CLM) combined with vital cell staining. There were not any significant differences in cartilage thickness of tested osteochondral sections among the different speeds or forces. During the mRFE probe treatments at different speeds, CLM demonstrated that probe application at the speed of 1 mm/sec caused significantly greater chondrocyte death than at the speeds of 5 and 10 mm/sec, whereas there were no significant differences in chondrocyte death among the variable application forces (p > 0.05). This in vitro study demonstrated that RFE thermal penetration correlated most closely with probe application speed than application force for this mRFE probe. Improper use of mRFE may cause thermal injury on articular cartilage.
    Veterinary and Comparative Orthopaedics and Traumatology 02/2007; 20(1):34-7. · 1.03 Impact Factor
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    ABSTRACT: The purpose of this study was to develop a long-term model of cartilage injury that could be used to compare the effects of radiofrequency energy (RFE) and mechanical debridement as a treatment. Partial thickness fibrillation of patellar cartilage was created in 16 mature ponies. Three months after the initial surgery all injured patellae were randomly selected to receive one of the four treatments (n = 8/treatment): (1) control, (2) mechanical debridement with a motorized shaver, (3) TAC-CII RFE probe, and (4) CoVac 50 RFE probe. The ponies were euthanized 22 months after treatment. Macroscopic appearance of the cartilage surface was scored, vital cell staining was used to determine chondrocyte viability and light microscopy was used to grade the morphometric changes within the cartilage. Mechanical properties (aggregate modulus, Poisson's ratio and permeability) also were determined and compared to normal uninjured cartilage. There were no differences in the cartilage surface scores among the treatment groups and control samples (P > 0.05). The maximum depth of cell death and the percentage of dead area in control and mechanical debridement groups were significantly less than those in both RFE groups. There were no significant differences in maximum depth and the percentage of dead area between the two RFE treatment groups. Histologic scores demonstrated better cartilage morphology for the control and mechanical debridement groups than those of RFE groups. However, even with full thickness chondrocyte death, the matrix in the RFE treated sections was still retained and the mechanical properties of the treated cartilage did not differ from the mechanical debridement group. RFE caused greater chondrocyte death and more severe morphological changes compared to untreated degenerative cartilage and mechanical debridement in this model.
    Osteoarthritis and Cartilage 02/2007; 15(2):169-78. · 4.26 Impact Factor
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    ABSTRACT: The mechanisms that regulate functional adaptation of the articular ends of long bones are poorly understood. However, endochondral ossification of articular cartilage and modeling/remodeling of the subchondral plate and epiphyseal trabeculae are important components of the adaptive response. We performed a histologic study of the distal end of the third metacarpal/metatarsal bone of Thoroughbreds after bones were bulk-stained in basic fuchsin and calcified sections were prepared. The Thoroughbred racehorse is a model of an extreme athlete which experiences particularly high cyclic strains in distal limb bones. The following variables were quantified: microcrack boundary density in calcified cartilage (N.Cr/B.Bd); blood vessel boundary density in calcified cartilage (N.Ve/B.Bd); calcified cartilage width (Cl.Cg.Wi); duplication of the tidemark; and bone volume fraction of the subchondral plate (B.Ar/T.Ar). Measurements were made in five joint regions (lateral condyle and condylar groove; sagittal ridge; medial condylar and condylar groove). N.Cr/B.Bd was site-specific and was increased in the condylar groove region; this is the joint region from which parasagittal articular fatigue (condylar) fractures are typically propagated. Formation of resorption spaces in the subchondral plate was co-localized with microcracking. N.Ve/B.Bd was also site-specific. In the sagittal ridge region, N.Ve/B.Bd was increased, Cl.Cg.Wi was decreased, and B.Ar/T.Ar was decreased, when compared with the other joint regions. Multiple tidemarks were seen in all joint regions. Cumulative athletic activity was associated with a significant decrease in B.Ar/T.Ar in the condylar groove regions. N.Cr/B.Bd was positively correlated with B.Ar/T.Ar (P < 0.05, r(s) = 0.29) and N.Ve/B.Bd was negatively correlated with B.Ar/T.Ar (P < 0.005, r2 = 0.14) and Cl.Cg.Wi (P < 0.05, r2 = 0.07). We conclude that endochondral ossification of articular cartilage and modeling/remodeling of the subchondral plate promote initiation and propagation of site-specific fatigue microcracking of the joint surface, respectively, in this model. Microcracking of articular calcified cartilage likely represents mechanical failure of the joint surface. Propagation of microcracks into the subchondral plate is a critical factor in the pathogenesis of articular condylar fatigue (stress) fracture. Functional adaptation of the joint likely protects hyaline cartilage from injury in the short-term but may promote joint degeneration and osteoarthritis with ongoing athleticism.
