Archive | Basic Science RSS for this section

Sept. 11 Webinar – Assessment of Bone Health for the Orthopaedic Surgeon

Sept Webinar Speakers

Orthopaedic care teams can play an active role in evaluating and optimizing their patients’ bone health to help prevent primary and secondary fragility fractures and to improve postsurgical outcomes. In just about any orthopaedic scenario, helping patients optimize their bone health is an imperative for the delivery of quality care.

On Tuesday, September 11, 2018 at 8 pm EDTthe American Orthopaedic Association (AOA) and The Journal of Bone & Joint Surgery (JBJS) will host a complimentary one-hour webinar that will cover the basics of a bone-health assessment by orthopaedists.

  • Christopher Shuhart, MD will discuss the fundamentals of bone-related laboratory workups and bone densitometry studies.
  • Joe Lane, MD, FAOA will identify bone-health “red flags” in orthopaedic patients, including common nutritional deficiencies.
  • Paul Anderson, MD, FAOA will cover recent advances in bone-density measurements.

Moderated by Douglas Lundy, MD, MBA, FAOA, orthopaedic trauma surgeon at Resurgens Orthopaedics, this webinar will include a 15-minute live Q&A session during which attendees can ask questions of the panelists.

Seats are limited so REGISTER NOW.

JBJS 100: Proximal Humeral Fractures, Stem Cells

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:

Displaced Proximal Humeral Fractures: Classification and Evaluation
C Neer: JBJS, 1970 September; 52 (6): 1077
Complex distal humeral fractures have long challenged orthopaedic surgeons and their patients. Often the first step in fracture-management decision-making is classification, and in this 1970 study, Dr. Neer proposed a 6-group classification based on the presence or absence of displacement of one or more of the four major proximal segments. Since then, this classification has been variably adapted by multiple authors, but its usefulness remains intact.

The Effect of Implants Loaded with Autologous Mesenchymal Stem Cells on the Healing of Canine Segmental Bone Defects
S F Bruder, K H Kraus, V M Goldberg, S Kadiyala: JBJS, 1998 July; 80 (7): 985
Research into mesenchymal stem cells (MSCs) to augment healing of tendons, chondral and bone defects, and other connective tissues has taken off since these authors used autologous MSCs to help heal 21-mm segmental femoral defects. Radiographic union occurred rapidly at the interface between host bone and porous ceramic cylinders loaded with MSCs, and a large collar of bone had formed around the cell-loaded implants after 16 weeks.

JBJS 100: Gait Initiation, ACL Replacement

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 Initiation of Gait
R A Mann, J L Hagy, V White, D Liddell: JBJS, 1979 March; 61 (2): 232
Using electromyography and force-plate data, this study of 10 healthy men and women revealed that the deceptively simple motion of taking the first step from a standing position is initiated by the unbalanced body harnessing complex neural mechanisms, muscular activity, and biomechanical forces. The findings can inform today’s efforts to prevent falls among the elderly.

Replacement of the Anterior Cruciate Ligament using a Patellar Tendon Allograft
S P Arnoczky, R F Warren, M A Ashlock: JBJS, 1986 January; 68 (3): 376
Fresh or deep-frozen? That was the question researchers asked in this study of 25 dogs whose patellar tendons were replaced with one of these two types of allografts. The fresh allografts incited a marked inflammatory and rejection response, while the deep-frozen allografts appeared to be benign and behaved comparably to autogenous patellar tendon grafts. In the 30-plus years since this 1986 study, we have learned a lot about the immunogenicity and biologic character of transplanted allografts, and this important research continues.

PRP for Tennis Elbow: What’s the “Secret Sauce”?

Tennis Elbow Image 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. 

There are many suggested applications for platelet-rich plasma (PRP), including tendon repair, osteoarthritis, and other musculoskeletal conditions. However there is considerable controversy in the absence of convincing evidence about the optimal mix and concentration of white blood cells and platelets in PRP, and the most clinically effective nature and quantity of constituent cytokines or other biochemical agents in PRP.

Despite these lingering questions, PRP is commonly used to treat lateral epicondylitis (LE), commonly called “tennis elbow.” As with its other applications, the clinical use of PRP for painful tendons has received much attention, but its efficacy remains controversial.

To continue investigating the clinical effects of PRP and its individual components, researchers recruited 156 patients with LE and randomly divided them into those treated with a single injection of 2-mL autologous PRP and those who received only physical therapy without injection.1 Both groups used a tennis elbow strap and performed stretching and strengthening exercises for 24 weeks, at which point pain and functional improvements were assessed using the visual analog scale (VAS), Modified Mayo Clinic Performance Index for the elbow, and MRI. Levels of platelet-derived growth factor-AB (PDGF-AB), PDGF-BB, transforming growth factor-β (TGF-β), vascular endothelial growth factor, epithelial growth factor, and interleukin-1 β in the PRP were measured for statistical correlation with clinical scores.

At 24 weeks, all pain and functional variables—including VAS score, Mayo Clinic performance scores, and MRI grade—improved significantly in the PRP group, relative to the noninjection group (p < 0.05). The TGF-β level in the PRP significantly correlated with Mayo Clinic performance score and MRI grade improvement.

The PRP level of TGF-β appears to be important in tendon healing, but future studies will be required to determine the best relative concentrations of white blood cells and platelets that deliver specific cytokines such as TGF-β. However, these results help identify a viable protocol for measuring PRP efficacy in tendinopathies.

Reference

  1. Lim W, Park SH, Kim B, Kang SW, Lee JW, Moon YL. Relationship of cytokine levels and clinical effect on platelet-rich plasma-treated lateral epicondylitis. J Orthop Res. 2018 Mar;36(3):913-920. doi: 10.1002/jor.23714. Epub 2017 Sep 20. PMID: 28851099

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.