Whyne, Cari
Permanent URI for this collectionhttps://hdl.handle.net/1807/69799
Dr. Whyne's work integrates biomechanical analyses with clinical, epidemiological and basic science investigations of musculoskeletal injury and disease, with a final goal of translating findings into the clinic and bedside. Her work is primarily focused in the areas of skeletal metastases and biomechanical stabilization of the spine and lower extremity.
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Item Establishment and Image based evaluation of a New Preclinical Rat Model of Osteoblastic Bone Metastases(Springer, 2022-07-11) Ghomashchi, Soroush; Clement, Allison; Whyne, Cari M; Akens, Margarete KBone remodeling is disrupted in the presence of metastases and can present as osteolytic, osteoblastic or a mixture of the two. Established rat models of osteolytic and mixed metastases have been identified changes in structural and tissue-level properties of bone. The aim of this work was to establish a preclinical rat model of osteoblastic metastases and characterize bone quality changes through image-based evaluation. Female athymic rats (n = 22) were inoculated with human breast cancer cells ZR-75-1 and tumor development tracked over 3-4 months with bioluminescence and in-vivo µCT imaging. Bone tissue-level stereological features were quantified on ex-vivo µCT imaging. Histopathology verified the presence of osteoblastic bone. Bone mineral density distribution was assessed via backscattered electron microscopy. Newly formed osteoblastic bone was associated with reduced mineral content and increased heterogeneity leading to an overall degraded bone quality. Characterizing changes in osteoblastic bone properties is relevant to pre-clinical therapeutic testing and treatment planning.Item Diffusion-Tensor Imaging Versus Digitization in Reconstructing the Masseter Architecture(2018) Falcinelli, Cristina; Li, Zhi; Lam, Wilfred W; Stanisz, Greg J; Agur, Anne M; Whyne, Cari MAccurate characterization of the craniomaxillofacial (CMF) skeleton using finite element (FE) modeling requires representation of complex geometries, heterogeneous material distributions, and physiological loading. Musculature in CMF FE models are often modeled with simple link elements that do not account for fiber bundles (FBs) and their differential activation. Magnetic resonance (MR) diffusion-tensor imaging (DTI) enables reconstruction of the three-dimensional (3D) FB arrangement within a muscle. However, 3D quantitative validation of DTI-generated FBs is limited. This study compares 3D FB arrangement in terms of pennation angle (PA) and fiber bundle length (FBL) generated through DTI in a human masseter to manual digitization. CT, MR-proton density, and MR-DTI images were acquired from a single cadaveric specimen. Bone and masseter surfaces were reconstructed from CT and MR-proton density images, respectively. PA and FBL were estimated from FBs reconstructed from MR-DTI images using a streamline tracking (STT) algorithm (n = 193) and FBs identified through manual digitization (n = 181) and compared using the Mann-Whitney test. DTI-derived PAs did not differ from the digitized data (p = 0.411), suggesting that MR-DTI can be used to simulate FB orientation and the directionality of transmitted forces. Conversely, a significant difference was observed in FBL (p < 0.01) which may have resulted due to the tractography stopping criterion leading to early tract termination and greater length variability. Overall, this study demonstrated that DTI can yield muscle FB orientation data suitable to representative directionality of physiologic muscle loading in patient-specific CMF FE modeling.Item The Impact of an Open-Book Pelvic Ring Injury on Bone Strain: Validation of a Finite Element Model and Analysis Within the Gait Cycle(2021) Salo, Zoryana; Kreder, Hans; Whyne, Cari MarisaThe threshold for surgical stabilization for an open-book pelvic fracture is not well defined. The purpose of this research was to validate the biomechanical behavior of a specimen-specific pelvic finite element (FE) model with an open-book fracture with the biomechanical behavior of a cadaveric pelvis in double leg stance configuration under physiologic loading, and to utilize the validated model to compare open book versus intact strain patterns during gait. A cadaveric pelvis was experimentally tested