Tag Archive | knee osteoarthritis

Trimming the Fat (Pad) in 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. It has been sent to >3,000 members of the Orthopaedic Research Society (ORS). For more information about the ORS, visit http://www.ors.org

The knee joint is comprised of cartilage, fibrocartilage, bone, synovium, ligaments, a fibrous capsule, and adipose tissue, the last of which includes the large anterior infrapatellar fat pad (IFP). The role of synovial inflammatory cells and cytokines in knee osteoarthritis (OA) has been well studied. The IFP is also rich in stem cells and inflammatory cells. Because Hartley guinea pigs naturally develop a form of knee OA that is similar to human disease, researchers recently used them as a model for elucidating a possible role of the IFP in knee OA.1

Ten 3-month-old guinea pigs had a unilateral IFP excision from one knee, with sham surgery performed on the opposite knee. Hartley guinea pigs typically develop OA after three months, and this intervention sought to determine whether IFP excision protected against OA. Gait analysis data were collected prior to surgery and then monthly until the animals were harvested at 7 months of age, at which point researchers performed microcomputed tomography (microCT) and histopathology on all 20 knee joints.

In knees with IFP resection, fibrous connective tissue replaced the adipose tissue. Stride length was not statistically different for either hindlimb throughout the study. Joints with resected IFPs had a decreased microCT score compared to contralateral intact knees (p <0.0001), indicating healthier cartilage. Histopathologically, the mean modified Mankin score of knees with IFPs removed was 2.556 versus 12.56 in contralateral knees (p <0.0004).

Surgeons commonly resect the fat pad during reconstructive knee surgery in humans, with no known reports of adverse effects beyond decreased range of motion due to local fibrosis. A recent review of the contribution of the IFP and synovium to knee OA pain2 suggests that synovial tissue and adipose tissue may act as a “functional unit” and have a combined effect on OA pathogenesis and, in all probability, OA pain and progression.

References

  1. Afzali MF, Radakovich LB, Pixler ZC, Campbell MA, Sanford JL, Marolf AJ, Donahue T, Santangelo, Kelly S. Early removal of the infrapatellar fat pad beneficially alters the pathogenesis of primary osteoarthritis in the Hartley guinea pig ORS 2020 Annual Meeting Paper No.0166
  2. Belluzzi E, Stocco E, Pozzuoli A, Granzotto M, Porzionato A, Vettor R, De Caro R, Ruggieri P, Ramonda R, Rossato M, Favero M, Macchi V. Contribution of Infrapatellar Fat Pad and Synovial Membrane to Knee Osteoarthritis Pain. Biomed Res Int. 2019 Mar 31;2019:6390182. doi: 10.1155/2019/6390182. eCollection 2019.PMID: 31049352

Knee OA: Does It Start with Stiff Menisci or Soft Cartilage?

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.

As an orthopaedic surgeon, I often noticed the rigidity of the meniscus as I excised it during a total knee replacement. Focused on the job at hand, however, I never closely considered the involvement of menisci in degenerative joint disease. But German researchers recently hypothesized that early biomechanical changes in meniscal tissue occur before articular cartilage changes in knee osteoarthritis.1

To test their hypothesis, they dissected 12 cadaver knees with Kellgren-Lawrence (KL) scores between 1 and 2 and 12 knees with KL scores between 3 and 4. The menisci were carefully embedded in a cast of polymethylmethacrylate using bony attachments to hold the specimens for Einst testing at the anterior horn, pars intermedia, and posterior horn. (Instantaneous modulus of elasticity [Einst] is the measure of the initial response of a viscoelastic material to an initial load before long-term deformity occurs.)  The exposed tibial surface was then cut 10 mm below the joint for Einst testing at the same zones, and the researchers also measured the articular cartilage-to-cartilage contact area.

Mann-Whitney U-testing revealed higher meniscal Einst values with increasing degeneration for both lateral and medial menisci, while the underlying tibial articular cartilage showed a decrease in Einst in the medial compartment. These findings suggest that knee joint degeneration might very well begin with a stiffening of the menisci, followed by articular cartilage softening.