    Bone 03/2006; 38(3):342-9. · 3.82 Impact Factor
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    Journal of Orthopaedic Research 12/2005; 19(5):990 - 990. · 2.88 Impact Factor
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    ABSTRACT: Functional adaptation of bone normally protects the skeleton from fracture during daily activity. Accumulation of microcracking and loss of osteocytes have been implicated in the regulation and initiation of targeted (reparative) remodeling of bone and, in certain situations, the development of fatigue or stress fracture. We performed a histologic study of the dorsal cortex of the mid-diaphysis of the third metacarpal (Mc-III) bone of Thoroughbred racehorses after bones were bulk-stained in basic fuchsin and transverse calcified sections were prepared. The Thoroughbred racehorse is an extreme athlete whose Mc-III bone experiences particularly high cyclic strains during training and racing. A group of non-athletic horses was also included in the experiment. The following variables were quantified: activation frequency (Ac.f); bone formation rate (BFR); resorption space density (Rs.N/T.Ar); microcrack density (Cr.Dn); microcrack mean length (Cr.Le); microcrack surface density (Cr.S.Dn); osteocyte density (Ot.N/T.Ar; Ot.N/B.Ar); and bone volume fraction (B.Ar/T.Ar). Ac.f and BFR were estimated using a mathematical algorithm. Using confocal microscopy, bones were examined for fine microcracks, diffuse matrix injury, and disruption of the osteocyte syncytium. Low values for Cr.Dn (#/mm2) were found in both groups (0.022+/-0.008 and 0.013+/-0.006 for racing Thoroughbreds and non-athletic horses, respectively). There was no significant relationship between Cr.Dn and Ot.N/T.Ar; Ot.N/B.Ar, B.Ar/T.Ar, and Ot.N/T.Ar; Ot.N/B.Ar, and remodeling (Ac.f, Rs.N/T.Ar) and Ot.N/T.Ar; Ot.N/B.Ar. Intense remodeling of the Mc-III dorsal cortex was found in the racing Thoroughbreds (Ac.f 12.8+/-7.4 #/mm2/year; BFR 31.5+/-15.6%; Rs.N/T.Ar 0.19+/-0.09 #/mm2) and was significantly increased compared with non-athletic horses. Overall, remodeling was weakly correlated with Cr.Dn (r2=0.15, P<0.05). Subtle matrix injury, not detectable by bright-field microscopy, was particularly evident adjacent to resorption spaces in Thoroughbred bone. In non-athletic horses, disruption of the dendritic cell processes of osteocytes associated with cement lines and interstitial fragments was more evident. Taken together, these findings suggest that site-specific (targeted) induction of remodeling during functional adaptation of bone in a high-strain skeletal site is not dependent on accumulation of microcracking or loss of osteocytes. We hypothesize that athleticism can directly influence bone turnover in this extreme athlete through pathways that do not involve classical linear microcracks.
