Publications by authors named "Mathias P G Bostrom"

51 Publications

Ceramic composite with gentamicin decreases persistent infection and increases bone formation in a rat model of debrided osteomyelitis.

J Bone Jt Infect 2021 20;6(7):283-293. Epub 2021 Jul 20.

Department of Orthopaedic Surgery, Hospital for Special Surgery, New York, NY 10021, USA.

: Current methods of managing osteomyelitic voids after debridement are inadequate and result in significant morbidity to patients. Synthetic ceramic void fillers are appropriate for non-infected bone defects but serve as a nidus of re-infection in osteomyelitis after debridement. CERAMENT G (CG) is an injectable ceramic bone void filler which contains gentamicin and is currently being evaluated for use in osteomyelitic environments after debridement due to its theoretical ability to serve as a scaffold for healing while eliminating residual bacteria after debridement through the elution of antibiotics. The goal of this study was to evaluate (1) the rate of persistent infection and (2) new bone growth of a debrided osteomyelitic defect in a rat model which has been treated with either gentamicin-impregnated ceramic cement (CERAMENT G) or the same void filler without antibiotics (CERAMENT, CBVF). : Osteomyelitis was generated in the proximal tibia of Sprague Dawley rats, subsequently debrided, and the defect filled with either (1) CG ( ), (2) CBVF ( ), or (3) nothing ( ). Each group was euthanized after 6 weeks. Infection was detected through bacterial culture and histology. Bone growth was quantified using microCT. : Infection was not detected in defects treated with CG as compared with 35 % of defects ( ) treated with CBVF and 50 % ( ) of empty defects ( ). Bone volume in the defect of CG-treated rats was greater than the CBVF (0.21 vs. 0.17, ) and empty groups (0.21 vs. 0.11, ) at 6 weeks after implantation. : Ceramic void filler with gentamicin (CERAMENT G) decreased the rate of persistent infection and increased new bone growth as compared to the same void filler without antibiotics (CERAMENT) and an empty defect in a rat model of debrided osteomyelitis.
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http://dx.doi.org/10.5194/jbji-6-283-2021DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8320378PMC
July 2021

Changes in opioid discharge prescriptions after primary total hip and total knee arthroplasty affect opioid refill rates and morphine milligram equivalents : an institutional experience of 20,000 patients.

Bone Joint J 2021 07;103-B(7 Supple B):103-110

Department of Orthopedic Surgery, Adult Reconstruction and Joint Replacement, Hospital for Special Surgery, New York, New York, USA.

Aims: Due to the opioid epidemic in the USA, our service progressively decreased the number of opioid tablets prescribed at discharge after primary hip (THA) and knee (TKA) arthroplasty. The goal of this study was to analyze the effect on total morphine milligram equivalents (MMEs) prescribed and post-discharge opioid repeat prescriptions.

Methods: We retrospectively reviewed 19,428 patients undergoing a primary THA or TKA between 1 February 2016 and 31 December 2019. Two reductions in the number of opioid tablets prescribed at discharge were implemented over this time; as such, we analyzed three periods (P1, P2, and P3) with different routine discharge MME (750, 520, and 320 MMEs, respectively). We investigated 90-day refill rates, refill MMEs, and whether discharge MMEs were associated with represcribing in a multivariate model.

Results: A discharge prescription of < 400 MMEs was not a risk factor for opioid represcribing in the entire population (p = 0.772) or in opioid-naïve patients alone (p = 0.272). Procedure type was the most significant risk factor for narcotic represcribing, with unilateral TKA (hazard ratio (HR) = 5.62), bilateral TKA (HR = 6.32), and bilateral unicompartmental knee arthroplasty (UKA) (HR = 5.29) (all p < 0.001) being the highest risk for refills. For these three procedures, there was approximately a 5% to 6% increase in refills from P1 to P3 (p < 0.001); however, there was no significant increase in refill rates after any hip arthroplasty procedures. Total MMEs prescribed were significantly reduced from P1 to P3 (p < 0.001), leading to the equivalent of nearly 500,000 fewer oxycodone 5 mg tablets prescribed.

Conclusion: Decreasing opioids prescribed at discharge led to a statistically significant reduction in total MMEs prescribed. While the represcribing rate did not increase for any hip arthroplasty procedure, the overall refill rates increased by about 5% for most knee arthroplasty procedures. As such, we are now probably prescribing an appropriate amount of opioids at discharge for knee arthroplasty procedure, but further reductions may be possible for hip arthroplasty procedures. Cite this article:  2021;103-B(7 Supple B):103-110.
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http://dx.doi.org/10.1302/0301-620X.103B7.BJJ-2020-2392.R1DOI Listing
July 2021

Inhibition of PAD4 mediated neutrophil extracellular traps prevents fibrotic osseointegration failure in a tibial implant murine model : an animal study.

Bone Joint J 2021 Jul;103-B(7 Supple B):135-144

Arthroplasty Research Laboratory, Research Institute, Hospital for Special Surgery, New York, New York, USA.

Aims: Aseptic loosening is a leading cause of uncemented arthroplasty failure, often accompanied by fibrotic tissue at the bone-implant interface. A biological target, neutrophil extracellular traps (NETs), was investigated as a crucial connection between the innate immune system's response to injury, fibrotic tissue development, and proper bone healing. Prevalence of NETs in peri-implant fibrotic tissue from aseptic loosening patients was assessed. A murine model of osseointegration failure was used to test the hypothesis that inhibition (through mice that display defects in peptidyl arginine deiminase 4 (PAD4), an essential protein required for NETs) or resolution (via DNase 1 treatment, an enzyme that degrades the cytotoxic DNA matrix) of NETs can prevent osseointegration failure and formation of peri-implant fibrotic tissue.

Methods: Patient peri-implant fibrotic tissue was analyzed for NETs biomarkers. To enhance osseointegration in loose implant conditions, an innate immune system pathway (NETs) was either inhibited ( mice) or resolved with a pharmacological agent (DNase 1) in a murine model of osseointegration failure.

Results: NETs biomarkers were identified in peri-implant fibrotic tissue collected from aseptic loosening patients and at the bone-implant interface in a murine model of osseointegration failure. Inhibition ( ) or resolution (DNase 1) of NETs improved osseointegration and reduced fibrotic tissue despite loose implant conditions in mice.

Conclusion: This study identifies a biological target (NETs) for potential noninvasive treatments of aseptic loosening by discovering a novel connection between the innate immune system and post-injury bone remodelling caused by implant loosening. By inhibiting or resolving NETs in an osseointegration failure murine model, fibrotic tissue encapsulation around an implant is reduced and osseointegration is enhanced, despite loose implant conditions. Cite this article:  2021;103-B(7 Supple B):135-144.
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http://dx.doi.org/10.1302/0301-620X.103B7.BJJ-2020-2483.R1DOI Listing
July 2021

Analysis of the Basic Science Questions on the Orthopaedic In-Training Examination From 2014 to 2019.

J Am Acad Orthop Surg 2021 May 10. Epub 2021 May 10.

From the Hospital for Special Surgery, New York, NY.