The wide variation in Einst values uncovered in this study leaves open the possibility there is more than one pathway by which the biochemical response to meniscal cytokine expression would lead to subsequent articular cartilage breakdown. Nevertheless, the authors suggest that their findings might prompt the treatment and diagnostic paradigms of knee osteoarthritis to change, “focusing on the degeneration detection of the menisci instead of the articular cartilage.”

Reference 

  1. Seitz AM, Osthaus F, Ignatius A, Dürselen L. Degeneration alters first the biomechanical properties of human menisci before affecting the tibial cartilage. ORS 2020 Annual Meeting Paper No.0687

Tibial BME Not Associated with Adverse Post-HTO Outcomes

Medial opening-wedge high tibial osteotomy (MOHTO) is a tried-and-true joint preservation technique for medial compartment knee osteoarthritis with varus alignment. Multiple studies have shown good short- and medium-term Kaplan-Meier survival with MOHTO, but questions remain regarding potential factors that lead to deteriorating outcomes over time. One such question is whether the presence of medial tibial bone marrow edema (BME) in a varus-aligned knee prior to MOHTO might lead to worse outcomes or survival afterward.

In the December 2, 2020 issue of The Journal, Yang et al. investigated this question with a retrospective case series of 105 patients with preoperative BME on MRI who underwent MOHTO. The BME was reviewed and graded by 2 independent observers based on both the diameter of the lesion and the volume of the medial tibia affected. The researchers radiographically evaluated postoperative alignment correction and compared preoperative and postoperative patient-reported outcomes using the Hospital for Special Surgery (HSS) score, Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC), Knee Society Score (KSS), and Short Form-12 (SF-12).

At an average follow-up of 6.2 years, Yang et al. found significant improvements in all patient-reported outcomes—with no correlation between outcomes and the presence or extent of BME. Overall survival was 95.2% at 6.2 years, showing that the improvements were durable throughout the study period, despite the preoperative presence of BME.

Although it would have been helpful to have a comparison group to see whether there were any functional-outcome differences between patients with and without BME, this study shows that MOHTO is a reliable and effective treatment for patients with BME, at least up until 6 years. And certainly, as the authors assert in the final sentence, “Preoperative BME should not be considered a contraindication for MOHTO.”

Matthew R. Schmitz, MD
JBJS Deputy Editor for Social Media

July 2020 Article Exchange with JOSPT

For the last 6 years, JBJS has participated in an “article exchange” collaboration with the Journal of Orthopaedic & Sports Physical Therapy (JOSPT) to support multidisciplinary integration, continuity of care, and excellent patient outcomes in orthopaedics and sports medicine.

During the month of July 2020, JBJS and OrthoBuzz readers will have open access to the JOSPT systematic review and meta-analysis titled “Effectiveness of Weight-Loss Interventions for Reducing Pain and Disability in People with Common Musculoskeletal Disorders.”

The authors found low-credibility evidence that behavioral weight-loss interventions produced small to moderate improvements in pain intensity and disability in people with hip or knee osteoarthritis. They also found moderate-credibility evidence that combined diet and exercise weight-loss strategies improved pain intensity and disability compared to diet-only interventions for knee osteoarthritis.

PT More Effective than Steroid Injections for Knee OA

OrthoBuzz occasionally receives posts from guest bloggers. In response to a recent study in The New England Journal of Medicinethe following commentary comes from Jaime L. Bellamy, DO.

A majority of patients I see for knee osteoarthritis (OA) want a quick fix. Many would like to skip conservative treatment–activity modification, weight loss, physical therapy (PT), anti-inflammatory medication, and intra-articular steroid injections–and go straight to surgical management. Regarding nonoperative management of knee OA, the most recent AAOS Clinical Practice Guidelines “strongly” recommend that patients participate in PT and “inconclusively” recommend intra-articular steroid injections.1 Yet, in my clinical practice, I confess to typically offering a knee injection first, before PT.

