Publications by authors named "David T Felson"

345 Publications

Progression of Knee Osteoarthritis with use of Intra-articular Corticosteroids vs. Hyaluronic Acid.

Arthritis Rheumatol 2021 Nov 22. Epub 2021 Nov 22.

Department of Rheumatology, Boston University School of Medicine, Boston, MA.

Objective: To determine whether intra-articular corticosteroid injections are associated with increased knee osteoarthritis progression compared to hyaluronic acid injections which has been reported to delay OA progression and knee replacement.

Methods: We identified participants from two large cohort studies, the Osteoarthritis Initiative and the Multicenter Osteoarthritis Study. Study visits were performed at regular intervals and included questionnaires about intraarticular corticosteroid or hyaluronic acid injection use in the previous 6 months, incident total knee replacement and knee radiographs, which were obtained and interpreted in similar fashion. Outcomes were radiographic progression based on Kellgren and Lawrence grade and joint space narrowing for both cohorts; medial joint space width for Osteoarthritis Initiative participants; and incident total knee replacement. We compared pre- and post-injection x-rays to generate rate ratios of progression comparing corticosteroid injection with hyaluronic acid users. A Cox proportional hazards model was used to estimate rate of total knee replacement for both groups.

Results: We studied 791 participants (980 knees) with knee osteoarthritis, of whom 629 reported CSI use and 162 HAI use. Rate ratios of progression were similar between corticosteroid and hyaluronic acid injection users for Joint Space Narrowing (1.00 [95% CI 0.83-1.21]), Kellgren and Lawrence grade (1.03 [95% CI: 0.83 - 1.29]) and medial joint space width (1.03 [95% CI 0.72 - 1.48]). Hazard of total knee replacement was slightly lower for intraarticular corticosteroid compared to hyaluronic acid users (HR 0.75, 95% CI 0.51 - 1.09).

Conclusions: Intraarticular corticosteroid injections are not associated with increased risk of progression compared to hyaluronic acid.
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http://dx.doi.org/10.1002/art.42031DOI Listing
November 2021

Association of Physical Therapy Interventions With Long-term Opioid Use After Total Knee Replacement.

JAMA Netw Open 2021 Oct 1;4(10):e2131271. Epub 2021 Oct 1.

Department of Physical Therapy and Athletic Training, Boston University, Boston, Massachusetts.

Importance: Many individuals who undergo total knee replacement (TKR) become long-term opioid users after TKR. Associations of physical therapy (PT) interventions before or after TKR with long-term use of opioids are not known.

Objectives: To evaluate associations of PT interventions before and after TKR with long-term opioid use after TKR.

Design, Setting, And Participants: This cohort study used data from the OptumLabs Data Warehouse on 67 322 individuals aged 40 years or older who underwent TKR from January 1, 2001, to December 31, 2016, stratified by history of opioid use. The analyses for the study included data from January 1, 1999, to December 31, 2018.

Exposures: Any PT interventions within 90 days before or after TKR, post-TKR PT dose as number of sessions (ie, 1-5, 6-12, and ≥13 sessions), post-TKR PT timing as number of days to initiation of care (ie, <30 days, 31-60 days, or 61-90 days after TKR), and post-TKR PT type (ie, active vs passive).

Main Outcomes And Measures: The association of pre- and post-TKR PT with risk of long-term opioid use occurring more than 90 days after TKR was assessed using logistic regression while adjusting for confounders, including age, sex, race and ethnicity (Asian, Black, Hispanic, or White), obesity, type of insurance, geographical location, and physical and mental health comorbidities.

Results: A total of 38 408 opioid-naive individuals (21 336 women [55.6%]; mean [SD] age, 66.2 [9.2] years) and 28 914 opioid-experienced individuals (18 426 women [63.7%]; mean [SD] age, 64.4 [9.3] years) were included. Receipt of any PT before TKR was associated with lower odds of long-term opioid use in the opioid-naive (adjusted odds ratio [aOR], 0.75 [95% CI, 0.60-0.95]) and opioid-experienced (aOR, 0.75 [95% CI, 0.70-0.80]) cohorts. Receipt of any post-TKR PT was associated with lower odds of long-term use of opioids in the opioid-experienced cohort (aOR, 0.75 [95% CI, 0.70-0.79]). Compared with 1 to 5 sessions of PT after TKR, 6 to 12 sessions (aOR, 0.82 [95% CI, 0.75-0.90]) and 13 or more sessions (aOR, 0.71 [95% CI, 0.65-0.77) were associated with lower odds in the opioid-experienced cohort. Compared with initiation of PT within 30 days after TKR, initiation 31 to 60 days or 61 to 90 days after TKR were associated with greater odds in the opioid-naive (31-60 days: aOR, 1.45 [95% CI, 1.19-1.77]; 61-90 days: aOR, 2.15 [95% CI, 1.43-3.22]) and opioid-experienced (31-60 days: aOR, 1.10 [95% CI, 1.02-1.18]; 61-90 days: aOR, 1.32 [95% CI, 1.12-1.55]) cohorts. Compared with passive PT, active PT was not associated with long-term opioid use in the opioid-naive (aOR, 1.00 [95% CI, 0.81-1.24]) or opioid-experienced (aOR, 0.99 [95% CI, 0.92-1.07]) cohorts.

