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When Is a Fracture Good to Go?

Fracture Callus for OBuzzThis post comes from Fred Nelson, MD, an orthopaedic surgeon in the Department of Orthopedics at Henry Ford Hospital and a clinical associate professor at Wayne State Medical School. Some of Dr. Nelson’s tips go out weekly to more than 3,000 members of the Orthopaedic Research Society (ORS), and all are distributed to more than 30 orthopaedic residency programs. Those not sent to the ORS are periodically reposted in OrthoBuzz with the permission of Dr. Nelson. 

Determining when a fracture has healed enough for functional use can be difficult. The Radiographic Union Score for Tibia fractures (RUST) assesses fracture healing on a continuous scale from 4 to 12 points. Based on an evaluation of anteroposterior and lateral radiographs, RUST accounts for callus without visible fracture line (3 points), callus with visible fracture line (2 points), or absence of any callus (1 point) for each of four cortices. The modified RUST (mRUST) score subdivides the second parameter into two categories (callus present and bridging callus), creating a score ranging from 4 to 16 points. This tool has demonstrated high intraclass correlation coefficients (ICCs). However, until now, the correlation of these scores to mechanical properties of healed bone had not been demonstrated.

Cooke et al.1 evaluated both scores against the physical properties of bone healing by using a model of  closed, stabilized femur fractures in 8- to 12-week-old male mice. Control mice received a normal diet and an experimental group received a phosphate-restricted diet. The physical properties of bone healing were determined with micro-computed tomography (µCT) and torsion testing on postoperative days 14, 21, 35, and 42. There were 10 to 16 mice in each group at any given time-point.

RUST scores from five raters were determined from anteroposterior and lateral radiographic views constructed from the µCT scans. ICCs were 0.71 (mRUST) and 0.63 (RUST). Both RUST scores were positively correlated with callus bone mineral density, bone volume fraction, callus strength, and rigidity. Radiographically healed calluses with an mRUST score of ≥13 and a RUST score of ≥10 had excellent relationships to structural and biomechanical metrics.

Mechanical properties revealed the effects of delayed healing due to phosphate dietary restrictions at later time points, but no such distinctions were found in the RUST scores. Both the RUST and mRUST scores have high correlation to physical properties of bone healing, but this tool may not be reliable for detecting poor bone quality due to nutrient deficiencies.

Reference

  1. Cooke ME, Hussein AI, Lybrand KE, Wulff A, Simmons E, Choi JH, Litrenta J, Ricci WM, Nascone JW, O’Toole RV, Morgan EF, Gerstenfeld LC, Tornetta P 3rd. Correlation between RUST assessments of fracture healing to structural and biomechanical properties. J Orthop Res. 2018 Mar;36(3):945-953. doi: 10.1002/jor.23710. Epub 2017 Sep 20. PMID: 28833572 PMCID: PMC5823715 DOI: 10.1002/jor.23710

JBJS 100: THA Registries, Bone-Repair Growth Factors

JBJS 100Under one name or another, The Journal of Bone & Joint Surgery has published quality orthopaedic content spanning three centuries. In 1919, our publication was called the Journal of Orthopaedic Surgery, and the first volume of that journal was Volume 1 of what we know today as JBJS.

Thus, the 24 issues we turn out in 2018 will constitute our 100th volume. To help celebrate this milestone, throughout the year we will be spotlighting 100 of the most influential JBJS articles on OrthoBuzz, making the original content openly accessible for a limited time.

Unlike the scientific rigor of Journal content, the selection of this list was not entirely scientific. About half we picked from “JBJS Classics,” which were chosen previously by current and past JBJS Editors-in-Chief and Deputy Editors. We also selected JBJS articles that have been cited more than 1,000 times in other publications, according to Google Scholar search results. Finally, we considered “activity” on the Web of Science and The Journal’s websites.

We hope you enjoy and benefit from reading these groundbreaking articles from JBJS, as we mark our 100th volume. Here are two more, both from 2002:

The Swedish Total Hip Replacement Register
H Malchau, P Herberts, T Eisler, G Garellick, P Soderman: JBJS, 2002 November; 84 (Suppl 2): S2
In this 19-page analysis of data from the Swedish Total Hip Replacement Register, which was initiated in 1979, Malchau et al. pinpoint the striking clinical and socioeconomic effects of the Register’s first 20 years. The information captured by joint registries, especially in regions that provide universal health care coverage and thus maintain robust databases, has helped orthopaedic surgeons refine indications, surgical techniques, and implant choices.