I may change that practice in light of the randomized controlled trial (RCT) by Deyle et al. in the April 9, 2020 issue of The New England Journal of Medicine. The trial compared PT to glucocorticoid knee injections among 156 primary-care knee OA patients within a military health system. The primary outcome measure was the WOMAC score at 1 year. Secondary outcomes included the Alternate Step Test and the Timed Up and Go test.

Seventy-eight patients randomly assigned to each group were included in the analysis. The PT intervention included detailed home-exercise instructions and 8 sessions with a therapist over the initial 4- to 6-week period. Patients could also attend 1 to 3 PT sessions at the 4-month and 9-month reassessments. Knee-injection patients received 1 ml of triamcinolone acetonide (40 mg per milliliter) and 7 ml of 1% lidocaine up to three times in one year.

The mean baseline WOMAC scores were similar between the groups. However, at 1 year, the authors found a mean between-group difference of 18.8 points in WOMAC scores, favoring PT over injections. Secondary outcomes also favored PT over knee injections.

Regardless of this RCTs limitations, such as the lack of reporting on knee-injection techniques, the findings serve as a reminder to orthopaedists to recommend PT as an effective nonoperative treatment option for knee OA. Additionally, our primary care colleagues can use this data to help convince patients with knee OA that they do not need to rush in to see a surgeon.

Jaime L. Bellamy, DO (@jaimelbellamyDO) is an orthopaedic surgeon specializing in hip and knee reconstruction in Fort Bragg, NC and a member of the JBJS Social Media Advisory Board.

Reference

  1. AAOS Clinical Practice Guidelines, Treatment of Osteoarthritis of the Knee, 2nd Edition (2013), http://www.orthoguidelines.org/topic?id=1005, accessed 4/14/2020.

Curb Your Enthusiasm about Stem Cells for Knee OA

Mark Miller, MD is a professor of orthopaedic surgery at the University of Virginia, founder and co-director of the Miller Review Courses, and former deputy editor for sports medicine at JBJS. In a piece he authored recently for The Conversation, Dr. Miller labeled stem-cell treatments for knee osteoarthritis (OA) “unproven, expensive, and potentially dangerous.”

About 2 years ago, Dr. Miller himself underwent bilateral knee replacements for severe knee arthritis. He understands why patients may fall prey to misleading marketing hype that claims stem cell treatments can help people postpone or entirely avoid knee replacement. (See related OrthoBuzz post.) “My mission,” he writes, is to “try to keep the enthusiasm regarding new cutting-edge options in check,” adding that “the excitement about stem cells has outpaced the science,” especially when it comes to knee OA.

Although stem cell injections have been promoted as a way to regenerate cartilage in arthritic joints, Dr. Miller echoes the American Association of Hip and Knee Surgeons when he says that “there are no proven…therapies that can delay or reverse the progressive joint destruction that occurs with osteoarthritis.” Moreover, the do-no-harm part of the Hippocratic oath requires doctors to give their patients “a clear picture of the potential benefits and side effects of their treatment options,” writes Dr. Miller, who cited a December 20, 2018 New York Times article describing 12 patients who were hospitalized for serious infections after receiving stem cell injections into their knees, shoulders, or spines.

For their part, Dr. Miller says patients should employ the “buyer beware” concept because stem cell therapy for osteoarthritis is not only unproven but also expensive—and usually not covered by medical insurance. The best approach to knee OA, says Dr. Miller, is what is nowadays called shared decision making: “Physicians need to work closely with patients to help them understand their options and which choice may be best for them.”

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

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

Eschew the “Quick Fix” Approach to Early Knee OA

OrthoBuzz occasionally receives posts from guest bloggers. In response to a recent study in Arthritis Care & Researchthe following commentary comes from Jeffrey B. Stambough, MD.

As orthopaedic surgeons, we share a collective objective to help patients improve function while minimizing pain. When patients come to our office for a new clinical visit for knee osteoarthritis (OA), we spend time getting to know them and gathering information about their activities, limitations, and functional goals. We balance this patient-reported information with discrete data points, such as weight, range-of-motion restrictions, and radiographic disease classification. Based on the symptom duration and other factors, most patients are not candidates for a knee replacement at this first visit. However, despite the publication of clinical practice guidelines for the nonoperative management of knee OA in 2008, with an update in 2013, significant variation exists in how orthopaedists treat these patients.

