Publications by authors named "Sheldon Lin"

69 Publications

CORR Insights®: Low-energy Gunshot-induced Tibia Fractures: What Proportion Develop Complications?

Authors:
Sheldon Lin

Clin Orthop Relat Res 2021 May 5. Epub 2021 May 5.

S. Lin, Assistant Professor, Department of Orthopaedics, Rutgers-The New Jersey Medical School, Newark, NJ, USA.

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http://dx.doi.org/10.1097/CORR.0000000000001802DOI Listing
May 2021

Local insulin application has a dose-dependent effect on lumbar fusion in a rabbit model.

J Tissue Eng Regen Med 2021 May 12;15(5):442-452. Epub 2021 Mar 12.

Department of Orthopaedics, Rutgers-New Jersey Medical School, Newark, NJ, USA.

The purpose of this study was to determine if locally applied insulin has a dose-responsive effect on posterolateral lumbar fusion. Adult male New Zealand White rabbits underwent posterolateral intertransverse spinal fusions (PLFs) at L5-L6 using suboptimal amounts of autograft. Fusion sites were treated with collagen sponge soaked in saline (control, n = 11), or with insulin at low (5 or 10 units, n = 13), mid (20 units, n = 11), and high (40 units, n = 11) doses. Rabbits were euthanized at 6 weeks. The L5-L6 spine segment underwent manual palpation and radiographic evaluation performed by two fellowship trained spine surgeons blinded to treatment. Differences between groups were evaluated by analysis of variance on ranks followed by post-hoc Dunn's tests. Forty-three rabbits were euthanized at the planned 6 weeks endpoint, while three died or were euthanized prior to the endpoint. Radiographic evaluation found bilateral solid fusion in 10%, 31%, 60%, and 60% of the rabbits from the control and low, mid, and high-dose insulin-treated groups, respectively (p < 0.05). As per manual palpation, 7 of 10 rabbits in the mid-dose insulin group were fused as compared to 1 of 10 rabbits in the control group (p < 0.05). This study demonstrates that insulin enhanced the effectiveness of autograft to increase fusion success in the rabbit PLF model. The study indicates that insulin or insulin-mimetic compounds can be used to promote bone regeneration.
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http://dx.doi.org/10.1002/term.3182DOI Listing
May 2021

Low Intensity Pulsed Ultrasound Therapy (LIPUS): A review of evidence and potential applications in diabetics.

J Clin Orthop Trauma 2020 Jul 21;11(Suppl 4):S500-S505. Epub 2020 Apr 21.

Academic Team of Musculoskeletal Surgery, Leicester General Hospital, Gwendolen Road, Leicester, LE5 4PW, UK.

Low Intensity Pulsed Ultrasound Therapy (LIPUS) is a non-invasive treatment and aims to reduce fracture healing time and avoid non-union by delivering micro-mechanical stress to the bone to stimulate bone healing. In 2018, the National Institute for Health and Clinical Excellence (NICE) recommended that the evidence for LIPUS to promote healing of delayed-union and non-union fractures raised no major safety concerns, but the current evidence on efficacy is inadequate in quality. Little is known about the potential benefits of LIPUS for fracture healing in diabetic patients. In this article, we review the current evidence of LIPUS therapy both in animal and human studies and its possible application on fractures in diabetics.
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http://dx.doi.org/10.1016/j.jcot.2020.03.009DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7394837PMC
July 2020

Zinc as a Therapeutic Agent in Bone Regeneration.

Materials (Basel) 2020 May 12;13(10). Epub 2020 May 12.

Department of Biological Sciences, Seton Hall University, 400 South Orange Avenue, South Orange, NJ 07079, USA.

Zinc is an essential mineral that is required for normal skeletal growth and bone homeostasis. Furthermore, zinc appears to be able to promote bone regeneration. However, the cellular and molecular pathways through which zinc promotes bone growth, homeostasis, and regeneration are poorly understood. Zinc can positively affect chondrocyte and osteoblast functions, while inhibiting osteoclast activity, consistent with a beneficial role for zinc in bone homeostasis and regeneration. Based on the effects of zinc on skeletal cell populations and the role of zinc in skeletal growth, therapeutic approaches using zinc to improve bone regeneration are being developed. This review focuses on the role of zinc in bone growth, homeostasis, and regeneration while providing an overview of the existing studies that use zinc as a bone regeneration therapeutic.
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http://dx.doi.org/10.3390/ma13102211DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7287917PMC
May 2020

President and Program Chair's Introduction.

Foot Ankle Int 2018 09;39(2_suppl):75S

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http://dx.doi.org/10.1177/1071100718792905DOI Listing
September 2018

Medical Malpractice in Orthopedic Surgery: A Westlaw-Based Demographic Analysis.

Orthopedics 2018 Sep 26;41(5):e615-e620. Epub 2018 Jun 26.

