RESEARCH PROGRAMS AND AFFILIATIONS
Etiology and Prevention of Loss of Fixation in Cemented Knee Replacements: (PI: KA Mann) The overall goal of this study is to provide a mechanistic and functional understanding of the role of mechanical interlock between cement and bone in TKA fixation, and determine if implant fixation can be improved by mitigating the loss of interlock through use of an established drug therapy. In this competitive renewal, we will develop a cemented tibial replacement model in the rat that recapitulates the cement-bone interlock that occurs in human arthroplasty. We will: 1) investigate alterations in the morphology and micro-mechanics of TKA cement-bone interlock as a function of time with in vivo service, 2) investigate dynamic bone remodeling and cellular response as a function of position in the interlocked construct, 3) determine the longitudinal effect aging/osteoporosis on morphology, micro-mechanics, and cellular changes of cement-bone interlock for TKA using an ovariectomy (OVX) model, 4) determine if systemic dosing of an antiresorptive agent (zoledronic acid) can prevent loss of TKA interlock in normal and OVX cases, and 5) determine if local dosing of zoledronic acid from PMMA cement in TKA can confer a positive effect as similar to systemic dosing. (NIH funded: 2017-2022).
Predicting bone fracture in patients with metastatic disease. (PIs: TA Damron , KA Mann) 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, 2016-2019.)
Role of therapeutic radiation in increasing fracture risk of bone: (PI: T Damron) Using a murine model of radiation damage to the extremities 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)
Reducing Post-Radiotherapy Bone Fragility Through Orchestrated Cell Survival (PI: ME Oest) Using an established mouse model of limited field, clinically relevant fractionated irradiation, this proposal will investigate the natural time course and pharmacologic modulation of RTx-induced bone fragility in terms of local and distant cellular, tissue, and mechanical functions. Specifically, the goals are to 1) use an in vitro approach to identify RTx-upregulation of cytokine production by primary marrow cells that may regulate bone damage outside the irradiated field, comparing human and murine responses; 2) characterize the progression of marrow progenitor cell damage and recovery cycles post-RTx, including osteoblastic and osteoclastic lineages; 3) determine the efficacy of PTH as a progenitor cell radioprotectant; and 4) evaluate a short, tailored PTH-ZA co-treatment for radioprotection of progenitor cells, normalizing matrix remodeling, and restoring bone strength. Our overall goal is to identify translatable strategies to preserve post-RTx local and systemic bone quality and strength long-term, compatible with the clinical manifestation of fragility fractures years post-RTx. (NIH funded: 2017-2022).
Recent Representative Publications
- Damron TA, Mann KA. Evidence of negative effects of defect size and older patient age by quantitative CT-based 3D image analysis in ultraporous beta-tricalcium phosphate grafted extremity bone defects at one year. Adv Orthop Nov 1;2018:5304215
- Bartlow CM, Mann KA, Damron TA, Oest ME. Limited field radiation therapy results in decreased bone fracture toughness in a murine model. PLoS One 13(10):e0204928, 2018.
- Smallmann TV, Portner OT, Race A, Shekitka K, Mann K. Arthroscopic untethering of the fat pad of the knee: release or resection of the infrapatellar plica (ligaentum mucosum) and related structures of anterior knee pain. Arthroscopy Techniques 7(5):e575-e588, 2018.
- Liu C, Carrera R, Flamini V, Kenny L, Cabahug-Zuckerman P, George BM, Hunter D, Liu B, Singh G, Leucht P, Mann KA, Helms JA, Castillo AB. Effects of mechanical loading on cortical defect repair using a novel mechanobiological model of bone healing. Bone 108:145-155, 2018.
- Oest ME, Policastro CG, Mann KA, Zimmerman ND, Damron TA. Longitudinal effects of single hindlimb radiation therapy on bone strength and morphology at local and contralateral sites. J Bone Miner Res 33(1): 99-112, 2018.
- Goodheart JR, Miller MA, Oest ME, Mann KA. Trabecular Resorption Patterns of Cement-Bone Interlock Regions in Total Knee Replacements. J Orthop Res, 35: 2773-2780, 2017.
- Srinivasan P, Miller MA, Verdonschot N, Mann KA, Janssen D. A modeling approach demonstrating micromechanical changes in the tibial cemented interface due to in vivo service. J Biomech, 56: 19-25, 2017.
- Cyndari KI, Goodheart JR, Miller MA, Oest ME, Damron TA, Mann KA. Peri-implant distribution of polyethylene debris in postmortem-retrieved knee arthroplasties: Can polyethylene debris explain loss of cement-bone interlock in successful total knee arthroplasties? J Arthroplasty, 32(7): 2289-2300, 2017.
- Srinivasan P, Miller MA, Verdonschot N, Mann KA, Janssen D. Strain shielding in trabecular bone at the tibial cement-bone interface. J Mech Beh Biomed Mater, 66: 181-186, 2017.
- Bartlow CM, Oest ME, Mann KA, Zimmerman ND, Butt BB, Damron TA. PTH(1-34) and zoledronic acid have differing longitudinal effects on juvenile mouse femur strength and morphology. J Orthop Res 35(8): 1707-1715, 2017.