Upstate Orthopedics

Musculo-skeletal Science Research Center (MSRC)

The Musculo-skeletal Science Research Center (MSRC) is the research division of Upstate Orthopedics 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 and lower extremity biomechanics, and fracture fixation.

Research Programs

To remain on the cutting edge of orthopedic medicine, physicians at Upstate Orthopedics engage in research at the State University of New York (SUNY) Upstate. Our research division, the Musculo-skeletal Science Research Center (MSRC), houses several research faculty and research staff, as well as graduate students, residents, fellows, and clinical faculty from Upstate Orthopedics.

Current and future students at SUNY Upstate are encouraged to explore the research opportunities available at the MSRC and learn more about our research faculty.

Our research programs are a good fit for medical students with a background in biology, applied health, engineering, and technology. Many studies focus on musculoskeletal biology and biomechanics in order to solve orthopedic problems that cause limited mobility, loss of function, disease, or pain.

Research capabilities at MSRC include:

  • Mechanical testing frames including wrist and knee simulators
    3 multi-axial MTS servo-hydraulic frames, two single axis screw driven test frames, custom servo-hydraulic wrist simulator, knee simulators
  • Biomechanical measurement systems
    Tekscan pressure measurement, Flock of Birds and Polhemus and Polaris 6 dof motion measurement, Cyberglove hand motion systems, Kistler force plates, DVRT's, extensometers, LVDT's, crack and strain gage signal conditioners
  • Clinical musculoskeletal imaging technology
    Fluoroscan C-arm, 2 Portable x-ray units, Dyonics and Linvatec arthroscopy systems, Radiostereometric Analysis (RSA) facility
  • Clinical Bone Densitometry
    Stratec XCT2000 peripheral quantitative CT scanner, Lunar & Hologic DXA bone densitometersClinical bone densitometry scanner
  • Small animal bone imaging
    /CT40, Kodak Imaging Station 4000MM Pro fluorescent tissue imager. PMMA, frozen or paraffin sections are imaged with Nikon epifluorescent microscopes with Polaroid & SPOT cameras.
  • Tissue culture facilities for protein and gene analysis
    Two tissue culture facilites and separate facilities for protein and gene analysis are equipped with a Kodak Imaging Station 4000MM Pro (for DNA gels and luminescent and fluorescent Western blots), a Turner Biosystems Modulus II Microplate Reader (absorbance, fluorescent and luminescent assays), an ABI Prism 7000 qPCR, a Labconco vacuum lyophilizer, thermocyclers and a Nikon inverted fluorescent microscope mounted with a ColdSnap HG2 CCD camera.
  • Specialized Software:
    3D Studiomax, Geomagic, MIMICS, Patran and MARC finite element software

Research History

1960s

Bioelectricity and the Enhancement of Fracture Healing (1965 - 1985)

Faculty: RO Becker, BE Fredrickson, AA Marino, DG Murray, JA Spadaro, DA Webster

Some bone fractures do not heal or heal very slowly with prolonged pain and disability and require multiple surgeries. Some potential solutions to this problem grew out of early research on the small electrical currents associated with bone injuries and the reshaping process that is part of the healing and the skeleton's adaptation to changes in loading over time. Methods were developed first using implanted electrode wires and later non-invasive, non-surgical pulsing magnetic fields to enhance fracture healing in difficult cases and also to improve outcomes in spinal fusions. Extension of this work has led to alternative methods of treating bone infections following traumatic injury and also basic research to identify the mechanisms through which electromagnetic fields can influence bone cells and tissue growth and even the regeneration of missing structures. For his contributions, Robert O. Becker MD was awarded the Middleton Award in 1964 by the U.S. Veteran's Administration, the Nicholas Andry Award by the American Association of Bone and Joint Surgeons in 1979, and was twice nominated for the Nobel Prize.

The Body Electric, R.O. Becker, G. Selden, William Morrow Publisher, New York, 1985.

Generation of electric potentials by bone in response to mechanical stress. C.A.L. Bassett, R.O. Becker, Science 137: 1063-1064, 1962.

Stimulation of partial limb regeneration in rats. R.O. Becker, Nature 235: 109-111, 1972

Silver anode treatment of chronic osteomyelitis. D.A. Webster, J.A. Spadaro, R.O. Becker, S. Kramer, Clin. Orthop. Rel. Res. 161: 105-114, 1981.

The electrical control system regulating fracture healing in amphibians. R.O. Becker, D.G. Murray, Clin. Orthop. Rel. Res. 73: 169-198, 1970.

1970s

Development of a Total Knee Replacement (1972 - 1985)

Faculty: DG Murray, JA Shaw, JH Somerset

Many early total knee replacements experienced gross loosening of the components in part due to being implanted without rigorous laboratory testing. David Murray, MD came up with a new knee replacement design while on a trip to Mexico, which was in part based on the ball and socket joint of the hip. This was the first knee replacement design that included a tibial component consisting of a metal tray and stem with removable plastic (polyethelene) inserts. Dr. Murray started a research project between the Department of Orthopedic Surgery and the Department of Mechanical Engineering at Syracuse University to develop and test this new knee replacement design. Prototype implants were created, using the curvature of the inside of a tennis ball and these designs were tested for millions of cycles in a mechanical knee simulator. Only after additional successful testing was performed was the new design finalized and implanted into patients. The clinical success of the Variable Axis Knee was a remarkable improvement upon other early knee replacements. Current knee designs include many of its unique features.

Experience with the Variable Axis Knee Prosthesis. R. Rutledge, DA Webster, DG Murray, Clinical Orthopaedics and Related Research 205:146-52, 1986.

Total knee replacement with a Variable Axis Knee Prosthesis. DG Murray, Orthopedic Clinics of North America 13(1):155-72, 1982.

The Variable-Axis Knee Prosthesis. Two-year follow-up study. DG Murray, DA Webster, Journal of Bone and Joint Surgery (Am) 63(5): 687-94, 1981.

Knee Joint Simulator. JA Shaw, DG Murray, Clinical Orthopaedics and Related Research 94:15-23, 1973.

Anatomy and Biomechanics of the Ulnar Aspect of the Wrist (1978-2008)

Faculty: AK Palmer, WH Short, FW Werner

The ulnar aspect of the wrist has been referred to as the Low Back Pain of the upper extremity. Study of patients with ulnar wrist pain led to a need to understand the anatomy and biomechanics of this complex area. Cadaver anatomical studies led to biomechanical studies and the eventual naming of this complex area as the Triangular Fibrocartilage Complex (TFCC). This work received the Emanuel B. Kaplan award of the NY Hand Society in the late 70"s. Clinical application of this work led to the introduction of the "Classification and Treatment of Afflictions of the TFCC". Funding for this work was received from the American Society for Surgery of the Hand and National Institutes of Health.

The Triangular Fibrocartilage Complex of the Wrist: Anatomy and Function, AK Palmer, FW Werner. Journal of Hand Surgery, Vol. 6, No. 2, pp. 153-162, 1981.

Triangular fibrocartilage complex lesions: a classification. Palmer AK. J Hand Surg Am. 14(4):594-606, 1989. Review.

Biomechanics of the distal radioulnar joint. Palmer AK, Werner FW. Clin Orthop Relat Res. (187):26-35, 1984.

The stabilizing mechanism of the distal radioulnar joint during pronation and supination. Kihara H, Short WH, Werner FW, Fortino MD, Palmer AK. J Hand Surg Am. 20(6):930-6, 1995.

