I congratulate Vannabouathong et al. for the well-performed and relevant systematic review. In Germany, the Association of Scientific Medical Societies (AWMF) just published a guideline on the medical treatment of knee osteoarthritis (see: https://www.awmf.org/uploads/tx_szleitlinien/033-004l_S2k_Gonarthrose_2018-01_1.pdf), which comes to very similar conclusions as those presented in this systematic review.
The new German guideline suggests a four-stage algorithm starting with topical NSAIDs and escalating to oral NSAIDs (according to individual risks), then followed either by glucosamine, hyaluronic acid (HA), or corticosteroids, and ends finally with opioids. It was very useful that Vannabouathong et al. used the AAOS description for clinical significance, and it was elegant of them to include the effect of intra-articular placebo in their analysis of intra-articular treatments. This review compares treatment-group differences (not within-patient improvements) and considers that the placebo effect in osteoarthritis trials is typically large, particularly in the case of intra-articular injections. Consequently, the measured effect size would underestimate the clinical benefits for patients1, 2. It is valuable that this systematic review calculated the intra-articular placebo versus the oral placebo effect and added the resulting difference of 0.29 standard deviation (SD) units to the respective effect sizes of the intra-articular treatments.
This review concludes that the intra-articular injection of HA has the most concise effect estimate and exceeds the defined threshold of clinical importance of 0.5 SD units. Thus the clinical usefulness of HA is boosted from “possibly clinically important” to “clinically important” according to the AAOS definitions. This review also investigates HA formulations in terms of different molecular weights. It illustrates clearly the effect sizes of high-molecular-weight HA formulations between 1,500 kDa and 6,000 kDa, as well as those above 6,000 kDa.
One point requiring further discussion is that many patients have contraindications to NSAIDs due to comorbidities or comedications. Our new German guideline points out that NSAIDs are contraindicated for elderly patients (>60 years old) and those with existing ulcers, GI bleeding, or infections with H. pylori. Additional contraindicated factors are comedications such as corticosteroids, anticoagulants, or aspirin. In addition, the European Society for Clinical and Economic Aspects of Osteoporosis, Osteoarthritis and Musculoskeletal Diseases (ESCEO) reasons that oral NSAIDs have a moderate effect on pain relief, but they are associated with a 3- to 5-fold increase in the risk of upper GI complications, including peptic ulcer perforation, obstruction, and bleeding3.
Another analysis from the Coxib and Traditional NSAID Trialists (CNT) Collaboration shows that 2 to 4 out of 1,000 patients face GI complications after the daily intake of 150 mg of diclofenac. The same applies for 6 to 16 out of 1,000 patients taking 1,000 mg of ibuprofen per day4. An announcement of the Medicines Commission of the German Medical Profession also mentions high relative risks for GI complications associated with NSAIDs. The German guideline recommends intra-articular HA injections especially for individuals at risk for adverse NSAID side effects and for those for whom NSAIDs are not sufficiently effective.
The German guideline also discusses potentially beneficial effects of combining corticosteroids with HA. This should be a topic for a future systematic review.
Prof Joerg Jerosch is a professor of orthopaedic surgery at Johanna-Etienne Hospital in Neuss, Germany.
1. Bannuru RR et al., Therapeutic trajectory following intra-articular hyaluronic acid injection in knee osteoarthritis e meta-analysis, Osteoarthritis Cartilage. 2011 Jun;19(6):611-9. doi: 10.1016/j.joca.2010.09.014.
2. Bannuru RR et al., Comparative effectiveness of pharmacologic interventions for knee osteoarthritis: a systematic review and network meta-analysis, Ann Intern Med. 2015 Jan 6;162(1):46-54. doi: 10.7326/M14-1231
3. Bruyere O et al. A consensus statement on the European Society for Clinical and Economic Aspects of Osteoporosis and Osteoarthritis (ESCEO) algorithm for the management of knee osteoarthritis-From evidence-based medicine to the real-life setting. Semin Arthritis Rheum, 2016. 45(4 Suppl): p. S3-11
4. Bhala N et al., Coxib and traditional NSAID Trialists’ (CNT) Collaboration, Vascular and upper gastrointestinal effects of non-steroidal anti-inflammatory drugs: meta-analyses of individual participant data from randomised trials. Lancet 2013; 382(9894): 769-779
In a recent OrthoBuzz post, I commented on the apparent benefits to patients when Scottish hip-fracture guidelines were followed. Now, in a “closer-to-home” study in the May 16, 2018 issue of JBJS, Bedard et al. examine the effects of AAOS clinical practice guidelines (CPGs) on the use of injections for knee osteoarthritis (OA). The authors used an insurance database housing more than 1 million knee OA patients to evaluate the change in rates of corticosteroid and hyaluronic acid injections from 2007 to 2015. This date range includes the periods before and after the publication of the AAOS CPGs for knee arthritis (both the first edition, published in early 2009, and the second edition, published in late 2013).
