Musculo-Skeletal Science Research CenterInstitute for Human Performance The Musculo-skeletal Science Research Center (MSRC) is the research division of the Department of Orthopedic Surgery at the SUNY Upstate Medical University. Research at the MSRC has a primary focus in the areas of musculo-skeletal biology and biomechanics. Activities range from basic biomedical and engineering science research, to applied research, and clinical outcome assessment. There are strong collaborative efforts between scientist and clinician, and many of the research projects stem directly from the practice of orthopedic medicine here at Upstate. Research is currently focused in the areas of orthopedic oncology, joint replacement, spine surgery, sports medicine, prosthetics, osteoporosis and bone biology, upper extremity biomechanics, and fracture fixation. The MissionThe mission of the MSRC is to engage in the systematic, comprehensive, and multi-disciplinary study of musculo-skeletal performance in health and disease. The MSRC has a commitment to apply the findings from this research to the clinical setting, and to develop new approaches to maintaining and improving the performance, strength and mobility of the human musculo-skeletal system at all stages of life. MSRC GoalsConsistent with the efforts of the “Bone and Joint Decade 2000-2010” initiative (www.boneandjointdecade.org) we will strive to develop new research and education programs that will bring about significant advances in the knowledge, diagnosis and treatment of musculo-skeletal conditions. In the context of the Upstate Medical University we have developed several goals:
Research FundingResearch activities in the MSRC have been funded by federal, state, medical foundation, and corporate sponsors. As of January 2003, total research funding for the MSRC is approximately $1.5M/year. Current and recent sponsors include:
Facilities and ResourcesThe MSRC occupies 10,500 square feet on the 3 rd floor of the Institute for Human Performance. There are currently six research faculty and 15-20 research staff, graduate students, and fellows based in the labs. In addition, clinical faculty and residents from the department are also engaged in research at the MSRC. Facilities include: Mechanical Testing Frames:
Biomechanical Measurement Systems:
Musculo-skeletal Imaging:
Microscopy:
Cell and Molecular Biology:
Histological Sectioning:
Specialized Computer Hardware and Software:
MSRC Research ProjectsOrthopedic Oncologya1. Radiation Damage and Preserving Bone Growth after Radiotherapy:
a2. Radioprotectant Strategies in Pediatric Musculo-skeletal Neoplasms: (Inv: Allen, Hahn (Radiation Oncology) and Damron) The long-term goal of this work is to develop drug therapies that provides selective protection of the growth plate in pediatric patients undergoing radiation therapy for musculo-skeletal tumors such as Ewing's sarcoma and rhabdomyosarcoma. Current studies are focused on establishing whether candidate radioprotectant drugs have any protective effects on cell lines derived from these tumors. (Children's Miracle Network). a3. Effects of Radiation Therapy on Bone Metastases from Breast Cancer:
a4. Chemotherapy Induced Osteopenia and Correction:
a5. Bone Mineral Density in Survivors of Childhood Cancer: (Inv: Damron, Spadaro, Cherrick (Peds Oncology)) A cross-sectional population study in young adult survivors of solid pediatric tumors such as sarcomas and lymphomas is being undertaken. The purpose is to determine the occurrence of osteopenia/osteoporosis in this large group of patients from the Kids Now Off Therapy (K.N.O.T.) clinic that has previously been studied elsewhere only in small numbers. (Joseph C. Georg Fund of the Central New York Community Foundation) a6. Bisphosphonates for Low Bone Density in Childhood Cancer Survivors: (Inv: Damron, Spadaro, Allen, Cherrick (Peds Oncology), Stred (Peds Endocrinology), Moses (Endocrinology)) This prospective, randomized trial examines a subset of childhood cancer survivors with documented osteopenia due to growth hormone deficiency from cranial irradiation. The purpose is to determine whether the use of bisphosphonates in these young individuals is beneficial in correcting the low bone density when compared to Vitamin D and calcium alone. (Genentech, Proctor and Gamble) a7. Effect of Large Muscle Group Excision on Post-operative Function in Soft Tissue Sarcoma Patients: (Inv: Ordway, Seymour (PT), Kulkarni-Lambore (PT), Camporesi (Anesthesiology), Damron) Patients with soft tissue sarcomas require radical resection of large muscle groups which affect overall function, but in ways that are not well studied. This prospective study analyzes the change in gait, EMG, and physiologic function from pre-operatively to early and late post-operatively in order to determine the effects of and recovery process from this type of radical surgery. (Gait Analysis Facility funded by Children's Miracle Network) a8. Pre-operative versus Post-operative Radiation Effects on Post-operative Function Following Soft Tissue Sarcoma Resection:
