tion Orthopaedic Research Center

Memphis, TN, United States

tion Orthopaedic Research Center

Memphis, TN, United States
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Mihalko W.M.,tion Orthopaedic Research Center | Mihalko W.M.,University of Memphis | Creek A.T.,tion Orthopaedic Research Center | Creek A.T.,University of Memphis | And 5 more authors.
Journal of Arthroplasty | Year: 2011

Histologic analysis of the posterior cruciate ligament has been reported in the normal and osteoarthritic knee but not after cruciate-retaining (CR) total knee arthroplasty (TKA). Retention of the posterior cruciate ligament during TKA has been debated as to whether it is beneficial in stability and function. If the presence of mechanoreceptors is shown to be maintained in CR TKA, then there may be an argument for retention. This case report used a retrieval of a well-functioning TKA specimen that had a CR TKA. To prove the presence of mechanoreceptors within the ligament, immunohistochemistry techniques using S100 protein and neurofilament protein were used. This specimen had pacini and lamellar type of mechanoreceptors present on immunohistochemistry analysis. The presence or retention of mechanoreceptors and innervations of the ligament may indicate an advantage when retained during TKA. © 2011 Elsevier Inc.


Mihalko W.M.,University of Memphis | Mihalko W.M.,tion Orthopaedic Research Center | Conner D.J.,tion Orthopaedic Research Center | Conner D.J.,University of Memphis | And 2 more authors.
Clinical Orthopaedics and Related Research | Year: 2012

Background Assessment of patient function after TKA often focuses on implant alignment and daily activity capabilities, but the functional results and kinematics of the TKA are not easily predicted by some of these parameters during surgery. Questions/purposes We asked whether differences in implant alignment in the transverse plane may affect fluorokinematics and be one of the many variables that help explain the discrepancies in fluorokinematic results. Methods We utilized a computer model (LifeMODTM/ KneeSIM; LifeModeler, Inc, San Clemente, CA, USA) to show variability in polyethylene contact patterns. We imported components of a cruciate-retaining TKA into the model and subjected the systems to a simulated lunge. We modeled five different combinations of implant positioning in the transverse plane of both the femoral and tibial components in internal or external rotation and compared the resulting changes in joint rotations and displacements of these five variations to those for published fluorokinematic observations using the same modeled lunge-type maneuver for five patients. Results We observed variations in AP translation of the lateral and medial femoral condyles resembling several of those in the literature for individual patients with the same cruciate-retaining knee implant. The largest AP translational changes were seen with the tibia internally rotated 5°. Using the five different implant transverse plane alignment scenarios resulted in a coefficient of determination of 0.6 for the linear regression when compared to five subjects from a published fluorokinematic study. Conclusions Variations in implant positioning may be responsible for variations in fluorokinematics reported for individual subjects with the same implant design. Clinical Relevance If validated computermodeling can aid surgeons to predict the effects of individual implant alignment variations in TKA kinematics, a more personalized approach to implant positioning during TKA can be implemented.© The Association of Bone and Joint Surgeons® 2011.


Crockarell J.R.,Campbell University | Snearly C.M.,tion Orthopaedic Research Center
Journal of Arthroplasty | Year: 2012

Roentgen Monographic Analysis Tool (ROMAN) and Hip Analysis Suite (HAS) were used to analyze radiographs of a phantom hip model. Displacements of known magnitude and direction were produced using dial micrometers. Differences between the known displacement and the programs' reported displacement were compared. Hip Analysis Suite was superior with a median error of 0.075 mm (range, 0.019-0.205 mm) compared with 0.137 mm (range, 0.008-0.389 mm) for ROMAN (P = .002). Hip Analysis Suite was also more precise when evaluating intraobserver variability, with a standard deviation between radiographs of 0.007 mm (range, 0.002-0.009 mm), whereas ROMAN's standard deviation was 0.117 mm (range, 0.007-0.153 mm). Repeatability for HAS was 0.019 mm and 0.325 mm for ROMAN. Hip Analysis Suite was more accurate and precise than ROMAN under experimental conditions with digital radiographs. © 2012 Elsevier Inc.


Zhang K.,tion Orthopaedic Research Center | Mihalko W.M.,University of Memphis
Clinical Orthopaedics and Related Research | Year: 2012