The authors found that the rate of hyaluronic acid injections by orthopaedic surgeons decreased significantly after both publications of the guidelines and that the utilization of corticosteroid injections appears to have plateaued since the most recently published guidelines. Still, almost 40% of all of the patients in the cohort received a corticosteroid injection, with 13% having received a hyaluronic acid injection. In absolute numbers, those percentages represent more than half a million injections, despite the facts that the evidence supporting either injection for the treatment of knee OA is weak at best and that almost half of the patients receiving one of these injections ended up getting a total knee replacement within a year.
While the changes in practice revealed by Bedard et al. may seem relatively small, they are a step in the right direction toward value-based care. CPGs are easy to pick apart, but they are developed carefully and for a good reason—to provide us with evidence-based recommendations for excellent patient care. It is gratifying to see that such guidelines are having a positive impact in our field.
Chad A. Krueger, MD
JBJS Deputy Editor for Social Media
Every month, JBJS publishes a Specialty Update—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 OrthoBuzz Specialty Update summaries.
This month, OrthoBuzz asked Sheldon Lin, MD, co-author of the April 19, 2017 Specialty Update on foot and ankle surgery, to select the five most clinically compelling findings from among the more than 50 studies cited in the article.
–Recommendations for venous thromboembolism (VTE) prophylaxis in isolated foot and ankle fractures are conflicting. In a prospective study, Zheng et al.1 determined the incidence of VTE in 814 patients who received either low-molecular-weight heparin or placebo for 2 weeks postoperatively. The overall incidence of deep vein thrombosis was 0.98% in the heparin group and 2.01% in the placebo group, with no significant difference between the two. The risk factors were high body mass index (BMI) and advanced age. The authors concluded that routine chemical prophylaxis was not necessary in cases of isolated foot and ankle fractures.
Age and Total Ankle Arthroplasty
–Concerns regarding implant survivorship in younger patients have prompted investigations into the effect of age on total ankle arthroplasty outcomes. Demetracopoulos et al.2 prospectively compared patient-reported outcomes and revision rates in patients who were 70 years of age. At the 3.5-year follow-up, patients who were 70 years of age, although no differences were observed in pain, need for reoperation, or revision rates between groups.
Hallux Rigidus/Hallux Valgus
–Joint-preserving arthroplasties for hallux rigidus have been proposed as an alternative to first metatarsophalangeal joint arthrodesis. However, they have shown high rates of failure with associated bone loss, rendering salvage arthrodesis a more complicated procedure with worse outcomes. A Level-I study by Baumhauer et al.3 investigated the use of a synthetic cartilage implant that requires less bone resection than a traditional arthroplasty. Patients were randomized to implant and arthrodesis groups. At the 2-year follow-up, pain level, functional scores, and rates of revision surgical procedures were statistically equivalent in both groups. Secondary arthrodesis was required in <10% of the implant group and was considered to be a straightforward procedure because of preservation of bone stock.
–Hallux valgus surgical procedures are commonly performed under spinal, epidural, or regional anesthesia. Although peripheral nerve blocks have become increasingly popular with the advent of ultrasound, the associated learning curve has limited more widespread use. A Level-I study by Karaarslan et al.4 compared the efficacy of ultrasound-guided popliteal sciatic nerve blocks with spinal anesthesia in patients undergoing hallux valgus correction. The popliteal block group demonstrated decreased pain scores at every time point up to 12 hours postoperatively, longer time to first analgesic requirement, and increased patient satisfaction scores compared with the spinal anesthesia group. The popliteal block group also did not experience the adverse effects of hypotension, bradycardia, and urinary retention occasionally seen with spinal anesthesia.
–Orthobiologics continue to generate considerable interest within the orthopaedic community. Platelet-rich plasma and hyaluronic acid have been investigated as adjuncts to promote healing. In a Level-I study, Görmeli et al.5 randomized patients to receive platelet-rich plasma, hyaluronic acid, or saline solution injections following arthroscopic debridement and microfracture of talar osteochondral lesions. At the intermediate-term follow-up, the platelet-rich plasma and hyaluronic acid groups exhibited a significant increase in AOFAS scores and decrease in pain scores compared with the control group, with the platelet-rich plasma group showing the greatest improvement.
