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June 26, 2020  

COVID-19’s Musculoskeletal Manifestations

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 SARS-CoV-2 coronavirus that causes COVID-19 induces the expression of several cytokines and signaling molecules. The impact of these inflammatory mediators on the lungs is the most lethal effect and thus has drawn the most attention. However, COVID-19 can have potentially longer-lasting (but less deadly) musculoskeletal effects.

COVID-19 has not been affecting people long enough to study its effects completely, but we do know that the virus predominantly infects type-II pneumocytes that line the respiratory epithelium. These cells express angiotensin converting enzyme-2 (ACE2) and transmembrane protease, serine 2 (TMPRSS2). Disser et al. note that TMPRSS2 is also expressed in muscle tissue, while only smooth muscle cells and pericytes express ACE2. They add that either ACE2 or TMPRSS2 is expressed in cartilage, menisci, bone, and synovium.

Myalgia has been reported to occur in COVID-19 patients 25% to 50% of the time. The effect on muscle can be severe, with more seriously ill patients having higher levels of creatine kinase. After recovery, patients often show decreased strength and endurance, but it is not clear how much of that is due to deconditioning or to persisting muscle effects. Although arthralgia can also occur, it is hard to separate those symptoms from myalgia, and both may exist at the same time.

Examination of muscle specimens from autopsies of COVID-19 patients shows significant muscle destruction. It is not clear whether the osteoporosis and osteonecrosis sometimes seen with SARS-CoV-2 is due to the virus’s direct effect on bone or to the steroids used to treat patients with more severe cases.

Because it is probable that inflammation associated with cytokine release has an impact on musculoskeletal tissues, orthopaedic surgeons are likely to be faced with a variety of musculoskeletal symptoms in post COVID-19 patients. Preliminary data suggest that rehabilitation for both strength and endurance is effective among patients who recover from COVID-19, but it is not clear whether return to former conditioning levels occurs. The use of immunotherapies, such as IL-1 and IL-6 inhibitors, may have a positive impact on initial treatment in these patients.

May 28, 2020  

Surgery to Repair the Hip’s ‘Rotator Cuff’

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.

Symptoms from gluteus medius tendon tears are common in people older than 50 years, but they are hard to distinguish from referred pain due to lumbar spine conditions or hip disorders such as osteoarthritis and femoroacetabular impingement. Because conservative measures are often effective, surgical remedies are not commonly discussed in the literature.

An anatomical study of the gluteus medius tendon found that the posterior part of the tendon has a fan-like shape and converges onto the superoposterior facet of the greater trochanter. The anterolateral part runs posteroinferiorly toward the lateral facet of the greater trochanter. Both the posterior and anterolateral parts insert via fibrocartilage. Given the nonuniform structure of this tendon, the thin anterolateral part may be more prone to tears than the thick posterior part.

In another recent study, a single surgeon described his experience with 185 consecutive gluteus medius tendon tear repairs.1 Tendon changes were confirmed preoperatively on MRI. Roughening of all appropriate surfaces preceded multiple-suture repair through bone holes, with sutures in line with the tendon segment being attached. Of the 185 patients, 165 completed 5- to 10-year phone follow-ups. The average age was 69 and 92% were female. There was no histological evidence of bursitis in any case. Only 9 patients reported worse Oxford Hip Scores at the 5-year follow-up; deep vein thrombotic events occurred in 4% of patients despite prophylaxis. Other common gluteus medius tendon repair techniques include utilization of suture anchors through a mini-open2 or arthroscopic approach.

Unlike degenerative rotator cuff tears of the shoulder, both incomplete and complete acute tears of the gluteus medius respond well to repair surgery. More advanced degenerative gluteus medius tendon changes do not respond as well. It is not clear what the differences are in the mechanical and biochemical mechanisms of rotator cuff and gluteal tendon changes that make surgery to repair the former seemingly less successful than surgery to repair the latter. Nevertheless, these four studies show promise for surgical interventions that have a reasonable chance of being effective, with relatively low risk.

References

  1. Fox OJK, Wertheimer G, Walsh MJ. Primary Open Abductor Reconstruction: A 5 to 10-Year Study. J Arthroplasty. 2020 Apr;35(4):941-944. doi: 10.1016/j.arth.2019.11.012. Epub 2019 Nov 14. PMID: 31813815
  2. Caleb M Gulledge, Eric C Makhni. Open Gluteus Medius and Minimus Repair With Double-Row Technique and Bioinductive Implant Augmentation. Arthrosc Tech 2019 May 17;8(6):e585-e589. doi: 10.1016/j.eats.2019.01.019. eCollection 2019 Jun. PMID: 31334014 PMCID: PMC6620622
February 27, 2020  

Osteoarthritis Progression: Our Current Understanding

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.