under compressive loading in double leg stance, intact, and with a simulated open-book fracture. An intact FE model of this specimen was reanalyzed with an equivalent simulated open-book fracture. Comparison of the FE generated and experimentally measured strains yielded an R2 value of 0.92 for the open-book fracture configuration. Strain patterns in the intact and fractured models were compared throughout the gait cycle. In double leg stance and heel-strike/heel-off models, tensile strains decreased, especially in the pubic ramus contralateral to the injury, and compressive strains increased in the sacroiliac region of the injured side. In the midstance/midswing gait configuration, higher tensile and compressive FE strains were observed on the midstance side of the fractured versus intact model and decreased along the superior and inferior pubic rami and ischium, with midswing side strains reduced almost to zero in the fractured model. Identified in silico patterns align with clinical understanding of open-book fracture pathology suggesting future potential of FE models to quantify instability and optimize fixation strategies.Item Validating 3D face morphing towards improving pre-operative planning in facial reconstruction surgery(Taylor and Francis, 2021-01-22) Fishman, Z.; Liu, Jerry; Pope, Joshua; Fialkov, J.A.; Whyne, C.M.Pre-traumatic/pathologic 3D facial imaging is rarely available to guide craniofacial reconstruction. This study aims to independently validate the regional accuracy of a 3D morphable model to estimate face shapes from 2D photographs for craniofacial surgical planning. 3D shape estimates were generated using the Basel Face Model (BFM 2017) from 2D photographs of 100 multi-racial subjects in the Binghamton University 3D Facial Expression database. Accuracy was evaluated by the per-vertex Euclidean distance between the shape estimate and the true 3D scan within defined facial regions. The 3D estimates’ average RMS distance error across all facial regions was 2.68 ± 0.97 mm, based on photos analysed with 10,000 iterations. The eyes, cheek, chin, forehead and mouth regions fit within ~2.5 mm from the true face shape, representing only marginal perceptible error. The nose and temple regions had lower accuracy (~3.1 mm) for all subjects. Significant differences in the nose region were dependent on race (Caucasian: 2.4 mm, East-Asian: 4.8 mm) and sex (Male: 2.5 mm, Female: 3.6 mm). On average, 3D face shape estimates using the BFM yielded clinically acceptable accuracy sufficient for use in planning to guide several craniofacial reconstruction regions. However, in individual cases, considerable errors exceeded clinical limits.Item A two phase regulation of bone regeneration: IL-17F mediates osteoblastogenesis via C/EBP-β in vitro(2018-11) Wang, Yufa; Kim, Jieun; Chan, Andrea; Whyne, Cari; Nam, DianeT lymphocytes and pro-inflammatory cytokines, specifically interleukin-17F (IL-17F) have been identified as important regulators in bone regeneration during fracture repair. To better understand the molecular mechanisms of IL-17F-mediated osteoblastogenesis, a mouse pre-osteoblast cell line (MC3T3-E1) was utilized to characterize the intracellular signal transduction of IL-17F. Comparisons to the established canonical Wnt signaling pathway were made using Wnt3a ligand. Our results demonstrated greater bone marker gene expression in IL-17F-treated cells, compared to cells treated with Wnt3a. Western blot analysis confirmed degradation of β-catenin and up-regulation of two key proteins in osteoblast differentiation, Runx2 and C/EBP-β, in response to IL-17F treatment. RNA silencing of IL-17F receptors, IL-17Ra and IL-17Rc via siRNA transfection resulted in decreased expression of Act2, Runx2, and C/EBP-β, demonstrating the direct ligand-receptor interaction between IL-17F and IL-17Ra/c as an activator of osteoblastogenesis. Our findings suggest that IL-17F promotes osteoblast differentiation independent of the canonical Wnt pathway and β-catenin signaling, presenting new insights on modulating the adaptive immune response in the inflammatory phase, temporally distinct from the reparative and remodeling phases of fracture healing.Item Forehead Flap Templates for Nasal Reconstruction Digitally Developed From 2D and 3D Images(Lippincott, Williams & Wilkins, 2021-08) Fishman, Zachary; Whyne, Cari M.; Fialkov, Jeffery