Introduction: The Orthopaedic In-Training Examination (OITE), produced by the American Academy of Orthopaedic Surgeons (AAOS), plays an important role in the educational mission of orthopaedic residency programs nationwide. An up-to-date understanding of this examination is critical for programs to develop an appropriate curriculum and for individuals to identify learning resources. This study presents an updated analysis of the basic science section of the OITE from 2014 to 2019.

Methods: All questions from the OITE from 2014 to 2019 were reviewed. Each question from the basic science section was categorized by topic and taxonomy. The use of radiographic images or other clinical media was recorded. The reference section was analyzed for bibliometric factors. Pearson chi-square tests were used as appropriate for statistical comparison.

Results: In total, 185 of 1,600 questions in the basic science section were used over the 6-year study period (11.6%). The proportion of basic science questions ranged from 10.7% to 12.0% from year to year. The most frequently tested topics were cellular and molecular biology (23.8%), physiology/pathophysiology (16.8%), and pharmacology (10.8%). There was an increase in the number of biostatistics questions from 2017 to 2019 compared with the number from 2014 to 2016 (P = 0.02). The most common taxonomic category was knowledge recall (89.7%). A total of 383 references were cited from 122 sources. The 3 most common sources accounting for 44.4% of all citations were produced by the AAOS.

Discussion: The basic science section of the OITE accounts for approximately 11% of all questions, with the most common taxonomy being knowledge recall (89.7%). Recent tests have emphasized biostatistics, highlighting the importance of incorporating biostatistics into residency education. Reference materials produced by the AAOS were highly cited in this section.
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http://dx.doi.org/10.5435/JAAOS-D-20-00862DOI Listing
May 2021

The AAHKS Best Podium Presentation Research Award: Comparing the Efficacy of Irrigation Solutions on Staphylococcal Biofilm Formed on Arthroplasty Surfaces.

J Arthroplasty 2021 07 16;36(7S):S26-S32. Epub 2021 Feb 16.

Hospital for Special Surgery, Adult Reconstruction & Joint Replacement, NY.

Background: A diverse array of antibacterial solutions is utilized by orthopedic surgeons in an attempt to disperse bacterial biofilm. Few studies compare these agents against biofilm grown on clinically relevant orthopedic biomaterials, such as plastic, acrylic cement, and porous titanium.

Methods: MSSA biofilm was grown on plastic 48-well plates, polymethylmethacrylate cement beads and porous Ti-6Al-4V acetabular screw caps. Antibacterial solutions were tested according to manufacturer guidance and included: isotonic saline, vancomycin (1 mg/mL), polymyxin-bacitracin (500,000 U/L-50,000 U/L), povidone-iodine 0.3%, povidone-iodine 10%, a 1:1 combination of povidone-iodine 10% & 4% hydrogen peroxide, polyhexamethylene biguanide (PHMB) and betaine 0.04%, a commercial solution containing chlorhexidine gluconate (CHG) 0.05%, and a commercial solution containing benzalkonium chloride and ethanol. Twenty four and 72-hour biofilms were exposed to solutions for 3 minutes to reproduce intraoperative conditions. Solution efficacy was measured through sonication of treated surfaces followed by counting colony forming units and validated with a resazurin assay to assess cell viability. Experiments were performed in triplicate and repeated at least once. A three-fold log reduction in CFU counts versus controls was considered as a measure of solution efficacy.

Results: Saline, vancomycin and polymyxin-bacitracin were ineffective compared to other solutions against planktonic MSSA. Povidone-iodine 10% and a 1:1 solution of povidone-iodine 10% and 4% hydrogen peroxide were the only effective solutions against biofilm across all three surfaces and time points.

Conclusion: Commercial antibacterial solutions vary significantly in their efficacy against MSSA biofilm. Efficacy globally decreased as biofilm maturity increased. Increased solution cost did not confer increased efficacy.
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http://dx.doi.org/10.1016/j.arth.2021.02.033DOI Listing
July 2021

The Role of Electronic Learning in Orthopaedic Graduate Medical Training: A Consensus From Leaders in Orthopaedic Training Programs.

J Am Acad Orthop Surg 2021 04;29(8):317-325

From the Hospital for Special Surgery, New York, NY (Bostrom and Berger), the Department of Pediatrics, Children's Mercy Hospital, University of Missouri (Lewis), and Kansas City School of Medicine (Lewis), Kansas City, MO.

The US orthopaedic graduate medical education system is based on long established methods in education, but academic leaders at orthopaedic institutions now have the ability to use electronic learning innovations. Hospital for Special Surgery gathered graduate medical education leaders from orthopaedic training programs around the country and an electronic learning expert to review current orthopaedic residency and fellowship program practices. This group came to consensus with the following points: (1) current training methods do not take full advantage of available technology/innovations, (2) trainees inappropriately use electronic resources in the absence of or in an underdeveloped formal electronic training program, (3) trainees learn at different rates and in different ways requiring individualized plans for optimal content engagement, and (4) formal electronic learning programs better use time dedicated to educating trainees than informal programs. Orthopaedic graduate medical training programs that adopt these points can establish an electronic learning program to complement their traditional education program by (1) guaranteeing online content is standardized and approved, (2) reducing time spent covering standard lecture material and increasing time spent reviewing cases, and (3) engaging students of all learning backgrounds with content in both asynchronous and synchronous formats.
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http://dx.doi.org/10.5435/JAAOS-D-20-00821DOI Listing
April 2021

Systemic osteoprotegerin does not improve peri-implant bone volume or osseointegration in rabbits.

J Orthop Res 2021 Aug 27;39(8):1611-1621. Epub 2020 Oct 27.

Hospital for Special Surgery, New York, New York, USA.

Anti-RANKL (receptor activator of nuclear factor kappa-B ligand) agents function by blocking the differentiation of osteoclasts, thereby proving useful in the clinical management of postmenopausal osteoporosis. The effects of such agents on osseointegration is less well understood. The purpose of the current study was to investigate whether osteoprotegerin (OPG), an osteoclast inhibitor, enhances the known anabolic effects of mechanical loading (VEH) and intermittent PTH (iPTH) using a well-established rabbit model of osseointegration. In the first set of experiments, OPG was administered either alone or combined with iPTH to study its effects on measured bone mass. The second set of experiments was conducted using a higher dosage of OPG (10 mg/kg) to explore its early impact at the cellular and molecular levels. All subjects had mechanical load applied to the implant on one extremity, and no load applied on the contralateral side. In the first set of experiments, OPG alone decreased peri-implant bone mass compared to the mechanical loading group, whereas OPG + iPTH increased peri-implant bone mass compared to the OPG group. In the second set of experiments, high-dose OPG significantly decreased osteoclast number (-74.3%) at 1 week. However, this effect was not sustained as osteoclast number returned to baseline by 2 weeks. These results suggest that systemic administration of OPG does not enhance osseointegration, but rather has a detrimental effect.
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http://dx.doi.org/10.1002/jor.24884DOI Listing
August 2021

Analysis of Hip and Knee Reconstruction Questions on the Orthopedic In-Training Examination.

J Arthroplasty 2021 03 18;36(3):1156-1159. Epub 2020 Sep 18.

Department of Orthopaedic Surgery, Hospital for Special Surgery, New York, NY.