- Zheng X, Li DY, Wangyang Y, Zhang XC, Guo KJ, Zhao FC, Pang Y, Chen YX. Effect of chemical thromboprophylaxis on the rate of venous thromboembolism after treatment of foot and ankle fractures. Foot Ankle Int. 2016 Nov;37(11):1218-24.
- Demetracopoulos CA, Adams SB Jr, Queen RM, DeOrio JK, Nunley JA 2nd, Easley ME. Effect of age on outcomes in total ankle arthroplasty. Foot Ankle Int. 2015 Aug;36(8):871-80.
- Baumhauer JF, Singh D, Glazebrook M, Blundell C, De Vries G, Le ILD Nielsen D, Pedersen ME, Sakellariou A, Solan M, Wansbrough G, Younger AS, Daniels T; for and on behalf of the CARTIVA Motion Study Group. Prospective, randomized, multi-centered clinical trial assessing safety and efficacy of a synthetic cartilage implant versus first metatarsophalangeal arthrodesis in advanced hallux rigidus. Foot Ankle Int. 2016 May;37(5):457-69.
- Karaarslan S, Tekg¨ul ZT, S¸ ims¸ek E, Turan M, Karaman Y, Kaya A, Gönüllü M. Comparison between ultrasonography-guided popliteal sciatic nerve block and spinal anesthesia for hallux valgus repair. Foot Ankle Int. 2016 Jan;37(1):85-9. Epub 2015 Aug 20.
- Görmeli G, Karakaplan M, Görmeli CA, Sarıkaya B, Elmalı N, Ersoy Y. Clinical effects of platelet-rich plasma and hyaluronic acid as an additional therapy for talar osteochondral lesions treated with microfracture surgery: a prospective randomized clinical trial. Foot Ankle Int. 2015 Aug;36(8):891-900.
Orthopaedists frequently treat knee osteoarthritis with hyaluronic acid (HA) or corticosteroid injections, but which works better?
The 99 patients in a double-blinded randomized controlled trial by Tammachote et al. in the June 1, 2016 Journal of Bone & Joint Surgery received a single intra-articular injection of either 6 mL of hylan G-F 20, or 1 mL of 40-mg triamcinolone acetonide plus 5 mL of 1% lidocaine. At the six-month follow-up, both groups experienced significant and similar improvements in knee pain, function, and range of motion, without complications. But there were short-term distinctions: Triamcinolone relieved pain better and faster in the first week, after which the effect became similar to that of HA. Similarly, triamcinolone provided better functional improvement than HA at two weeks post-injection, but the effects of the two drugs were not statistically distinguishable after that.
In commenting on this study, Paul Levin, MD, says that its findings “support the [AAOS] clinical practice guideline of a strong recommendation against the use of hyaluronic acid.” He goes on to do a quick cost analysis showing that if 1.2 million people received a single cortisone injection (approximately $10 each) and another 1.2 million people received a single HA injection (per-injection prices ranging from $250 to more than $1000), the yearly medication cost would be $300 million to $1.2 billion for HA, versus $12 million for corticosteroid.
Dr. Levin says explaining both clinical and cost considerations to patients can be challenging. “It is easier, more efficient, and less acrimonious to comply with our patient’s request for [HA],” he writes. But he reminds orthopaedists that “bioethical principles along with the concept of shared decision-making do require a physician to spend the necessary time to educate his or her patients.”
Every month, JBJS publishes a Specialty Update—a review of the most pertinent and impactful studies published in the orthopaedic literature during the previous year in 13 subspecialties. Here is a summary of selected findings from Level I and II studies cited in the January 20, 2016 Specialty Update on adult reconstructive knee surgery:
Nonsurgical Management and Osteotomy
- A Cochrane database review found that land-based therapeutic exercise programs were modestly beneficial to patients with knee arthritis. Individualized programs were more effective than exercise classes or home-exercise programs.1
- A study comparing intravenous administration of tanezumab versus naproxen and placebo in patients with hip and knee osteoarthritis found that tanezumab effectively relieved pain and improved function at week 16.2
- A comparison of platelet-rich plasma (PRP) injections and hyaluronic acid (HA) injections found both treatments to be equally effective in improving knee function and reducing symptoms as measured by the IKDC subjective score.3
- A study comparing opening-wedge and closing-wedge high tibial osteotomy found that among patients who did not go on to conversion to TKA, there were no between-group differences in clinical or radiographic outcomes at six years of follow-up.