A recent study that evaluated the risk of facing a malpractice claim by physician specialty found that orthopedic surgeons were at a significantly greater risk of being sued than other medical specialists. To date, no studies have characterized trends in orthopedic surgery malpractice claims. The Westlaw legal database was used to locate state and federal jury verdicts and settlements related to medical malpractice and orthopedic surgery from 2010 to 2016. Eighty-one cases were analyzed. The mean age of the affected patients and/or plaintiffs was 53.4 years. Spine surgery (21 cases; 25.9%), knee surgery (17 cases; 21.0%), and hip surgery (11 cases; 13.6%) were litigated most often. Procedural error (71 cases; 87.7%) and negligence (58 cases; 71.6%) were the 2 most commonly cited reasons for litigation. The jury found in favor of the defendant in most (50 cases; 61.7%) of the cases. The mean plaintiff (17 cases; 21.0%) verdict payout was $3,015,872, and the mean settlement (13 cases; 16.0%) value was $1,570,833. Unnecessary surgery (odds ratio [OR], 12.29; 95% confidence interval [CI], 1.91-108.46; P=.040) and surgery resulting in death (OR, 26.26; 95% CI, 2.55-497.42; P=.040) were significant predictors of a verdict in favor of the plaintiff. Patient death (OR, 0.05; 95% CI, 0.01-0.38; P=.021) and male patient sex (OR, 0.26; 95% CI, 0.09-0.71; P=.033) were significant negative predictors of a verdict in favor of the defendant. The jury found in favor of the defendant orthopedic surgeon in most cases. Procedural error and/or negligence were cited most commonly by the plaintiffs as the bases for the claims. Verdicts in favor of the plaintiffs resulted in payouts nearly double those of settlements. [Orthopedics. 2018; 41(5):e615-e620.].
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http://dx.doi.org/10.3928/01477447-20180621-06DOI Listing
September 2018

What's New in Foot and Ankle Surgery.

J Bone Joint Surg Am 2018 May;100(10):892-898

Department of Orthopaedics, Rutgers New Jersey School of Medicine, Newark, New Jersey.

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http://dx.doi.org/10.2106/JBJS.17.01672DOI Listing
May 2018

Evidence based review of literature on detriments to healing of diabetic foot ulcers.

Foot Ankle Surg 2017 Dec 23;23(4):215-224. Epub 2016 Apr 23.

Dalhousie University, Queen Elizabeth II Health Sciences Center Halifax Infirmary (Suite 4867), 1796 Summer Street, Halifax, Nova Scotia B3H3A7, Canada. Electronic address:

Background: Diabetes mellitus places a substantial burden on society worldwide. Diabetic foot ulcers are a challenging problem for clinicians. Seven generally accepted detriments to healing of diabetic foot ulcers were identified: infection, glycaemic control, vascular supply, smoking, nutrition, deformity and offloading. The aim of this paper is to present a comprehensive evidence based review of the literature available on detriments to healing of diabetic foot ulcers.

Method: A research question was generated for each of the detriments to healing and a comprehensive review of the literature was performed using the Pubmed database in July 2014. All articles were assessed for relevancy and a level of evidence was assigned. An analysis of the total body of literature was used to assign a grade of recommendation to each detriment.

Results: Grade A recommendation was assigned to offloading as there was good evidence supporting this intervention. Grade B recommendation was assigned to deformity as there was fair evidence consistent with the hypothesis. Infection and vascular supply had poor quality evidence supporting the research question and grade C recommendation was assigned. Grade I recommendation was assigned to glycaemic control, smoking and nutrition as there was insufficient and conflicting evidence available.

Conclusion: Our literature review revealed good evidence for some factors and insufficient literature on others. Further studies are needed to provide quality evidence regarding detriments to healing of diabetic ulcers.
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http://dx.doi.org/10.1016/j.fas.2016.04.002DOI Listing
December 2017

What's New in Foot and Ankle Surgery.

J Bone Joint Surg Am 2017 04;99(8):700-706

1Department of Orthopaedics, New Jersey Medical School, Newark, New Jersey.

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http://dx.doi.org/10.2106/JBJS.16.01603DOI Listing
April 2017

Biologics Fusion.

Foot Ankle Spec 2017 Feb;10(1):43-45

Assistant Professor of Orthopaedic Surgery Foot and Ankle Fellowship Director University of Virginia Charlottesville, VA.

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http://dx.doi.org/10.1177/1938640016689170DOI Listing
February 2017

Effects of local vanadium delivery on diabetic fracture healing.

J Orthop Res 2017 10 8;35(10):2174-2180. Epub 2017 Mar 8.

Department of Orthopaedics, Rutgers New Jersey Medical School, 90 Bergen Street, Suite 7300, Newark, New Jersey 07101.

This study evaluated the effect of local vanadyl acetylacetonate (VAC), an insulin mimetic agent, upon the early and late parameters of fracture healing in rats using a standard femur fracture model. Mechanical testing, and radiographic scoring were performed, as well as histomorphometry, including percent bone, percent cartilage, and osteoclast numbers. Fractures treated with local 1.5 mg/kg VAC possessed significantly increased mechanical properties compared to controls at 6 weeks post-fracture, including increased torque to failure (15%; p = 0.046), shear modulus (89%; p = 0.043), and shear stress (81%; p = 0.009). The radiographic scoring analysis showed increased cortical bridging at 4 weeks and 6 weeks (119%; p = 0.036 and 209%; p = 0.002) in 1.5 mg/kg VAC treated groups. Histomorphometry of the fracture callus at days 10 and 14 showed increased percent cartilage (121%; p = 0.009 and 45%; p = 0.035) and percent mineralized tissue (66%; p = 0.035 and 58%; p = 0.006) with local VAC treated groups compared to control. Additionally, fewer osteoclasts were observed in the local VAC treated animals as compared to controls at day 14 (0.45% ± 0.29% vs. 0.83% ± 0.36% of callus area; p = 0.032). The results suggest local administration of VAC acts to modulate osteoclast activity and increase percentage of early callus cartilage, ultimately enhancing mechanical properties comparably to non-diabetic animals treated with local VAC. © 2017 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 35:2174-2180, 2017.
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http://dx.doi.org/10.1002/jor.23521DOI Listing
October 2017

Local Zinc Chloride Release From a Calcium Sulfate Carrier Enhances Fracture Healing.

