Orthopedic Research at SUNY Upstate

Key - Bold: Faculty; Italics: Resident/Fellow; Underline: Upstate Med/Grad student.

• Flood MG, Wie BJ, Sullivan MP. Perforation of the Knee Joint Following Antegrade Intramedullary Nailing of a Comminuted Femoral Diaphyseal Fracture: A Case Report. Cureus. 2022 May 5. PMID 35677006
• Flood MG, Bauer MR, Sullivan MP. Radiographic Considerations for Pediatric Supracondylar Humerus Fractures. Journal of Pediatric Orthopedics – B. 2022 March 31. PMID 35357346
• Sullivan MP, Bonilla K, Donegan D. Malrotation of long bone. Orthop Clin North Am. 2021 May 7. PMID 34053567
• Sullivan MP, Telgheder ZL, Kleweno CP. Three Dimensional Computed Tomography Posterior Iliac Oblique Images Enhance Preoperative Planning for Acetabular Fracture Surgery - Journal of Surgical Orthopaedic Advances. Spring 2021;30(1):50-54. PMID 33861195
• Telgheder ZL, Albanese MA, Bloom DS, Kurra S, Sullivan MP “A Comparison of Complications and Union Rates in Intramedullary Nailing of Femoral Shaft Fractures Treated with Open Versus Closed Reduction”. Orthopedics. 2020 Mar1; 43(2): 103-107. PMID 31881084 doi: 10.3928/01477447-20191223-03
• Damron TA “CORR Insights: Is There an Association Between Prophylactic Femur Stabilization and Survival in Patients with Metastatic Bone Disease?” Clinical Orthopaedics and Related Research. 2020 Mar; 478(3): 547-549. PMID 31389883 doi: 10.1097/CORR.0000000000000880
• Mann KA, Miller MA, Tatusko ME, Oest ME “Similitude of Cement-Bone Micromechanics in Cemented Rat and Human Knee Replacement”. Journal of Orthopaedic Surgery. 2020 Jul; 38(7): 1529-1537. PMID 32167182 doi: 1002/jor.24661
• Damron TA, Mann KA “Fracture Risk Assessment and Clinical Decision Making for Patients with Metastatic Bone Disease” Journal of Orthopedic Research. 2020 Jun; 38(6): 1175-1190. PMID 32162711 doi: 1002/jor.24660
• Mandair GS, Oest ME, Mann KA, Morris MD, Damron TA, Kohn DH “Radiation-Induced Changes to Bone Composition Extend Beyond Periosteal Bone” Bone Reports. 2020 Mar 28; 12: 100262. PMID 32258252 doi: 1016/j.bonr.2020.100262
• Damron TA “CORR Insights: Is Treatment with Denosumab Associated with Local Recurrence in Patients with Giant Cell Tumor of Bone Treated with Curettage? A Systematic Review” Clinical Orthopaedics and Related Research. 2020 May; 478(5): 1086-1088. PMID 32187094 doi: 1097/CORR.0000000000001217
• Serrano R, Mir HR, Sagi HC, Horwitz DS, Ketz JP, Kistler BJ, Quade JH, Beebe MJ, Au BK, Sanders RW, Shah AR “Modern Results of Functional Bracing of Humeral Shaft Fractures: A Multicenter Retrospective Analysis” Journal of Orthopaedic Trauma. 2020Apr; 34(4): 206-209. PMID 31923040 doi: 1097/BOT.0000000000001666
• Dowthwaite J “A Geriatric Exercise Program May Yield Multiple Benefits” Journal of Bone and Mineral Research. 2020 Mar; 35(3): 417-418. PMID 31671214 doi: 1002/jbmr.3897
• Murtaza H, Arain AR, Anoushiravani A, Thadani S, de le Rosa G, Naous R, Damron TA “Cytokeratin-Positive Osteosarcoma Simulating Sarcomatoid Metastatic Carcinoma” Case Reports in Orthopedics. 2020 Feb 4; 2020:3761015. PMID 32089927 doi: 10.1155/2020/3761015
• Badve SA, Forman JE, Levi AD, Kurra S, Riew KD, Lavelle WF“Employment Status for the First Decade Following Randomization to Cervical Disc Arthroplasty Versus Fusion” Spine. 2020; October 15; 45(20): 1411-1418. PMID 32453224 doi: 1097/BRS.0000000000003565