Background: It is vital for orthopedic residents and residency programs to have a current understanding of the materials and resources utilized on the Orthopedic In-Training Examination (OITE) to tailor resident educational curricula accordingly. This study presents an updated analysis of the hip and knee section of the OITE.

Methods: All OITE questions related to hip and knee reconstruction over six examinations between 2014 and 2019 were analyzed for topic, subtopic, taxonomy, imaging modalities, resident performance, and references.

Results: There were 166 hip and knee reconstruction questions of 1600 OITE questions (10.4%) over a six-year period. The most commonly tested topics include mechanical properties of total knee and hip implants (10.8%), instability after THA (10.8%), periprosthetic fracture (10.2%), and prosthetic joint infection (10.2%). A total of 362 references were cited from 68 different sources. The most common sources were JOA, JBJS, JAAOS, and CORR, which were collectively responsible for 68% of all citations. There was an average publication lag of 7.1 years, with 75% of all citations falling within 10 years of the question date. Compared with a prior analysis from 2005 and 2009, there were significantly more complex multistep questions regarding treatment and fewer one-step knowledge recall questions (P = .003). Similarly, recent tests had significantly more questions involving interpretation of radiographs (55%, P < .001) and advanced imaging (9.6%, P < .001), compared with a decade ago.

Conclusions: The OITE continues to evolve over time, incorporating recent literature and topics. The current analysis identifies high-yield topics and resources that can guide resident preparation for the OITE hip and knee section.
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http://dx.doi.org/10.1016/j.arth.2020.09.018DOI Listing
March 2021

Joint Replacements in Individuals With Skeletal Dysplasias: One Institution's Experience and Response to Operative Complications.

J Arthroplasty 2020 08 9;35(8):1993-2001. Epub 2020 Apr 9.

Department of Orthopedic Surgery, Hospital for Special Surgery, New York, New York.

Background: Skeletal dysplasias are a heterogeneous group of >400 genetic disorders characterized by abnormal bone growth. Many individuals experience joint pain and limitation, coming to require joint replacement much earlier than the average-statured population. In addition, prosthesis survival rate is less in the dysplastic population. The purpose of this study is to identify risk factors for surgery and provide recommendations to improve surgical outcomes.

Methods: This a retrospective review of 29 individuals with a skeletal dysplasia who had 64 joint replacements between April 1985 and January 2019 at a single institution. We collected demographics, physical examination, medical history, imaging studies, surgical indication, and complications.

Results: Spondyloepiphyseal dysplasia was the most common skeletal dysplasia (7), followed by pseudoachondroplasia (4) and multiple epiphyseal dysplasia (4). Average age of the cohort was 40.6 years (range 14-64). Hip arthroplasty (34) was the most commonly performed surgery. The majority of arthroplasties (75%) required custom components. Complication rate was 37.3%, most commonly pulmonary embolism (3) and pneumonia (3). Most complications (81.8%) occurred in individuals with either a pre-existing cardiopulmonary comorbidity or lumbar/sacral deformity. Body mass index did not correlate with complication severity (R = -0.042, P = .752) or rate (R = 0.006, P = .963).

Conclusion: Surgical complications are highest in patients with pre-existing cardiopulmonary conditions. Body mass index does not predict complications in this cohort. Preoperative evaluations for individuals with skeletal dysplasias should include comprehensive work-up of spine issues and extraskeletal systems that present an operative risk. Intraoperative protocol should include special consideration for placement on the table, airway maintenance, and spinal cord monitoring in select cases.
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http://dx.doi.org/10.1016/j.arth.2020.04.007DOI Listing
August 2020

Loading modality and age influence teriparatide-induced bone formation in the human femoral neck.

Bone 2020 07 21;136:115373. Epub 2020 Apr 21.

Department of Medicine, Columbia University, 622 West 168th St., New York, NY 10032, USA. Electronic address:

Teriparatide (TPTD) reduces risk of both vertebral and nonvertebral fracture, but increases bone mineral density (BMD) much more at the spine than the hip. TPTD and mechanical loading may have a synergistic anabolic effect on BMD, which may help explain these site-specific differences. Under normal daily activity, the femoral neck (FN) is under bending, placing one side under tension and the other under compression. We sought to further understand the relationship between mechanical loading and TPTD at the hip by investigating the effect of tensile versus compressive loading on TPTD stimulated bone formation indices in the human FN. Thirty-eight patients receiving total hip replacements for osteoarthritis were randomized to receive placebo (PBO) or TPTD for a mean treatment duration of 6 weeks prior to surgery, and double tetracycline labeling was administered to allow assessment of bone formation. The FN was harvested during surgery and analyzed for dynamic bone formation indices in the compressive and tensile regions of the endocortical and periosteal envelopes. Regression models relating outcome measures to patient characteristics including sex, age, body weight, and FN geometry were also analyzed. Overall, bone formation was higher with TPTD versus placebo on the endocortical surface, but not the periosteal surface. The level of bone formation in both TPTD and placebo groups was greater on the tensile endocortical surface and the compressive periosteal surface. There was a trend toward decreased endocortical eroded surface with TPTD in the compressive but not the tensile region. Patient age and sex explained the greatest variability in endocortical bone formation, and patient body mass and sex explained the greatest variability in periosteal bone formation. Our data represent the first dynamic comparison of teriparatide treatment under two loading modalities in human FN samples. Future work could determine whether specific hip loading intervention could amplify the benefits of teriparatide on the hip in clinical settings.
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http://dx.doi.org/10.1016/j.bone.2020.115373DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7263665PMC
July 2020

Correction to: Mechanically Induced Periprosthetic Osteolysis: A Systematic Review.

HSS J 2020 Feb 17;16(1):103. Epub 2019 Dec 17.

4Linköping University, 581 83 Linköping, Sweden.

[This corrects the article DOI: 10.1007/s11420-018-9641-5.].
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http://dx.doi.org/10.1007/s11420-019-09725-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6973800PMC
February 2020

Mechanically Induced Periprosthetic Osteolysis: A Systematic Review.

HSS J 2019 Oct 9;15(3):286-296. Epub 2018 Nov 9.

4Linköping University, 581 83 Linköping, Sweden.

Background: Peri-prosthetic bone loss can result from chemical, biological, and mechanical factors. Mechanical stimulation via fluid pressure and flow at the bone-implant interface may be a significant cause. Evidence supporting mechanically induced osteolysis continues to grow, but there is no synthesis of published clinical and basic science data.

Questions/purposes: We sought to review the literature on two questions: (1) What published evidence supports the concept of mechanically induced osteolysis? (2) What is the proposed mechanism of mechanically induced osteolysis, and does it differ from that of particle-induced osteolysis?

Methods: A systematic review was performed of the PubMed and Web of Science databases. Additional relevant articles were recommended by the senior authors based on their expert opinion. Abstracts were reviewed and the manuscripts pertaining to the study questions were read in full. Studies showing support of mechanically induced osteolysis were quantified and findings summarized.

Results: We identified 49 articles of experimental design supporting the hypothesis that mechanical stimulation of peri-prosthetic bone from fluid pressure and flow can induce osteolysis. While the molecular mechanisms may overlap with those implicated in particle-induced osteolysis, mechanically induced osteolysis appears to be mediated by distinct and parallel pathways.