Our understating of the progression pathways in knee osteoarthritis (OA) has evolved dramatically in recent years, as described in a recent review article.1 Over the past 2 decades, we have come to view the knee joint as an organ unto itself (with cartilage, synovium, bone, ligaments, and capsule). In the knee, we add to the mix the meniscus, which not only guides motion but is responsible for weight distribution on articular cartilage. Investigations into the etiology and progression of knee OA have merged joint mechanics with insights from studies of inflammation and immunology.

Woodell-May and Sommerfeld examine the process of knee OA as a wound-healing response. Triggered by damage-associated molecular patterns, the innate immune system is typically the first responder to this process. The acute phase in wound healing is short and involves infiltration of neutrophils. In response to neutrophil signals, monocytes migrate from the vessels and differentiate into macrophages, initially type I (inflammatory), which help form the granulation tissue seen in wound healing.

One take-home from the review article is that OA progression may be driven by the chronic inflammation associated with continuing efforts to heal. The back-and-forth between stimulating inflammation (M1 macrophages) and modulating inflammation (M2 macrophages) seems to be predominately driven from the synovium. In addition, specific receptors and intracellular kinases (such as toll-like receptors and mitogen-activated protein kinase) are upregulated in many OA samples.

M1 macrophages promote the elaboration of TNFα and IL-1 by synovial cells. Both cytokines are also active in rheumatoid arthritis (RA). Biologic treatment directed at either one of those cytokines can be effective in RA, but such treatment does not appear to be effective in OA. Over the past decade, the use of autologous conditioned serum (serum drawn off after blood is exposed to glass beads and incubated) has been studied in an attempt to reduce IL-1 activity. The conditioned serum also seems to affect TNFα and has shown some early promise in OA cases.

This burgeoning basic-science knowledge about OA has the potential to lead to disease-modifying treatments, which would revolutionize how orthopaedists approach OA treatment.

Reference
1. Woodell-May JE, Sommerfeld SD. Role of Inflammation and the Immune System in the Progression of Osteoarthritis. J Orthop Res. 2020 Feb;38(2):253-257. doi: 10.1002/jor.24457. Epub 2019 Sep 12. Review. PMID: 31469192

January 23, 2020  

Pulsed EMF Stimulation for Tendon Healing? Stay Tuned

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 effects of electrical currents on early wound healing are well known and studied. The possibility that stimulation of bone formation could be induced with a pulsed electromagnetic field (PEMF) was investigated in the 1960s and translated into clinical use by the 1970s. But the clinical use of PEMF for tendon disorders has not met with similar success.

The precise mechanisms by which these fields affect different tissues is easier to study with the tools we have available today. The measurable parameters of PEMF are intensity, duration, frequency, and duty cycle (percent of time the field is on). Nevertheless, many questions about the possible adverse effects of these fields, their focal delivery, and their possible clinical applications remain unanswered.

In a study of human tendon cells, researchers artificially induced inflammatory cues in cultures using different concentrations of IL‐1β.1 When 1 ng/mL of IL‐1β was used, subsequent cytokine and metalloprotease expression was measured at 1, 2, 3, and 7 days after various PEMF exposures.

The PEMF exposure parameters that most evidently decreased the production of IL-6 and tumor necrosis factor-α (TNF-α) were 4 mT, 5 Hz, and a 50% duty cycle. Those same parameters decreased the expression of TNFα, IL-6, IL-8, COX-2, MMP-1, MMP-2, and MMP-3, while at the same time increasing gene expression of the anti-inflammatory proteins IL-4, IL-10, and TIMP-1. However, the combination of 5 mT and 50% duty cycle had a negative impact on cell viability.

These preliminary results may help guide future investigations, but the authors note that the parameters for optimal PEMF effectiveness on tendon cells may vary with time from insult, further complicating the selection of field parameters.

Reference

  1. Vinhas A, Rodrigues MT, Gonçalves AI, Reis RL, Gomes ME. Pulsed Electromagnetic Field Modulates Tendon Cells Response in IL-1β-Conditioned Environment. J Orthop Res. 2020 Jan;38(1):160-172. doi: 10.1002/jor.24538. Epub 2019 Dec 10.
December 16, 2019  

Shedding Low-Level Laser Light on Knee OA

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.