The Role of Growth Factors in the Repair of Bone: Biology and Clinical Applications
J R Lieberman, A Daluiski, T A Einhorn: JBJS, 2002 June; 84 (6): 1032
Countless studies related to tissue engineering and the musculoskeletal system have been published in the 16 years since this Current Concepts Review  appeared in JBJS. Yet this article remains an essential primer for understanding how growth factors affect cells and tissues—and the possible applications for using growth factors to accelerate fracture healing, treat nonunions, and enhance spinal fusion.

ADHD and a Drug that Treats It Raise Risk of Some Fractures

Stress Fx for OBuzz Few physicians or patients associate attention deficit hyperactivity disorder (ADHD) with an increased risk of traumatic or stress-related fractures. However, in the June 6, 2018 issue of JBJS, a study by Ben-Ami et al. corroborates previous research suggesting that such associations exist. The authors evaluated 100,000 Israeli Defense Forces recruits and found that subjects diagnosed with ADHD were significantly more likely to sustain a traumatic fracture than recruits having no ADHD diagnosis. Furthermore, they found that recruits with ADHD who were taking the stimulant methylphenidate to treat their symptoms had a significantly increased risk of sustaining a stress fracture compared to both recruits without ADHD and recruits who had ADHD but did not take the medication.

The association between methylphenidate exposure and increased risk of stress fracture makes sense, based on animal studies showing that the drug leads to increased bone resorption. However, until now I was unaware that patients with ADHD are at an increased risk of traumatic fracture as well. The authors postulate that such an association is secondary to the fact that ADHD often manifests with compulsive or inattentive behavior that may predispose these patients to injuring themselves. That theory is further supported by this study’s finding that the risk of traumatic fracture fell when those with ADHD took stimulant medications to control their symptoms.

When one considers that upwards of 5% of school-aged children and another 4% of  adults in the US are prescribed stimulant medication (not to mention the estimated 5% to 35% of US college students who abuse stimulants without prescription), these findings take on great importance.  Because of the large number of children and adults who rely on methylphenidate to control ADHD symptoms, it is important for both primary care physicians and orthopaedic surgeons to understand the association between this medication and stress fractures.

Although limited by the vulnerabilities typically found in observational, retrospective designs, this study’s findings add to a growing body of evidence highlighting the potential fracture risks associated with stimulant medication. We probably encounter patients taking such medications on a regular basis in our practices. These data should prompt us to ask more questions of patients who have sustained stress fractures to determine whether stimulant medication usage may be an underlying cause.

Chad A. Krueger, MD
JBJS Deputy Editor for Social Media

JBJS 100: Massive Rotator Cuff Tears, Continuous Passive Motion

JBJS 100Under one name or another, The Journal of Bone & Joint Surgery has published quality orthopaedic content spanning three centuries. In 1919, our publication was called the Journal of Orthopaedic Surgery, and the first volume of that journal was Volume 1 of what we know today as JBJS.

Thus, the 24 issues we turn out in 2018 will constitute our 100th volume. To help celebrate this milestone, throughout the year we will be spotlighting 100 of the most influential JBJS articles on OrthoBuzz, making the original content openly accessible for a limited time.

Unlike the scientific rigor of Journal content, the selection of this list was not entirely scientific. About half we picked from “JBJS Classics,” which were chosen previously by current and past JBJS Editors-in-Chief and Deputy Editors. We also selected JBJS articles that have been cited more than 1,000 times in other publications, according to Google Scholar search results. Finally, we considered “activity” on the Web of Science and The Journal’s websites.

We hope you enjoy and benefit from reading these groundbreaking articles from JBJS, as we mark our 100th volume. Here are two more:

The Outcome and Repair Integrity of Completely Arthroscopically Repaired Large and Massive Rotator Cuff Tears
L M Galatz, C M Ball, S A Teefey, W D Middleton, K Yamaguchi: JBJS, 2004 February; 86 (2): 219
In one of the earliest studies to investigate the relationship between the anatomic integrity of arthroscopic rotator cuff repair and clinical outcome, these authors found that the rate of recurrent defects was high but that at 12 months after surgery, patients experienced excellent pain relief and functional improvement. However, at the 2-year follow-up, the clinical results had deteriorated substantially. Investigations into the relationship between cuff-repair integrity and clinical outcomes are ongoing.