J Orthop Trauma 2017 Mar;31(3):168-174

*Department of Orthopaedics, Rutgers New Jersey Medical School, Newark, NJ; †Department of Biological Sciences, Seton Hall University, South Orange, NJ; and ‡Department of Biochemistry and Molecular Biology, Rutgers New Jersey Medical School, Newark, NJ.

Background: This study examined the efficacy of calcium sulfate (CaSO4) as a carrier for intramedullary delivery of zinc chloride (ZnCl2) to treat fracture healing in a BB Wistar rat model. A non-carrier-mediated injection of 3.0 mg/kg of ZnCl2 has previously been shown to enhance fracture healing.

Methods: A heterogeneous mixture of ZnCl2 and CaSO4 was administered into the intramedullary femoral canal and a mid-diaphyseal femur fracture was created unilaterally. Early and late parameters of fracture healing were assessed using biomechanical testing, radiographic scoring, quantitative histomorphometry (for percentage of new cartilage and bone within the fracture callus), and long-term histologic evaluation.

Results: Fractures treated with 1.0 mg/kg of ZnCl2/CaSO4 demonstrated a significantly higher maximum torque to failure compared with both CaSO4 (P = 0.048) and saline (P = 0.005) controls at 4 weeks postfracture (396.4 versus 251.3 versus 178.7 N mm, respectively). Statistically significant increases in torsional rigidity, effective shear modulus, and effective shear stress were also found, as well as a 3.5 times increase in radiographic score (based on bone union). Histologic examination of the fracture callus indicated enhanced chondrogenesis at day 14 postfracture, with increased percent cartilage for the ZnCl2/CaSO4 group compared with saline (P = 0.0004) and CaSO4 (P = 0.0453) controls. Long-term radiographic and histologic evaluation revealed no abnormal bone formation or infection up to 12 weeks postoperatively.

Conclusions: The effective dose of ZnCl2 augmentation for the enhancement of fracture healing in rats was reduced 3-fold in this study compared with previous findings. Furthermore, CaSO4 acted synergistically with ZnCl2 to increase the mechanical strength and stability at the fracture site.
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http://dx.doi.org/10.1097/BOT.0000000000000748DOI Listing
March 2017

Orthobiologic in Foot Ankle.

Authors:
Sheldon S Lin

Foot Ankle Clin 2016 Dec;21(4):xiii-xiv

Rutgers New Jersey Medical School, Department of Orthopaedics, Suite 7300, Doctor's Office Center, 90 Bergen Street, Newark, NJ 07101-1709, USA. Electronic address:

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http://dx.doi.org/10.1016/j.fcl.2016.09.001DOI Listing
December 2016

The Role of Orthobiologics in Fracture Healing and Arthrodesis.

Foot Ankle Clin 2016 Dec;21(4):727-737

Department of Orthopaedics, Rutgers New Jersey Medical School, 140 Bergen Street, ACC Building, Suite D-1610, Newark, NJ 07103, USA.

Nonunion after tibial shaft fracture and hindfoot arthrodesis remains a major problem. Known risk factors include advanced age, immunosuppression, smoking, and diabetes. Several factors must be considered in the fracture healing process. This review evaluates the efficacy of orthobiologics in improving union rates after fracture or arthrodesis. Use of compounds have shown increased cellular proliferation experimentally. Percutaneous autologous bone marrow has shown increased cellular proliferation. Matrix supplementation has shown significant improvements in bone healing. Several studies have highlighted the importance of adequate graft fill over graft type. Patients at increased risk for nonunion would benefit most from these adjuvant therapies.
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http://dx.doi.org/10.1016/j.fcl.2016.07.003DOI Listing
December 2016

The Importance of Sufficient Graft Material in Achieving Foot or Ankle Fusion.

J Bone Joint Surg Am 2016 Aug;98(15):1260-7

Department of Orthopaedics, University of Rochester School of Medicine and Dentistry, Rochester, New York.

Background: Nonunion, an important complication following foot and ankle arthrodesis, causes substantial morbidity and disability. In patients undergoing hindfoot and ankle arthrodesis, autogenous bone graft (autograft) or a suitable alternative is often used to promote osseous fusion across the joint. This study assessed the importance of adequate graft material in the fusion space to achieve joint fusion during ankle and hindfoot arthrodesis.