A.The forehead flap is the gold standard procedure for nasal reconstruction to address a partial or complete rhinectomy. Traditionally, the 3D nasal defect is manually templated intra-operatively to design the 2D flap shape on intact morphology. In this clinical study, digital pre-operative planning is used to template with computer-assisted design and manufacturing (CAD-CAM). Pre-operative digital templates were implemented for 3 representative patients (1 in supplementary material). This includes designs for a hemi-rhinectomy case from 3D mirroring, a partial total rhinectomy case generated from a 3D scan, and a total rhinectomy case generated from a 3D morphable model based on a pre-pathology 2D photo. Digital unwrapping flattened the patient’s 3D nasal geometry designs to 2D skin flap shapes. Finally, the 2D designs were printed as traceable intra-operative templates at a 1:1 scale. This clinical study demonstrates the application of digital 3D preoperative templating to improve workflow for nasal reconstruction.Item The impact of metastasis on the mineral phase of vertebral bone tissue(Elsevier, 2017-05) Burke, Mikhail; Atkins, Ayelet; Kiss, Alex; Akens, Margarete; Yee, Albert; Whyne, CariThe negative impact of metastases on the mechanical performance of vertebral bone is often attributed to reduced bone density and/or compromised architecture. However limited characterization has been done on the impact of metastasis on the mineralization of bone tissue and resulting changes in material behaviour. This study aimed to evaluate the impact of metastasis on micro and nano scale characteristics of the mineral phase of bone, specifically mineral crystal growth, homogeneity of mineralization and changes in intrinsic material properties. Female athymic rats were inoculated with HeLa or Ace-1 cancer cells lines producing osteolytic or mixed (osteolytic & osteoblastic) metastases respectively (N=17 per group). A maximum of 21 days was allowed between inoculation and sacrifice of inoculated rats and healthy age-matched uninoculated controls (N=11). X-ray diffraction was used to assess average crystal size in crushed L1-L3 vertebrae; backscatter electron microscopy and nanoindentation were utilized to evaluate modifications in bone mineral density distribution and material behaviour (tissue hardness and modulus) in sagittal-sectioned, embedded and polished L5 vertebrae. HeLa inoculated samples showed reduced mineral crystal width compared to healthy controls. While both types of metastatic involvement reduced tissue mineral content, pathological osteoblastic bone, specific to Ace-1 inoculated samples, significantly decreased tissue mineral homogeneity, whereas osteolytic bone from HeLa samples saw a slight increase in homogeneity. The modulus and hardness of pathological osteoblastic bone was diminished compared to all other bone. Elucidating changes in material behaviour and mineralization of bone tissue is key to defining bone quality in the presence of metastatic involvement.Item Structural biomechanics of the craniomaxillofacial skeleton under maximal masticatory loading: Inferences and critical analysis based on a validated computational model(Elsevier, 2017-06) Pakdel, Amir R; Whyne, Cari M; Fialkov, Jeffrey AThe trend towards optimizing stabilization of the craniomaxillofacial skeleton (CMFS) with the minimum amount of fixation required to achieve union, and away from maximizing rigidity, requires a quantitative understanding of craniomaxillofacial biomechanics. This study uses computational modeling to quantify the structural biomechanics of the CMFS under maximal physiologic masticatory loading.Item Collagen fibril organization within rat vertebral bone modified with metastatic involvement(Elsevier, 2017-08) Burke, Mikhail; Golaraei, Ahmad; Atkins, Ayelet; Akens, Margarete; Barzda, Virginijus; Whyne, CariMetastatic involvement diminishes the mechanical integrity of vertebral bone, however its specific impact on the structural characteristics of a primary constituent of bone tissue, the collagen-I fibril matrix, has not been adequately characterized. Female athymic rats were inoculated with HeLa or Ace-1 cancer cells lines producing osteolytic or mixed (osteolytic & osteoblastic) metastases respectively. A maximum of 21days was allowed between inoculation and rat sacrifice for vertebrae extraction. Linear