Low-level laser therapy (LLLT) has been used in multiple countries to treat the pain and function deficits associated with knee osteoarthritis (OA). The wavelength typically used is in the near-infrared region. However, this therapy is not recommended by most clinical guidelines, including those of the Osteoarthritis Research Society International. The hesitancy to recommend LLLT is due largely to conflicting published findings and unresolved dose-related issues such as wavelength, intensity, and frequency of treatment. For treating knee OA, the World Association for Laser Therapy (WALT) recommends applying four times the laser dose with continuous rather than pulsed irradiation.

To try to resolve conflicting evidence, Stausholm et al. conducted a systematic review and meta-analysis of randomized, placebo-controlled trials of LLLT, distilling 22 trials from 2,735 initially identified articles.1 Pain, as measured by a 0 to 100 mm visual analog scale (VAS), was significantly reduced by LLLT compared with placebo at the end of therapy (14.23 mm VAS; 95% CI 7.31 to 21.14) and during follow-ups 1 to 12 weeks later (15.92 mm VAS; 95% CI 6.47 to 25.37). Subgroup analysis revealed that pain was significantly reduced by the recommended LLLT doses compared with placebo at the end of therapy (18.71 mm VAS; 95% CI 9.42 to 27.99) and during follow-ups 2 to 12 weeks after the end of therapy (23.23 mm VAS; 95% CI 10.60 to 35.86).

Pain reduction from the recommended doses peaked during follow-ups 2 to 4 weeks after the end of therapy. Disability was also significantly reduced by LLLT, and no adverse events were reported in any of the studies. Notably, in light of JBJS Editor-in-Chief Marc Swiontkowski’s recent comments about the quality of meta-analyses, this meta-analysis was reported in accordance with PRISMA guidelines and all included trials were evaluated for risk of bias.

What remains unclear is how far past the skin the varied wavelengths and intensities (usually 1 to 8 Joules) of laser energy penetrate. Likewise, tissue heating has not been measured or analyzed. Still, at present, it appears that LLLT used with WALT guidelines is a safe and potentially effective treatment for the pain and dysfunction of knee OA.

Reference

  1. Stausholm MB, Naterstad IF Msc, Joensen J, Lopes-Martins RÁB, Sæbø H Msc, Lund H, Fersum KV, Bjordal JM. Efficacy of low-level laser therapy on pain and disability in knee osteoarthritis: systematic review and meta-analysis of randomised placebo-controlled trials. BMJ Open. 2019 Oct 28;9(10):e031142. doi: 10.1136/bmjopen-2019-031142. PMID: 31662383
December 11, 2019  

What’s New in Musculoskeletal Basic Science 2019

Every month, JBJS publishes a review of the most pertinent and impactful studies published in the orthopaedic literature during the previous year in 13 subspecialties. Click here for a collection of all such OrthoBuzz summaries. This month, co-author Philipp B. Leucht, MD selected the most clinically compelling findings from the 40 studies summarized in the December 4, 2019 “What’s New in Musculoskeletal Basic Science.”

Muscle Regeneration
–Recent findings about the cellular players in muscle regeneration may allow further development of clinical treatment options for patients with muscle sprains, tears, and loss. Toward that end, Wosczyna et al. established the crucial role of fibroadipogenic progenitors (FAPs, also called mesenchymal stromal cells) in muscle repair and maintenance.1 Using a mouse model, the researchers showed that FAPs are necessary for muscle regeneration by supporting muscle stem cells.

Bone-Brain Crosstalk
–The bone-derived hormone osteocalcin supports development of the musculoskeletal system and the brain. Osteocalcin can regulate anxiety and cognition in adult mice, and Obri et al. postulated that declining levels of osteocalcin may be responsible for the cognitive decline seen in aging.2 This finding may spur investigations into exogenous treatment with osteocalcin to restore brain function.

Tendon Regeneration
–Tendon cells express the transcription factor Scleraxis, which has facilitated the identification of the tendon stem progenitor cell (TSPC). Best and Loiselle identified a Scleraxis-positive cell population in the bridging scar tissue after tendon injury.3 These findings suggest that TSPCs are present in the adult tendon and contribute to the healing response; however, their small number does not result in successful tendon regeneration, but rather in scar formation with interspersed tendon tissue.

–Abraham et al. identified the upregulation of NF-κB (nuclear factor kappa-light-chain-enhancer of activated B cells) and its downstream targets in tendinopathy-affected human rotator cuff tendons.4 Using a transgenic mouse model in which IKKß (inhibitor of nuclear factor kappa-B kinase subunit beta), a key regulator of inflammation, was overexpressed, they demonstrated the development of tendinopathy in mouse rotator cuff tendons. The deletion of IKKß had a protective effect from chronic overuse.