Conclusions And Relevance: This cohort study suggests that receipt of PT intervention before and after TKR, receipt of 6 or more sessions of PT care after TKR, and initiation of PT care within 30 days after TKR were associated with lower odds of long-term opioid use. These findings suggest that PT may help reduce the risk of long-term opioid use after TKR.
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http://dx.doi.org/10.1001/jamanetworkopen.2021.31271DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8552057PMC
October 2021

Assessment of bone marrow oedema-like lesions using MRI in patellofemoral knee osteoarthritis: comparison of different MRI pulse sequences.

Br J Radiol 2021 Aug 14;94(1124):20201367. Epub 2021 Jul 14.

Division of Informatics, Imaging & Data Sciences, School of Health Sciences, Faculty of Biology, Medicine & Health, University of Manchester, Manchester, United Kingdom.

Objective: To compare bone marrow oedema-like lesion (BML) volume in subjects with symptomatic patellofemoral (PF) knee osteoarthritis (OA) using four different MRI sequences and to determine reliability of BML volume assessment using these sequences and their correlation with pain.

Methods: 76 males and females (mean age 55.8 years) with symptomatic patellofemoral knee OA had 1.5 T MRI scans. PD fat suppressed (FS), STIR, contrast-enhanced (CE) W FS, and 3D W fast field echo (FFE) sequences were obtained. All sequences were assessed by one reader, including repeat assessment of 15 knees using manual segmentation and the measurements were compared. We used random-effects panel linear regression to look for differences in the log-transformed BML volume (due to positive skew in the BML volume distribution) between sequences and to determine associations between BML volumes and knee pain.

Results: 58 subjects had PF BMLs present on at least one sequence. Median BML volume measured using W FFE sequence was significantly smaller (224.7 mm, interquartile range [IQR] 82.50-607.95) than the other three sequences. BML volume was greatest on the CE sequence (1129.8 mm, IQR 467.28-3166.02). Compared to CE sequence, BML volumes were slightly lower when assessed using PDFS (proportional difference = 0.79; 95% confidence interval [CI] 0.62, 1.01) and STIR sequences (proportional difference = 0.85; 95% CI 0.67, 1.08). There were strong correlations between BML volume on PDFS, STIR, and CE W FS sequences (ρ = 0.98). Correlations were lower between these three sequences and W FFE (ρ = 0.80-0.81). Intraclass correlation coefficients were excellent for proton density fat-suppressed, short-tau inversion recovery, and CE W FS sequences (0.991-0.995), while the ICC for W FFE was good at 0.88. We found no significant association between BML volumes assessed using any of the sequences and knee pain.

Conclusion: W FFE sequences were less reliable and measured considerably smaller BML volume compared to other sequences. BML volume was larger when assessed using the contrast enhanced W FS though not statistically significantly different from BMLs when assessed using PDFS and STIR sequences.

Advances In Knowledge: This is the first study to assess BMLs by four different MRI pulse sequences on the same data set, including different fluid sensitive sequences and gradient echo type sequence.
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http://dx.doi.org/10.1259/bjr.20201367DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8523191PMC
August 2021

MRI-Assessed Subchondral Cysts and Incident Knee Pain and Knee Osteoarthritis: data from the Multicentre Osteoarthritis Study.

Arthritis Rheumatol 2021 Jul 5. Epub 2021 Jul 5.

Department of Epidemiology and Biostatistics, University of California San Francisco, 550 16th St, San Francisco, CA, 94158, USA.

Objective: Our aim was to examine whether knee subchondral cysts, measured on magnetic resonance imaging (MRI), were associated with incident knee OA outcomes.