The Biological Effect of Continuous Passive Motion on the Healing of Full-thickness Defects in Articular Cartilage: An Experimental Investigation in the Rabbit
R B Salter, D F Simmonds, B W Malcolm, E J Rumble, D Macmichael, N D Clements: JBJS, 1980 January; 62 (8): 1232
In this paper, Salter and colleagues hypothesized that “continuous passive motion [CPM] of a synovial joint in vivo would have a beneficial biological effect on the healing of full-thickness defects in articular cartilage.” They found that CPM stimulated more rapid and complete cartilage restoration than either immobilization or intermittent active motion, and since then CPM has been commonly used in humans after cartilage repair. However, CPM’s actual efficacy in people—after cartilage repair or total knee arthroplasty—remains controversial.

Preparing PRP: More Questions than Answers

This post comes from Fred Nelson, MD, an orthopaedic surgeon in the Department of Orthopedics at Henry Ford Hospital and a clinical associate professor at Wayne State Medical School. Some of Dr. Nelson’s tips go out weekly to more than 3,000 members of the Orthopaedic Research Society (ORS), and all are distributed to more than 30 orthopaedic residency programs. Those not sent to the ORS are periodically reposted in OrthoBuzz with the permission of Dr. Nelson. 

The use of platelet-rich plasma (PRP) in the treatment of tendinitis, some sports injuries, and osteoarthritis has been popularized over the past decade. Because there is “minimal” manipulation of biologic products such as PRP, their preparation is not subject to the rigid standards used for the development of pharmacologic products.

In a recent study of autologous PRP, investigators hypothesized that “lower levels of inflammatory cytokines (ICs) within PRP stimulate positive chondrocyte and macrophage responses irrespective of the age and OA disease state of the PRP donor”1. To test this hypothesis, investigators made PRP preparations from young healthy individuals and older patients with end-stage OA using a modified double-spin protocol. The level of inflammatory cytokines (ICs) was identified in all PRP preparations. Chondrocytes were isolated from normal-appearing cartilage harvested from an arthritic knee during total joint arthroplasty. Alginate beads were created for culture and were treated with 10% PRP on days 0 and 2 of a 4-day culture period.

The results contradicted the hypothesis. There were a number of adverse results in the cultures treated with PRP donated by the OA group. Macrophage activation increased with OA disease status/age of the PRP donor. PRP from OA subjects significantly upregulated TNF-α (p <0.001) and MMP-9 (p<0.0001) in macrophage cultures irrespective of whether the PRP had “high” or “low” IC levels. Additionally, PRP from donors with OA decreased Col2a1 (p<0.05) and SOX9 (p<0.05) expression more than PRP from healthy donors, irrespective of IC grouping.

According to these findings, the functional effects of PRP appear to be dependent on the age and disease status of the plasma donor, as opposed to the IC concentration. This suggests that a more complex interaction with age or OA-related molecular factors might dictate the effect of PRP.

In a separate study, the issue of variation of PRP preparations in research was evaluated by Delphi consensus and other methodologies.2 One key consensus of the PRP experts was the importance of detailing the cellular composition of whole blood and the delivered PRP. The experts also noted marked individual variation in PRP and the need for a clear understanding of the factors influencing such variation.

References

  1. O’Donnell C, Migliore E, Grandi FC, Lingampalli N, Raghu H, Giori N N, J, Indelli PF, Robinson WH, Bhutani N, Chu CR. Donor Specific Effects of Platelet-Rich Plasma for the Treatment of Osteoarthritis Trans Orthop Res Sco. 2018. Paper 0063
  2. Murray IR, Geeslin AG, Goudie EB, Petrigliano FA, LaPrade RF. Minimum Information for Studies Evaluating Biologics in Orthopaedics (MIBO): Platelet-Rich Plasma and Mesenchymal Stem Cells. J Bone Joint Surg Am. 2017 May 17;99(10):809-819. doi: 10.2106/JBJS.16.00793

Overselling Stem Cells?