Bone Regeneration
–Successful bone healing after fracture is highly dependent on the presence and activation of skeletal stem cells. Chan et al. precisely defined the human skeletal stem cell (hSSC), demonstrated the hSSC’s role in human fracture repair, and provided evidence that these cells generate a bone marrow-supportive niche.5 These cells also give rise to bone, cartilage, and stromal progenitor cells.

References

  1. Wosczyna MN, Konishi CT, Perez Carbajal EE, Wang TT, Walsh RA, Gan Q, Wagner MW, Rando TA. Mesenchymal stromal cells are required for regeneration and homeostatic maintenance of skeletal muscle. Cell Rep.2019 May 14;27(7):2029-2035.e5.
  2. Obri A, Khrimian L, Karsenty G, Oury F. Osteocalcin in the brain: from embryonic development to age-related decline in cognition. Nat Rev Endocrinol.2018 Mar;14(3):174-82. Epub 2018 Jan 29.
  3. Best KT, Loiselle AE. Scleraxis lineage cells contribute to organized bridging tissue during tendon healing and identify a subpopulation of resident tendon cells. FASEB J.2019 Jul;33(7):8578-87. Epub 2019 Apr 5.
  4. Abraham AC, Shah SA, Golman M, Song L, Li X, Kurtaliaj I, Akbar M, Millar NL, Abu-Amer Y, Galatz LM, Thomopoulos S. Targeting the NF-κB signaling pathway in chronic tendon disease. Sci Transl Med.2019 Feb 27;11(481):eaav4319.
  5. Chan CKF, Gulati GS, Sinha R, Tompkins JV, Lopez M, Carter AC, Ransom RC, Reinisch A, Wearda T, Murphy M, Brewer RE, Koepke LS, Marecic O, Manjunath A, Seo EY, Leavitt T, Lu WJ, Nguyen A, Conley SD, Salhotra A, Ambrosi TH, Borrelli MR, Siebel T, Chan K, Schallmoser K, Seita J, Sahoo D, Goodnough H, Bishop J, Gardner M, Majeti R, Wan DC, Goodman S, Weissman IL, Chang HY, Longaker MT. Identification of the human skeletal stem cell. 2018; Sep 20;175(1):43-56.e21.
November 18, 2019  

Sprifermin: Another Shot at Joint Preservation

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.

To date, we have found only one documented disease-modifying intervention that slows the progression of knee osteoarthritis (OA)—weight loss.1 There are few positive findings about drugs or other therapeutic interventions that might prolong the life of the human joint. However, sprifermin, a recombinant human fibroblast growth factor that can be genetically engineered from bacteria, has been tested in a randomized proof-of-concept trial as an intra-articular injection in humans,2 with modestly promising results.

In a very recent study on the effect of sprifermin and several other potentially disease-modifying compounds on bovine chondrocytes, researchers used 3D cultures to assess chondrocyte proliferation and/or extracellular matrix production.3 All of the growth factors evaluated, including sprifermin, resulted in elevated markers of anabolic chondrocyte activity. For the most part, cyclic doses were more effective than continuous doses over 4 weeks. Of importance, only sprifermin decreased type I collagen expression and had no hypertrophic effects. The authors conclude in the abstract that “these results confirm that sprifermin is a promising disease-modifying OA drug.”

In a 5-year randomized human dose-finding trial,4 patients with symptomatic knee OA were divided into 5 groups, as follows:

  1. 100 μg of sprifermin administered every 6 months (n = 110)
  2. 100 μg of sprifermin administered every 12 months (n = 110)
  3. 30 μg of sprifermin administered every 6 months (n = 111)
  4. 30 μg of sprifermin administered every 12 months (n = 110)
  5. Placebo injections administered every 6 months (n = 108)

The greatest changes in the primary endpoint—increased total femorotibial joint cartilage thickness from baseline to 2 years—was 0.05 mm (95% CI, 0.03 to 0.07 mm) in the group that received 100 μg of sprifermin every 6 months and 0.04 mm (95% CI, 0.02 to 0.06 mm) in the group that received 100 μg of sprifermin every 12 months. However, compared with the placebo group, those receiving sprifermin had no statistically different change in WOMAC scores. On average, 40% of all the patients in the study experienced arthralgia associated with the injections.