1980s

A Wrist Joint Motion Simulator - how it helped define wrist biomechanics (1981-2016)

Faculty: BJ Harley, AK Palmer, WH Short, JH Somerset, FW Werner

Beginning with the classic paper by Dobyns and Linscheid on Carpal Instability in 1972, there has been great interest in the intrinsic and extrinsic ligamentous anatomy of the wrist and clinical problems related to ligamentous disruption and resultant abnormal wrist biomechanics. Based on a clinical review of patients treated for carpal instability at the Mayo Clinic, we began to study carpal mechanics and carpal instability through anatomical and biomechanical studies. This work led to the development of the first wrist joint motion simulator in the United States. Under computer control, it pulls on up to 9 cadaver wrist and finger tendons to cause repeatable wrist motion. During wrist motion the tendon forces and the motion of specific carpal bones were measured. To visualize carpal bone motion in the intact wrist and after simulated injury using the wrist motion simulator, 3-dimensional images of each bone were computer animated using the experimental data as input. The simulator has been used to determine the consequences of torn wrist ligaments on the motion of the carpal bones, the loading in the forearm bones and to evaluate total wrist replacements. This novel approach has clearly demonstrated the importance of testing the wrist with dynamic motion and continues to be used today to study various surgical repairs or treatments of the injured or arthritic wrist. This work was funded by the Centers for Disease Control and National Institutes of Health.

Wrist Joint Motion Simulator FW Werner, AK Palmer, JH Somerset, JJ Tong, DB Gillison, MD Fortino, and WH Short. Journal of Orthopaedic Research 14:639-646, 1996.

A Dynamic Biomechanical Study of Scaphoid Instability, WH Short, FW Werner, MD Fortino, AK Palmer, KA Mann. Journal of Hand Surgery 20A:986-999, 1995.

Biomechanical Evaluation of Ligamentous Stabilizers of the Scaphoid and Lunate WH Short, FW Werner, JK Green, S Masaoka. Journal of Hand Surgery. 27A:991-1002, 2002.

Force in the scapholnate interosseous ligament during active wrist motion. C Dimitris, FW Werner, DA Joyce, BJ Harley, J Hand Surg Am 40(8):1525-33, 2015.

Biomechanics of the Treatment of Spinal Burst Fractures (1987 - 1993)

Faculty: JC Bayley, WT Edwards, BE Fredrickson, KA Mann, HA Yuan

Burst fractures of the spine are caused by high energy impacts, usually as a result from a fall from a height or sudden deceleration such as an automobile accident. Prior to the mid 1980s, these fractures were thought of as flexion/compression injuries because of the shape of the vertebrae after fracture. We performed impact experiments on isolated lumbar spine sections and found that axial impacts could produce fractures that were similar to what is found clinically. Further, we found that bone fragments that were displaced into the spinal canal could be deflected away from the spinal cord by distraction of the spine. Correction of the flexion deformity (kyphosis), by itself, did not adequately remove the bone fragment from the spinal canal. This line of research led to the 1992 Volvo Award for research led by Dr. Bruce Fredrickson. This work was funded by the Orthopedic Research and Education Foundation.

1992 Volvo Award in experimental studies. Vertebral burst fractures: An experimental, morphologic, and radiographic study. Fredrickson, B.E., Edwards, W.T., Rauschning, W., Bayley, J.C., Yuan, H.A. Spine 17 (9), pp. 1012-1021, 1992.

Reduction of the intracanal fragment in experimental burst fractures. Fredrickson, B.E., Mann, K.A., Yuan, H.A., Lubicky, J.P. Spine 13 (3), pp. 267-271,1988.

Conservative treatment of fractures of the thoracic and lumbar spine. Krompinger, W.J., Fredrickson, B.E., Mino, D.E., Yuan, H.A. Orthopedic Clinics of North America 17 (1), pp. 161-170, 1986.

1990s

Biomechanical Assessment and Treatment of the Intervertebral Disc in the Lumbar Spine (1992-2016)

Faculty: MJ Allen, WT Edwards, AH Fayyazi, BE Fredrickson, WF Lavelle, NR Ordway, MH Sun, RA Tallarico, HA Yuan

Degeneration and herniation of the intervertebral disc can result in debilitating back and leg pain by altering the normal function of the spinal cord and nerve roots. When non-surgical treatments fail, spine surgery is used to relieve the pain. Surgical procedures either eliminate the motion at the diseased spine segments through use of a spinal fusion or retain the motion of the segment with an intervertebral disc replacement. We have been investigating the biomechanics of the normal and diseased lumbar spine as well as novel surgical approaches and implant technologies. We helped develop one of the earliest nucleus replacements and developed new methods to assess the function of this new class of implants. Our research has focused on how the spine adapts to these surgical procedures and/or new implant designs. One aspect of this research led to the 1997 Lyman Smith, MD Award for research by Nathaniel Ordway, PE.

Positional Effects of Transforaminal Interbody Spacer Placement at the L5-S1 Intervertebral Disc Space: A Biomechanical Study. R.A. Tallarico, W.F. Lavelle, A.J. Bianco, J.L. Taormina, N.R. Ordway. The Spine Journal, 14(12): 3018-3024, 2014.

Changes in Neuroforaminal Height with 2 Level Axial Presacral Lumbar Interbody Fusion at L4-S1. S.V. Marawar, N.R. Ordway, J.W. Jung, M.H. Sun. International Journal of Spine Surgery, 8, doi:10.14444/1002, 2014.

Biomechanical Assessment and Fatigue Characteristics of an Articulating Nucleus Implant. N.R. Ordway, W.F. Lavelle, T. Brown, Q-B Bao. International Journal of Spine Surgery, 7: e109-117, 2013.

Comparison of Cobb technique, quantitative motion analysis, and radiostereometric analysis in measurement of segmental range of motions following lumbar total disc arthroplasty. S-A Park, N.R. Ordway, A.H. Fayyazi, B.E. Fredrickson, H.A. Yuan. Journal of Spinal Disorders and Techniques, 22(8): 602-609, 2009.

Peak stresses observed in the posterior lateral anulus. W.T. Edwards, N.R. Ordway, Y. Zheng, G.M. McCullen, Z. Han, H.A. Yuan. Spine 26(16):1753-1759, 2001.

Growth Plate Radiation Effects, Radioprotection, and Radiorecovery (1994 - 2010)

Faculty: TA Damron, BS Margulies, FA Middleton, JA Spadaro

When children receive radiotherapy for malignancy, their growth plates may be damaged, resulting in growth arrest, limb length discrepancy, and angular deformity. To date, no solution has been found for this problem, but researchers here have built a solid foundation for potentially clinically beneficial future interventions. In 1994, a drug developed during cold war years as a chemoradioprotectant at Walter Reed Medical Center, WR-2721 (Amifostine), was being investigated for its chemoprotectant effects; Upstate Medical University was the site for pharmacokinetic evaluation in this multi-institutional study sponsored by what was then the Pediatric Oncology Group. Conversations about potential orthopedic oncology uses of WR-2721 between pediatric oncologists Abdul Souid, MD and Ron Dubowy, MD and orthopedic oncologist Tim Damron, MD led to the suggestion of its potential as a radioprotectant drug for children with radiosensitive sarcomas. An animal experiment showed for the first time that radioprotection of growth plate cartilage could be accomplished successfully. Subsequent work led to demonstration of further success with various radioprotectant and even novel radiorecovery agents. Integral to this work was the ground-breaking technique of separating the layers of the growth plate for individual molecular analysis by means of laser capture microdissection. This technique, developed in our laboratory, has provided the basis for understanding of the complex molecular changes in the growth plate over time, between zones, and after the damaging effects of radiotherapy. This work was funded by the Children's Miracle Network, Orthopaedic Research and Education Foundation, and National Institutes of Health-National Cancer Institute.