Methods: This study used data from a previously published clinical trial of grafting material (recombinant human platelet-derived growth factor-BB with beta-tricalcium phosphate [rhPDGF-BB/β-TCP] or autograft) for healing in hindfoot and ankle arthrodesis to correlate the amount of graft fill at 9 weeks with ultimate healing. Patients who received supplemental graft material for ankle or hindfoot arthrodesis for end-stage ankle or hindfoot arthritis were stratified according to nonunion risk factors and surgical fusion site. Patients underwent arthrodesis using standard rigid internal fixation. Graft fill was defined as "adequate" if the material occupied ≥50% of the cross-sectional area of the fusion space on a computed tomography (CT) scan made at 9 weeks. Fusion was defined as osseous bridging of ≥50% of each articulation on a CT scan made at 24 weeks. Three hundred and seventy-nine patients with 573 joints (383 managed with rhPDGF-BB/β-TCP and 190 managed with autograft) that underwent arthrodesis had complete follow-up with 9-week and 24-week CT scans available.

Results: Overall, 472 (82%) of 573 joints had adequate graft fill; of those, 383 (81%) were successfully fused at 24 weeks compared with 21 (21%) of 101 joints without adequate graft fill (p < 0.0001). Absolute fusion rate differences (joints with adequate fill minus those without adequate fill) were consistent across joints (61% to 63%) and for graft materials. The overall odds ratio (OR) of successful fusion in joints with adequate graft fill compared with those without adequate graft fill was 16.4 (95% confidence interval, 9.6 to 27.9).

Conclusions: This study demonstrates an association between the amount of graft material and successful hindfoot and ankle arthrodesis. Graft material filling of ≥50% of the fusion space at 9 weeks, regardless of type or origin, was associated with significantly higher fusion rates at 24 weeks.

Level Of Evidence: Therapeutic Level II. See Instructions for Authors for a complete description of levels of evidence.
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http://dx.doi.org/10.2106/JBJS.15.00879DOI Listing
August 2016

Effect on Clinical Outcome and Growth Factor Synthesis With Adjunctive Use of Pulsed Electromagnetic Fields for Fifth Metatarsal Nonunion Fracture: A Double-Blind Randomized Study.

Foot Ankle Int 2016 Sep 10;37(9):919-23. Epub 2016 Jun 10.

Department of Orthopedics, Rutgers, New Jersey Medical School, NJ, USA.

Background: Electromagnetic bone growth stimulators have been found to biologically enhance the bone healing environment, with upregulation of numerous growth factors. The purpose of the study was to quantify the effect, in vivo, of pulsed electromagnetic fields (PEMFs) on growth factor expression and healing time in fifth metatarsal nonunions.

Methods: This was a prospective, randomized, double-blind trial of patients, cared for by 2 fellowship-trained orthopedic foot and ankle surgeons. Inclusion criteria consisted of patients between 18 and 75 years old who had been diagnosed with a fifth metatarsal delayed or nonunion, with no progressive signs of healing for a minimum of 3 months. Eight patients met inclusion criteria and were randomized to receive either an active stimulation or placebo PEMF device. Each patient then underwent an open biopsy of the fracture site and was fitted with the appropriate PEMF device. The biopsy was analyzed for messenger-ribonucleic acid (mRNA) levels using quantitative competitive reverse transcription polymerase chain reaction (QT-RT-PCR). Three weeks later, the patient underwent repeat biopsy and open reduction and internal fixation of the nonunion site. The patients were followed at 2- to 4-week intervals with serial radiographs and were graded by the number of cortices of healing.

Results: All fractures healed, with an average time to complete radiographic union of 14.7 weeks and 8.9 weeks for the inactive and active PEMF groups, respectively. A significant increase in placental growth factor (PIGF) level was found after active PEMF treatment (P = .043). Other factors trended higher following active PEMF including brain-derived neurotrophic factor (BDNF), bone morphogenetic protein (BMP) -7, and BMP-5.

Conclusion: The adjunctive use of PEMF for fifth metatarsal fracture nonunions produced a significant increase in local placental growth factor. PEMF also produced trends toward higher levels of multiple other factors and faster average time to radiographic union compared to unstimulated controls.

Level Of Evidence: Level I, prospective randomized trial.
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http://dx.doi.org/10.1177/1071100716652621DOI Listing
September 2016

What's New in Foot and Ankle Surgery.

J Bone Joint Surg Am 2016 May;98(10):874-80

Department of Orthopaedics, New Jersey Medical School, Rutgers University, Newark, New Jersey.

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http://dx.doi.org/10.2106/JBJS.16.00001DOI Listing
May 2016

Mode & mechanism of low intensity pulsed ultrasound (LIPUS) in fracture repair.

Ultrasonics 2016 08 9;70:45-52. Epub 2016 Apr 9.

Kanagawa Dental University, Graduate School of Dentistry, Yokosuka, Japan.