• Heitner HD, Werner FW, Cavallaro SM, Willsey SR, Harley BJ“Biomechanical Evaluation of Distal Radioulnar Joint Instability and Adams Procedure” Journal of Hand Surgery. 2020 Oct; 45(10): 909-917. PMID 32690338 doi 1016/j.jhsa.2020.05.014
• Telgheder ZL, Kistler BJ “Ski and Snowboard-Related Orthopedic Injuries” Orthopedic Clinics of North America. 2020 Oct; 51(4): 461-469. PMID 32950215 doi:1016/j.ocl.2020.06.004
• Lavelle WF “CORR Insights: Minimum Clinically Important Differences of the Hospital for Special Surgery Dysphagia and Dysphonia Inventory and Other Dysphagia Measurements in Patients Undergoing ACDF” Clinical Orthopedics and Research. 2020 October; 478(10): 2321-2323. PMID 32379133 doi 1097/CORR.0000000000001298
• Werner FW, Tucci ER, Daly BT, Harley BJ “Changes in Scaphoid and Lunate Position and Loading at Two Wrist Pushup Positions”. Current Rheumatology Reviews. 2020; 16(3): 201-205. PMID 30526465 doi: 2174/1573397115666181210170202
• Wollstein R, Rubinstend R, Friedlander S, Werner FW “Capitate and Lunate Morphology in Normal Wrist Radiographs – A Pilot Study” Current Rheumatology Reviews. 2020; 16(3): 210-214. PMID 30520379 doi: 10.2174/1573397115666181205165642
• Alam M, Shufflebarger HL, Rush AJ, Rosas S, Lavelle WF, Sponseller PD, Asghar J “Delayed Quadriparesis After Posterior Spinal Fusion for Scoliosis: A Case Series” Spine Deformity. 2020 October; 8(5): 1075-1080. PMID 32274769 doi:1007/s43390-020-00113-5
• Worden NJ, Ash KJ, Ordway NR, Miller MA, Mann KA, Vandeventer GM, Valenzano DM, Hart R, Kayano M, Hayashi K “Radiographic and Biomechanical Assessment of Three Implant Designs for Canine Cementless Total Hip Replacement” Veterinary and Comparative Orthopaedics and Traumatology. 2020 Nov;33(6): 417-427. PMID 32971544 doi: 10.1055/s-0040-1715476
• Bedard T, Mohammed M, Serinelli S, Damron TA “Atypical Enostoses – Series of Ten Cases and Literature Review” Medicine (Kaunas). 2020 October; 56(10): 534. PMID 33065973 doi: 10.3390/medicina56100534
• Yoon JW, Welch RL, Alamin T, Lavelle WF, Cheng I, Perez-Cruet M, Fielding LC, Sasso RC, Linovitz RJ, Kim KD, Welch WC “Remote Virtual Spinal Evaluation in the Era of COVID-19” International Journal of Spine Surgery. 2020; June 30: 433-440: 14(3). No PubMed ID. doi: 10.14444/7057
• Kurra S, Rashid A, Yirenkyi H, Castle P, Lavelle WF “Outcomes of Negative Pressure Wound Therapies in the Management of Spine Surgical Site Wound Infections” International Journal of Spine Surgery. 2020 Oct: 14(5): 772-777. PMID 33046536 doi: 10.14444/7110
• Lal DN, El-Zammar A, Naous R, Damron TA “Intra-articular Extraskeletal EWSR1-Negative NR4A3-Positive Myxoid Chondrosarcoma: A Case Report” JBJS Case Connect. 2020 Apr-Jun; 10(2): e0614. PMID 32649120 doi: 10.2106/JBJS.CC.19.00614
• Sawyer SW, Zhang K, Horton JA, Soman P “Perfusion-based Co-culture Model System for Bone Tissue Engineering” AIMS Bioeng. 2020; 7(2): 91-105. PMID 33163623 doi: 10.3934/bioeng.2020009
• Romeo AA, Erickson BJ, Costouros J, Long N, Klassen J, Araghi A, Brown J, Setter K, Port J, Tyndall W, Verma NN, Sears B “Eclipse Stemless Shoulder Prosthesis vs. Univers II Shoulder Prosthesis: A Multicenter, Prospective Randomized Controlled Trial” Journal of Shoulder and Elbow Surgery. 2020 Nov;29(11):2200-2212 PMID 32707325 doi: 10.1016/j.jse.2020.07.004