Background Although normal cruciate ligaments and those in patients with osteoarthritic (OA) knees contain mechanoreceptors, it is unclear whether they are present after functioning in a cruciate-retaining total knee arthroplasty (TKA). Questions/purposes We therefore determined if the areas occupied by mechanoreceptors in the human posterior cruciate ligament (PCL) are similar in patients with osteoarthritis and in patients who have had TKA with retention of the PCL. Methods We identified five cruciate-retaining TKA specimens from a retrieval program and obtained five PCLs during cruciate-sacrificing TKA from patients with OA; the retrieved specimens had been in place 5 to 12 years. The whole en bloc PCL specimens were harvested for the study. These specimens were then sectioned to a thickness of 8 lm and mounted on microscope slides. Two transverse cross-sections from the distal third from each specimen 100 lm apart were then subjected to immunohistochemistry with neurofilament protein (NFP) and S-100 protein. Results All five PCL specimens in each group revealed multiple areas of positive stained elements with both S-100 protein and NFP immunohistochemical staining. Morphologically, these elements appear to correspond to Pacinilike, Golgilike, and fusiform types of mechanoreceptors. We observed no difference in positive staining mechanoreceptor elements as a percentage of area in the osteoarthritis and TKA groups. Conclusion Mechanoreceptors appear to occupy similar areas before and after implantation of a TKA. Clinical Relevance If mechanoreceptors continue to function after cruciate-retaining TKA, then it may continue to participate in proprioception of the knee after TKA. © The Association of Bone and Joint Surgeons® 2012.


Komatsu D.E.,tion Orthopaedic Research Center | Mary M.N.,tion Orthopaedic Research Center | Schroeder R.J.,tion Orthopaedic Research Center | Robling A.G.,Indiana University | And 3 more authors.
Journal of Orthopaedic Research | Year: 2010

While the importance of Wnt signaling in skeletal development and homeostasis is well documented, little is known regarding its function in fracture repair. We hypothesized that activation and inactivation of Wnt signaling would enhance and impair fracture repair, respectively. Femoral fractures were generated in Lrp5 knockout mice (Lrp5-/-) and wild-type littermates (Lrp5+/+), as well as C57BL/6 mice. Lrp5-/- and Lrp5+/+mice were untreated, while C57BL/6 mice were treated 2x/week with vehicle or anti-Dkk1 antibodies (Dkk1 Ab) initiated immediately postoperatively (Day 0) or 4 days postoperatively (Day 4). Fractures were radiographed weekly until sacrifice at day 28, followed by DXA, pQCT, and biomechanical analyses. Lrp5-/- mice showed impaired repair compared to Lrp5+/+ mice, as evidenced by reduced callus area, BMC, BMD,and biomechanical properties. The effects of Dkk1 Ab treatment depended on the timing of initiation. Day 0 initiation enhanced repair, with significant gains seen for callus area, BMC, BMD, and biomechanical properties, whereas Day 4 initiation had no effect. These results validated our hypothesis that Wnt signaling influences fracture repair, with prompt activation enhancing repair and inactivation impairing it. Furthermore, these data suggest that activation of Wnt signaling during fracture repair may have clinical utility in facilitating fracture repair. © 2010 Orthopaedic Research Society. Published by Wiley Periodicals, Inc.


Komatsu D.E.,tion Orthopaedic Research Center | Warden S.J.,Indiana University
Journal of Cellular Biochemistry | Year: 2010

Fracture repair is a complex process involving timed cellular recruitment, gene expression, and synthesis of compounds that regenerate native tissue to restore the mechanical integrity, and thus function of injured bone. While the majority of fractures heal without complication, this takes time and a subset of patients (∼10%) experience healing delays, extending their morbidity and treatment costs. Consequently, there is a need for efficacious therapeutics for the intervention of fracture healing. Recent studies into the molecular control of fracture repair and advances in the understanding of the skeleton as a whole have resulted in the identification of numerous novel targets and compounds for such intervention. These include traditional agents such bone morphogenetic proteins and other growth factors, but also relatively newer compounds such as parathyroid hormone and modulators of the Wnt signaling pathway. These agents, along with others, are discussed in the current article in terms of their investigative status and potential for clinical implementation. Hopefully, these agents, as well as others yet to be discovered, will demonstrate sufficient clinical utility for successful intervention of fracture healing. This may have significant implications for the duration of morbidity and costs associated with traumatic bone fractures. © 2009 Wiley-Liss, Inc.


Komatsu D.E.,State University of New York at Stony Brook | Thanos P.K.,Brookhaven National Laboratory | Thanos P.K.,U.S. National Institutes of Health | Mary M.N.,St Jude Childrens Research Hospital | And 7 more authors.
Bone | Year: 2012

Methylphenidate (MP) is a psychostimulant widely prescribed to treat Attention Deficit Hyperactivity Disorder (ADHD). Although generally well tolerated, growth deficits have been reported in children and adolescents undergoing MP treatment. This study was designed to elucidate the skeletal effects of chronic MP administration in adolescent rats. Male, 4-week-old rats received one of two doses of MP (MP-Low or MP-High) delivered for 8. h a day via drinking water, or were untreated (water only). After 13. weeks, half were sacrificed (N = 12/group) and the remaining rats were left to recover, untreated for 5 additional weeks. Femora, tibiae, and L5 vertebra were analyzed using calipers, DXA, and mechanical testing. Immediately following treatment, MP decreased femoral anterior-posterior diameter (5% and 9% for MP-Low and MP-High, respectively), femoral and tibial bone mineral density (BMD) (6% and 5% for MP-High femora and tibiae, respectively), and bone mineral content (BMC) (9% for MP-High femora and tibiae). In addition, femora from MP treated rats had reduced ultimate force (20% for MP-High) and energy to failure (20% and 33% for MP-Low and MP-High, respectively). However, after recovery, there were no statistically significant differences for any measured parameters. Despite these effects on the appendicular skeleton, no differences were identified between vertebral samples at either time-point. In summary, MP treatment resulted in smaller, less mineralized, and weaker bones at appendicular sites, but did not affect the axial site. Although these effects were ameliorated within 5. weeks, these data suggest that adolescents undergoing MP treatment may be at an increased risk for long bone fractures. © 2012 Elsevier Inc.