It has been 30years since the first level one clinical trial demonstrated low intensity pulsed ultrasound (LIPUS) could accelerate fracture repair. Since 1994 numerous investigations have been performed on the effect of LIPUS. The majority of these studies have used the same signal parameters comprised of an intensity of 30mW/cm(2) SATA, an ultrasound carrier frequency of 1.5MHz, pulsed at 1kHz with an exposure time of 20minutes per day. These studies show that a biological response is stimulated in the cell which produces bioactive molecules. The production of these molecules, linked with observations demonstrating the enhanced effects on mineralization by LIPUS, might be considered the general manner, or mode, of how LIPUS stimulates fractures to heal. We propose a mechanism for how the LIPUS signal can enhance fracture repair by combining the findings of numerous studies. The LIPUS signal is transmitted through tissue to the bone, where cells translate this mechanical signal to a biochemical response via integrin mechano-receptors. The cells enhance the production of cyclo-oxygenese 2 (COX-2) which in turn stimulates molecules to enhance fracture repair. The aim of this review is to present the state of the art data related to LIPUS effects and mechanism.
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http://dx.doi.org/10.1016/j.ultras.2016.03.016DOI Listing
August 2016

Zinc has insulin-mimetic properties which enhance spinal fusion in a rat model.

Spine J 2016 06 2;16(6):777-83. Epub 2016 Feb 2.

Department of Orthopaedics, Rutgers University, New Jersey Medical School, 90 Bergen St, Suite 7300, Newark, NJ 07101, USA.

Background Context: Previous studies have found that insulin or insulin-like growth factor treatment can stimulate fracture healing in diabetic and normal animal models, and increase fusion rates in a rat spinal fusion model. Insulin-mimetic agents, such as zinc, have demonstrated antidiabetic effects in animal and human studies, and these agents that mimic the effects of insulin could produce the same beneficial effects on bone regeneration and spinal fusion.

Purpose: The purpose of this study was to analyze the effects of locally applied zinc on spinal fusion in a rat model.

Study Design/setting: Institutional Animal Care and Use Committee-approved animal study using Sprague-Dawley rats was used as the study design.

Methods: Thirty Sprague-Dawley rats (450-500 g) underwent L4-L5 posterolateral lumbar fusion (PLF). After decortication and application of approximately 0.3 g of autograft per side, one of three pellets were added to each site: high-dose zinc calcium sulfate (ZnCaSO4), low-dose ZnCaSO4 (half of the high dose), or a control palmitic acid pellet (no Zn dose). Systemic blood glucose levels were measured 24 hours postoperatively. Rats were sacrificed after 8weeks and the PLFs analyzed qualitatively by manual palpation and radiograph review, and quantitatively by micro-computed tomography (CT) analysis of bone volume and trabecular thickness. Statistical analyses with p-values set at .05 were accomplished with analysis of variance, followed by posthoc tests for quantitative data, or Mann-Whitney rank tests for qualitative assessments.

Results: Compared with controls, the low-dose zinc group demonstrated a significantly higher manual palpation grade (p=.011), radiographic score (p=.045), and bone formation on micro-CT (172.9 mm(3) vs. 126.7 mm(3) for controls) (p<.01). The high-dose zinc also demonstrated a significantly higher radiographic score (p=.017) and bone formation on micro-CT (172.7 mm(3) vs. 126.7 mm(3)) (p<.01) versus controls, and was trending toward higher manual palpation scores (p=.058).

Conclusions: This study demonstrates the potential benefit of a locally applied insulin-mimetic agent, such as zinc, in a rat lumbar fusion model. Previous studies have demonstrated the benefits of local insulin application in the same model, and it appears that zinc has similar effects.
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http://dx.doi.org/10.1016/j.spinee.2016.01.190DOI Listing
June 2016

Orthobiologics in Foot and Ankle Surgery.

J Am Acad Orthop Surg 2016 Feb;24(2):113-22

From Rutgers New Jersey Medical School, Department of Orthopedics, Newark, NJ.

Exploration into the molecular aspects of the healing process has led to the development of autologous and recombinant biologic agents. These products, collectively known as orthobiologics, have the potential to optimize favorable outcomes with respect to bone and soft-tissue restoration and to maximize the natural healing response. These orthobiologics include platelet-derived growth factor, bone morphogenetic proteins, and platelet-rich plasma. Although the usefulness of these growth factors is well described in various fields of surgery, few data exist to support or oppose the specific application of growth factors in foot and ankle surgery.
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http://dx.doi.org/10.5435/JAAOS-D-14-00155DOI Listing
February 2016

Polymerase Chain Reaction molecular diagnostic technology for monitoring chronic osteomyelitis.

J Exp Orthop 2014 Dec 15;1(1). Epub 2014 Aug 15.

Department of Orthopaedic Surgery, Thomas Jefferson University, Philadelphia, PA, USA.

Background: Osteomyelitis is a devastating condition whose treatment relies on the detection of bacteria. The current standard of microbiology culture may not be adequate. Molecular biology based diagnostic procedures for detecting bacteria in orthopaedic infections was previously established, but has not been applied to the setting of chronic osteomyelitis. We aim to determine the applicability of molecular diagnostic procedures for monitoring chronic osteomyelitis, and to evaluate if these procedures are superior to standard culture methods of osteomyelitis detection.

Methods: A rabbit experimental model of chronic osteomyelitis was used; infection was induced in the proximal, medial aspect of the tibia with Staphylococcus aureus at titers ranging from 1 × 10(2) to 1 × 10(6) colony forming units. At 28 days post-infection, animals were sacrificed, and the tibias were examined radiographically, harvested, and assayed for the presence of bacteria. Two bacterial detection methods were used: (1) standard microbiological culturing, and (2) polymerase chain reaction (PCR) based diagnostic method to detect bacterial genomic DNA.