Federal Grants

Biochemical and Biomechanical Changes to Bone Following Radiotherapy

NIH/NIAMS R01 Award #AR065419-01

Dates of Approved Project: 7/1/2014 – 6/30/2020 (NCE)

$1,673,512 (total costs)

Principal Investigator: TA Damron

Co-investigators: ME Oest, KA Mann

 

Pathophysiology of Radiation-induced Bone Disease

NIH/NIAMS Award #5R00AR066737-04

Dates of Approved Project: 5/20/2016 – 4/30/2020

$747,000 (total costs)

Principle Investigator: JA Horton

 

Reducing Post-Radiotherapy Bone Fragility Through Orchestrated Cell Survival

NIH/NIAMS R01 Award #AR070142

Dates of Approved Project: 08/01/2017 – 07/31/2022

$1,782,000 (total costs)

Principal Investigator: ME Oest

Co-investigators: KA Mann, TA Damron, JA Horton

 

Etiology and Prevention of Loss of Fixation in Cemented Knee Replacements

NIH/NIAMS R01 Award #AR04201719

Dates of Approved Project: 08/01/2017 – 07/31/2022

$1,782,000 (total costs)

Principal Investigator: KA Mann

Co-investigators: ME Oest, TA Damron, JA Horton

 

In Vitro Model to Study the Role of Microvascular Physiology in Regulating Osteogenesis

NIH/NIAMS Award #1R21AR076642-01        

Funding Period: 9/1/2020 – 8/31/2022   

$198,000 (total costs)

PI: Pranav Soman, SU

Co-Investigator: JA Horton

 

Osteocyte Signaling Within Mineralized Lacuna-Canaliculi Microenvironment

NIH/NIAMS Award #1R21AR076645-01

Funding Period: 9/1/2020 – 8/31/2022

$201,720 (total costs)

PI: Pranav Soman, SU

Consultant: JA Horton

 

Foundation Grants

Role of Mesenchymal Stem Cells in Post-radiation Bone Recovery in Pediatric Sarcoma Patients: Investigation in an Animal Model

Jim and Juli Boeheim Foundation

Dates of approved project: 12/2013 – 12/2023

$150,000 (total direct costs)

Principal Investigator(s):  TA Damron, ME Oest

Co-investigator: JA Horton

 

Role of Marrow Adiposity in Skeletal Metastasis of Breast Cancer

Carol M. Baldwin Breast Cancer Research Award

Dates of approved project: 12/1/2017 – 11/30/2020

$50,000 (total costs)

Principle Investigator: JA Horton

 

Mechanisms Regulating Dysfunctional Repair of Post-Radiotherapy Bone Fragility Fractures

SUNY Upstate Cancer Center Translational Research Pilot Grant

Dates of approved project: 07/01/2019 – 06/30/2021

$48,500 (direct costs)

Principal Investigators: ME Oest and TA Damron

 

Targeted Inhibition of EWS:Fli1 for Treatment and Radiosensitization of Ewing sarcoma

SUNY Upstate Cancer Center Translational Research Pilot Grant                 

Dates of Approved Project: 6/15/2019 – 6/14/2021

$45,000 (total costs)

Principal Investigator: JA Horton

 

Treatment of Tumor Associated Osteolysis in Ewing Sarcoma

Upstate Foundation Pediatric Cancer Research Fund

Dates of Approved Project: 7/15/2020 – 6/30 2021

$25,000 (total costs)

Principal Investigator: JA Horton

1960s

Bioelectricity and the Enhancement of Fracture Healing

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

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

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

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

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

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

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

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

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

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

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

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

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

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.

The Musculo-skeletal Science Research Center (MSRC) occupies 10,000 square feet on the 3rd floor of the Institute for Human Performance on the SUNY Upstate Campus.

Physical Address:

Musculoskeletal Science Research Center
Institute For Human Performance
Rm. 3202, 505 Irving Ave.
Syracuse, NY 13210
Map & directions

Mailing address:

Orthopedic Research
Upstate Medical University
IHP 3202
750 East Adams Street
Syracuse, NY 13210

Phone: (315) 464-9950
Fax: 315 464-6638
Name: Kristen Hyer, Resident/Fellow and Research Project Administrator
Email: hyerk@upstate.edu