Restoration of growth plate function following radiotherapy is driven by increased proliferative and synthetic activity of expansions of chodrocyte clones. JA Horton, BS Margulies, JA Strauss, JT Bariteau, TA Damron. Journal of Orthopaedic Research 24(10):1945-56, 2006.

Sequential histomorphometric analysis of the growth plate following irradiation with and without radioprotection Damron, T.A., Margulies, B.S., Strauss, J.A., O'Hara, K., Spadaro, J.A., Farnum, C.E. Journal of Bone and Joint Surgery - A 85 (7), pp. 1302-1313, 2003.

Amifostine before fractionated irradiation protects bone growth in rats better than fractionation alone Damron, T.A., Margulies, B., Biskup, D., Spadaro, J.A. International Journal of Radiation Oncology Biology Physics 50 (2), pp. 479-483, 2001.

Sparing radiation-induced damage to the physis by radioprotectant drugs: Laboratory analysis in a rat model Tamurian, R.M., Damron, T.A., Spadaro, J.A. Journal of Orthopaedic Research 17 (2), pp. 286-292, 1999.

Development and Maintenance of Skeletal Characteristics Associated with Gymnastic Loading During Growth. (1997-2016)

Faculty: TA Scerpella, JA Spadaro

Enhancement of bone mass and structure is an important strategy for the prevention of osteoporosis and fracture. Mechanical loading appears to increase bone acquisition during growth, yet the extent to which these benefits are maintained is unclear. Our ongoing research uses gymnastics as a model of pediatric mechanical loading, evaluating improvement of peak bone mass, structure, and strength and assessing maintenance of benefits to adulthood. The goal is to provide a foundation for the development of an adolescent exercise prescription to improve ultimate bone health.

Female gymnasts and non gymnasts were recruited at a baseline age of 7-12 years. Annual dual energy X-ray absorptiometry (DXA) scans of the forearm, hip, lumbar spine, and total body assess bone characteristics, complemented by contemporaneous peripheral quantitative computed tomography scans. Other measurements include annual muscle strength tests, as well as semi-annual assessments of diet, physical activity, body size/composition and physical maturity. Initial results suggest that exposure to gymnastic loading during growth yields persistent skeletal benefits in indices of bone mass, size and theoretical strength. More conclusive longitudinal evidence will support development of more widely applicable modalities for skeletal enhancement. This research has led to several young investigator awards for Dr. Dowthwaite (International Bone and Mineral Society 2007, International Congress for Children’s Bone Health 2007, American Society for Bone and Mineral Research 2007, International Sun Valley Workshop on Skeletal Biology 2008).

Dose related association of impact activity and bone mineral density in prepubertal girls. Scerpella TA, Davenport M, Morganti C, Kanaley JA, Johnson LM. Calcif Tiss Int 72(1)24-31, 2003.

Maturity and activity-related differences in bone mineral density: Tanner I vs. II and gymnasts vs. non-gymnasts. Dowthwaite JN, DiStefano JG, Ploutz-Snyder RJ, Kanaley JA, Scerpella TA. Bone 39 (4): 895-900, 2006.

Skeletal geometry and indices of bone strength in artistic gymnasts. Invited review, Dowthwaite JN, TA Scerpella. J Musculoskelet Neuronal Interact 9(4):198-214, 2009.

Skeletal benefits of pre-menarcheal gymnastic activity are retained after activity cessation. Scerpella TA, Dowthwaite JN, Gero N, Kanaley JA, Ploutz-Snyder RJ. Pediatric Exercise Science 22(1): 21-33, 2010.

Breast Cancer and Bone (1997 - 2016)

Faculty: MJ Allen, TA Damron and KA Mann

One in eight women will develop breast cancer at some point in their life. The majority of women with advanced breast cancer develop secondary tumors (metastases) in their bones. Although these bone metastases are not usually life threatening, they cause significant pain, restrict the patient’s ability to carry out activities of daily living, and weaken the bone to the point where spontaneous fractures (known as “pathological fractures”) may occur. In 1995, Matthew Allen’s mother, Kate, was diagnosed with an aggressive form of breast cancer that subsequently spread to bone. This personal experience led to the development of a research effort aimed at better understanding the interactions between breast cancer and bone with the goal developing improved therapies for patients with bone metastases. An animal model was developed that mimicked many of the key features of bone metastasis, including localized bone destruction and increased bone fragility. Treatment with radiation therapy was shown to be capable of killing tumor but incapable of preventing bone fragility. We successfully used bisphosponates (drugs that are widely used to treat osteoporosis in women) and anabolic agents (drugs that build new bone) to reduce the risk of pathological fracture in the mouse model. We developed a computer modeling approach to predict the risk of pathological in mouse bone, with the long-term goal of translating this into clinical use in patients with bone metastases. This work has been extended to a cohort of human patients where we have validated rigidity analysis methods and developed a finite element approach to predict fracture risk in breast cancer patients.

This work was funded by the Orthopaedic Research and Education Foundation, the New York State Department of Health, the US Army Breast Cancer Research Program, the Carol M. Baldwin Breast Cancer Research Fund, the Musculoskeletal Tumor Society, and the Kate Allen Breast Cancer Fund, established in memory of Kate Allen (1935-2000).

Arrington S.A., Damron T.A., Mann K.A and Allen M.J. Concurrent administration of zoledronic acid and irradiation leads to improved bone density, biomechanical strength, and microarchitecture in a mouse model of tumor-induced osteolysis.with zoledronic acid. Journal of Surgical Oncology 97: 284-290, 2008.

Arrington S.A., Schoonmaker J.E., Damron T.A., Mann K.A and Allen M.J. Temporal changes in bone mass and mechanical properties in a murine model of tumor osteolysis. Bone 38: 359-367, 2006.

Damron TA, Nazarian A, Entezari V, Brown C, Grant W, Calderon N, Zurakowski D, Terek RM, Anderson ME, Cheng EY, Aboulafia AJ, Gebhardt MC, Snyder BD. CT-based structural rigidity analysis is more accurate than Mirels scoring for fracture prediction in metastatic femoral lesions. Clinical Orthop Related Research 474(3): 643-51, 2016.

Goodheart JR, Cleary RJ, Damron TA, Mann KA. Simulating activities of daily living with finite element analysis improves fracture prediction for patients with metastatic femoral lesions. Journal of Orthopedic Research 33(8): 1226-34, 2015.

Investigations on the Cause of Loosening of Total Joint Replacements (1999 - 2016)

Faculty: MJ Allen, DC Ayers, TA Damron, KA Mann, ME Oest, A Race

Joint replacements are a very successful procedure to restore function to diseased or fractured hips and knees. Despite their widespread use, a large number of second surgeries to replace loose joint replacements are performed. Research efforts have focused on determining why these joint replacements become loose, how surgical procedures can be modified to improve fixation, and studies of the biologic response using animal models and detailed studies of autopsy retrieved implants. We found that certain cements used to fix implants to bone result in defects at the implant interface. In addition, roughened stem surfaces, when cemented in place can result in defects at the same interfaces. More recent work has shown that joint replacements retrieved at autopsy have interfaces that are very different from those created in the lab, due to dramatic biologic changes to the bone. Mechanisms of trabecular bone loss are currently being explored using cell culture systems with fluid loading. This finding has implications as to how these joint replacements function and could improve implant designs in the future to last longer. Another strategy investigated in our lab has been to study the effects of bone anti-resorptive drugs to prevent bone loss after implantation. This approach shows promise to help implants from becoming loose and also possibly reduce the need for surgery for those that do become loose. This work was funded by the Whitaker Foundation and National Institutes of Health.

Effects of alendronate on particle-induced osteolysis in a rat model Millett, P.J., Allen, M.J., Bostrom, M.P.G. Journal of Bone and Joint Surgery - Series A 84 (2), pp. 236-249, 2002.