Results: The molecular diagnostic method was highly sensitive and accurate, and detected low titer infections that were undetected by radiographic and microbiological methods. By using two sets of PCR primers, one for a universal bacterial gene (16S rRNA) and one for a species-specific gene (nuc), the molecular protocol allowed both the detection and speciation of the bacterial infection.

Conclusions: The use of the PCR-based method was effective for high-sensitivity detection and identification of bacteria associated with chronic osteomyelitis in a rabbit model. Our findings illustrate the applicability of PCR for monitoring chronic osteomyelitis, which may be useful for improved detection of osteomyelitis organisms in humans.
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http://dx.doi.org/10.1186/s40634-014-0009-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4648848PMC
December 2014

The effect of locally delivered recombinant human bone morphogenetic protein-2 with hydroxyapatite/tri-calcium phosphate on the biomechanical properties of bone in diabetes-related osteoporosis.

J Orthop Traumatol 2015 Jun 25;16(2):151-9. Epub 2014 Nov 25.

Division of Orthopaedic Trauma, Department of Orthopaedic Surgery, NYU Hospital for Joint Diseases, 301 E 17th Street, Suite 1402, New York, NY, 10003, USA,

Background: Recombinant human bone morphogenetic protein-2 (rhBMP-2) is particularly effective in improving osteogenesis in patients with diminished bone healing capabilities, such as individuals with type 1 diabetes mellitus (T1DM) who have impaired bone healing capabilities and increased risk of developing osteoporosis. This study measured the effects of rhBMP-2 treatment on osteogenesis by observing the dose-dependent effect of localized delivery of rhBMP-2 on biomechanical parameters of bone using a hydroxyapatite/tri-calcium phosphate (HA/TCP) carrier in a T1DM-related osteoporosis animal model.

Materials And Methods: Two different doses of rhBMP-2 (LD low dose, HD high dose) with a HA/TCP carrier were injected into the femoral intramedullary canal of rats with T1DM-related osteoporosis. Two more diabetic rat groups were injected with saline alone and with HA/TCP carrier alone. Radiographs and micro-computed tomography were utilized for qualitative assessment of bone mineral density (BMD). Biomechanical testing occurred at 4- and 8-week time points; parameters tested included torque to failure, torsional rigidity, shear stress, and shear modulus.

Results: At the 4-week time point, the LD and HD groups both exhibited significantly higher BMD than controls; at the 8-week time point, the HD group exhibited significantly higher BMD than controls. Biomechanical testing revealed dose-dependent, higher trends in all parameters tested at the 4- and 8-week time points, with minimal significant differences.

Conclusions: Groups treated with rhBMP-2 demonstrated improved bone mineral density at both 4 and 8 weeks compared to control saline groups, in addition to strong trends towards improvement of intrinsic and extrinsic biomechanical properties when compared to control groups. Data revealed trends toward dose-dependent increases in peak torque, torsional rigidity, shear stress, and shear modulus 4 weeks after rhBMP-2 treatment.

Level Of Evidence: Not applicable.
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http://dx.doi.org/10.1007/s10195-014-0327-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4441641PMC
June 2015

A not-so-systematic review.

Can J Surg 2014 Oct;57(5):E150-1

Project Professor, Division of Molecular and Cellular Biology of Mineralized Tissues, Department of Oral Sciences, Kanagawa Dental University, Graduate School of Dentistry, Yokosuka, Japan.

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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4183692PMC
http://dx.doi.org/10.1503/cjs.009514DOI Listing
October 2014

Local manganese chloride treatment accelerates fracture healing in a rat model.

J Orthop Res 2015 Jan 17;33(1):122-30. Epub 2014 Sep 17.

Department of Orthopaedics, Rutgers-New Jersey Medical School, 90 Bergen Street, Suite 7300, Newark, New Jersey, 07103.

This study investigated the effects of local delivery of manganese chloride (MnCl2), an insulin-mimetic compound, upon fracture healing using a rat femoral fracture model. Mechanical testing, histomorphometry, and immunohistochemistry were performed to assess early and late parameters of fracture healing. At 4 weeks post-fracture, maximum torque to failure was 70% higher (P<0.05) and maximum torsional rigidity increased 133% (P<0.05) in animals treated with 0.125 mg/kg MnCl2 compared to saline controls. Histological analysis of the fracture callus revealed percent new mineralized tissue was 17% higher (P<0.05) at day 10. Immunohistochemical analysis of the 0.125 mg/kg MnCl2 treated group, compared to saline controls, showed a 379% increase in the density of VEGF-C+ cells. In addition, compared to saline controls, the 0.125 mg/kg MnCl2 treated group showed a 233% and 150% increase in blood vessel density in the subperiosteal region at day 10 post-fracture as assessed by detection of PECAM and smooth muscle α actin, respectively. The results suggest that local MnCl2 treatment accelerates fracture healing by increasing mechanical parameters via a potential mechanism of amplified early angiogenesis leading to increased osteogenesis. Therefore, local administration of MnCl2 is a potential therapeutic adjunct for fracture healing.
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http://dx.doi.org/10.1002/jor.22733DOI Listing
January 2015

Local ZnCl2 accelerates fracture healing.

