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:
- 100 μg of sprifermin administered every 6 months (n = 110)
- 100 μg of sprifermin administered every 12 months (n = 110)
- 30 μg of sprifermin administered every 6 months (n = 111)
- 30 μg of sprifermin administered every 12 months (n = 110)
- 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).
- 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.
- 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.
- 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.
- 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
OrthoBuzz occasionally receives posts from guest bloggers. In response to a recent study in Arthritis Care & Research, the 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.
The obesity epidemic continues throughout much of the developed world. Among the morbidly obese (BMI ≥40 kg/m2), we have a group of patients in whom arthritis is very likely to develop due to excessive loading of articular cartilage, chronic inflammation, and alignment problems. At the same time, many arthroplasty surgeons are wary of treating morbidly obese patients with surgery because of the increased perioperative risks. Although many of these patients still benefit greatly from joint replacement, in today’s “value-based care” environment, some institutions have implemented BMI cutoff thresholds for performing knee or hip arthroplasty. Others have set weight-loss requirements before they will schedule lower-extremity arthroplasty for morbidly obese patients. One still-unanswered question along these lines is: how much weight does a morbidly obese patient need to lose preoperatively in order to improve the outcome after a knee replacement?
Keeney et al. address that question in the August 21, 2019 issue of The Journal. In a retrospective cohort study, the authors evaluated outcomes among 203 morbidly obese patients who underwent a total knee arthroplasty (TKA). They found that a loss of 20 pounds preoperatively was associated with a shorter length of stay and a lower chance of being discharged to a rehab or skilled nursing facility rather than home. However, a 20-pound weight loss had no impact on surgical time or functional outcomes, as measured with the PROMIS-10 physical component score. Of note, only 14% of the evaluated patients lost at least 20 pounds preoperatively (highlighting the difficulty of losing weight in general and among this patient population in particular). There were no benefits of any kind in patients who lost only 5 or 10 pounds preoperatively.
While this study’s sample size is small, the findings provide evidence surgeons can use to encourage (or insist upon) larger amounts of weight loss before arthroplasty procedures in morbidly obese patients. In this study, the patients who lost at least 20 pounds remained morbidly or severely obese, and all the patients eventually regained most or all of the weight they lost. Still, the conclusion that at least 20 pounds of weight loss is beneficial for morbidly obese patients prior to a TKA remains sound. Because of the magnitude of this public health issue, we need more high-quality outcomes research (preferably using more knee-specific functional measures) on preoperative management of morbidly obese patients who are considering lower-extremity arthroplasty.
Marc Swiontkowski, MD
Previously this month, Chad A. Krueger, MD, JBJS Deputy Editor for Social Media, selected what he deemed to be the most clinically compelling findings from among the more than 150 studies cited in the January 17, 2018 Specialty Update on Adult Reconstructive Knee Surgery. In this OrthoBuzz post, Gwo-Chin Lee, MD, author of the Specialty Update on Adult Reconstructive Knee Surgery, selects his “top five.”
Nonoperative Knee OA Treatment
—Atukorala et al. found a significant dose-response relationship between all KOOS subscales and percentage of weight change across all weight-change categories. Participants required ≥7.7% of weight loss to achieve a minimal clinically important improvement in function.1
—A prospective cohort study showed that patients undergoing arthroscopic procedures for degenerative meniscal tears did not have clinically meaningful differences in outcomes compared with patients with traumatic meniscal tears.2
Postoperative Pain Management
—Authors of a Cochrane Systematic Review ascertained that liposomal bupivacaine at the surgical site appears to reduce postoperative pain compared with placebo. However, because of the low quality and volume of evidence, it is not possible to determine its effect compared with conventional agents.3
Avoiding Post-TKA Complications
—In a randomized trial, the use of a tourniquet resulted in upregulation of peptidase activity within the vastus medialis but did not result in an increase in muscular degradation products. The authors concluded that the relationship between tourniquet-induced ischemia and muscle atrophy is complex and poorly understood.4
—The authors of a registry study found no evidence that fondaparinux, enoxaparin, or warfarin are superior to aspirin in the prevention of PE, DVT, or VTE—or that aspirin is safer than these alternatives. However, enoxaparin is as safe as aspirin with respect to bleeding, and fondaparinux is as safe as aspirin with respect to risk of wound complications.5
- Atukorala I, Makovey J, Lawler L, Messier SP, Bennell K, Hunter DJ. Is there a dose-response relationship between weight loss and symptom improvement in persons with knee osteoarthritis? Arthritis Care Res (Hoboken). 2016 Aug;68 (8):1106-14.
- Thorlund JB, Englund M, Christensen R, Nissen N, Pihl K, Jørgensen U, Schjerning J, Lohmander LS. Patient reported outcomes in patients undergoing arthroscopic partial meniscectomy for traumatic or degenerative meniscal tears: comparative prospective cohort study. BMJ. 2017 Feb 2;356:j356.
- Hamilton TW, Athanassoglou V, Mellon S, Strickland LH, Trivella M, Murray D, Pandit HG. Liposomal bupivacaine infiltration at the surgical site for the management of postoperative pain. Cochrane Database Syst Rev. 2017 Feb 1;2:CD011419.
- Jawhar A, Hermanns S, Ponelies N, Obertacke U, Roehl H. Tourniquet-induced ischaemia during total knee arthroplasty results in higher proteolytic activities within vastus medialis cells: a randomized clinical trial. Knee Surg Sports Traumatol Arthrosc. 2016 Oct;24(10):3313-21. Epub 2015 Nov 14.
- Cafri G, Paxton EW, Chen Y, Cheetham CT, Gould MK, Sluggett J, Bini SA, Khatod M. Comparative effectiveness and safety of drug prophylaxis for prevention of venous thromboembolism after total knee arthroplasty. J Arthroplasty. 2017 Nov;32(11):3524-28.e1. Epub 2017 May 31.