    Bone 07/2005; 37(1):16-24. · 3.82 Impact Factor
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    ABSTRACT: Cyclic loading induces fatigue in bone and initiates a complex, functionally adaptive response. We investigated the effect of a single period of fatigue on the histologic structure and biomechanical properties of bone. The ulnae of 40 rats were subjected to cyclic fatigue (-6000 microepsilon) unilaterally until 40% loss of stiffness developed, followed by 14 days of adaptation. The contralateral ulna served as a treatment control (n = 20 rats), and a baseline loaded/non-loaded group (n = 20 rats/group) was included. Bones from 10 rats/group were examined histologically and the remaining bones (10 rats/group) were tested mechanically. The following measurements were collected: volumetric bone mineral density (vBMD); ultimate force (Fu); stiffness (S); energy-to-failure (U); cortical area (Ct.Ar); microcrack density (Cr.Dn); microcrack mean length (Cr.Le); microcrack surface density (Cr.S.Dn); osteocyte density (Ot.N/T.Ar and Ot.N/TV); bone volume fraction (B.Ar/T.Ar); resorption space density (Rs.N/Ct.Ar); and maximum and minimum area moments of inertia (IMAX and IMIN). Using confocal microscopy, the bones were examined for diffuse matrix injury, canalicular disruption, and osteocyte disruption. The adapted bones had increased B.Ar, IMAX, and IMIN in the mid-diaphysis. Fatigue loading decreased structural properties and induced linear microcracking. At 14 days, adaptation restored structural properties and microcracking was partially repaired. There was a significant nonlinear relationship between Ot.N/T.Ar and B.Ar/T.Ar during adaptation. Disruption of osteocytes was observed adjacent to microcracks immediately after fatigue loading, and this did not change after the period of adaptation. In fatigue-loaded bone distant from microcracks, diffuse matrix injury and canalicular disruption were often co-localized and were increased in the lateral (tension) cortex. These changes were partially reversed after adaptation. Loss of canalicular staining and the presence of blind-ends in regions with matrix injury were suggestive of rupture of dendritic cell processes. Taken together, these data support the general hypothesis that the osteocyte syncytium can respond to cyclic loading and influence targeted remodeling during functional adaptation. Changes in the appearance of the osteocyte syncytium were found in fatigue-loaded bone with and without linear microcracks. We hypothesize that the number of dendritic cell processes that experience load-related disruption may determine osteocyte metabolic responses to loading and influence targeted remodeling.
    Bone 11/2004; 35(4):881-91. · 3.82 Impact Factor
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    ABSTRACT: Failure of bone adaptation to protect the skeleton from fatigue fracture is common, and site-specific accumulation and coalescence of microcracking in regions of high strain during cyclic loading is considered a key factor that decreases the resistance of whole bones to fracture. We investigated the effect of cyclic fatigue loading on the monotonic structural properties of the rat ulna during accumulation and coalescence of microcracks. Cyclic end-loading of the ulna was performed at 4 Hz ex vivo at an initial peak strain of -6000 muepsilon to 20% loss of stiffness (n = 7) or 40% loss of stiffness (n = 7) bilaterally. A 0% loss of stiffness monotonically loaded control group (n = 7) was also included. Volumetric bone mineral density (vBMD), ultimate strength (F(u)), stiffness (S), and energy-to-failure (U) were determined in one ulna and in the contralateral ulna vBMD, cortical bone area (B.Ar), maximum and minimum second moments of inertia (I(MAX) and I(MIN)), microcrack density (Cr.Dn), microcrack mean length (Cr.Le), and microcrack surface density (Cr.S.Dn) were determined. In two additional groups of rats, cyclic end-loading of the ulna was also performed ex vivo unilaterally to 20% loss of stiffness (n = 10) and 40% loss of stiffness (n = 10) and then vBMD, F(u), S, U, B.Ar, I(MAX), and I(MIN) were determined bilaterally. Fatigue loading had incremental degradative effects on ulna structural properties. This decreased resistance to fracture was associated with accumulation and coalescence of branching arrays of microcracks within the cortex of the ulna. Microcracking was most prominent in the middiaphysis and corresponded to the region of the bone that fractured during monotonic structural testing. Fatigue loading influenced the relationship between bone cross-sectional geometry and vBMD and ulna structural properties. At 40% loss of stiffness, F(u), S, and U were all significantly correlated with cross-sectional bone geometry and vBMD, whereas this was not the case at 20% loss of stiffness and with the 0% loss of stiffness monotonic control ulnae. We also found a biologically significant individual animal effect. Larger ulnae required a higher number of load cycles for fatigue to develop, retained higher strength, and accumulated a greater amount of microcracking at the end of the cyclic fatigue testing. Small increases in bone size and density can substantially improve the resistance of whole bones to fracture as microcracking accumulates and coalesces during cyclic fatigue loading.