polarization-in, polarization-out (PIPO) second harmonic generation (SHG) and transmission electron microscopy (TEM) imaging was utilized to assess the impact of metastatic involvement on collagen fibril organization. Increased observations of deviations in the typical plywood motif or a parallel packing structure and an increased average measured susceptibility ratio (related to relative degree of in-plane vs. out-plane fibrils in the analyzed tissue area) in bone adjacent to metastatic involvement was indicative of change in fibrilar organization compared to healthy controls. In particular, collagen-I fibrils in tumour-induced osteoblastic bone growth showed no adherence to the plywood motif or parallel packing structure seen in healthy lamellar bone, exhibiting a much higher susceptibility ratio and degree of fibril disorder. Negative correlations were established between measured susceptibility ratios and the hardness and modulus of metastatic bone tissue assessed in a previous study. Characterizing modifications in tissue level properties is key in defining bone quality in the presence of metastatic disease and their potential impact on material behaviour.Item Analysis of pelvic strain in different gait configurations in a validated cohort of computed tomography based finite element models(2017-11-07) Salo, Zoryana; Beek, Maarten; Wright, David; Maloul, Asmaa; Whyne, Cari MarisaThe pelvis functions to transmit upper body loads to the lower limbs and is critical in human locomotion. Semi-automated, landmark-based finite element (FE) morphing and mapping techniques eliminate the need for segmentation and have shown to accelerate the generation of multiple specimen-specific pelvic FE models to enable the study of pelvic mechanical behaviour. The purpose of this research was to produce an experimentally validated cohort of specimen-specific FE models of the human pelvis and to use this cohort to analyze pelvic strain patterns during gait. Using an initially segmented specimen-specific pelvic FE model asa source model, four more specimen-specific pelvic FE models were generated from target clinical CT scans using landmark-based morphing and mapping techniques. FE strains from the five models were compared to the experimental strains obtained from cadaveric testing via linear regression analysis, (R2 values ranging from 0.70 to 0.93). Inter-specimen variability in FE strain distributions was seen among the five specimen-specific pelvic FE models. The validated cohort of specimen-specific pelvic FE models was utilized to examine pelvic strains at different phases of the gait cycle. Each validated specimen-specific FE model was reconfigured into gait cycle phases representing heel-strike/heel-off and midstance/midswing. No significant difference was found in the double-leg stance and heel-strike/heel-off models (p=0.40). A trend was observed between double-leg stance and midstance/midswing models (p=0.07), and a significant difference was found between heel-strike/heel-off models and midstance/midswing models (p=0.02). Significant differences were also found in comparing right vs. left models (heel-strike/heel-off p=0.14, midstance/midswing p=0.04).Item Determination of 3D PSFs from computed tomography reconstructed x-ray images of spherical objects and the effects of sphere radii(2019-11) Robert, Normand; Mainprize, James G; Whyne, CariPurpose: A method was developed to obtain three dimensional (3D) point spread functions (PSFs) of reconstructed x-ray volumetric images using spheres of known diameters. The algorithm consists of a sphere localization step using template matching applied to the entire volume. Richardson Lucy (RL) deconvolution is used atypically to determine the PSF from the reconstructed x-ray image and a model of the sphere. The resulting PSF is arbitrary i.e., there are no assumptions of separability or symmetry. Oversampling is not used, and sample spacing matches the image. The effect of sphere radius on PSF estimate reproducibility is investigated. Methods: Phantoms were constructed by suspending 5 polytetrafluoroethylene (PTFE) spheres having known radii equal to 4.77, 7.95, 9.52, 12.68 and 19.53 mm in an agar solution. The phantom included a 25 µm steel wire to calculate a line spread function (LSF). The phantom was imaged and reconstructed with a Medtronic surgical O-Arm 23 times and a Toshiba Aquilion