J Orthop Res 2014 Jun 26;32(6):834-41. Epub 2014 Feb 26.

Rutgers New Jersey Medical School, Department of Orthopaedics, 90 Bergen Street, Suite 7300, Newark, New Jersey, 07103.

This study evaluated the effect of local zinc chloride (ZnCl2 ), an insulin mimetic agent, upon the early and late parameters of fracture healing in rats using a standard femur fracture model. Mechanical testing, radiographic scoring, histomorphometry, qualitative histological scoring, PCNA immunohistochemistry, and local growth factor analysis were performed. Fractures treated with local ZnCl2 possessed significantly increased mechanical properties compared to controls at 4 weeks post fracture. The radiographic scoring analysis showed increased cortical bridging at 4 weeks in the 1.0 (p=0.0015) and 3.0 (p<0.0001) mg/kg ZnCl2 treated groups. Histomorphometry of the fracture callus at day 7 showed 177% increase (p=0.036) in percent cartilage and 133% increase (p=0.002) in percent mineralized tissue with local ZnCl2 treatment compared to controls. Qualitative histological scoring showed a 2.1× higher value at day 7 in the ZnCl2 treated group compared to control (p = 0.004). Cell proliferation and growth factors, VEGF and IGF-I, within fracture calluses treated with local ZnCl2 were increased at day 7. The results suggest local administration of ZnCl2 increases cell proliferation, causing increased growth factor production which yields improved chondrogenesis and endochondral ossification. Ultimately, these events lead to accelerated fracture healing as early as 4 weeks post fracture.
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http://dx.doi.org/10.1002/jor.22593DOI Listing
June 2014

Local vanadium release from a calcium sulfate carrier accelerates fracture healing.

J Orthop Res 2014 May 30;32(5):727-34. Epub 2013 Dec 30.

Department of Orthopaedics, Rutgers New Jersey Medical School, 90 Bergen Street, Suite 7300, Newark, New Jersey, 07103.

This study evaluated the efficacy of using calcium sulfate (CaSO4 ) as a carrier for intramedullary delivery of an organic vanadium salt, vanadyl acetylacetonate (VAC) after femoral fracture. VAC can act as an insulin-mimetic and can be used to accelerate fracture healing in rats. A heterogenous mixture of VAC and CaSO4 was delivered to the fracture site of BB Wistar rats, and mechanical testing, histomorphometry, micro-computed tomography (micro-CT) were performed to measure healing. At 4 weeks after fracture, maximum torque to failure, effective shear modulus, and effective shear stress were all significantly higher (p < 0.05) in rats treated with 0.25 mg/kg VAC-CaSO4 as compared to carrier control rats. Histomorphometry found a 71% increase in percent cartilage matrix (p < 0.05) and a 64% decrease in percent mineralized tissue (p < 0.05) at 2 weeks after fracture in rats treated with 0.25 mg/kg of VAC-CaSO4 . Micro-CT analyses at 4 weeks found a more organized callus structure and higher trending maximum connected z-ray. fraction for VAC-CaSO4 groups. Evaluation of radiographs and serial histological sections at 12 weeks did not show any evidence of ectopic bone formation. As compared to previous studies, CaSO4 was an effective carrier for reducing the dose of VAC required to accelerate femoral fracture healing in rats.
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http://dx.doi.org/10.1002/jor.22570DOI Listing
May 2014

Survey on the need for bone graft in foot and ankle fusion surgery.

Foot Ankle Int 2013 Dec 28;34(12):1629-33. Epub 2013 Aug 28.

University of Rochester School of Medicine and Dentistry, Rochester, NY, USA.

Background: Generally, autologous bone graft is felt to be an important treatment adjunct in the presence of structural deformity, surface irregularities, defects (due to trauma, surgery, or degenerative changes), or underlying comorbidities that predispose the patient to healing challenges. This study assessed the prognostic and predictive factors used in the clinical decision making for bone graft supplementation in foot and ankle fusion surgery.

Methods: Utilizing standard survey research methodology, key-informant interviews, pretesting, and pilot testing; a survey was constructed. The survey consisted of a web-based 5-point Likert-type scale (never, seldom, sometimes, almost always, always) listing 14 clinical and 11 radiologic criteria that may influence the use of autologous bone grafting or other biologic augmentation in foot and ankle surgery. This survey was sent to Orthopaedic Foot and Ankle Surgeons in North America and Canada.

Results: A total of 48 foot and ankle surgeons completed the blinded survey (73% response rate). More than 70% of responders felt bone graft was almost always (AA) or always (A) indicated in prior nonunion of the indicated joint (96%). Fewer than 50% of respondents felt poor soft tissue integrity (20%), prior foot and ankle infection (20%), and current foot and ankle infection (4%) needed bone graft. Radiologic factors marked as AA or A in over 70% of responders include radiographic evidence of nonunion (96%), avascular necrosis (87%), and others. Factors chosen as AA or A by fewer than 50% of surgeons include prior adjacent joint fusions (47%), intra-articular deformity (31%), and extra-articular deformity (13%).