Conclusions: The role of mechanical stimuli is increasingly recognized in the pathogenesis of peri-prosthetic osteolysis. Current research aims to elucidate the molecular mechanisms to better target therapeutic interventions.
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http://dx.doi.org/10.1007/s11420-018-9641-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6778158PMC
October 2019

Vancomycin-laden calcium phosphate-calcium sulfate composite allows bone formation in a rat infection model.

PLoS One 2019 19;14(9):e0222034. Epub 2019 Sep 19.

Hospital for Special Surgery, New York, New York, United States of America.

Objective: Local antibiotic delivery systems with differing chemical and mechanical properties have been developed to assist in the management of osteomyelitis. We investigated the bone conductive and resorptive capabilities of a calcium phosphate-calcium sulfate (CaP/CaS) composite compared with commercially available polymethylmethacrylate (PMMA). In addition, we compared the in vivo preventative and treatment efficacies of both biomaterials in a proven osteomyelitis model.

Methods: Sixty-four, male Sprague-Dawley rats were inoculated with 10 μl of 1.5 x 108 CFU/ml of Staphylococcus aureus in a surgically drilled defect in the right proximal tibia. Infected animals were randomly allocated into prevention and treatment groups with 32 rats each. In the prevention group, the defect was filled with a plug containing either PMMA or CaP/CaS immediately after the inoculation. In the treatment group, the infected defects were irrigated, debrided, and filled with either a PMMA or CaP/CaS plug. Both CaP/CaS and PMMA were impregnated with 10% weight of vancomycin. Rats were sacrificed 6 weeks after cement insertion. Infection was detected by bacterial culture and histological analysis. Bone formation in the defect was assessed with micro-computed tomography and histology.

Results: No bacteria were detected in any group. Both the prevention and treatment groups using CaP/CaS had significantly more bone volume fraction, bone area, and cartilage area than the PMMA groups.

Conclusions: When loaded with 10% of vancomycin, CaP/CaS and PMMA have the same efficacy for treatment and prevention of osteomyelitis. CaP/CaS enhances bone defect healing through improved bone remodeling in our osteomyelitis rat model.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0222034PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6752756PMC
March 2020

Disruption of the Gut Microbiome Increases the Risk of Periprosthetic Joint Infection in Mice.

Clin Orthop Relat Res 2019 Nov;477(11):2588-2598

C. J. Hernandez, X. Yang, G. Ji, Y. Niu, A. S. Sethuraman, J. Koressel, M. Shirley, M. W. Fields, S. Chyou, T. M. Li, F. P. Ross, T. T. Lu, A. V. Carli, M. P. G. Bostrom, Hospital for Special Surgery, New York, NY, USA C. J. Hernandez, M. Luna, Sibley School of Mechanical and Aerospace Engineering, Cornell University, Ithaca, NY, USA C. J. Hernandez, R. L. Callahan, I. L. Brito, Meinig School of Biomedical Engineering, Cornell University, Ithaca, NY, USA.

Background: Periprosthetic joint infection (PJI) is one of the most devastating complications of total joint arthroplasty. Given the mortality and morbidity associated with PJI and the challenges in treating it, there has been increased interest in risk factors that can be modified before surgery. In this study, we used a novel mouse model to consider the role of the gut microbiome as a risk factor for PJI.

Questions/purposes: (1) Does the state of the gut microbiota before surgery influence the likelihood of developing an established infection in a mouse model of PJI? (2) How does the state of the gut microbiota before surgery influence the local and systemic response to the presence of an established infection in a mouse model of PJI?

Methods: Male C57Bl/6 mice were divided into two groups: those with modified microbiome [INCREMENT]microbiome (n = 40) and untreated mice (n = 42). In [INCREMENT]microbiome mice, the gut flora were modified using oral neomycin and ampicillin from 4 weeks to 16 weeks of age. Mice received a titanium tibial implant to mimic a joint implant and a local inoculation of Staphylococcus aureus in the synovial space (10 colony forming units [CFUs]). The proportion of animals developing an established infection in each group was determined by CFU count. The local and systemic response to established infection was determined using CFU counts in surrounding joint tissues, analysis of gait, radiographs, body weight, serum markers of inflammation, and immune cell profiles and was compared with animals that received the inoculation but resisted infection.

Results: A greater proportion of animals with disrupted gut microbiota had infection (29 of 40 [73%]) than did untreated animals (21 of 42 [50%]; odds ratio, 2.63, 95% CI, 1.04-6.61; p = 0.035). The immune response to established infection in mice with altered microbiota was muted; serum amyloid A, a marker of systemic infection in mice, was greater than in mice with disrupted gut microbiota with infection (689 µg/dL; range, 68-2437 µg/dL, p < 0.05); infection associated increases in monocytes and neutrophils in the spleen and local lymph node in untreated mice but not were not observed in mice with disrupted gut microbiota.

Conclusions: The findings from this in vivo mouse model suggest that the gut microbiota may influence susceptibility to PJI.

Clinical Relevance: These preclinical findings support the idea that the state of the gut microbiome before surgery may influence the development of PJI and justify further preclinical and clinical studies to develop appropriate microbiome-based interventions.
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http://dx.doi.org/10.1097/CORR.0000000000000851DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6903863PMC
November 2019

Has Tranexamic Acid in Total Knee Arthroplasty Made Tourniquet Use Obsolete?

HSS J 2018 Oct 15;14(3):338-340. Epub 2018 Aug 15.

Department of Orthopaedic Surgery, Hospital for Special Surgery, 535 East 70th Street, New York, NY 10021 USA.

The application of tranexamic acid (TXA) in total joint arthroplasty has dramatically improved peri-operative blood management. In light of these benefits, a study by Huang et al., "Intravenous and Topical Tranexamic Acid Alone Are Superior to Tourniquet Use for Primary Total Knee Arthroplasty," evaluates the need for continued use of the intra-operative tourniquet, which remains a routine practice with documented benefits and adverse effects. This review evaluates the study's design and critically interprets its findings for clinical practice. Through a prospective, randomized trial, Huang et al. demonstrated that among selected patients undergoing primary total knee arthroplasty, the use of a tourniquet results in no reduction in blood loss beyond that provided by TXA alone. Moreover, the use of TXA without a tourniquet led to improved early clinical outcomes such as reduced post-operative swelling, improved knee range of motion at discharge, and enhanced patient satisfaction. As medicine is practiced in an increasingly value-driven environment, this study provides a useful method for evaluating the utility of commonly used interventions. Its findings highlight the need for future investigations into the optimal administration of TXA in total knee arthroplasty.
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http://dx.doi.org/10.1007/s11420-018-9627-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6148574PMC
October 2018

Vancomycin-Loaded Polymethylmethacrylate Spacers Fail to Eradicate Periprosthetic Joint Infection in a Clinically Representative Mouse Model.

J Bone Joint Surg Am 2018 Jun;100(11):e76

Hospital for Special Surgery, New York, NY.

Background: Periprosthetic joint infection (PJI) remains a devastating complication following total joint arthroplasty. Current animal models of PJI do not effectively recreate the clinical condition and thus provide limited help in understanding why treatments fail. We developed a mouse model of the first-stage surgery of a 2-stage revision for PJI involving a 3-dimensionally printed Ti-6Al-4V implant and a mouse-sized cement spacer that elutes vancomycin.