One CT 20 times. A sharp reconstruction kernel exhibiting a non-monotonic PSF was used with the Toshiba CT. PSFs and LSFs were computed for all of the images and repeated estimates were used to compute mean and standard deviation values for every point of the PSFs and LSFs. The PSFs from spheres were converted to LSFs and compared to the wire LSF. Results: The standard deviations of the PSF estimates exhibit a decreasing trend as the sphere radius is increased. The PSF from the smallest 4.77 mm sphere is the least reproducible. The normalized root mean square difference between the mean LSF derived from the 4.77 mm radius sphere and the mean wire LSF is 2.0% for the O-arm and 1.2% for the CT. Conclusion: RL deconvolution provides a method to estimate generalized (no separability or other simplifying assumptions) 3D PSFs from spheres. X-ray noise in images acquired with typical clinical protocols cause noticeable variations in PSF estimates which can be mitigated by selecting larger spheres and combining PSF estimates from different images.Item Elevated Microdamage Spatially Correlates with Stress in Metastatic Vertebrae(Springer Nature, 2019-04) Atkins, Ayelet; Burke, Mikhail; Samiezadeh, Saeid; Akens, Margarete K; Hardisty, Michael; Whyne, Cari MMetastasis of cancer to the spine impacts bone quality. This study aims to characterize vertebral microdamage secondary to metastatic disease considering the pattern of damage and its relationship to stress and strain under load. Osteolytic and mixed osteolytic/osteoblastic vertebral metastases were produced in athymic rats via HeLa cervical or canine Ace-1 prostate cancer cell inoculation, respectively. After 21 days, excised motion segments (T12-L2) were µCT scanned, stained with BaSO4 and re-imaged. T13-L2 motion segments were loaded in axial compression to induce microdamage, re-stained and re-imaged. L1 (loaded) and T12 (unloaded) vertebrae were fixed, sample blocks cut, polished and BSE imaged. µFE models were generated of all L1 vertebrae with displacement boundary conditions applied based on the loaded µCT images. µCT stereological analysis, BSE analysis and µFE derived von Mises stress and principal strains were quantitatively compared (ANOVA), spatial correlations determined and patterns of microdamage assessed qualitatively. BaSO4 identified microdamage was found to be spatially correlated with regions of high stress in µFEA. Load-induced microdamage was shown to be elevated in the presence of osteolytic and mixed metastatic disease, with diffuse, crossed hatched areas of microdamage present in addition to linear microdamage and microfractures in metastatic tissue, suggesting diminished bone quality.Item Modeling and measuring average nasal asymmetry by dorsum midline and nose tip lateral deviation(Elsevier, 2021-04) Fishman, Z; Whyne, C M; Hope, A; Fialkov, J AIn rhinoplasty and nasal reconstruction, achieving symmetry is critical for optimal patient outcomes and reducing re-operation rates. Assessing nasal asymmetry is challenging, both pre- and intra-operatively, if based on only a surgeons' visual perception to assess and adjust the small distances important to cosmesis (<2-3 mm). To measure nasal symmetry, we first developed an algorithm to analyze lateral nasal deviation on facial three-dimensional (3D) scans captured by external surface scanning. In this, nasal deviation is measured by first registering a 3D facial scan to orthogonal axes in order to remove tilt. The lateral position of the nasal midline is then found across transverse planes along the dorsum and nasal tip regions by probing midpoints 1 and 2 mm back from the local maximum projection. The nasal deviation measurement algorithm was validated on a simulated asymmetrical nose model with known nasal deviation. Simulated deviations were applied to the symmetrical average nose using an exponential twist away from the face, with control of the maximum deviation and degree of curvature. Modeled deviations were evaluated with the algorithm at clinically negligible (0.02-0.06 mm) average differences and for small lateral deviations (1-5 mm). Nasal deviation using the algorithms was then measured for the 100 multi-ethnic subjects in the Binghamton University 3D Facial Expression database. Average values for maximum lateral deviation, deviation across the whole nose, and deviation at the nose tip were