    Bone 09/2003; 33(2):197-205. · 3.82 Impact Factor
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    ABSTRACT: Measurement of markers of cartilage pathology in synovial fluid may provide clinical rheumatologists and osteoarthritis (OA) researchers important information for early diagnosis of OA as well as a method for monitoring disease progression and response to treatment. This study demonstrates the value of this approach in an established model of OA (cranial cruciate ligament rupture) at a point distant enough from the original surgical manipulation so as to have little to no effect on the marker concentrations. The objective of this study was to determine whether measurement of markers of cartilage collagen cleavage and proteoglycan turnover in synovial fluid from a canine model could be used to detect cartilage changes following the onset of joint instability during the development of OA. A model of joint instability that develops OA was created in 18 mature dogs using monopolar radiofrequency energy (MRFE). MRFE was arthroscopically applied to one cranial cruciate ligament (CCL) while the contralateral CCL was sham treated. The treated CCLs ruptured approximately 8 weeks (55 +/- 1.6 days) after MRFE treatment. Synovial fluid was collected at time zero prior to MRFE treatment, 4 weeks after MRFE treatment, and at 4, 8, and 16 weeks after CCL rupture. Synovial fluid concentrations of the neoepitope COL2-3/4C long (type II collagen cleavage by collagenase) and epitopes 3B3(-) (proteoglycan aggrecan sulfation) and 846 (associated with aggrecan synthesis) were analyzed. Compared to sham treated joints, the synovial fluid concentrations of COL2-3/4C long and 3B3(-) were significantly increased 2.2 fold and 2.9 fold, respectively, in joints with MRFE treated CCLs following CCL rupture. Concentrations of the 846 epitope in synovial fluid showed a trend toward an increase, which was not significant, after CCL rupture. Concentrations of the collagenase-cleaved type II collagen neoepitope and 3B3(-) epitope in synovial fluid were significantly increased by 4 weeks and remained elevated for at least 16 weeks after CCL rupture. This suggests that in dogs the COL2-3/4C long neoepitope and 3B3(-) epitope are sensitive markers for changes in joint cartilage turnover in joints that are developing OA.
    Osteoarthritis and Cartilage 09/2002; 10(8):662-9. · 4.26 Impact Factor
  • M J Lopez, L A DeTemple, Y Lu, M D Markel
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    ABSTRACT: To evaluate the effect of monopolar radiofrequency energy (RFE) on intact and lacerated meniscal tissue. In vitro study. Application of monopolar RFE to soft tissue for treatment of various musculoskeletal disorders has been explored recently, although its effect on meniscal tissue has not been critically evaluated. Monopolar RFE denatures and fuses collagen. Given that menisci are composed primarily of type I collagen, we proposed that RFE could be applied to meniscal tears with minimal effect on healthy meniscal tissue. Adult sheep menisci were given 1 of 2 treatments (65 degrees C, 15 W or 75 degrees C, 10 W) with a monopolar RFE generator. Specimens were processed for scanning electron microscopy (SEM), transmission electron microscopy (TEM), light microscopy, and confocal laser microscopy. A computer-based area-determination program was used to calculate the treated area in confocal laser images. SEM changes in treated tissue consisted of surface smoothing with collagen fibril fusion. Changes apparent with TEM included tissue homogenization with loss of cross-striations and fusion of collagen fibrils. Histologic changes consisted of fusion and loss of collagen fiber individualization, pyknosis of fibrochondrocyte nuclei, and loss of lacunae surrounding fibrochondrocytes. There were clear demarcations between treated and untreated tissue with both treatments. There were no discernible differences between treatment groups on SEM, TEM, or histologic examination. Confocal laser microscopic evaluations showed distinct treatment areas. The mean area affected ranged from 6.6% for 65 degrees C, 15 W to 8.8% for 75 degrees C, 10 W. The primary effects of monopolar RFE treatment of menisci in this study were consistent with thermal tissue damage limited to the treatment area. Monopolar RFE treatment of a meniscal laceration may stabilize the tear by fusing collagenous tissue in the surrounding area and prevent propagation along tissue lines. This study presents preliminary in vitro results. Further studies are necessary before clinical applications can be recommended.