a9. Prophylactic Stabilization of Impending Proximal Femur Fractures: (Inv: Damron, Werner) Metastatic carcinoma and multiple myeloma frequently result in destruction of bone, particularly in the proximal femur where the risk of fracture is high. In order to avoid painful, debilitating fractures, intramedullary stabilization with rods is often undertaken. This laboratory study examines commonly utilized rods placed in human femurs to determine the most biomechanically desirable construct for this situation. (Howmedica/Osteonics) Adult Reconstruction – Joint Replacementsb1. Interface Failure in Total Joint Replacements: (Inv: Mann, Race) Loosening of joint replacements often initiates at the component interfaces. We are investigating the role of mechanical loading on interface failure of cemented joint replacements using fatigue loading of the stem-cement and cement-bone interfaces. Both experimental and computational tools are used to address this issue. The long term goal is to be able to predict how implant systems will fail such that appropriate design changes can be made to improve longevity of joint replacements. (National Institutes of Health) b2. Mechanobiology of the Cement-Bone Interface: (Inv: Mann, Allen) When cemented implants loosen, a fibrous tissue layer often results at the cement-bone interface. While mechanical overloading is thought to play a role in this process, the actual relationship between mechanical loading and biologic response is not known. The goals of this study are to elucidate the mechanical and biologic contributions to implant loosening.
(Inv: Mann, Race, Allen) We are investigating the mechanical characteristics of and biologic response to a number of bone cements used in orthopedic practice. While PMMA based bone cements have been used for over four decades, the optimal conditions in terms of surgical technique, handling characteristics, and long-term performance have not been determined. Laboratory fatigue studies are performed using realistic conditions to determine how these complex systems perform. (National Institutes of Health, Corporate). b4. Pharmacological Strategies for Implant Osteolysis:
b5. Preclinical Evaluation of Novel Biomaterials:
b6. A comparison of Effectiveness of Antibiotic Bone Cements with Tobramycin Formulations: (Inv. Webster, Spadaro). This study is to examine the effectiveness of new formulations of the antibiotic, Tobramycin, added to methyl-methacrylate bone cements for in joint surgery and treatment for bone lesions. The study will be performed in vitro looking at elution rates and antibacterial efficiency. (Pharma-Tek, Inc.). b7. Fatigue Crack Morphology in Cemented Hips:
(Inv: Race, Mann, Gilbert (SU)) A novel design of femoral stem is required to meet certain fatigue failure standards, but there is no standard test of the stem/cement/femur construct. Cemented stems are not yet optimized and novel designs have sometimes had surprisingly poor clinical results, so a robust pre-clinical test is required. b9. Biomechanical Evaluation of Total Knee Replacement Malalignment:
b10. Cyclic testing of Total Knee Replacements: (Inv: Werner) Long and short term fatigue testing of total knee replacements implanted into cadaver knees is being conducted to assess their potential for loosening and for changes in joint kinematics (Corporate Funding). Spine Surgeryc1. Biomechanical Assessment of Nucleus Replacement:
c2. The Use of Radiostereometric Analysis (RSA) in Spinal Surgery:
(Inv: Connolly, Ordway, Yuan) Interbody fusion of the spine is a method to eliminate abnormal motion, instability, and pain associated with degenerative conditions. There are a variety of approaches and implants available to the surgeon in order to achieve the desired result. We are investigating a variety of approaches and implant systems with regards to their biomechanical benefit and clinical safety. (DePuy AcroMed) Sports Medicined1. Experimental Model to Create a Snowboarder's Fracture:
d2. Skiboot Injuries: The Effect of Variable Hamstring Loading on ACL Strain: (Inv: Anvari, Webster, Werner) Increased ACL strain can occur when the tail of the ski lands first and the quadriceps is highly activated. This, at times, has resulted in ACL tears or injury. This biomechanical study is examining whether increased hamstrings loading will decrease the ACL strain and thus support the beneficial effect of clinical hamstrings strength training. Prosthetics
(Inv: Seymour, Ordway) The 3C100 C-leg (computerized leg) is one of the newest prosthetic innovations on the market for individuals with an above knee amputation. However, there has been limited research regarding the clinical effectiveness of this device. We are quantitatively studying the functional differences of individuals with the C-leg in comparison to their hydraulic prosthesis. (Otto Bock Health Care) Osteoporosis and Bone Biologyf1. Osteoporosis Among Women and Girls with Mobility Impairments: (Inv: Turk (PM&R), Spadaro). This is a cross-sectional study to examine bone density among people who have a variety of physical disabilities leading to mobility impairment. Many are wheelchair bound or cannot walk without assistance. The study aims at recruiting 200 women age 10-45 years from the community and will compare bone density measured by DXA at several sites to factors such as functional activity, dietary history and medical condition. (Centers for Disease Control). f2. Effects of Electromagnetic Fields on Bone Cell Signaling in Vitro and in Vivo:
f3. Feasibility and Dosing Study of PEMF for the treatment of Osteopenia:
Upper Extremity Biomechanicsg1. Biomechanical Evaluation of Ulnar Carpal Impaction: (Inv: Harley, Werner) Ulnar Impaction is a disorder in which the distal ulna impacts against the carpal bones causing ulnar sided wrist pain, tenderness and often decreased grip strength. To determine which factors cause excessive ulnar loading, a dynamic biomechanical cadaver model is being used to measure load transfer across the wrist joint. g2. Causes and Treatments of Wrist Instability: (Inv: Short, Werner) Our long term goal is to understand the role of soft tissue structures in stabilizing the wrist joint and to optimize surgical treatments. Using a wrist joint motion simulator, changes in scaphoid and lunate kinematics are measured and animated to differentiate between the roles of various structures and repairs. (Centers for Disease Control). g3. Repair of the Ulnar Collateral Ligament of the Thumb: A Biomechanical Study: (Inv: Harley, Werner) Improved healing of the ulnar collateral ligament of the thumb may occur with the addition of motion that gently stresses the repair. This in vitro study is examining whether a suture anchor repair of the ulnar collateral ligament is strong enough to withstand an early active motion protocol and restore normal kinematics. Fracture Fixationh1. Intramedullary Rod Fixation: (Inv: Shannon, Dhawan, Geel, Webster, Werner) Despite improvements in intramedullary rod fixation for long bone fractures, a number of questions remain. Two separate biomechanical studies are examining axial, bending, and torsional properties of various systems available for adult and pediatric fractures. |
(Inv: Damron, Spadaro, Farnum (Cornell)): The rat growth plate is being used to study the cellular mechanisms, extent of radiation damage, and ways to preserve growth with radioprotectants given during exposure. We use histomorphometry, radiography, densitometry and immunohistochemistry with the aim of improving treatment options in children with cancer. (National Institutes of Health and the Children's Miracle Network.) 
(Inv: Allen, Hahn (Radiation Oncology), Mann and Damron) Bone metastases are the most common complication in women with advanced breast cancer. Bone pain, hypercalcemia and pathological fracture are important causes of morbidity and mortality in these patients. Although radiation therapy is effective in controlling bone pain it is not effective in preventing pathological fracture. Our research seeks to characterize the cellular and molecular effects of radiation on bone metastases and to use this information to develop improved therapies for women with bone metastases. (NY State Department of Health, The Carol M. Baldwin Breast Cancer Research Fund, and the Orthopaedic Research and Education Foundation).
(Inv: Damron, Spadaro, Allen) The exact mechanisms for osteopenia and osteoporosis in survivors of childhood cancer are poorly studied. The rat model is used to examine individual potentially important variables, including toxic chemotherapeutic agents and cranial irradiation, as well as their prevention and correction. 