measured to provide context to deviation measurements in surgical planning. This research presents a new nasal assessment tool that can be useful in improving symmetry in rhinoplasty and reconstruction.Item Biomechanical Properties of Metastatically Involved Osteolytic Bone(Springer Nature, 2020-12) Whyne, Cari M; Ferguson, Dallis; Clement, Allison; Rangrez, Mohammedayaz; Hardisty, MichaelSkeletal metastasis involves the uncoupling of physiologic bone remodeling resulting in abnormal bone turnover and radical changes in bony architecture, density, and quality. Bone strength assessment and fracture risk prediction are critical in clinical treatment decision-making. This review focuses on bone tissue and structural mechanisms altered by osteolytic metastasis and the resulting changes to its material and mechanical behavior.Item Influence of pelvic shape on strain patterns: A computational analysis using finite element mesh morphing techniques(Elsevier, 2021-02) Salo, Zoryana; Kreder, Hans; Whyne, Cari MarisaThe pelvis functions to transmit upper body loads to the lower limbs and is critical in human locomotion. Semi-automated, finite element (FE) morphing techniques eliminate the need for segmentation and have shown to accelerate the generation of multiple specimen-specific pelvic FE models to enable the study of pelvic mechanical behaviour. The purpose of this research was to produce simulated human pelvic FE models representing android, gynecoid, anthropoid and platypelloid morphologies and to isolate differences in strain patterns due to anatomic shape under physiologic loading. Using five initially generated specimen-specific FE models, each specimen-specific FE model was reconfigured into three different morphologies using FE mesh morphing techniques. Significantly different strains were found comparing the gynecoid (classical female pelvis') to the android ('true male pelvis') models (p = 0.040), with strains twice as high in the superior pubic rami. No significant differences were seen in comparing overall strains between the other pelvic shapes (p = 0.61-0.126). The highest strain regions in all models were found in the supra-acetabular regions, with high strains also found in the regions of the superior pubic rami, the greater sciatic notch and sacral regions about the L5 vertebrae. Quantifying the contributions of shape to strain in the pelvis may increase the understanding of sex and patient-specific differences in fracture risk and motivate the consideration of treatment strategies that account for anatomic pelvic differences.Item Seglearn: A Python Package for Learning Sequences and Time Series(JMLR, 2018-11) Burns, David M.; Whyne, Cari M.seglearn is an open-source Python package for performing machine learning on time series or sequences. The implementation provides a flexible pipeline for tackling classification, regression, and forecasting problems with multivariate sequence and contextual data. Sequences and series may be learned directly with deep learning models or via feature representation with classical machine learning estimators. This package is compatible with scikit-learn and is listed under scikit-learn ”Related Projects”. The package depends on numpy, scipy, and scikit-learn. seglearn is distributed under the BSD 3-Clause License. Documentation includes a detailed API description, user guide, and examples. Unit tests provide a high degree of code coverage. Source code and documentation can be downloaded from https://github.com/dmbee/seglearn.Item Adherence Tracking With Smart Watches for Shoulder Physiotherapy in Rotator Cuff Pathology: Protocol for a Longitudinal Cohort Study(JMIR Publications, 2020-07-05) Burns, David; Razmjou, Helen; Shaw, James; Richards, Robin; McLachlin, Stewart; Hardisty, Michael; Henry, Patrick; Whyne, CariBackground: Physiotherapy is essential for the successful rehabilitation of common shoulder injuries and following shoulder surgery. Patients may receive some training and supervision for shoulder physiotherapy through private pay or private insurance, but they are typically responsible for performing most of their physiotherapy independently at home. It is unknown how often patients perform their home exercises and if these exercises are performed correctly without supervision. There are no established tools for measuring this. It is, therefore, unclear if the full