Micromechanics of postmortem-retrieved cement-bone interfaces. Miller MA, Eberhardt AW, Cleary RJ, Verdonschot N, Mann KA. Journal of Orthopedic Research 28(2): 170-177, 2010.

Cement-implant interface gaps explain the poor results of CMW3 for femoral stem fixation: A cadaver study of migration, fatigue and mantle morphology. Race A, Miller MA, Clarke MT, Mann KA. Acta Orthopaedica 76(5): 679-87, 2005.

Oest ME, Miller MA, Howard KI, Mann KA. A novel loading system to produce supraphysiologic oscillatory fluid shear stress. J Biomech, 47(2):518-25, 2016.

2000s

Mechanisms of skeletal development, growth and maturation (2004-2016)

Faculty: TA Damron, JA Horton, BS Margulies, FA Middleton, JA Spadaro

The cellular precursors of the skeletal system first appear very early embryonic development, and gradually become form the bones, cartilage, muscles, tendons and an ligaments that give our bodies shape and allow us to move. While fully formed at birth, the skeletal system continues to grow throughout childhood, mature during adolescence, and maintained throughout adulthood. Many disorders of the skeletal system can be traced back to errors in development due to genetic, toxic or physiologic insults. However, much remains to be learned about these disorders, so that they may be prevented or better treated. Our research team seeks to study the mechanisms that govern normal musculoskeletal development, so that we may better understand the how skeletal diseases rooted in developmental errors may be treated. This research has been supported by grants from the National Cancer Institute, the National Institute of Arthritis and Musculoskeletal and Skin Diseases, the Children’s Miracle Network, and the Central New York Community Foundation.

Microarray analysis of perichondral and reserve growth plate zones identifies differential gene expressions and signal pathways. M Zhang, MR Pritchard, FA Middleton, JA Horton, TA Damron. Bone 43(3):511-20, 2008.

Ontogeny of skeletal maturation in the juvenile rat. JA Horton, JT Bariteau, RM Loomis, JA Strauss, TA Damron. The Anatomical Record 291(3):283-92, 2008.

Microarray analysis of proliferative and hypertrophic growth plate zones identifies differentiation markers and signal pathways Y Wang, FA Middleton, JA Horton, L Reichel, CE Farnum, TA Damron, Bone 35 (6), pp. 1273-1293, 2004.

Pre-clinical testing of novel strategies to treat pediatric musculoskeletal sarcoma (2004-2016)

Faculty: MJ Allen, TA Damron, JA Horton, BS Margulies

Musculoskeletal sarcomas are a family of cancers that affect the connective tissues, and are treated by a specially trained orthopedic oncologist. Several types of sarcoma, including osteosarcoma, rhabdomyosarcoma and Ewing Sarcoma, are particularly prevalent in children and adolescents, and require multimodality treatment regimes that may include surgery, chemotherapy and radiotherapy. Even with the most aggressive treatment plans, these childhood cancers can be fatal in up to 84% of cases, depending on the type, location and stage of disease. Furthermore, the best available treatment strategies can result in lifelong toxicity syndromes affecting the quality of life in survivorship. By focusing on the unique molecular characteristics of these pediatric cancers, our research group seeks to develop more effective and less toxic treatment strategies that will improve the duration and lifelong quality of survivorship for these children. Critical to this goal is the development of animal models as a disease-relevant platform for testing of new treatment strategies. This research has been supported by grants from the National Cancer Institute, the National Institute of Arthritis and Musculoskeletal and Skin Diseases, the Children’s Miracle Network, Jim and Juli Boeheim Foundation and the Page Trucking Foundation.

Ewing’s sarcoma of bone tumor cells produces MCSF that stimulates monocyte profileration in a novel mouse model of Ewing’s sarcoma of bone. BS Margulies, SD DeBoyace, TA Damron, MJ Allen. Bone. 79 p121-30, 2015.

Physeal bystander effects in rhabdomyosarcoma radiotherapy: experiments in a new xenograft model. JA Horton, JA Strauss, MJ Allen, TA Damron. Sarcoma. 2011:815190, 2011.

Metastatic oestosarcoma gene expression differs in vitro and in vivo. JW Lisle, JY Choi, JA Horton, MJ Allen, TA Damron. Clinical orthopaedics and related research. (2008) 466(9):2071-80, 2008.

2010s

Advancements in Understanding and Treatment of Spinal Deformity (2010-2016)

Faculty: SA Albanese, WF Lavelle, NR Ordway

The spinal column is a linked series of segments (vertebrae) that allow the trunk to flex and rotate in a variety of directions. Spinal pathologies that affect the geometry of the segments or the connective tissues (adolescent scoliosis or adult deformity) can result in spinal alignment and functional issues that lead to pain and disfigurement. Deformity is a three dimensional issue affecting the spine. Based on the severity and the potential for progression, the treatment of deformity is observation, bracing or surgical correction. The last thirty years have seen the evolution of numerous posterior as well as anterior spinal instrumentation techniques for surgical correction. We have been conducting biomechanical studies on the kinematics and kinetics of this linked structure as well as imaging studies on the morphological features of the segments to gain a better understanding of corrective surgical procedures. A portion of this work led to the James H. Beaty Scientific Poster Award at the 2012 Pediatric Orthopaedic Society of North America conference.

An Initial Biomechanical Investigation of Fusionless Anterior Tether Constructs for Controlled Scoliosis Correction. W.F. Lavelle, M. Moldavsky, Y. Cai, N.R. Ordway, B.S. Bucklen. The Spine Journal, in press, 2016.

V. Simpson, B. Clair, N.R. Ordway, S.A. Albanese, W.F. Lavelle: Are Traditional Radiographic Methods Accurate Predictors of Pedicle Morphology? Spine, in press, 2016.

Factors Affecting Dimensional Accuracy of 3D-Printed Anatomical Structures Derived from CT Data. K. Ogden, C. Asian, G. Tillapaugh-Fay, N.R. Ordway, D. Diallo, P. Soman. Journal of Digital Imaging, 28:654-633, 2015.

Towards a Better Understanding of Direct Vertebral Rotation for AIS Surgery: Development of a Multi-segmental Biomechanical Model and Factors Affecting Correction. S. Badve, N.R. Ordway, S.A. Albanese, W.F. Lavelle. The Spine Journal, 15(5): 1034-1040, 2015.

Bone Fragility Following Radiotherapy (2010-2016)

Faculty: MJ Allen, TA Damron, JA Horton, KA Mann, ME Oest

Despite advances in radiation therapy techniques to treat cancer, post- radiation fragility fractures of the skeleton remain a significant health concern. Little is known about the mechanical and biochemical changes to the bone following radiotherapy, although it is known that the bone becomes brittle. One area of work focuses on understanding changes to the bone material and chemistry following radiation treatment, and proposes several clinical interventions that could prevent the adverse changes to bone. A second area investigates the role of radiation therapy in a pediatric population. This work was funded by the National Institutes of Health, Jim and Juli Boeheim Foundation, Page Trucking Foundation.

Local irradiation alters bone morphology and increased bone fragility in a mouse model. Wernle JD, Damron TA, Allen MJ, Mann KA. J Biomech. 43(14):2738-46, 2010.

Raman spectroscopy demonstrates prolonged alteration of bone chemical composition following extremity localized irradiation, Gong B, Oest ME, Mann KA, Damron TA, Morris MD, Bone. 57(1):252-8, 2013.

Long-term loss of osteoclasts and unopposed cortical mineral apposition following limited field irradiation. Oest ME, Franken V, Kuchera T, Strauss J, Damron TA., J Orthop Res. 33(3):334-42, 2015.