Methods: Vancomycin was mixed with polymethylmethacrylate (PMMA) cement and inserted into custom-made mouse-sized spacer molds. Twenty C57BL/6 mice received a proximal tibial implant and an intra-articular injection of 3 × 10 colony-forming units of Staphylococcus aureus Xen36. At 2 weeks, 9 mice underwent irrigation and debridement of the leg with revision of the implant to an articulating vancomycin-loaded PMMA spacer. Postoperatively, mice underwent radiography and serum inflammatory-marker measurements. Following euthanasia of the mice at 6 weeks, bone and soft tissues were homogenized to quantify bacteria within periprosthetic tissues. Implants and articulating spacers were either sonicated to quantify adherent bacteria or examined under scanning electron microscopy (SEM) to characterize the biofilm.

Results: Vancomycin-loaded PMMA spacers eluted vancomycin for ≤144 hours and retained antimicrobial activity. Control mice had elevated levels of inflammatory markers, radiographic evidence of septic loosening of the implant, and osseous destruction. Mice treated with a vancomycin-loaded PMMA spacer had significantly lower levels of inflammatory markers (p < 0.01), preserved tibial bone, and no intra-articular purulence. Retrieved vancomycin-loaded spacers exhibited significantly lower bacterial counts compared with implants (p < 0.001). However, bacterial counts in periprosthetic tissue did not significantly differ between the groups. SEM identified S. aureus encased within biofilm on control implants, while vancomycin-loaded spacers contained no bacteria.

Conclusions: This animal model is a clinically representative model of PJI treatment. The results suggest that the antimicrobial effects of PMMA spacers are tightly confined to the articular space and must be utilized in conjunction with thorough tissue debridement and systemic antibiotics.

Clinical Relevance: These data provide what we believe to be the first insight into the effect of antibiotic-loaded cement spacers in a clinically relevant animal model and justify the adjunctive use of intravenous antibiotics when performing a 2-stage revision for PJI.
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http://dx.doi.org/10.2106/JBJS.17.01100DOI Listing
June 2018

Selected Heat-Sensitive Antibiotics Are Not Inactivated During Polymethylmethacrylate Curing and Can Be Used in Cement Spacers for Periprosthetic Joint Infection.

J Arthroplasty 2018 06 1;33(6):1930-1935. Epub 2018 Feb 1.

Hospital for Special Surgery, New York, NY.

Background: Antibiotic use in polymethylmethacrylate (PMMA) spacers has historically been limited to those which are "heat-stable" and thus retain their antimicrobial properties after exposure to the high temperatures which occur during PMMA curing.

Methods: This study examines the requirement of "heat stability" by measuring temperatures of Palacos and Simplex PMMA as they cure inside commercial silicone molds of the distal femur and proximal tibia. Temperature probes attached to thermocouples were placed at various depths inside the molds and temperatures were recorded for 20 minutes after PMMA introduced and a temperature curve for each PMMA product was determined. A "heat-stable" antibiotic, vancomycin, and a "heat-sensitive" antibiotic, ceftazidime, were placed in a programmable thermocycler and exposed to the same profile of PMMA curing temperatures. Antimicrobial activity against Staphylococcus aureus was compared for heat-treated antibiotics vs room temperature controls.

Results: Peak PMMA temperatures were significantly higher in tibial (115.2°C) vs femoral (85.1°C; P < .001) spacers. In the hottest spacers, temperatures exceeded 100°C for 3 minutes. Simplex PMMA produced significantly higher temperatures (P < .05) compared with Palacos. Vancomycin bioactivity did not change against S aureus with heat exposure. Ceftazidime bioactivity did not change when exposed to femoral temperature profiles and was reduced only 2-fold with tibial profiles.

Conclusion: The curing temperatures of PMMA in knee spacers are not high enough or maintained long enough to significantly affect the antimicrobial efficacy of ceftazidime, a known "heat-sensitive" antibiotic. Future studies should investigate if more "heat-sensitive" antibiotics could be used clinically in PMMA spacers.
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http://dx.doi.org/10.1016/j.arth.2018.01.034DOI Listing
June 2018

An in vivo model of a mechanically-induced bone marrow lesion.

J Biomech 2017 11 13;64:258-261. Epub 2017 Oct 13.

Sibley School of Mechanical and Aerospace Engineering, Cornell University, Ithaca, NY, USA; Meinig School of Biomedical Engineering, Cornell University, Ithaca, NY, USA; Hospital for Special Surgery, New York, NY, USA. Electronic address:

Bone marrow lesions (BMLs) are radiologic abnormalities in magnetic resonance images of subchondral bone that are correlated with osteoarthritis. Little is known about the physiologic processes within a BML, although BMLs are associated with mechanical stress, bone tissue microdamage and increased bone remodeling. Here we establish a rabbit model to study the pathophysiology of BMLs. We hypothesized that in vivo loads that generate microdamage in cancellous bone would also create BMLs and increase bone remodeling. In vivo cyclic loading (0.2-2.0 MPa in compression for 10,000 cycles at 2 Hz) was applied to epiphyseal cancellous bone in the distal femurs of New Zealand white rabbits (n=3, right limb loaded, left limb controls experienced surgery but no loading). Magnetic resonance images were collected using short tau inversion recovery (STIR) and T1 weighted sequences at 1 and 2 weeks after surgery/loading and histological analysis of the BML was performed after euthanasia to examine tissue microdamage and remodeling. Loaded limbs displayed BMLs while control limbs showed only a small BML-like signal caused by surgery. Histological analysis of the BML at 2 weeks after loading showed increased tissue microdamage (p=0.03) and bone resorption (p=0.01) as compared to controls. The model described here displays the hallmarks of load-induced BMLs, supporting the use of the model to examine changes in bone during the development, progression and treatment of BMLs.
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http://dx.doi.org/10.1016/j.jbiomech.2017.09.020DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5694366PMC
November 2017

Comparative Assessment of Grit, Conscientiousness, and Self-Control in Applicants Interviewing for Residency Positions and Current Orthopaedic Surgery Residents.

J Surg Educ 2018 May - Jun;75(3):557-563. Epub 2017 Sep 28.

Academic Training, Education and Academic Affairs Division, Hospital for Special Surgery, New York, New York. Electronic address:

Objective: The purpose of this study was to quantify grit, conscientiousness, and self-control in orthopaedic residency applicants and current orthopaedic surgery residents. As part of a continual reassessment of the selection process, this study will help to improve this process by assessing the introduction of these non-cognitive assessments. This is the first study to both evaluate and compare the applicants' scores to those of current residents. This introduction will allow selection of not only the current top performers but those who have the wherewithal (read grit) to sustain their efforts throughout their residency.

Design: A cross-sectional study composed of a confidential electronic survey consisting of a 17-item Grit scale, 10-item Self-control scale, and 9-item Conscientiousness scale was completed by medical school applicants and orthopaedic residents.

Setting: Department of Orthopaedic Surgery, Hospital for Special Surgery.