PubMed | tion Orthopaedic Research Center
Type: Journal Article | Journal: Journal of orthopaedic research : official publication of the Orthopaedic Research Society | Year: 2010

While the importance of Wnt signaling in skeletal development and homeostasis is well documented, little is known regarding its function in fracture repair. We hypothesized that activation and inactivation of Wnt signaling would enhance and impair fracture repair, respectively. Femoral fractures were generated in Lrp5 knockout mice (Lrp5-/-) and wild-type littermates (Lrp5+/+), as well as C57BL/6 mice. Lrp5-/- and Lrp5+/+ mice were untreated, while C57BL/6 mice were treated 2x/week with vehicle or anti-Dkk1 antibodies (Dkk1 Ab) initiated immediately postoperatively (Day 0) or 4 days postoperatively (Day 4). Fractures were radiographed weekly until sacrifice at day 28, followed by DXA, pQCT, and biomechanical analyses. Lrp5-/- mice showed impaired repair compared to Lrp5+/+ mice, as evidenced by reduced callus area, BMC, BMD, and biomechanical properties. The effects of Dkk1 Ab treatment depended on the timing of initiation. Day 0 initiation enhanced repair, with significant gains seen for callus area, BMC, BMD, and biomechanical properties, whereas Day 4 initiation had no effect. These results validated our hypothesis that Wnt signaling influences fracture repair, with prompt activation enhancing repair and inactivation impairing it. Furthermore, these data suggest that activation of Wnt signaling during fracture repair may have clinical utility in facilitating fracture repair.


PubMed | tion Orthopaedic Research Center
Type: Journal Article | Journal: Journal of cellular biochemistry | Year: 2010

Fracture repair is a complex process involving timed cellular recruitment, gene expression, and synthesis of compounds that regenerate native tissue to restore the mechanical integrity, and thus function of injured bone. While the majority of fractures heal without complication, this takes time and a subset of patients ( approximately 10%) experience healing delays, extending their morbidity and treatment costs. Consequently, there is a need for efficacious therapeutics for the intervention of fracture healing. Recent studies into the molecular control of fracture repair and advances in the understanding of the skeleton as a whole have resulted in the identification of numerous novel targets and compounds for such intervention. These include traditional agents such bone morphogenetic proteins and other growth factors, but also relatively newer compounds such as parathyroid hormone and modulators of the Wnt signaling pathway. These agents, along with others, are discussed in the current article in terms of their investigative status and potential for clinical implementation. Hopefully, these agents, as well as others yet to be discovered, will demonstrate sufficient clinical utility for successful intervention of fracture healing. This may have significant implications for the duration of morbidity and costs associated with traumatic bone fractures.


PubMed | tion Orthopaedic Research Center
Type: Journal Article | Journal: Clinical orthopaedics and related research | Year: 2012

Although normal cruciate ligaments and those in patients with osteoarthritic (OA) knees contain mechanoreceptors, it is unclear whether they are present after functioning in a cruciate-retaining total knee arthroplasty (TKA).We therefore determined if the areas occupied by mechanoreceptors in the human posterior cruciate ligament (PCL) are similar in patients with osteoarthritis and in patients who have had TKA with retention of the PCL.We identified five cruciate-retaining TKA specimens from a retrieval program and obtained five PCLs during cruciate-sacrificing TKA from patients with OA; the retrieved specimens had been in place 5 to 12 years. The whole en bloc PCL specimens were harvested for the study. These specimens were then sectioned to a thickness of 8 m and mounted on microscope slides. Two transverse cross-sections from the distal third from each specimen 100 m apart were then subjected to immunohistochemistry with neurofilament protein (NFP) and S-100 protein.All five PCL specimens in each group revealed multiple areas of positive stained elements with both S-100 protein and NFP immunohistochemical staining. Morphologically, these elements appear to correspond to Pacinilike, Golgilike, and fusiform types of mechanoreceptors. We observed no difference in positive staining mechanoreceptor elements as a percentage of area in the osteoarthritis and TKA groups.Mechanoreceptors appear to occupy similar areas before and after implantation of a TKA.If mechanoreceptors continue to function after cruciate-retaining TKA, then it may continue to participate in proprioception of the knee after TKA.

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