Facilities & Resources

Our research physicians study a wide range of topics in orthopedics, such as cancer, sports medicine, osteoporosis, spinal interventions, and fractures. Study results help our physicians provide better care for patients in the clinic using research-based methods of treatment.

The Musculo-skeletal Science Research Center (MSRC) occupies 10,000 square feet on the 3rd floor of the Institute for Human Performance. There are currently seven research faculty and numerous research staff, graduate students, and fellows based in the labs. In addition, clinical faculty and residents from Upstate Orthopedics are also engaged in research at the MSRC.

Musculoskeletal Research Laboratory Institute For Human Performance
Rm. 3202, 505 Irving Ave.
Syracuse, NY 13210
Map & directions
Phone: (315) 464-9950
Fax: 315 464-6638
Name: Stephanie Russell, MSRC Office Coordinator
Email: russells@upstate.edu

Research Faculty

Timothy A. Damron, MD

Timothy A. Damron, MD

Professor

Upstate Bone and Joint Center
6620 Fly Road
East Syracuse, NY 13057
damront@upstate.edu
(315) 464-4472

Current Appointments

Hospital Campus

  • Downtown
  • Community

Clinical Section Affiliations

  • Orthopedic Surgery: Joint Reconstructive Surgery, Orthopedic Oncology 
  • Upstate Cancer Center: Orthopedics 
  • Women's Health Network: Urgent/After Hours Care, Women's Bone Health/Orthopedic Surgery

Research Programs and Affiliations

  • Biomedical Sciences Program 
  • Orthopedic Surgery 
  • Physiology Program

Clinic/Unit

Education & Fellowships

Fellowship: Mayo Clinic, 1994
Residency: University of Wisconsin Hospitals and Clinics, 1993
MD: University of Illinois College of Medicine, 1988

Clinical Interests

Pediatric and adult bone and soft-tissue tumors, Synovial proliferation disorders (PVNs, synovial chondromatosis), Metastatic disease to bone, Joint reconstructive surgery

Research Interests

Radioprotectant strategies: pediatric growth plate. Treatment of Fractures in Pathology Bone, Reconstructive Alternatives: Limb-Sparing Sarcoma Surgery, Genetics of Pagetoid Osteosarcoma

Clinical Trials

A Randomized Trial to Assess Patient Quality of Life and Function after Alternative Surgeries for Pathologic Fractures of the Femur
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Prophylactic Antibiotic Regimens in Tumor Surgery (PARITY): A Multi-Center Randomized Controlled Study Comparing Alternative Antibiotic Regimens in Patients Undergoing Tumor Resections with Endoprosthetic Replacements
Read more

Specialties & Certification

  • Orthopedic Surgery
  • Oncology

Diseases & Conditions Treated

  • Adult Lymphoma 
  • Arthritis 
  • Benign Bone Tumors 
  • Benign Soft-Tissue Masses 
  • Bone Cancer 
  • Broken Ankle 
  • Broken Arm 
  • Broken Collarbone 
  • Broken Elbow 
  • Broken Finger 
  • Broken Leg 
  • Broken Toe 
  • Broken Wrist 
  • Childhood Cancers 
  • Chondrosarcoma 
  • Ewing Tumor 
  • Fracture 
  • Ganglion Cyst 
  • Head and Neck Tumors and Masses 
  • Hip Dysplasia 
  • Hip Fracture 
  • Leg Deformities 
  • Malignant Bone Tumors 
  • Malignant Soft-Tissue Tumors 
  • Melanoma 
  • Metastatic Bone Disease 
  • Metastatic Soft-Tissue Disease 
  • Neuro-Oncology Cancers 
  • Neurofibromatosis 
  • Osteopenia 
  • Osteoporosis 
  • Osteosarcoma 
  • Paget's Disease of Bone 
  • Pediatric Fractures 
  • Pigmented Villonodular Synovitis (PVNS) 
  • Rhabdomyosarcoma 
  • Rheumatoid Arthritis 
  • Sarcoma 
  • Septic Arthritis 
  • Simple Bone Cysts 
  • Skin or Soft Tissue Abscess 
  • Skin/Soft Tissue Infections 
  • Slipped Capital Femoral Epiphysis 
  • Soft-Tissue Sarcomas 
  • Stress Fractures 
  • Synovial Chondromatosis 
  • Trauma

Treats

  • Adults and Children

Treatments/Services

  • Axillary Node Dissection 
  • Biopsy of Bone Lesions 
  • Biopsy of Soft-Tissue Masses 
  • Bone Grafting 
  • Bone Marrow Aspiration 
  • Bone Marrow Biopsy 
  • Bone Sarcoma Surgery 
  • Clinical Trials 
  • Computed Tomography (CT) Scan 
  • Curettage of Bone Lesions 
  • Debridement 
  • Diagnostic Assessment 
  • Excision of Bone Lesions 
  • Excision of Soft-Tissue Masses 
  • Fracture Treatment of Ankle 
  • Fracture Treatment of Arm 
  • Fracture Treatment of Clavicle 
  • Fracture Treatment of Elbow 
  • Fracture Treatment of Femur 
  • Fracture Treatment of Foot 
  • Fracture Treatment of Hand 
  • Fracture Treatment of Hip 
  • Fracture Treatment of Patella 
  • Fracture Treatment of Ribs 
  • Fracture Treatment of Shoulder 
  • Fracture Treatment of Spine 
  • Fracture Treatment of Tibia 
  • Fracture Treatment of Wrist 
  • Hardware Removal 
  • Hip Revision 
  • Inguinal Node Dissection 
  • Knee Arthroscopy 
  • Knee Revision 
  • MR Imaging 
  • Neuroplasty 
  • Pediatric Spine Tumor Surgery 
  • Reconstructive Surgery 
  • Soft Tissue Bursa Injection 
  • Soft-Tissue Sarcoma Surgery 
  • Synovectomy 
  • Total Hip Replacement 
  • Total Knee Replacement 
  • Total Shoulder Joint Replacement 
  • Trauma Care 
  • Tru-Cut Core Biopsy in Office 
  • Wound Care 
  • X-Ray

Current Hospital Privileges

  • Upstate University Hospital

Publications

PubMed

Research

Growth plate and bone radioprotection and radiorecovery

Our laboratory has been funded continuously by the NIH since 2000 for our work evaluating the mechanisms of damaging effects of irradiation on bone growth. Most recently, the focus has been on selective stimulation of radiorecovery pathways. This work involves in vitro and in vivo work with histomorphometric, immunohistochemical, and molecular evaluation at the RNA and protein level. This area of research is relevant to children being treated for bone and soft-tissue sarcomas.

Osteosarcomas

Utilizing both in vitro and in vivo work including an orthotopic intraosseous osteosarcoma injection model, differential expression of genes and pathways related to metastatic potential are being evaluated.

Chemotherapy related osteoporosis

Our laboratory has established the high prevalence of premature low bone mineral density in young adults following chemotherapy for pediatric malignancies, including bone and soft-tissue sarcomas. However, the specific mechanisms of this adverse outcome have not been elucidated. Furthermore, the precise role of specific novel agents in the simultaneous treatment of osteosarcoma and low bone mineral density has yet to be explored, leaving room for exploration and development of new treatments.

Radiation associated fractures

Building upon our extensive experience exploring the damaging effects of irradiation treatments on growth plate function in pediatric patients with malignant bone and soft-tissue tumors, an in vivo nude mouse model has been established to evaluate the more common problem of fracture following bone irradiation. This problem spans numerous specialties, including gynecologic oncology, where pelvic irradiation frequently leads to pelvic stress fractures, as well as pediatric oncology, adult oncology, radiation oncology, and orthopedics.