Participants: Fifty-six (100%) medical student applicants (mean age = 27) were invited to participate in our study following a full day of interviews. Forty-five residents (mean age = 31) were asked and 32 (72%) completed the same surveys 4 months later.

Results: There was a significant difference in grit for medical students (M = 4.19, SD = 0.34) and residents (M =3.86, SD = 0.48); t(86) = 3.76, p = 0.000. All grit subscales were also significantly different for medical students versus residents. Medical students (conscientiousness M = 4.60, SD = 0.41; self-control M = 3.51, SD = 0.30) and residents (conscientiousness M = 4.42, SD = 0.53; self-control M = 3.31, SD = 0.73) scored similarly in the conscientiousness t(86) = 1.75, p = 0.084 and self-control scales t(86) = 1.74, p = 0.086. Academic performance indicators such as the USMLE scores and residency ranking were also compared among medical student applicants.

Conclusions: The similar and above average levels of conscientiousness and self-control demonstrate the persevering nature of the individual who elects to pursue an orthopaedic residency program. Although the grit levels were different between medical school student and residents, they were above average for both groups, again demonstrating the type of individual willing to pursue an orthopaedic residency program. This study was the first to demonstrate varying degrees of grit for high-performing students versus residents in a competitive program, which seems to suggest that grit can vary over time. Future studies will investigate the validity of these non-cognitive variables in predicting achievement prospectively in a residency program.
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http://dx.doi.org/10.1016/j.jsurg.2017.09.002DOI Listing
September 2019

Quantification of Peri-Implant Bacterial Load and in Vivo Biofilm Formation in an Innovative, Clinically Representative Mouse Model of Periprosthetic Joint Infection.

J Bone Joint Surg Am 2017 Mar;99(6):e25

1Hospital for Special Surgery, New York, NY 2University of Rochester, Rochester, New York.

Background: Periprosthetic joint infection (PJI) is a devastating complication following total joint arthroplasty. Current animal models of PJI are limited because of a lack of quantitative methods and failure to effectively recreate the periprosthetic space. We therefore developed a murine PJI model involving a 3-dimensionally printed Ti-6Al-4V implant capable of bearing weight and permitting quantitative analysis of periprosthetic bacterial load and evaluation of biofilm.

Methods: Twenty-five 12-week-old C57BL/6 mice received a unilateral proximal tibial implant and intra-articular injection of either 3 × 10 colony forming units (CFUs) of Staphylococcus aureus Xen 36 or saline solution. Postoperatively, mice underwent gait analysis, knee radiographs, and serum inflammatory marker measurements. Following euthanasia at 2 or 6 weeks, bone and soft tissues were homogenized to quantify bacteria within periprosthetic tissues. Implants were either sonicated to quantify adherent bacteria or examined under scanning electron microscopy (SEM) to characterize biofilm.

Results: All mice survived surgery and were not systemically septic. The control mice immediately tolerated weight-bearing and had normal inflammatory markers and radiographic signs of osseointegration. Infected mice had difficulty walking over time, exhibited radiographic findings of septic implant loosening, and had significantly elevated inflammatory markers. Periprosthetic tissues of the infected animals displayed a mean of 4.46 × 10 CFUs of S. aureus at 2 weeks and 2.53 × 10 CFUs at 6 weeks. Viable S. aureus was quantified on retrieved implant surfaces. SEM demonstrated S. aureus cocci in clusters encased within biofilm.

Conclusions: This animal model is, to our knowledge, the most clinically representative PJI replication to date. It is the first that we know of to produce infection through the same method hypothesized to occur clinically, utilize a weight-bearing implant that can osseointegrate, and provide quantitative data on 8 aspects of PJI, including radiographic features, inflammatory markers, and bacterial loads.

Clinical Relevance: This novel animal model is, to our knowledge, the first to provide a load-bearing translational representation of clinical PJI that effectively recreates the periprosthetic space.
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http://dx.doi.org/10.2106/JBJS.16.00815DOI Listing
March 2017

Developing a Clinically Representative Model of Periprosthetic Joint Infection.

J Bone Joint Surg Am 2016 Oct;98(19):1666-1676

Hospital for Special Surgery, New York, NY

➤The poor treatment outcomes for periprosthetic joint infection (PJI) reflect the limited understanding that currently exists regarding the pathogenesis of this devastating clinical problem.➤Current animal models of PJI are limited in their translational nature primarily because of their inability to recreate the periprosthetic environment.➤A greater mechanistic understanding of the musculoskeletal and immune systems of small animals, such as mice and rats, provides a more robust platform for modeling and examining the pathogenesis of PJI.➤A clinically representative PJI model must involve an implant that recreates the periprosthetic space and be amenable to methodologies that identify implant biofilm as well as quantify the peri-implant bacterial load.
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http://dx.doi.org/10.2106/JBJS.15.01432DOI Listing
October 2016

Monitoring the Progression of Spontaneous Articular Cartilage Healing with Infrared Spectroscopy.

Cartilage 2015 Jul;6(3):174-84

Department of Bioengineering, Temple University, Philadelphia, PA, USA.

Objective: Evaluation of early compositional changes in healing articular cartilage is critical for understanding tissue repair and for therapeutic decision-making. Fourier transform infrared imaging spectroscopy (FT-IRIS) can be used to assess the molecular composition of harvested repair tissue. Furthermore, use of an infrared fiber-optic probe (IFOP) has the potential for translation to a clinical setting to provide molecular information in situ. In the current study, we determined the feasibility of IFOP assessment of cartilage repair tissue in a rabbit model, and assessed correlations with gold-standard histology.

Design: Bilateral osteochondral defects were generated in mature white New Zealand rabbits, and IFOP data obtained from defect and adjacent regions at 2, 4, 6, 8, 12, and 16 weeks postsurgery. Tissues were assessed histologically using the modified O'Driscoll score, by FT-IRIS, and by partial least squares (PLS) modeling of IFOP spectra.

Results: The FT-IRIS parameters of collagen content, proteoglycan content, and collagen index correlated significantly with modified O'Driscoll score (P = 0.05, 0.002, and 0.02, respectively), indicative of their sensitivity to tissue healing. Repair tissue IFOP spectra were distinguished from normal tissue IFOP spectra in all samples by PLS analysis. However, the PLS model for prediction of histological score had a high prediction error, which was attributed to the spectral information being acquired from the tissue surface only.

Conclusion: The strong correlations between FT-IRIS data and histological score support further development of the IFOP technique for clinical applications, although further studies to optimize data collection from the full sample depths are required.
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http://dx.doi.org/10.1177/1947603515572874DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4481387PMC
July 2015

Intermittent Parathyroid Hormone Enhances Cancellous Osseointegration of a Novel Murine Tibial Implant.

J Bone Joint Surg Am 2015 Jul;97(13):1074-83

Hospital for Special Surgery, 535 East 70th Street, New York, NY 10021. E-mail address for X. Yang:

Background: Long-term fixation of uncemented joint implants requires early mechanical stability and implant osseointegration. To date, osseointegration has been unreliable and remains a major challenge in cementless total knee arthroplasty. We developed a murine model in which an intra-articular proximal tibial titanium implant with a roughened stem can be loaded through the knee joint. Using this model, we tested the hypothesis that intermittent injection of parathyroid hormone (iPTH) would increase proximal tibial cancellous osseointegration.