Implants, Instrumentation, and Technique
- A comparison of highly cross-linked and conventional polyethylene in posterior cruciate-substituting TKA found no differences in pain, function, and radiographic outcomes at a mean of 5.9 years.
- A randomized study of 140 patients that compared the use of patient-specific instrumentation (PSI) and conventional instrumentation found no differences in clinical, operative, and radiographic results.4
- In a randomized trial of 200 patients, the use of electromagnetic computer navigation resulted in insignificantly fewer outliers from the target alignment, compared with the use of conventional instrumentation. There were no between-group differences in clinical outcomes.5
- In a prospective randomized trial, the use of computer-assisted navigation during TKA resulted in lower systemic embolic loads, compared with TKA performed using conventional intramedullary instrumentation.
- A randomized controlled trial comparing kinematically and mechanically aligned TKA found that kinematic alignment with patient-specific guides provided better pain relief and restored better function and range of motion than mechanical alignment using conventional instruments.6
- A randomized study of selective patellar resurfacing in 327 knees followed for a mean of 7.8 years found higher satisfaction among patients with a resurfaced patella.7
Pain and Blood Management
- A randomized controlled trial comparing femoral and adductor canal blocks found that adductor canal blocks decreased time to discharge readiness without an increase in narcotic consumption.8
- A trial comparing periarticular injections (PAIs) of liposomal bupivacaine with conventional bupivacaine PAI found no between-group differences in VAS pain scores 72 hours postoperatively or in patient narcotic consumption.9
- A double-blinded randomized trial comparing topical versus intravenous administration of tranexamic acid found no significant differences in estimated blood loss or complications.
Rehabilitation and Complications
- A randomized trial of 205 post-TKA patients found no differences in WOMAC scores for pain, function, and stiffness in groups that received telerehabilitation or face-to-face home therapy.
- A randomized trial found that Kinesio Taping helped reduce postoperative pain and swelling and improved knee extension during early postoperative rehabilitation.10
- A trial comparing oral edoxaban and subcutaneous enoxaparin for post-TKA thromboprophylaxis found that edoxaban was the more effective agent. The incidence of bleeding events was similar in both groups.11
- Fransen M, McConnell S, Harmer AR, Van der Esch M, Simic M, Bennell KL.Exercise for osteoarthritis of the knee. Cochrane Database Syst Rev.2015;1:CD004376. Epub 2015 Jan 9.
- Ekman EF, Gimbel JS, Bello AE, Smith MD, Keller DS, Annis KM, Brown MT, WestCR, Verburg KM. Efficacy and safety of intravenous tanezumab for the symptomatic treatment of osteoarthritis: 2 randomized controlled trials versus naproxen. J Rheumatol. 2014 Nov;41(11):2249-59. Epub 2014 Oct 1.
- Filardo G, Di Matteo B, Di Martino A, Merli ML, Cenacchi A, Fornasari P, MarcacciM, Kon E. Platelet-rich plasma intra-articular knee injections show no superiority versus viscosupplementation: a randomized controlled trial. Am J Sports Med. 2015Jul;43(7):1575-82. Epub 2015 May 7.
- Abane L, Anract P, Boisgard S, Descamps S, Courpied JP, Hamadouche M. A comparison of patient-specific and conventional instrumentation for total knee arthroplasty: a multicentre randomised controlled trial. Bone Joint J. 2015 Jan;97-B(1):56-63.
- Blyth MJ, Smith JR, Anthony IC, Strict NE, Rowe PJ, Jones BG. Electromagnetic navigation in total knee arthroplasty-a single center, randomized, single-blind study comparing the results with conventional techniques. J Arthroplasty. 2015Feb;30(2):199-205. Epub 2014 Sep 16.
- Dossett HG, Estrada NA, Swartz GJ, LeFevre GW, Kwasman BG. A randomised controlled trial of kinematically and mechanically aligned total knee replacements: two-year clinical results. Bone Joint J. 2014 Jul;96-B(7):907-13.
- Roberts DW, Hayes TD, Tate CT, Lesko JP. Selective patellar resurfacing in total knee arthroplasty: a prospective, randomized, double-blind study. J Arthroplasty.2015 Feb;30(2):216-22. Epub 2014 Sep 28.