Selected references (please refer to PubMed link for complete list)

Arrington S, Damron TA, Mann KA, Allen MJ. Concurrent administration of zoledronic zcid and irradiation leads to improved bone density, microarchitecture and biomechanical strength in a mouse model of tumor-induced osteolysis. Accepted for publication in J Surg Oncol, November 2007.

Arrington SA, Schoonmaker JE, Damron TA, Mann KA, Allen MJ. Temporal changes in bone mass and mechanical properties in a murine model of tumor osteolysis. Bone 2006 Mar;38(3):359-67. 2005 Nov 5 [Epub ahead of print].

Damron TA, Horton J, Naqvi A, Loomis RM, Margulies BS, Strauss JA, CE Farnum, Spadaro JA. Combination radioprotectants maintain chondrocyte proliferation better than single agents by decreasing early parathyroid hormone related protein changes after growth plate irradiation. Radiation Research 2006 Mar;265(3):350-8.

Damron TA, Ward WG, Stewart A. Osteosarcoma, chondrosarcoma, and Ewings sarcoma: National Cancer Database Report. Clin Orthop Relat Res [Epub ahead of print 2007 Mar 22] 459:40-47, 2007.

Horton JA, Bariteau JT, Loomis RM, Strauss JA, Damron TA. Ontogeny of skeletal maturation in the juvenile rat. Anat Rec.2008 Mar;291(3):283-92.

Horton JA, Margulies BS, Strauss JA, Bariteau JT, Damron TA, Spadaro JA, Farnum CE. Restoration of growth plate function following radiotherapy is driven by increased proliferative and synthetic activity of expansions of chondrocytic clones. J Orthop Res [Epub ahead of print 2006 Aug 17] 2006 Oct;24(10):1945-56.

Margulies BS, Horton JA, Wang Y, Damron TA, Allen MJ. Effects of radiation therapy on chondrocytes in vitro. Calcif Tissue Int. 2006 May;78(5):302-13. Epub 2006 May 9.

Spadaro JA, Damron TA, Horton JA, Margulies BS, Murray GM, Clemente DA, Strauss JA. Density and structural changes in the bone of growing rats after weekly alendronate administration with and without a methotrexate challenge. J Orthop Res. 2006 May;24(5):936-44.

Spadaro JA, Horton JA, Margulies BS, Strauss JA, Farnum CE, Damron TA. Radioprotectant combinations spare radiation-induced damage to the physis more than fractionation alone. International Journal of Radiation Biology, 2005 Oct;81(10):759-65.

Wang Y, Zhang M, Middleton FA, Horton JA, Pritchard M, Spadaro JA, Farnum CE, Damron TA. Connective tissue growth factor and insulin-like growth factor 2 show upregulation in early growth plate radiorecovery response following irradiation. Cells Tissues Organs. 2007;186(3):192-203. Epub 2007 Jul 12.

Zhang M, Wang Y, Middleton FA, Horton JA, Farnum CE, Damron TA. Growth plate zonal microarray analysis shows upregulation of extracellular matrix genes and down-regulation of metalloproteinsaes and cathepsins following irradiation. Connective Tissue International [Epub ahead of print 5 Jun 2007].

Kenneth A. Mann, PhD

Kenneth A. Mann, PhD

Professor

3216 Institute For Human Performance
505 Irving Ave.
Syracuse, NY 13210
mannk@upstate.edu
(315) 464-5540

Current Appointments

Hospital Campus

  • Downtown

Research Programs and Affiliations

  • Biomedical Sciences Program
  • Orthopedic Surgery
  • Physiology Program

Web Resources

Education & Fellowships

  • PhD: Cornell University, 1991, Mechanical Engineering (Biomechanics)
  • MS: Pennsylvania State University, 1985, Bioengineering
  • BS: Virginia Tech, 1983, Engineering Science and Mechanics

Research Interests

  • Micro-mechanics of implant interfaces; damage evolution of joint replacements and biomaterials; in vivo models of tumor osteolysis and prediction of fracture risk; general orthopedic biomechanics.

Publications

Research

Research Interests

Micromechanics and micro-mechanical modeling of bone-implant interfaces: Implant fixation is vital to long-term success of mechanically loaded implant systems. Surprisingly little is known about the load transfer mechanisms and motion at the length scales of trabeculae (~1mm) and below. In addition, there are often dramatic changes in bone remodeling around implants with in vivo use. For cemented implants, the loss of interlock between trabeculae and cement can be dramatic. We have been performing in vitro experiments on small components of bone-implant interfaces in which small (micron scale) loading is applied in tension, compression, and shear. We incorporate digital image correlation techniques to map local strain fields subjected to loading. The long-term goal here is to improve our understanding of local motions at the interface and how motion is related to bony response. Both experimental and computational models are performed on laboratory prepared and post-mortem retrieved specimens. (NIH funded: 2012-2017).

Predicting bone fracture in patients with metastatic disease. Primary tumors, such as breast and prostate cancer, can metastasize to bone cause bone destruction and bone fracture. Predicting whether a bone with metastatic disease will fracture remains a clinical challenge. Clinical scoring systems based on X-ray and patient pain levels are not good predictors for determining which bones require surgical stabilization. We are using Finite Element (FE) modeling of clinical CT scan sets in collaboration with Dr. Timothy Damron to determine activities of daily living that are predictive of fracture.The long term goal is to use FE as a tool to help surgeons decide which patients to stabilize from those that are not at risk of fracture. (Funding from Baldwin Foundation, 2013-2015.)

Role of therapeutic radiation in increasing fracture risk of bone: Using a murine model of radiation damage to the extremities (PI: T Damron, Co-inv: M Oest-Upstate, M Morris-U Michigan) we are investigating the implications of bony remodeling in terms of structure and fundamental changes to bone material fracture resistance and chemical changes to the bone. We are using biomechanical strength tests and fracture toughness tests to monitor changes in bone structure and material properties with time, radiation dose, and anabolic, antiresorptive and radioprotection treatments. We are also using a combination of voxel-based finite element modeling with material damage models and comparing these to experiments to gain a better understanding of bone ‘brittle’ behavior. (NIH funded: 2014-2019)

Recent Representative Publications

  1.  Howard KI, Miller MA, Damron TA, Mann KA. The distribution of implant fixation for femoral components of TKA: A postmortem retrieval study. J Arthroplasty, 29(9): 1863-1870, 2014. 
  2. Miller MA, Terbush MJ, Goodheart JR, Izant TH, Mann KA. Increased initial cement-bone interlock correlates with reduced TKA micro-motion following in vivo service. J Biomechanics, 47:2460-2466, 2014.
  3. Goodheart JR, Miller MA, Mann KA. In vivo loss of cement-bone interlock reduces fixation strength in total knee arthroplasties. J Orthop Res. 32(8): 1052-60, 2014.
  4. Mann KA, Miller MA, Goodheart JR, Izant TH, Cleary RJ. Peri-implant bone strains and micro-motion following in vivo service: A postmortem retrieval study of 22 tibial components from totak knee replacements. J Orthop Res. 32(3): 355-61, 2014.
  5. Oest ME, Miller MA, Howard KI, Mann KA. A novel in vitro loading system to produce supraphysiologic oscillatory fluid shear stress. J Biomech, 47(2):518-25, 2014.
  6. Miller MA, Goodheart JR, Izant TH, Rimnac CM, Cleary RJ, Mann KA. Loss of cement-bone interlock in retrieved tibial components. Clin Orthop Rel Res, 472(1):304-13, 2014.
  7. Mann KA, Miller MA. Fluid-structure interactions in micro-interlocked regions of the cement-bone interface. Computer Methods in Biomechanics and Biomedical Engineering, 17(16): 1809-20, 2014.
  8. Gong B, Oest ME, Mann KA, Damron TA, Morris MD. Raman Spectroscopy demonstrates prolonged alteration of bone chemical composition following extremity localized irradiation. Bone, 57(1): 252-258, 2013.
  9. Keenawinna L, Oest ME, Mann KA, Spadaro JA, Damron TA. Zoledronic Acid Prevents Loss of Trabecular Bone Following Focal Irradiation in Mice.Radiation Research, 180(1):89-99, 2013.
  10. Murphy CT, Eberhardt WC, Calhoun BH, Mann KA, Mann DA. Effect of angle on flow-induced vibrations of pinniped vibrissae. PLOS One, 8(7), July 2013.