This guideline–practice disconnect is emphasized in findings from a recent study in Arthritis Care & Research that examined nonoperative knee OA management practices during clinic visits between 2007 and 2015. The authors found that the overall prescription of NSAID and opioid medications increased 2- and 3-fold, respectively, over that time, while recommendations for lifestyle interventions, self-directed activity, and physical therapy decreased by about 50%.

To me, the most troubling finding from this study is the sharp increase in narcotic prescriptions, because recent evidence demonstrates that narcotics do not effectively treat arthritis pain. Moreover, for patients who go on to arthroplasty, recent studies have found that preoperative opioid use portends worse postsurgical outcomes in terms of higher revision rates,  worse function scores, and decreased knee motion.

The findings from this study also speak to a larger societal issue for doctors and patients alike: the desire for a “quick fix.”  Despite the time pressure from increasing EHR documentation burdens, dwindling reimbursements, or lack of local resources, we owe it to our patients to counsel them on lifestyle modifications and self-management strategies to help them stay mobile, lose weight (if necessary), and take charge of their joint health. As orthopaedic surgeons, we must continue to strive to de-emphasize opioid pain medication when treating knee OA patients and support them in a holistic manner to ensure their overall health and the function and longevity of their native knee joint.

Jeffrey B. Stambough, MD is an orthopaedic hip and knee surgeon, an assistant professor of orthopaedic surgery at University of Arkansas for Medical Sciences, and a member of the JBJS Social Media Advisory Board.

MRI for Detecting Rapidly Progressive Knee OA: No Crystal Ball

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.

Knee osteoarthritis (KOA) typically develops over a decade or more. However, 1 in 5 people with KOA have more pain and disability at onset, have accelerated radiographic knee osteoarthritis (AKOA), and experience end-stage disease within 4 years. The use of demographics and clinical findings has resulted in only a 40% rate of correctly classifying patients who will develop AKOA instead of longer-term KOA.

Investigators recently conducted a case–control study using data from the OsteoArthritis Initiative (OAI), including demographic, clinical, and biochemical data, along with radiographic and magnetic resonance (MR) imaging data.1 The researchers hypothesized that the addition of an MR imaging-based scoring system would more accurately identify patients at risk for AKOA. They used classification and regression tree (CART) models to assess the ability of baseline MR features to classify participants who will develop AKOA and whether adding baseline MR features to an existing model improved classification of adults who will develop AKOA.

The existing model consisted of clinical data that included pain, function, physical exam findings, and quality-of-life measures. Demographic data included age, sex, and BMI collected at baseline. Biochemical data included high-sensitivity C-reactive protein and serum blood sugar. Data obtained from MR imaging scores included bone marrow lesion volume, effusion-synovitis volume, cartilage damage index, meniscal extrusion and degeneration, cruciate ligament degeneration, and patellar fat pad changes.

Contrary to the hypothesis, the CART models with and without MR features each explained approximately 40% of the variability. Adding MR-based features to the model improved specificity (0.90 vs. 0.82), but lowered sensitivity (0.62 vs. 0.70). Interestingly, the authors found that serum glucose, effusion-synovitis volume, and cruciate ligament degeneration were statistically important variables in classifying individuals who are likely to develop AKOA.

The clinical take home is that early MR data may be useful in sorting out mechanical complaints, but not in determining who will develop AKOA. In contrast, in later stages of KOA, MR images may reveal far greater damage than can be detected on radiographs.

Reference

  1. Price LL, Harkey MS, Ward RJ, MacKay JW, Zhang M, Pang J, Davis JE, McAlindon TE, Lo GH, Amin M, Eaton CB, Lu B, Duryea J, Barbe MF, Driban JB. Role of Magnetic Resonance Imaging in Classifying Individuals Who Will Develop Accelerated Radiographic Knee Osteoarthritis. J Orthop Res. 2019 Nov;37(11):2420-2428. doi: 10.1002/jor.24413. Epub 2019 Jul 29. PMID: 31297900