More certainty about the efficacy, safety, and durability of sprifermin may come when data from the remaining 3 years of this study are analyzed (see ClinicalTrials.gov identifier NCT01919164).

References

  1. Gersing AS, Solka M, Joseph GB, Schwaiger BJ, Heilmeier U, Feuerriegel G, Nevitt MC, McCulloch CE, Link TM. Progression of cartilage degeneration and clinical symptoms in obese and overweight individuals is dependent on the amount of weight loss: 48-month data from the Osteoarthritis Initiative. Osteoarthritis Cartilage. 2016 Jul;24(7):1126-34. doi: 10.1016/j.joca.2016.01.984. PMID: 26828356 PMCID: PMC4907808.
  2. Lohmander LS, Hellot S, Dreher D, et al. 2014. Intraarticular sprifermin (recombinant human fibroblast growth factor 18) in knee osteoarthritis: a randomized, double-blind, placebo-controlled trial. Arthritis Rheumatol. 66(7):1820–31.
  3. Müller S, Lindemann S, Gigout A. Effects of sprifermin, IGF1, IGF2, BMP7 or CNP on bovine chondrocytes in monolayer and 3D culture. J Orthop Res. 2019 Oct 14. doi: 10.1002/jor.24491. [Epub ahead of print] PMID: 31608492.
  4. Hochberg MC, Guermazi A, Guehring H, Aydemir A, Wax S, Fleuranceau-Morel P, Bihlet AR, Byrjalsen I, Andersen JR, Eckstein F. Effect of Intra-Articular Sprifermin vs Placebo on Femorotibial Joint Cartilage Thickness in Patients With OsteoarthritisThe FORWARD Randomized Clinical Trial. JAMA. 2019;322(14):1360-1370. doi:10.1001/jama.2019.14735
October 1, 2019  

Glycation and Rotator Cuff Degeneration

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.

Advanced glycation end products (AGEs) form through a nonenzymatic process by which reducing sugars undergo Maillard rearrangement with amino acids. During rearrangement, the carbonyl group of the sugar reacts with the amino group of the amino acid, producing N-substituted glycosylamine and water.

During cooking, glycation occurs at 140° to 165° C (280° to 330° F), resulting in the browning of foods such as bread and French fries. This nonenzymatic reaction also occurs at human body temperature over decades. AGE formation can decrease the viscoelasticity and tensile strength of human tissue, resulting in increased mechanical stiffness that affects bone, ligaments, cartilage, and menisci. In cartilage, the excessive accumulation of AGEs leads to a more brittle matrix that is susceptible to fatigue and failure. AGEs also contribute to the etiology of several diabetic complications, including adhesive capsulitis of the shoulder.

Rotator cuff degeneration and tears become more common with age. Accumulated mechanical loads and anatomic variation play a large role. The role of AGEs in rotator cuff degeneration and tears has been suspected, but the exact mechanisms remain in question. Investigators recently showed that AGEs have detrimental effects on human rotator cuff-derived cells in vitro and on intact rat infraspinatus tendons ex vivo.1

In Vitro Findings
Rotator cuff-derived cells were obtained from 12 torn cuff edges during supraspinatus tendon repairs in patients with an average age 64.8 years. The cells were cultured in (1) regular medium with 500 μg/mL AGEs (high-AGE group), (2) regular medium with 100 μg/mL AGEs (low-AGE group), and (3) regular medium alone (control group). Cell viability was significantly suppressed in the high-AGE group relative to the control group. Vascular endothelial growth factor secretion was significantly greater in the high- and low-AGE groups than in the control group. Immunofluorescence stain demonstrated enhancement of hypoxia-inducible factor-1α, reactive oxygen species expressions, and cell apoptosis in the high- and low-AGE groups compared with the control group.

Ex Vivo Findings
Four upper limbs with intact rotator cuff tendons were harvested from 10-week old rats and cultured in regular medium or regular medium with 500 μg/mL AGEs. Mechanical testing showed significantly higher tensile strength in the control group than in the AGE group.

These results beg the question as to whether reduction of AGEs might delay or prevent rotator cuff senescence-related degeneration.