Jason A. Horton, PhD

Jason A. Horton, PhD

Assistant Professor

3119 Institute For Human Performance
505 Irving Ave.
Syracuse, NY 13210
hortonj@upstate.edu
(315) 464-5540

Current Appointments

Hospital Campus

  • Downtown

Research Programs and Affiliations

  • Biomedical Sciences Program

Education & Fellowships

  • Fellowship: National Institutes of Health, 2015, Craniofacial and Skeletal Development
  • Fellowship: National Cancer Institute, NIH, Bethesda, MD, 2014, Radiation Oncology
  • PhD: SUNY Upstate Medical University, 2011, Physiology
  • BS: Oswego State University, 2000, Biology, Bio-cultural Anthropology

Research Interests

  • Skeletal development, maturation and maintenance; Mesenchymal stem cell biology; Radiobiology of skeletal tissues; Radiosensitization of pediatric musculoskeletal sarcoma.

Associations/Memberships

  • American Association for the Advancement of Science (AAAS)
  • American Society for Bone and Mineral Research (ASBMR)

Publications

Research

Skeletal development, maturation and maintenance: The structures that form the skeleton arise very early in embryonic development, continue to grow during childhood, and are actively remodeled throughout our lives. My research in this area focuses on how intercellular signaling between bone forming osteoblasts, bone resorbing osteoclasts, hematopoietic and vascular cells, along with input from systemic endocrine stimuli, collaboratively regulate bone integrity. Perturbation of these signaling circuits can lead to variety of structural and metabolic bone diseases, such as osteoporosis, and can result in fractures. Greater understanding of signaling within this bone microenvironment may translate to new strategies to prevent or correct bone disease.

Mesenchymal stem cell biology: Mesenchymal stem cells (MSCs) derive from the embryonic mesoderm and give rise to the connective tissues throughout the body. Lineage restricted derivatives of these cells persist through post-natal growth, and function in maintenance and repair of connective tissues throughout our life span. Whether these MSC's persist post-natally as truly, multipotent 'stem cells' is unresolved due to a lack of sufficiently specific molecular markers, which identify these cells in situ. My research in this area focuses on identifying the factors that specify differentiation of MSC and their post-natal derivatives, toward the bone, cartilage, and adipose lineages. Better understanding of the biology of these cells will enhance our ability to identify these cells, and may facilitate the use of such cells in therapeutic applications.

Radiobiology of skeletal tissues: Ionizing radiation is used in the treatment of many solid cancers, but can cause collateral damage to healthy tissues surrounding the targeted tumor. Occasionally, irradiation of skeletal structures is unavoidable, and can result in localized radiation-induced bone disease, and elevated susceptibility to atraumatic fracture. My research in this area will study the radiobiologic response of the bone microenvironment, to determine the mechanisms that result in persistent osteogenitor depletion and replacement of hematopoietic marrow with adipose tissue. The goal of this line of research is to develop strategies which prevent or repair bone damage resulting from radiation exposure, and minimize the impact of radiation-induced bone disease on the quality of life of cancer survivors.

Radiosensitization of pediatric musculoskeletal sarcoma: Sarcomas are a family of cancers that develop in connective tissues such as the muscle or bone. Ewing's sarcoma and rhabdomyosarcoma, which develop in bone and muscle respectively, are pediatric cancers with a tendency to occur adjacent to areas of active bone growth. In addition to surgery and chemotherapy, ionizing radiation is used to treat these cancers, but may result in permanent damage to growing bone including asymmetric growth arrest, angular deformity and increased susceptibility to fracture. The severity of bone injury is largely determined by the dose of radiation that the bone receives. Therefore it is reasoned that strategies which selectively sensitize tumor tissue to radiation could lower the dose of radiation needed to achieve local control, and minimize collateral injury of adjacent healthy tissue.

Megan Oest, PhD

Megan Oest, PhD

Assistant Professor

3111 Institute For Human Performance
505 Irving Ave.
Syracuse, NY 13210
oestm@upstate.edu (315) 464-5540

Current Appointments

Hospital Campus

  • Downtown

Research Programs and Affiliations

  • Biomedical Sciences Program
  • Orthopedic Surgery

Education & Fellowships

  • Postdoctoral Fellow: Virginia Tech, 2008
  • PhD: Georgia Institute of Technology, 2007, Bioengineering
  • BS: Oregon State University, 2001, Bioengineering

Research Interests

  • Radiation damage to bone and progenitor cells; mechanical regulation of bone cell behavior; osteoclast lineage cells; orthopedic tissue engineering.

HealthLinkOnAir Radio Interview

Publications

Research

ResearchCellular Mechanisms Mediating Therapeutic Radiation Damage to Bone: A common complication following focal radiation therapy for soft tissue sarcoma is late-onset insufficiency fracture of the bone. While radiation-induced morphological changes to the bone have been documented, these changes alone do not explain the increased risk for fragility fracture. Using a mouse model of focal hindlimb irradiation, we have documented an early, transient increase in osteoclast numbers followed by persistent loss of osteoclasts long-term, and extensive modifications to the bone matrix post-irradiation. These alterations in osteoclast number correlate temporally with loss of trabecular bone. Persistence of poor quality bone matrix post-irradiation highlights the importance of retaining functional osteoclast and osteoclast progenitor cell populations long-term. We are characterizing this radiation-induced progenitor cell damage and osteoclast dysfunction, and investigating potential preventative pharmacologic interventions. (Funding: Baldwin Foundation)

ResearchBiochemical and Mechanical Alterations to Bone Following Radiotherapy: Radiation-induced bone fragility is best explained using a model that assumes embrittlement of bone's material properties following radiation. We hypothesize that this embrittlement may occur through biochemical alterations to the organic matrix and alterations to mineral crystallinity. Using Raman spectroscopy, mechanical testing, and assessment of advanced glycation end product accumulation, we are exploring time and location-dependent biochemical alterations to bone following radiation therapy. (Funding: NIH/NIAMS, PI: Timothy Damron, Co-Is: Kenneth Mann, David Kohn & Michael Morris at UMichigan)

ResearchNovel Biomaterials for Stabilization and Repair of Critically Sized Bone Defects: We are investigating the use of novel shape-memory polymer scaffolds and electrospun shape-memory polymer sleeves as methods of rapidly stabilizing bone defects, reconstructing comminuted fractures, and delivering antimicrobial and osteoinductive agents to facilitate autologous repair long-term. We have completed preliminary testing of this technology in a mouse femoral defect model, and are scaling up to larger animal models for eventual human application. (Funding: Nappi Family Awards, co-PI: James Henderson, Syracuse University)

Publications:

  1. Oest ME, Mann KA, Zimmerman ND, Damron TA. (2016) PTH(1-34) transiently protects against radiation-induced bone damage. Calcified Tissue International epub ahead of print.
  2. Baker RM, Tseng L-F, Iannolo MT, Oest ME, Henderson JH. (2016) Self-deploying shape memory polymer scaffolds for grafting and stabilizing complex bone defects: a mouse femoral segmental defect study. Biomaterials 76:388-398.
  3. Oest ME, Franken V, Kuchera T, Strauss J, Damron TA. (2015) Long-term loss of osteoclasts and unopposed cortical mineral apposition following limited field irradiation. Journal of Orthopaedic Research 33(3): 334-342.
  4. Oest ME, Damron TA. (2014) Focal therapeutic irradiation induces an early transient increase in bone glycation. Radiation Research 181(4):439-43.
  5. Oest ME, Miller MA, Howard KI, Mann KA. (2014) A novel in vitro loading system to produce supraphysiologic fluid shear stress. Journal of Biomechanics 47(2):518-525.
  6. Gong B, Oest ME, Mann KA, Damron TA, Morris MD. (2013) Raman Spectroscopy Demonstrates Prolonged Alteration of Bone Chemical Composition Following Extremity Localized Irradiation. Bone 57(1):252-258.
  7. Keenawinna L, Oest ME, Mann KA, Spadaro JA, Damron TA. (2013) Zoledronic Acid Prevents Loss of Trabecular Bone Following Focal Irradiation in Mice. Journal of Radiation Research 180(1):89-99.
  8. Wojtowitcz AM, Shekaran A, Oest ME, Dupont KM, Templeman KL, Hutmacher DW, Guldberg RE, Garcia AJ. (2010) Coating of biomaterial scaffolds with the collagen-mimetic peptide GFOGER for bone defect repair. Biomaterials, 31(9): 2574-2582.
  9. Liang C, Oest ME, Jones JC, Prater MR. (2009) Gestational high saturated fat diet alters C57BL/6 mouse perinatal skeletal formation. Birth Defects Research Part B Developmental and Reproductive Toxicology, 86(5):377-384.
  10. Liang C, Oest ME, Prater MR. (2009) Intrauterine exposure to high saturated fat diet elevates risk of adult-onset chronic diseases in C57Bl/6 mice. Birth Defects Research Part B Developmental and Reproductive Toxicology, 86(5):362-369.
  11. Oest ME, Jones JC, Hatfield C, Prater MR. (2008) Micro-CT evaluation of murine fetal skeletal development yields greater morphometric precision over traditional clear-staining methods. Birth Defects Research Part B Developmental and Reproductive Toxicology 83(6):582-589.
  12. Guldberg RE, Duvall CL, Peister A, Oest ME, Lin AS, Palmer AW, Levenston ME. (2008) 3D imaging of tissue integration with porous biomaterials. Biomaterials 29 (28):3757-3761.
  13. Guldberg RE, Oest ME, Dupont K, Peister A, Deutsch E, Kolambkar Y, Mooney D. (2007) Biologic augmentation of polymer scaffolds for bone repair. Journal of Musculoskeletal and Neuronal Interactions 7(4):333-334.
  14. Duty AO, Oest ME, Guldberg RE. (2007) Cyclic mechanical compression in vivo increases mineralization of cell-seeded polymeric orthopaedic tissue constructs. Journal of Biomechanical Engineering 129(4):531-539.
  15. Oest ME, Dupont KM, Kong, HJ, Mooney, DJ, Guldberg RE. (2007) Quantitative assessment of scaffold and growth factor-mediated repair of critically sized bone defects. Journal of Orthopaedic Research 25(7):941-950.
  16. Rai B, Oest ME, Dupont KM, Ho KH, Teoh SH, Guldberg RE. (2007) Combination of platelet-rich plasma with polycaprolactone-tricalcium phosphate scaffolds for segmental bone defect repair. Journal of Biomedical Materials Research A 81(4):888-899.
  17. Guldberg RE, Oest ME, Lin AS, Ito H, Chao X, Gromov K, Goater JJ, Koefoed M, Schwarz EM, O'Keefe RJ, Zhang X. (2004) Functional integration of tissue-engineered bone constructs. Journal of Musculoskeletal and Neuronal Interactions 4(4):399-400.
  18. Guldberg RE, Ballock RT, Boyan BD, Duvall CL, Lin AS, Nagaraja S, Oest ME, Phillips J, Porter BD, Robertson G, Taylor WR. (2003) Analyzing bone, blood vessels, and biomaterials with microcomputed tomography. IEEE Engineering in Medicine and Biology 22(5):77-83.
  19. Bower CK, Parker JE, Higgins AZ, Oest ME, Wilson JT, Valentine BA, Bothwell MK, McGuire J. (2002) Protein antimicrobial barriers to bacterial adhesion: in vitro and in vivo evaluation of nisin-treated implantable materials. Colloids and Surfaces B: Biointerfaces 25(1):81-90.

Nathaniel R. Ordway, MS, PE

Nathaniel R. Ordway, MS, PE

Assistant Professor

3219 Institute For Human Performance
505 Irving Ave.
Syracuse, NY 13210
ordwayn@upstate.edu
(315) 464-6462

Current Appointments

Hospital Campus

  • Downtown

Research Programs and Affiliations

  • College of Health Professions
  • Orthopedic Surgery

Web Resources

Education & Fellowships

  • MS: Clemson University, 1989, Bioengineering
  • BS: Boston University, 1987, Biomedical Engineering

Research Interests,

  • Clinical and experimental spine biomechanics; Motion analysis and functional assessment

Publications

PubMed

Research

The Use of Radiostereometric Analysis (RSA) in Spinal Surgery

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 focused on clinical studies using RSA to evaluate fusion, discectomy, intervertebral disc replacement and dynamic stabilization.

Pedicle Screw Fixation in Osteoporotic Bone

Pedicle screw fixation in osteoporotic bone is problematic. Failure of fixation at the screw-bone interface can lead to mechanical and neurological complications. This is especially true in patients with osteoporosis who require pedicle screw fixation for progressive fracture deformity or neurological deterioration. We have been investigating pedicle screw features and techniques in order to optimize the fixation strength of the screw-bone interface.

Biomechanical Assessment of Nucleus Replacement

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 annulus.

Frederick W. Werner, MME, PE

Frederick W. Werner, MME, PE

Professor

3214 Institute For Human Performance
505 Irving Ave.
Syracuse, NY 13210
315 464-9950

Current Appointments

Hospital Campus

  • Downtown

Research Programs and Affiliations

  • Orthopedic Surgery

Web Resources

Education & Fellowships

  • MS: Cornell University, 1975, Mechanical Engineering
  • BS: Cornell University, 1972, Mechanical Engineering

Research Interests

  • Experimental biomechanics of the upper and lower extremities as related to the function of normal, diseased and surgically repaired soft tissues and joints.

Publications

Research

Causes and Treatments of Wrist Instability. With WH Short, LG Sutton:

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.

Biomechanical Evaluation of Ulnar Carpal Impaction. With BJ Harley, LG Sutton:

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 and the distal radioulnar joint.

Evaluation of Surgical Treatments of the Wrist. With BJ Harley, AK Palmer, WH Short, LG Sutton:

Surgical treatments for the wrist such as proximal row carpectomy, 4 corner fusion, total wrist replacement and cubital tunnel release are being studied using various biomechanical models.

Dynamic, Cyclic testing of Total Knee Replacements and Surgical Treatments of the Knee Joint. With JP Cannizzaro, MG Scuderi, LG Sutton:

Two dynamic knee simulators are used to move cadaver knees through either gait or deep knee bend motions. These simulators are used to quantify either kinematic or contact pressure changes due to releasing various ligaments, cartilage coring or the use of a knee replacement.

Shoulder and Elbow Biomechanics. With K Setter, LG Sutton:

Experimental and analytical models are used to evaluate shoulder implant fixation and stability and elbow ligament repair methods.

Professor Emeritus

  • Andrew K. Palmer, MD
  • David Murray, MD
  • Hansen Yuan, MD
  • Joseph Spadaro, PhD
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