Stem Cells for OBuzzThis post comes from Fred Nelson, MD, an orthopaedic surgeon in the Department of Orthopedics at Henry Ford Hospital and a clinical associate professor at Wayne State Medical School. Some of Dr. Nelson’s tips go out weekly to more than 3,000 members of the Orthopaedic Research Society (ORS), and all are distributed to more than 30 orthopaedic residency programs. Those not sent to the ORS are periodically reposted in OrthoBuzz with the permission of Dr. Nelson.

In orthopaedics, the term “biologics” is often applied to cell-based therapies. There are a number of centers using mesenchymal stem cells (MSCs) in musculoskeletal medicine, and a recent systematic review assessed the quality of literature and procedural specifics surrounding MSC therapy for osteoarthritis (OA)1.

The authors searched four large scientific databases for studies investigating MSCs for OA treatment. Among the 61 articles analyzed, 2,390 OA patients were treated, most with adipose-derived stem cells (ADSCs) (n = 29 studies) or bone marrow-derived stem cells (BMSCs) (n = 30 studies), though the preparation techniques varied within each group. In a subanalysis of 5 Level I and 9 Level II studies (288 patients), researchers found that 8 studies used BMSCs, 5 used ADSCs, and 1 used peripheral blood stem cells. A risk-of-bias analysis showed 5 Level I studies at low risk, 7 Level II studies at moderate risk, and 2 Level II studies at high risk. The authors concluded that although there is a “notion” that MSC therapy has a positive effect on OA patients, there is limited high-quality evidence and a dearth of long-term follow-up.

Despite the low-quality evidence and the many questions surrounding MSCs for treating OA, there are an estimated 570 clinics in the US marketing “stem cell” treatments for orthopaedic problems2. The American Academy of Orthopaedic Surgeons (AAOS) and the National Institute of Arthritis and Musculoskeletal and Skin Diseases recently convened a symposium on this issue. According to Constance Chu, MD, professor of orthopaedic surgery at Stanford University and the symposium program chair, the objective was to establish a clear, collective impact agenda for the clinical evaluation, use, and optimization of biologics in orthopaedics, and to develop a guidance document on clinically meaningful endpoints and outcome metrics for the evaluation of biologics used in orthopaedics.

Symposium attendees examined the possible use of registries to generate clinical evidence on the use of biologics in orthopaedics. Registry models that could be employed to obtain data on practice patterns and early warning of potential issues include the American Joint Replacement Registry, the Kaiser Registry, and the International Cartilage Repair Registry. Another model could be a biorepository-linked registry similar to what has been established at the VA Hospital in Palo Alto, California, where samples from platelet-rich plasma are stored for later comparison with clinical outcomes.

References

  1. Jevotovsky DS, Alfonso AR, Einhorn TA, Chiu ES. Osteoarthritis and Stem Cell Therapy in Humans: A Systematic Review, Osteoarthritis and Cartilage (2018), doi: 10.1016/ j.joca.2018.02.906.
  2. Symposium by The American Academy of Orthopaedic Surgeons and the National Institute of Arthritis and Musculoskeletal and Skin Diseases. “Optimizing Clinical Use of Biologics in Orthopaedic Surgery,” Feb. 15–17, 2018, at Stanford University.

For Biceps Tenodesis, Bone-Tunnel and Cortical-Surface Fixation Are Equally Good

Cortical Surface Attachment for OBuzzMany orthopaedic procedures involve reattaching a tendon to bone, but the decision as to whether that fixation is made through a bone tunnel or by cortical-surface attachment is usually left up to the surgeon’s preference. In the March 21, 2018 issue of The Journal of Bone & Joint Surgery, Tan et al. attempted to determine which fixation technique, in a rabbit model, provides better tendon-to-bone healing.

The rabbits in the bone-tunnel group and the cortical surface attachment group were killed 8 weeks after biceps tenodesis surgery, and the authors performed detailed biomechanical testing, microcomputed tomography analysis, and histological analysis to evaluate the tendon healing. Here’s what they found:

  • There were no significant between-group differences in mean failure loads or stiffness.
  • There were no significant between-group differences in mean volume of newly formed bone or in the mineral density of newly formed bone.
  • In both groups, histological analysis revealed tendon-bone interdigitation and early fibrocartilaginous zone formation on the outer cortical surface. (This article includes interactive digital whole-slide images of cortical surface attachment and bone-tunnel fixation.)