Reference

  1. Mifune Y, Inui A, Muto T, Nishimoto H, Kataoka T, Kurosawa T, Yamaura K, Mukohara S, Niikura T, Kokubu T, Kuroda R. Influence of advanced glycation end products on rotator cuff. J Shoulder Elbow Surg. 2019 Aug;28(8):1490-1496. doi: 10.1016/j.jse.2019.01.022. Epub 2019 Apr 10. PMID: 30981546
September 25, 2019  

Stop Adding Antibiotics to Irrigation Solutions

The rate of adoption of knowledge gleaned from multiple well-done randomized clinical trials into medical practice is disappointingly slow. This has been well-documented in cardiovascular medicine, and the examples in orthopaedic surgery are embarrassingly similar. A corollary phenomenon exists with the slow rate of transfer of information from basic science studies to orthopaedic clinical practice.

These “disconnects” occur largely because we tend to adopt the practices of our residency faculty, often without any rational inquiry. Having been an oral examiner for the Part II ABOS Oral Boards, I frequently asked, “Why did you decide on that approach to the patient’s problem?” And I often heard in response, “That’s the way it was done in my residency.”

In the September 18, 2019 issue of The Journal, Goswami et al,. report findings from a well-designed in vitro study demonstrating that the common practice of adding the antibiotics polymyxin and bacitracin to irrigation solution to lower the risk of infection is not based on sound evidence. While adding antibiotics might make intuitive sense, according to these authors, it is “a futile exercise.”

After testing 8 different irrigation solutions for efficacy against S. aureus and E. coli and for toxicity to musculoskeletal cells, Goswami et al. concluded that “our results provide further support for the use of dilute povidone-iodine because of its bactericidal properties, relatively limited toxicity,… and modest cost.” They go on to say that their findings bring into question the widespread usage of polymyxin-bacitracin.

Certainly, we need to assemble more evidence from additional research to identify the optimal irrigation solution for orthopaedic surgery, but in the interim, we should probably stop using polymyxin-bacitracin. Doing so would have the added benefits of lowering costs and not exacerbating the serious problem of antimicrobial resistance. There are many areas of clinical practice where we have no evidence either for against a particular approach. But when we do have solid evidence, even if it’s from an in vitro study, we should work together to improve the rates of adoption into clinical practice.

Marc Swiontkowski, MD
JBJS Editor-in-Chief

August 29, 2019  

Who Doesn’t Have a Screw Loose?

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.

Fracture fixation with a plate and screws has been around for a century—and so has the problem of screw loosening. Part of the cause of screw loosening seems to be toggling caused by radial forces arising from plate micromotion. Several decades ago, locked screws were designed to prevent loosening and provide better fixation, but screws still loosen.

Two tests can predict screw loosening associated with bone microfracture and absorption: axial pullout stress and toggling radial stress. Recent studies have investigated two hypotheses: radial stress is a predominant cause of screw loosening, and bone resorption is triggered by high radial stress.

Finite Element Analyses

A finite elemental model was used to replicate fixation of a tibial fracture with a 3-mm gap using either a dynamic compression plate (DCP) or locking compression plate (LCP).1 The model included contact with bone, tension on screw insertion, and the placement of two inner screws and one outer screw on either side of the fracture for an 8-hole plate. Axial loading, torsional loading, and bending were applied. Forces exceeding 55 megapascal (MPa) were considered adequate to cause microfracture, whether by radial or axial force. (For reference, 55 MPa is just about 8,000 pounds per square inch.)

The principal finding was that more bone was damaged by radial than by axial stress in both types of plates. Both plate types had more bone damaged by radial stress at the central two screws than at the two end screws for all bending models.

Radiographic Analyses

A separate study evaluated clinical radiographs of fixation for humeral, radial, ulnar, femoral, and tibial shaft fractures. Researchers looked for screw migration or bone absorption of  ≥1 mm around the screw. Both DCPs and LCPs were reviewed.

Researchers found that the outer screws loosened only after the inner screws loosened. There were 3 cases of bone loss with no loosening, 17 cases of bone loss with screw displacement, and no cases of screw loosening without bone loss. This strongly suggests that bone loss must occur for loosening to take place and that the earliest screw loosening occurs closer to the facture site.

Taken together, these results imply that the use of larger inner screws and/or the use of a different angle of fixation might reduce bone absorption that leads to loosening. In addition, radial stress testing might be more important than axial testing. Still, LCPs remain superior at resisting axial loading and bending moments, while DCPs remain superior at resisting torsional loading of unstable fractures.

Reference

  1. Feng X, Lin G, Fang CX, Lu WW, Chen B, Leung FKL. Bone resorption triggered by high radial stress: The mechanism of screw loosening in plate fixation of long bone fractures. J Orthop Res. 2019 Jul;37(7):1498-1507. doi: 10.1002/jor.24286. Epub 2019 Apr 8 PMID: 30908687
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