Conclusions: There was some uniformity of agreement on the number of both clinical and radiologic factors that prompt a surgeon to utilize autologous bone graft to try to avoid the complication of nonunion. Surgeons may wish to consider these factors when making a decision on the use of bone graft to supplement fusion.
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http://dx.doi.org/10.1177/1071100713503815DOI Listing
December 2013

Recombinant human platelet-derived growth factor-BB and beta-tricalcium phosphate (rhPDGF-BB/β-TCP): an alternative to autogenous bone graft.

J Bone Joint Surg Am 2013 Jul;95(13):1184-92

Department of Orthopaedic Surgery, The Warren Alpert School of Medicine at Brown University, Rhode Island Hospital, 593 Eddy Street, Providence, RI 02903, USA.

Background: Joint arthrodesis employing autogenous bone graft (autograft) remains a mainstay in the treatment of many foot and ankle problems. However, graft harvest can lead to perioperative morbidity and increased cost. We tested the hypothesis that purified recombinant human platelet-derived growth factor-BB (rhPDGF-BB) homodimer combined with an osteoconductive matrix (beta-tricalcium phosphate [β-TCP]) would be a safe and effective alternative to autograft.

Methods: A total of 434 patients were enrolled in thirty-seven clinical sites across North America in a prospective, randomized (2:1), controlled, non-inferiority clinical trial to compare the safety and efficacy of the combination rhPDGF-BB and β-TCP with those of autograft in patients requiring hindfoot or ankle arthrodesis. Radiographic, clinical, functional, and quality-of-life end points were assessed through fifty-two weeks postoperatively.

Results: Two hundred and sixty patients (394 joints) underwent arthrodesis with use of rhPDGF-BB/β-TCP. One hundred and thirty-seven patients (203 joints) underwent arthrodesis with use of autograft. With regard to the primary end point, 159 patients (61.2% [262 joints (66.5%)]) in the rhPDGF-BB/β-TCP group and eighty-five patients (62.0% [127 joints (62.6%)]) in the autograft group were fused as determined by computed tomography at six months (p < 0.05). Clinically, 224 patients (86.2%) [348 joints (88.3%)]) in the rhPDGF-BB/β-TCP group were considered healed at fifty-two weeks, compared with 120 patients (87.6% [177 joints (87.2%)] in the autograft group (p = 0.008). Overall, fourteen of sixteen secondary end points at twenty-four weeks and fifteen of sixteen secondary end points at fifty-two weeks demonstrated statistical non-inferiority between the groups, and patients in the rhPDGF-BB/β-TCP group were found to have less pain and an improved safety profile.

Conclusions: In patients requiring hindfoot or ankle arthrodesis, treatment with rhPDGF-BB/β-TCP resulted in comparable fusion rates, less pain, and fewer side effects as compared with treatment with autograft.
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http://dx.doi.org/10.2106/JBJS.K.01422DOI Listing
July 2013

Displacement of the sustentacular fragment in intra-articular calcaneal fractures.

J Bone Joint Surg Am 2013 Jun;95(11):995-1000

Department of Orthopaedic Surgery, University of Medicine and Dentistry of New Jersey, New Jersey Medical School, 90 Bergen Street, Suite 7300, Newark, NJ 07103, USA.

Background: The sustentacular fragment in displaced intra-articular calcaneal fractures has historically been portrayed as a "constant fragment," bound to the talus by the interosseous and deltoid ligament complex. Operative treatment typically occurs through a lateral approach, with the remaining calcaneus being reconstructed back to the sustentaculum. We hypothesized that the sustentacular fragment in displaced intra-articular calcaneal fractures does not maintain its relationship to the talus. The purpose of this study was to characterize the frequency, magnitude, and mode of displacement of the sustentacular fragment.

Methods: Computed tomographic (CT) scans of eighty-eight patients with 100 displaced intra-articular calcaneal fractures admitted to our level-I trauma center over a five-year period were retrospectively reviewed. Basic patient demographics and mechanisms of injury were recorded. CT scans were graded according to the Sanders classification, and associated injuries were noted. Angulation and translation of the sustentacular fragment as well as gapping and intra-articular fractures of the middle facet were examined. Angulation exceeding 10° and translation of more than 3 mm were considered diagnostic of displacement.

Results: Overall, the sustentacular fragment was displaced in forty-two of the 100 fractures. Twenty-five of one hundred calcanei had sustentacular fragment angulation of >10°, twenty-four had sustentacular translation >3 mm, twenty had fracture diastasis of the middle facet, and twenty-one had a displaced intra-articular fracture of the calcaneal middle facet. Fractures involving greater than 50% of the posterior facet (consistent with Sanders Type-B and Type-C fracture lines) demonstrated a significant increase in relative risk of angulation and translation of the sustentacular fragment as well as gapping and intra-articular fractures of the middle facet. Three-part or four-part fractures also showed a significant association with overall displacement of the sustentaculum.

Conclusions: This study is the first to our knowledge to quantify in a detailed manner the displacement of the sustentacular fragment as occurring with calcaneal fractures. This displacement disproves the "constant" theory of the sustentacular fragment, and it may alter the quality of the fracture reduction and affect patient outcome. An alternative surgical approach may be indicated for the treatment of certain calcaneal fracture patterns with sustentacular displacement.

Level Of Evidence: Diagnostic Level II. See Instructions for Authors for a complete description of levels of evidence.
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http://dx.doi.org/10.2106/JBJS.L.01498DOI Listing
June 2013