These findings led the authors to conclude that “tendon fixation in a bone tunnel and on the cortical surface resulted in similar healing profiles.” Because both techniques facilitate good tendon-to-bone healing, surgeon preference will probably continue to dictate the decision to use one method over another.

Webinar on March 29 – Spondylolysis in Adolescents: Diagnosis, Treatment, and Outcomes

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Low back pain is not typically thought to be a pediatric issue; however, this condition occurs in 33% of adolescents each year—a rate similar to that seen in adults. The most common identifiable cause of low back pain in the adolescent is spondylolysis, a defect in the pars interarticularis. How is this condition best diagnosed and treated? Do oblique radiographs help diagnose spondylolysis in adolescents? What kind of short- and long-term clinical outcomes can adolescents—and especially adolescent athletes—diagnosed with acute spondylolysis expect to have? What factors might predict long-term outcomes?

These important and clinically applicable questions will be addressed during a complimentary LIVE webinar, hosted jointly by the Journal of Orthopaedic & Sports Physical Therapy (JOSPT) and The Journal of Bone & Joint Surgery (JBJS).

JBJS presenter, Peter Passias, MD, will discuss findings from a retrospective study of adolescents with and without L5 spondylolysis to address whether oblique radiographic views add value in the diagnosis of this cause of low back pain. This paper specifically addresses whether the diagnostic benefit of four-view studies outweighs the additional cost and radiation exposure, especially for young people.

JOSPT co-author Mitchell Selhorst, DPT, OCS, will share the results of a retrospective review of acute spondylolytic injuries in young athletes. This study reports long-term clinical outcomes for these patients and identifies significant predictors of these outcomes.

Moderated by JBJS Deputy Editor Andrew J. Schoenfeld, MD, who specializes in spondylolisthesis, spinal stenosis, and spinal surgery, the webinar will include additional insights from expert commentators, Chris Bono, MD,from Brigham and Women’s Hospital in Boston, and Michael Allen, PT, from Cincinnati Children’s Hospital Medical Center. The last 15 minutes will be devoted to a live Q&A session between the audience and panelists.

Space is limited, so Register Now.

Fragility Fracture Risk Prediction: Beyond BMD

BMD for OBuzzThis basic science tip comes from Fred Nelson, MD, an orthopaedic surgeon in the Department of Orthopedics at Henry Ford Hospital and a clinical associate professor at Wayne State Medical School. Some of Dr. Nelson’s tips go out weekly to more than 3,000 members of the Orthopaedic Research Society (ORS), and all are distributed to more than 30 orthopaedic residency programs. Those not sent to the ORS are periodically reposted in OrthoBuzz with the permission of Dr. Nelson.

Bone mineral density (BMD)—a measure of both cortical and trabecular bone—has been widely used as an index of bone fragility. The femoral neck and lumbar vertebrae are the areas most commonly measured with BMD, but hip osteoarthritis and lumbar spondylosis can mask systemic osteoporosis. In addition, the most common fragility fractures occur at the distal radius.

Investigators conducted a prospective study using high-resolution peripheral quantitative computed tomography (HR-pQCT) of the distal radius and tibia to determine whether baseline skeletal parameters could predict fragility fractures in women. A second goal was to establish whether women who have fragility fractures experience bone loss at a faster rate than those who do not have fractures.

Among 149 women older than 60 years who had baseline and 5-year follow-up HR-pQCT, 22 had a fragility fracture during the study period and 127 did not. HR-pQCT is able to record total bone mineral density (Tt.BMD), trabecular bone mineral density (Tb.BMD), trabecular number (Tb.N), and trabecular separation (Tb.Sp).

The analysis showed that women with fragility fractures had lower baseline Tt.BMD (19%), Tb.BMD (25%), and Tb.N (14%), along with higher Tb.Sp (19%) than women who did not experience a fracture. Analysis of the tibia measures yielded similar results, showing that women with incident fracture had lower Tt.BMD (15%), Tb.BMD (12%), cortical thickness (14%), and cortical area (12%). Also, women with fractures had lower failure load (10%) with higher total area and trabecular area than women without fractures.