- Machi AT, Sztain JF, Kormylo NJ, Madison SJ, Abramson WB, Monahan AM,Khatibi B, Ball ST, Gonzales FB, Sessler DI, Mascha EJ, You J, Nakanote KA, IlfeldBM. Discharge readiness after tricompartment knee arthroplasty: adductor canal versus femoral continuous nerve blocks-a dual-center, randomized trial.Anesthesiology. 2015 Aug;123(2):444-56
- Schroer WC, Diesfeld PG, LeMarr AR, Morton DJ, Reedy ME. Does extended-release liposomal bupivacaine better control pain than bupivacaine after total knee arthroplasty (TKA)? A prospective, randomized clinical trial. J Arthroplasty. 2015Sep;30(9)(Suppl):64-7. Epub 2015 Jun 3.
- Donec V, Kriščiūnas A.The effectiveness of Kinesio Taping after total knee replacement in early postoperative rehabilitation period. A randomized controlled trial. Eur J Phys Rehabil Med. 2014 Aug;50(4):363-71. Epub 2014 May 13.
- Fuji T, Wang CJ, Fujita S, Kawai Y, Nakamura M, Kimura T, Ibusuki K, Ushida H, Abe K, Tachibana S.Safety and efficacy of edoxaban, an oral factor Xa inhibitor, versus enoxaparin for thromboprophylaxis after total knee arthroplasty: the STARS E-3 trial. Thromb Res. 2014 Dec;134(6):1198-204. Epub 2014 Sep 21.
A “Clinical Therapeutics” article in the March 12, 2015 New England Journal of Medicine focuses on viscosupplementation for knee osteoarthritis (OA). In presenting a case vignette and making a therapeutic recommendation, Australian author David Hunter, MB, PhD, invokes the old, 2008 AAOS clinical practice guideline (CPG), which, according to Dr. Hunter, “determined that the evidence was inconclusive and a recommendation could not be made for or against the use of intraarticular hyaluronate.” However, the AAOS updated CPGs for knee OA in 2013, and the guideline for viscosupplementation changed substantially. It now reads: “We cannot recommend using hyaluronic acid for patients with symptomatic osteoarthritis of the knee,” and that recommendation receives a “Strong” rating, based on evidence from more recent research studies.
In the end, the patient in the case vignette—a 67-year-old woman with knee pain, radiographic signs of knee OA, and a BMI of 32—was advised not to use hyaluronate injections and instead was encouraged to lose weight and undertake a muscle-strengthening exercise program.
We stumbled upon three recent studies of knee osteoarthritis (OA) that shed interesting new light on a condition that all orthopaedists deal with.
–A “network” meta-analysis in the Annals of Internal Medicine looked at 137 randomized trials of OA treatments comprising more than 33,000 participants. Treatments analyzed included acetaminophen, diclofenac, ibuprofen, naproxen, celecoxib, intra-articular (IA) steroids, IA hyaluronic acid, oral placebo, and IA placebo. For pain, all active treatments except acetaminophen yielded clinically significant improvement. IA hyaluronic acid came out on top for pain relief, although the authors postulated that an “integrated” placebo effect may explain that finding.
–A cost-modeling study in Arthritis Care & Research, co-authored by JBJS Deputy Editors for Methodology and Biostatistics Jeffrey Katz, MD and Elena Losina, PhD, revealed that the per-patient cost attributable to symptomatic knee OA over 28 years is $12,400. Any expanded indications for total knee arthroplasty (TKA) and a trend toward increased willingness among patients to undergo knee surgery will increase that cost. The researchers found that patients tried nonsurgical regimens for a mean of 13.3 years before opting for TKA, and they stress the need for more effective nonoperative therapies for knee OA.
–Wine drinkers, rejoice! A retrospective case-control study in Arthritis Research & Therapy found that people who drank four to six glasses of wine per week were less likely to develop knee OA than nondrinkers. Meanwhile, beer drinkers may want to switch to wine. The same study found that people who drank 8 to 19 half-pints of suds per week had an increased risk of developing knee OA. Researchers found no link between total alcohol consumption and risk of knee OA. The authors postulate that the resveratrol found in wine may be chondroprotective, and that the linkage between beer and increased blood levels of uric acid may explain the opposite finding. It’s wise to remember that studies investigating one or two dietary items can be less-than-definitive because they are usually retrospective, subject to recall bias, and do not account for complex interactions among many nutrients.