Methods: Ten-week-old female C57BL/6 mice received a subcutaneous injection of PTH (40 μg/kg/day) or a vehicle (n = 45 per treatment group) five days per week for six weeks, at which time the baseline group was killed (n = 6 per treatment group) and an implant was inserted into the proximal part of the tibiae of the remaining mice. Injections were continued until the animals were killed at one week (n = 7 per treatment group), two weeks (n = 14 per treatment group), or four weeks (n = 17 per treatment group) after implantation. Outcomes included peri-implant bone morphology as analyzed with micro-computed tomography (microCT), osseointegration percentage and bone area fraction as shown with backscattered electron microscopy, cellular composition as demonstrated by immunohistochemical analysis, and pullout strength as measured with mechanical testing.

Results: Preimplantation iPTH increased the epiphyseal bone volume fraction by 31.6%. When the data at post-implantation weeks 1, 2, and 4 were averaged for the iPTH-treated mice, the bone volume fraction was 74.5% higher in the peri-implant region and 168% higher distal to the implant compared with the bone volume fractions in the same regions in the vehicle-treated mice. Additionally, the trabecular number was 84.8% greater in the peri-implant region and 74.3% greater distal to the implant. Metaphyseal osseointegration and bone area fraction were 28.1% and 70.1% higher, respectively, in the iPTH-treated mice than in the vehicle-treated mice, and the maximum implant pullout strength was 30.9% greater. iPTH also increased osteoblast and osteoclast density by 65.2% and 47.0%, respectively, relative to the values in the vehicle group, when the data at post-implantation weeks 1 and 2 were averaged.

Conclusions: iPTH increased osseointegration, cancellous mass, and the strength of the bone-implant interface.

Clinical Relevance: Our murine model is an excellent platform on which to study biological enhancement of cancellous osseointegration.
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http://dx.doi.org/10.2106/JBJS.N.01052DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4574908PMC
July 2015

Tissue-level remodeling simulations of cancellous bone capture effects of in vivo loading in a rabbit model.

J Biomech 2015 Mar 29;48(5):875-82. Epub 2014 Dec 29.

Sibley School of Mechanical & Aerospace Engineering, Cornell University, Ithaca, NY, USA; Hospital for Special Surgery, New York, NY, USA. Electronic address:

The adaptation of cancellous bone to mechanical stimuli occurs throughout normal skeletal growth and aging, as well as in response to surgery, disease and device implantation. Previously we developed an in vivo cancellous loading model in the distal lateral femur of the rabbit. In response to daily in vivo loading for four weeks, bone mass increased, trabeculae thickened and the apparent modulus of the underlying cancellous bone increased. Here, we simulated our prior in vivo rabbit loading experiment using a cell-based tissue remodeling algorithm (Mullender et al., 1994) and compared the results to the in vivo experimental data published previously. Cancellous bone tissue was added or removed from the surface of trabeculae in regions of high and low mechanical stimulus, respectively. To examine the effect of material properties on mechanically regulated adaptation, we implemented both a homogeneous material model and a model where the relative density of tissue was lower for new and surface bone tissue compared to interior tissue. The simulations captured the changes in histomorphometric parameters and mechanical properties measured in the in vivo experiment illustrating the ability of computational simulations to predict the effect of mechanically regulated adaptation on cancellous bone histomorphometry and apparent modulus.
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http://dx.doi.org/10.1016/j.jbiomech.2014.12.011DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4361179PMC
March 2015

The contribution of bone and cartilage to the near-infrared spectrum of osteochondral tissue.

Appl Spectrosc 2014 1;68(10):1168-75. Epub 2014 Oct 1.

Temple University, Department of Bioengineering, College of Engineering, 1947 North 12th Street, Philadelphia, PA 19122 USA.

Near-infrared (NIR) spectroscopy has been used to assess hyaline cartilage quality in human and animal osteochondral tissues. However, due to the lack of NIR signal from bone phosphate and the relatively deep penetration depth of the radiation, the separate contributions of cartilage and bone to the spectral signatures have not been well defined. The objectives of the current study were (1) to improve the understanding of the contributions of bone and cartilage to NIR spectra acquired from osteochondral tissue and (2) to assess the ability of this nondestructive method to predict cartilage thickness and modified Mankin grade of human tibial plateau articular cartilage. Near-infrared spectra were acquired from samples of bovine bone and cartilage with varying thicknesses and from 22 tibial plateaus harvested from patients undergoing knee replacement surgery. The spectra were recorded from regions of the tibial plateaus with varying degrees of degradation, and the cartilage thickness and modified Mankin grade of these regions were assessed histologically. The spectra from bone and cartilage samples of known thicknesses were investigated to identify spectral regions that were distinct for these two tissues. Univariate and multivariate linear regression methods were used to correlate modified Mankin grade and cartilage thickness with NIR spectral changes. The ratio of the NIR absorbances associated with water at 5270 and 7085 cm(-1) was the best differentiator of cartilage and bone spectra. The NIR prediction models for thickness and Mankin grade calculated using partial least squares regression were more accurate than were univariate-based prediction models, with a root mean square errors of cross-validation of 0.42 mm (for thickness) and 1.3 (for modified Mankin grade). We conclude that NIR spectroscopy may be used to simultaneously assess articular cartilage thickness and modified Mankin grade, based in part on differences in spectral contributions from bone and cartilage.
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http://dx.doi.org/10.1366/13-07327DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4235673PMC
May 2015

Emerging ideas: Instability-induced periprosthetic osteolysis is not dependent on the fibrous tissue interface.

Clin Orthop Relat Res 2013 Jun 6;471(6):1758-62. Epub 2013 Mar 6.

Department of Orthopaedic Surgery Adult Reconstruction and Joint Replacement Division, Hospital for Special Surgery, 535 E 70th Street, New York, NY 10021, USA.

Background: Stable initial fixation of a total joint arthroplasty implant is critical to avoid the risk of aseptic loosening and premature clinical failure. With implant motion, a fibrous tissue layer forms at the bone-implant interface, leading to implant migration and periprosthetic osteolysis. At the time of implant revision surgery, proresorptive signaling cytokines are expressed in the periimplant fibrous membrane. However, the exact role of this fibrous tissue in causing periprosthetic osteolysis attributable to instability remains unknown.

Questions/hypotheses: We propose an alternative mechanism of periprosthetic osteolysis independent of the fibrous tissue layer, where pressurized fluid flow along the bone-implant interface activates mechanosensitive osteocytes in the periprosthetic bone, causing the release of proresorptive cytokines and subsequent osteoclast differentiation and osteolysis.

Method Of Study: An animal model for instability-induced osteolysis that mimics the periprosthetic bone-implant interface will be used. In this model, a fibrous tissue membrane is allowed to form in the periprosthetic zone, and pressurized fluid flow transmitted through this membrane reliably creates osteolytic lesions in the periprosthetic bone. In this study, half of the rats will have the fibrous tissue present, while the other half will not. We will determine whether the fibrous tissue membrane is essential for the release of proosteoclastic cytokines, leading to osteoclast differentiation and periprosthetic bone loss, by measuring the volume of bone resorption and presence of proresorptive cytokines at the bone-implant interface.