For each standard deviation decrease of a measure at the distal radius, the odds ratio for fragility fracture was 2.1 for Tt.BMD. 2.0 for Tb.BMD, and 1.7 for Tb.N. ORs for those measures at the tibia were similar.

In contrast to these findings, the annualized percent rate of bone loss was not different between groups with and without fractures. These results suggest that future fragility-fracture risk prediction should rely at least as much on bone architecture and strength as on simple BMD measurements.

Reference
Burt LA, Manske SL, Hanley DA, Boyd SK. Lower Bone Density, Impaired Microarchitecture, and Strength Predict Future Fragility Fracture in Postmenopausal Women: 5-Year Follow-up of the Calgary CaMos Cohort. J Bone Miner Res. 2018 Jan 24. doi: 10.1002/jbmr.3347 PMID: 29363165

Prosthetic Metal Allergies: The Mystery Continues

Metal Hypersensitivity for OBuzzThis basic science tip comes from Fred Nelson, MD, an orthopaedic surgeon in the Department of Orthopedics at Henry Ford Hospital and a clinical associate professor at Wayne State Medical School. Some of Dr. Nelson’s tips go out weekly to more than 3,000 members of the Orthopaedic Research Society (ORS), and all are distributed to more than 30 orthopaedic residency programs. Those not sent to the ORS are periodically reposted in OrthoBuzz with the permission of Dr. Nelson.

Immunosensitivity to metallic implants has been recognized for years, with the principal research focus on joint arthroplasty components. While cutaneous metal allergies are relatively common (as prevalent as 20%), immunosensitivity to implanted metal is much less common.

On their own, metal ions in the body such as nickel and cobalt do not cause immune responses, although high levels can be toxic to specific organs. However, when these ions associate with proteins in the plasma they may form haptens. These molecules in turn may bring about delayed hypersensitivity reactions.

Reactions to metals appear to be type IV (delayed) hypersensitivity responses leading to activation of T-lymphocytes, which in turn release inflammatory cytokines. While Langerhans cells in skin respond to direct or indirect antigen presentation, we don’t know which cells are involved in intra- and extra-articular manifestations in total joint arthroplasty. The skin response may include eczematous and/or erythematous papular lesions; within the affected limb, pain, swelling, and stiffness may be regional responses.

Determining cause and effect remains problematic. We have not yet conclusively determined whether symptoms from joint implants are due to metal sensitivity.  The diagnosis of metal immunosensitivty is based on exclusion of complications such as infection, aseptic loosening, mechanical malalignment, and, less commonly, complex regional pain syndrome and overstuffing.

The two most utilized tests for implant metal allergies are cutaneous patch testing and lymphocyte transformation testing. Unfortunately, cutaneous testing may not reflect the process in the joint, and preoperative patch screening has not proven to be beneficial. Lymphocyte transformation testing is expensive, not validated, and unavailable for many.

Alternatives include use of implants coated with titanium nitride, zirconia nitride, or zirconium oxide, or the use of “hypoallergenic” metals such as titanium and oxinium. However, except in the setting of revision, the clinical and cost effectiveness of these metals remain to be confirmed. The one relative certainty related to this issue is to use alternative-metal implants in patients with known severe systemic or cutaneous metal sensitivity.

References

Nima Eftekhary, MD; Nicholas Shepard, MD; Daniel Wiznia, MD; Richard Iorio, MD; William J. Long, MD, FRCSC; and Jonathan Vigdorchik, MD. Metal Hypersensitivity in Total Joint Arthroplasty https://icjr.net/articles/metal-hypersensitivity-in-total-joint-arthroplasty

Arif Razak, BSc, MBChB, MRCS; Ananthan D. Ebinesan, MBChB, MRCS; Charalambos P. Charalambous, BSc, MBChB, MSc, MD, FRCS (Tr & Orth). Metal Hypersensitivity in Patients with Conventional Orthopaedic Implants. JBJS Reviews; 2014 Feb 4; 2 (2).10.2106/JBJS.RVW.M.00082