    Arthroscopy The Journal of Arthroscopic and Related Surgery 08/2001; 17(6):613-9. · 3.10 Impact Factor
  • W T Cook, M M Smith, M D Markel, J W Grant
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    ABSTRACT: To determine total stiffness and gap stiffness of an external fixation system in a canine mandibular fracture gap model incorporating a full interdental pin as the only point of rostral fixation in a bilateral type-I external fixator. 10 canine mandibles. Bilateral mandibular ostectomies were performed between premolars 3 and 4. A type-I external fixator incorporating a full interdental pin was placed to stabilize a 0.5-cm fracture gap. Four pin configurations (intact mandibular bodies with fixator; ostectomized mandibular bodies and complete fixator; ostectomized mandibular bodies with caudal pins of rostral fragment cut; ostectomized mandibular bodies with all pins of rostral fragment cut) were tested in dorsoventral bending 5 times on each mandible. The full interdental pin remained intact in all configurations. Total stiffness and gap stiffness were determined for each configuration on a materials testing machine. Total stiffness of intact mandibles was significantly greater than that of ostectomized mandibles, regardless of external fixator configuration. However, total stiffness and gap stiffness were not significantly different among different external fixator configurations applied to ostectomized mandibles. External fixator configurations with only the full interdental pin engaging the rostral fragment were as stiff as configurations that had 2 or 4 additional pins in the rostral fragment for the applied loads. External fixators for rostral mandibular fractures may be rigidly secured with rostral fragment implants applied extracortically, avoiding iatrogenic trauma to teeth and tooth roots.
    American Journal of Veterinary Research 05/2001; 62(4):576-80. · 1.35 Impact Factor
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    ABSTRACT: This study compared the effect of augmentation of allograft host bone junctions with recombinant human bone morphogenetic protein-2 (rhBMP-2) on an absorbable collagen sponge (ACS), autogenous cancellous bone graft (CBG), and a collagen sponge alone in a canine intercalary femoral defect model repaired with a frozen allograft. Outcome assessment included serial radiographs, dual energy X-ray absorptiometry scans, and gait analyses, and mechanical testing and histology of post-mortem specimens. The distal junction healed more quickly and completely with rhBMP-2 than ACS alone based on qualitative radiography and histologic evaluations. The primary tissue in the unhealed gaps in the ACS group was fibrous connective tissue. The proximal allograft host bone junction had complete bone union in the three treatment groups. There was significantly greater new bone callus formation at both junctions with rhBMP-2 than with CBG or ACS alone that resulted in increased bone density around the allograft host bone junctions. All dogs shifted their weight from the treated leg to the contralateral pelvic limb immediately after surgery. Weight bearing forces were redistributed equally between the pelvic limbs at 12 weeks after surgery with rhBMP-2, at 16 weeks after surgery with CBG, and at 24 weeks after surgery with ACS alone. Bending and compressive stiffnesses of the whole treated femora were equal to the contralateral control femora in all treatment groups, whereas torsional rigidities of the whole treated femora for the CBG and ACS groups were significantly less than the control. Both the proximal and distal junctions the treated with rhBMP-2 had torsional stiffnesses and strengths equal to intact control bones. Ultimate failure torques of the proximal junctions of the CBG group and of both junctions of the ACS group were significantly less than the BMP-treated bones. Augmentation of the allograft host bone junctions with rhBMP-2 on an ACS gave results for all parameters measured that equaled or exceeded autogenous graft in this canine intercalary femoral defect model.