Significance: We will determine whether the fibrous tissue membrane is crucial for osteoclastogenic signaling in the setting of periimplant osteolysis. In the future, this will allow us to test therapeutic interventions, such as specific cytokine inhibitors or alterations in implant design, which may translate into new, clinically relevant strategies to prevent osteolysis.
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http://dx.doi.org/10.1007/s11999-013-2896-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3706676PMC
June 2013

Trabecular bone adaptation to loading in a rabbit model is not magnitude-dependent.

J Orthop Res 2013 Jun 19;31(6):930-4. Epub 2013 Feb 19.

Hospital for Special Surgery, 535 East 70th Street, New York, New York 10021, USA.

Although mechanical loading is known to influence trabecular bone adaptation, the role of specific loading parameters requires further investigation. Previous studies demonstrated that the number of loading cycles and loading duration modulate the adaptive response of trabecular bone in a rabbit model of applied loading. In the current study, we investigated the influence of load magnitude on the adaptive response of trabecular bone using the rabbit model. Cyclic compressive loads, producing peak pressures of either 0.5 or 1.0 MPa, were applied daily (5 days/week) at 1 Hz and 50 cycles/day for 4 weeks post-operatively to the trabecular bone on the lateral side of the distal right femur, while the left side served as an nonloaded control. The adaptive response was characterized by microcomputed tomography and histomorphometry. Bone volume fraction, bone mineral content, tissue mineral density, and mineral apposition rate (MAR) increased in loaded limbs compared to the contralateral control limbs. No load magnitude dependent difference was observed, which may reflect the critical role of loading compared to the operated, nonloaded contralateral limb. The increased MAR suggests that loading stimulated new bone formation rather than just maintaining bone volume. The absence of a dose-dependent response of trabecular bone observed in this study suggests that a range of load magnitudes should be examined for biophysical therapies aimed at augmenting current treatments to enhance long-term fixation of orthopedic devices.
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http://dx.doi.org/10.1002/jor.22316DOI Listing
June 2013

Infrared fiber optic probe evaluation of degenerative cartilage correlates to histological grading.

Am J Sports Med 2012 Dec 29;40(12):2853-61. Epub 2012 Oct 29.

Department of Bioengineering, Temple University, Philadelphia, PA 19122, USA.

Background: Osteoarthritis (OA), a degenerative cartilage disease, results in alterations of the chemical and structural properties of tissue. Arthroscopic evaluation of full-depth tissue composition is limited and would require tissue harvesting, which is inappropriate in daily routine. Fourier transform infrared (FT-IR) spectroscopy is a modality based on molecular vibrations of matrix components that can be used in conjunction with fiber optics to acquire quantitative compositional data from the cartilage matrix.

Purpose: To develop a model based on infrared spectra of articular cartilage to predict the histological Mankin score as an indicator of tissue quality.

Study Design: Comparative laboratory study.

Methods: Infrared fiber optic probe (IFOP) spectra were collected from nearly normal and more degraded regions of tibial plateau articular cartilage harvested during knee arthroplasty (N = 61). Each region was graded using a modified Mankin score. A multivariate partial least squares algorithm using second-derivative spectra was developed to predict the histological modified Mankin score.

Results: The partial least squares model derived from IFOP spectra predicted the modified Mankin score with a prediction error of approximately 1.4, which resulted in approximately 72% of the Mankin-scored tissues being predicted correctly and 96% being predicted within 1 grade of their true score.

Conclusion: These data demonstrate that IFOP spectral parameters correlate with histological tissue grade and can be used to provide information on tissue composition.

Clinical Relevance: Infrared fiber optic probe studies have significant potential for the evaluation of cartilage tissue quality without the need for tissue harvest. Combined with arthroscopy, IFOP analysis could facilitate the definition of tissue margins in debridement procedures.
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http://dx.doi.org/10.1177/0363546512462009DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4235670PMC
December 2012

The effects of PTH, loading and surgical insult on cancellous bone at the bone-implant interface in the rabbit.

Bone 2013 Feb 18;52(2):718-24. Epub 2012 May 18.

Hospital for Special Surgery, New York, NY 10021, USA.

Enhancing the quantity and quality of cancellous bone with anabolic pharmacologic agents may lead to more successful outcomes of non-cemented joint replacements. Using a novel rabbit model of cancellous bone loading, we examined two specific questions regarding bone formation at the bone-implant interface: (1) does the administration of intermittent PTH, a potent anabolic agent, and mechanical loading individually and combined enhance the peri-implant cancellous bone volume fraction; and, (2) does surgical trauma enhance the anabolic effect of PTH on peri-implant bone volume fraction. In this model, PTH enhanced peri-implant bone volume fraction by 30% in loaded bone, while mechanical loading alone increased bone volume fraction modestly (+10%). Combined mechanical loading and PTH treatment had no synergistic effect on any cancellous parameters. However, a strong combined effect was found in bone volume fraction with combined surgery and PTH treatment (+34%) compared to intact control limbs. Adaptive changes in the cancellous bone tissue included increased ultimate stress and enhanced remodeling activity. The number of proliferative osteoblasts increased as did their expression of pro-collagen 1 and PTH receptor 1, and the number of TRAP positive osteoclasts also increased. In summary, both loading and intermittent PTH treatment enhanced peri-implant bone volume, and surgery and PTH treatment had a strong combined effect. This finding is of clinical importance since enhancing early osseointegration in the post-surgical period has numerous potential benefits.
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http://dx.doi.org/10.1016/j.bone.2012.05.005DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4142202PMC
February 2013

An analysis of the hip and knee reconstruction section of the orthopaedic in-training examination.

Orthopedics 2011 Sep 9;34(9):e550-5. Epub 2011 Sep 9.

Hospital for Special Surgery, 535 E 70th St, New York, NY 10021, USA.

This article analyzes the hip and knee reconstruction section of the Orthopaedic In-Training Examination (OITE). All of the hip and knee reconstruction questions from 2005 to 2009 were analyzed, and the following data were recorded: number of questions per year in the hip and knee section, total number of questions on the OITE per year, national average score by year in training, references cited, taxonomy classification of each question, topics that were tested, imaging modalities used for a given question, and treatment modalities tested. Eight percent to 9% of the questions on the OITE each year were hip and knee reconstruction-related questions. Performance improved with each year in training, but not by a statistically significant amount. The most commonly tested topics over the past 5 years were anatomy and physiology, ligament and/or gap balancing during total knee arthroplasty (TKA), surgical approaches, properties of polyethylene, periprosthetic fractures about an arthroplasty, and questions dealing with the mechanical properties of implants. In 4 out of 5 years, the majority of questions were classified as Taxonomy 1 (knowledge and recall). The bulk of the questions each year did not require the examinee to interpret a radiograph or make a treatment decision. The most common references cited were from Journal of Bone and Joint Surgery (American), followed by the Journal of Arthroplasty. This detailed analysis of the hip and knee reconstruction section of the OITE should improve resident performance, and may serve as a study tool for the OITE.
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http://dx.doi.org/10.3928/01477447-20110714-10DOI Listing
September 2011
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