(Inv: Ordway, Seymour (PT), Kulkarni-Lambore (PT), Damron) Patients with soft tissue sarcomas may receive adjuvant irradiation before or after their tumor resection. While subjective results suggest a late functional advantage for patients undergoing preoperative irradiation, this problem has yet to be studied objectively by gait analysis and EMG. This ongoing study is intended to determine whether the subjective reported results bear out under objective laboratory analysis. (Gait Analysis Facility funded by Children's Miracle Network)
b3. Bone Cement Studies:
(Inv: Allen) Aseptic implant loosening occurs when the interface between an implant and the surrounding bone is damaged. Retrieval studies have shown that inflammatory responses to particulate wear debris leads to the bone destruction (osteolysis) that triggers loosening. The purpose of this study is to use an established rat model of implant osteolysis to screen candidate drug therapies for implant osteolysis (Comparative Bone Biology Fund, SUNY Upstate Medical University). 
(Inv: Allen, Sacks (IHP Imaging Core), Ordway, Mann, Gilbert (SU)) Ongoing preclinical studies are being conducted on a number of new implant materials, including novel titanium alloys, resorbable bone graft substitutes for spine fusion, and a liquid-liquid bone cement for total joint replacement (Corporate sponsors).
(Inv: Race, Mann) We have developed an automated serial grinding and imaging system to study the three-dimensional architecture of micro-cracks in the cement mantle surrounding a femoral stem. This technique has been used to study fatigue damage in vitro and will be applied next to post-mortem retrievals. Such detailed mapping of fatigue damage will provide insights into failure mechanisms, which will lead to improved designs of femoral stem. ( National Institutes of Health). 
b8. Pre-Clinical Testing of Cemented Femoral Stems
(Inv: Gerber, Ayers, Werner) During total knee replacement surgery, varus or valgus malpositioning of the tibial component may cause increased loosening or implant wear and may lead to revision surgery. This biomechanical study is examining the effect of varus/valgus malalignment on tibio-femoral mechanics during surgical trial reduction and simulated gait loading (Corporate Funding). 
(Inv: Yuan, Ordway) Degeneration and herniation of the intervertebral disc can result in the stimulation of mechanical and/or chemical pain generators. Replacement of the intervertebral disc has been attempted in the past, however replacement of the entire disc may not be necessary in a number of clinical situations. We have been investigating novel new approaches and technologies that focus on replacement of only the nucleus and sustaining the integrity of the anulus. (Stryker-Howmedica-Osteonics, Disc Dynamics) 
(Inv: Ordway, Sacks(IHP Imaging Core), Fredrickson, Yuan) RSA is a technique that quantifies how bones (and/or an implant) move with respect to each other using biplanar radiography. RSA has the potential to answer many clinical questions with regards to spinal surgery. Our current efforts have focussed on examining the accuracy and reliability of the technique as it relates to spinal procedures. Clinical studies have started using RSA to evaluate lumbar fusion, intervertebral disc replacement and orthotic lumbar bracing. (DePuy AcroMed, Spine Solutions, Orthofix) 
c3. Biomechanical Assessment of Lumbar Fusion Constructs: 
(Inv: Dunn(Emerg Med), Wojcik(Emerg Med), Ordway) Forty-two percent of snowboarding injuries are emergent and fifty percent of ankle injuries are fractures. We are investigating one of the most common ankle fractures among snowboarders; a fracture to the lateral process of the talus. In vitro biomechanical tests are being performed to examine how this fracture occurs. (Emergency Medicine Foundation) 
e1. Evaluation of the 3C100 C-leg Prosthetic Knee Joint: 
(Inv: Spadaro, Allen). The mechanism of electrical field interaction with bone cells is still unclear and the effects can vary with conditions. The purpose of this research is to determine if osteoblast/osteoclast signaling, and particularly the OPG/RANK-L mechanism can be manipulated with such fields which are conveniently applied using non-invasive pulsing magnetic fields (PEMFs). In vivo models have already shown effects of PEMFs on calcium uptake in calvarial bone which may result from effects, directly or indirectly on osteoclasts. 
(Inv: Spadaro, Short, Feiglin (Radiology), Sheehe (Neurosci. Physiol.). This is a clinical trial designed to use the disuse osteopenia (bone loss) that occurs in the forearm following cast immobilization due to fracture or surgery to see if a pulsing electromagnetic field (PEMF) will reduce this loss or accelerate the recovery of bone. 80 subjects will be recruited and will apply a PEMF transducer on their affected forearm for a few hours daily for 8 weeks. Bone density in the forearm will be followed for 1 year using DXA densitometry. (National Institutes of Health-NIAMS). 
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