benefit of shoulder physiotherapy treatments is being realized. Objective: The proposed research will (1) validate a smartwatch and machine learning (ML) approach for evaluating adherence to shoulder exercise participation and technique in a clinical patient population with rotator cuff pathology; (2) quantify the rate of home physiotherapy adherence, determine the effects of adherence on recovery, and identify barriers to successful adherence; and (3) develop and pilot test an ethically conscious adherence-driven rehabilitation program that individualizes patient care based on their capacity to effectively participate in their home physiotherapy. Methods: This research will be conducted in 2 phases. The first phase is a prospective longitudinal cohort study, involving 120 patients undergoing physiotherapy for rotator cuff pathology. Patients will be issued a smartwatch that will record 9-axis inertial sensor data while they perform physiotherapy exercises both in the clinic and in the home setting. The data collected in the clinic under supervision will be used to train and validate our ML algorithms that classify shoulder physiotherapy exercise. The validated algorithms will then be used to assess home physiotherapy adherence from the inertial data collected at home. Validated outcome measures, including the Disabilities of the Arm, Shoulder, and Hand questionnaire; Numeric Pain Rating Scale; range of motion; shoulder strength; and work status, will be collected pretreatment, monthly through treatment, and at a final follow-up of 12 months. We will then relate improvement in patient outcomes to measured physiotherapy adherence and patient baseline variables in univariate and multivariate analyses. The second phase of this research will involve the evaluation of a novel rehabilitation program in a cohort of 20 patients. The program will promote patient physiotherapy engagement via the developed technology and support adherence-driven care decisions. Results: As of December 2019, 71 patients were screened for enrollment in the noninterventional validation phase of this study; 65 patients met the inclusion and exclusion criteria. Of these, 46 patients consented and 19 declined to participate in the study. Only 2 patients de-enrolled from the study and data collection is ongoing for the remaining 44. Conclusions: This study will provide new and important insights into shoulder physiotherapy adherence, the relationship between adherence and recovery, barriers to better adherence, and methods for addressing them. International Registered Report Identifier (IRRID): DERR1-10.2196/17841Item Lithium for Fracture Treatment (LiFT): a double-blind randomised control trial protocol(BMJ, 2020-01-07) Nam, Diane; Balasuberamaniam, Phumeena; Milner, Katrine; Kunz, Monica; Vachhani, Kathak; Kiss, Alex; Whyne, CariIntroduction: Fracture healing can fail in up to 10% of cases despite appropriate treatment. While lithium has been the standard treatment for bipolar disorder, it may also have a significant impact to increase bone healing in patients with long bone fractures. To translate this knowledge into clinical practice, a randomised clinical trial (RCT) is proposed. Methods and analysis: A multicentre double blind, placebo-controlled RCT is proposed to evaluate the efficacy of lithium to increase the rate and predictability of long bone fracture healing in healthy adults compared to lactose placebo treatment. 160 healthy individuals from 18 to 55 years of age presenting with shaft fractures of the femur, tibia/fibula, humerus or clavicle will be eligible. Fractures will be randomised to placebo (lactose) or treatment (300 mg lithium carbonate) group within 2 weeks of the injury. The primary outcome measure will be radiographic union defined as visible callus bridging on three of the four cortices at the fracture site using a validated radiographic union score. Secondary outcome measures will include functional assessment and pain scoring. Ethics and dissemination: Participant confidentiality will be maintained with publication of results. Research Ethics Board Approval: Sunnybrook Research Institute (REB # 356–2016). Health Canada Approval (HC6-24-C201560). Results of the main trial and secondary endpoints will be submitted for publication in a peer-reviewed journal and presented at conferences. Trial registration number: NCT02999022.