    Journal of Orthopaedic Research 04/2001; 19(2):308-17. · 2.88 Impact Factor
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    ABSTRACT: The purpose of this study was to determine the effect of recombinant human bone morphogenetic protein type 2 (rhBMP-2) on the histomorphometry of femoral allograft-host bone union and allograft remodeling. A 6 cm mid-diaphyseal femoral defect was created and filled with an allograft stabilized with an interlocking nail in 21 dogs. Dogs were randomly divided into three equal groups and the allograft-host bone junctions and the mid-diaphyses of the allografts were treated with either an absorbable collagen sponge (ACS) loaded with rhBMP-2 (BMP group), an autogenous cancellous bone graft (CBG group), or ACS loaded with buffer solution (ACS group). All dogs received daily tetracycline until sacrifice at 24 weeks to label new bone formation. Histomorphometric analyses on sections of proximal and distal allograft-host bone junctions and the mid-diaphyseal portion of allografts were performed using fluorescent and regular light microscopy. Analyses of the host bone and junctions between allograft and host bone revealed significantly greater new bone formation and larger osteon radii in the BMP group compared to CBG and ACS groups and contralateral intact bone. Porosity in CBG and ACS groups was significantly higher than in the BMP group, which had similar values to intact bone. In transverse sections of allografts, the largest pore diameters were present in the CBG group. Based on all parameters measured, significantly higher bone turnover occurred in the outer cortical area of the allograft in all groups as compared to the inner cortical and mid-cortical areas. New bone formation and osteon radius/osteon width in allografts were similar for all three groups. Higher porosity and larger pore diameters in the CBG and ACS groups suggested higher bone resorption versus formation in these groups compared to the BMP group. The results of this study reveal more balanced allograft bone resorption and bone formation in the BMP group, with greater resorptive activity in the CBG and ACS groups. However, neither rhBMP-2 nor autogenous bone graft increased allograft incorporation when compared to the negative control (ACS group). © 2001 Orthopaedic Research Society. Published by Elsevier Science Ltd. All rights reserved.
    Journal of Orthopaedic Research 02/2001; 19(2):318 - 327. · 2.88 Impact Factor
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    ABSTRACT: To evaluate chondrocyte viability using confocal laser microscopy (CLM) following exposure to bipolar radiofrequency energy (bRFE) and to contrast CLM with standard light microscopy (LM) techniques. In vitro analysis using chondromalacic human cartilage. Twelve fresh chondral specimens were treated with the ArthroCare 2000 bRFE system (ArthroCare, Sunnyvale, CA) coupled with 1 of 2 types of probes and at 3 energy delivery settings (S2, S4, S6). A sham-operated group was treated with no energy delivered. Specimens were analyzed for chondrocyte viability and chondral morphology with CLM using fluorescent vital cell staining and with LM using H&E and safranin-O staining. LM with H&E staining showed smoothing of fine fronds of fibrillated cartilage; thickened fronds were minimally modified. Chondrocyte nuclei were present and not morphologically different than nuclei within sham-operated and adjacent untreated regions. LM with safranin-O staining showed a clear demarcation between treated and untreated regions. CLM, however, showed chondrocyte death: the depth and width of chondrocyte death increased with increasing bRFE settings. CLM showed that bRFE delivered through the probes investigated created significant chondrocyte death. These changes were not apparent using LM techniques.
    Arthroscopy The Journal of Arthroscopic and Related Surgery 02/2001; 17(2):117-23. · 3.10 Impact Factor

Publication Stats

2k Citations
265.75 Total Impact Points


  • 1993–2012
    • University of Wisconsin, Madison
      • • School of Veterinary Medicine
      • • Department of Orthopedics and Rehabilitation
      • • Department of Medical Sciences
      • • Department of Surgical Sciences
      • • Department of Medicine
      Madison, MS, United States
    • Cornell University
      • Department of Clinical Sciences
      Ithaca, NY, United States
  • 2001
    • Texas A&M University
      College Station, Texas, United States
  • 1989–1995
    • Mayo Clinic - Rochester
      • Department of Orthopedics
      Rochester, MN, United States
    • University of Pennsylvania
      • School of Veterinary Medicine
      Philadelphia, PA, United States
  • 1990–1994
    • Mayo Foundation for Medical Education and Research
      • Department of Orthopedics
      Scottsdale, AZ, United States
  • 1988
    • University of California, Davis
      • School of Veterinary Medicine
      Davis, CA, United States