Methods: We used longitudinal data from the Multicentre Osteoarthritis Study (MOST), a community-based cohort of risk factors for knee OA. Participants without a history of knee surgery and/or inflammatory arthritis (i.e., rheumatoid arthritis and gout) were followed for 84-months for incident outcomes; i) radiographic knee OA (RKOA) (Kellgren-Lawrence (KL) ≥2), ii) symptomatic RKOA (RKOA and frequent knee pain) and iii) frequent knee pain (in participants with/without RKOA). Subchondral cysts were scored on baseline MRIs of one knee in a subset of participants. Multiple logistic regression, with adjustment for participant characteristics and other baseline knee MRI findings, was used to assess whether subchondral cysts were predictive of incident outcomes.

Results: Incident RKOA, symptomatic RKOA and frequent knee pain occurred in 22.8%, 17.0% and 28.8% (no RKOA) / 43.7% (with RKOA) of participants eligible for each outcome, respectively. Adjusting for age, sex and BMI, the presence of subchondral cysts was not associated with incident RKOA, but was associated with increased odds of incident symptomatic RKOA (OR: 1.92 (95% CI: 1.16 to 3.19) and knee pain in those with baseline RKOA (2.11 (0.87 to 5.12). Stronger and significant associations were observed for outcomes based on consistent reports of frequent pain within approximately one month.

Conclusions: Subchondral cysts are likely to be a secondary phenomenon, rather than a primary trigger, of RKOA, and may predict symptoms in knees with existing disease.
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http://dx.doi.org/10.1002/art.41917DOI Listing
July 2021

Subchondral Bone Length in Knee Osteoarthritis: A Deep Learning-Derived Imaging Measure and Its Association With Radiographic and Clinical Outcomes.

Arthritis Rheumatol 2021 May 11. Epub 2021 May 11.

Boston University, Boston, Massachusetts.

Objective: To develop a bone shape measure that reflects the extent of cartilage loss and bone flattening in knee osteoarthritis (OA) and test it against estimates of disease severity.

Methods: A fast region-based convolutional neural network was trained to crop the knee joints in sagittal dual-echo steady-state magnetic resonance imaging sequences obtained from the Osteoarthritis Initiative (OAI). Publicly available annotations of the cartilage and menisci were used as references to annotate the tibia and the femur in 61 knees. Another deep neural network (U-Net) was developed to learn these annotations. Model predictions were compared to radiologist-driven annotations on an independent test set (27 knees). The U-Net was applied to automatically extract the knee joint structures on the larger OAI data set (n = 9,434 knees). We defined subchondral bone length (SBL), a novel shape measure characterizing the extent of overlying cartilage and bone flattening, and examined its relationship with radiographic joint space narrowing (JSN), concurrent pain and disability (according to the Western Ontario and McMaster Universities Osteoarthritis Index), as well as subsequent partial or total knee replacement. Odds ratios (ORs) and 95% confidence intervals (95% CIs) for each outcome were estimated using relative changes in SBL from the OAI data set stratified into quartiles.

Results: The mean SBL values for knees with JSN were consistently different from knees without JSN. Greater changes of SBL from baseline were associated with greater pain and disability. For knees with medial or lateral JSN, the ORs for future knee replacement between the lowest and highest quartiles corresponding to SBL changes were 5.68 (95% CI 3.90-8.27) and 7.19 (95% CI 3.71-13.95), respectively.

Conclusion: SBL quantified OA status based on JSN severity and shows promise as an imaging marker in predicting clinical and structural OA outcomes.
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http://dx.doi.org/10.1002/art.41808DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8581065PMC
May 2021

Knee osteonecrosis incidence from two real-world data sources.

Osteoarthr Cartil Open 2021 Jun 16;3(2). Epub 2021 Apr 16.

Boston University School of Medicine, Boston, MA, USA.

Background: Anti-nerve growth factor (NGF) has shown promise for osteoarthritis (OA) pain efficacy, but an unanticipated joint safety signal occurred in trials. To what extent this was related to OA natural history, or was a consequence of anti-NGF agents is unclear. Of the adverse joint safety events identified, osteonecrosis has specific diagnostic codes available in the medical record to enable assessment of its frequency in the general community. We therefore investigated the rates of knee osteonecrosis in three real-world cohorts using two data sources to place these trial data in context.

Methods: We used data from UK-based IQVIA Medical Research Data (IMRD) of adults diagnosed with incident knee OA between 2000-2018 to examine the incidence of knee osteonecrosis using different definitions. Additionally, we evaluated the incidence of knee osteonecrosis in the year prior to knee replacement in IMRD and among US Medicare beneficiaries who received a knee replacement in 2011-2014.

Results: In IMRD, among 122,343 subjects with incident knee OA (mean age 68 years, 58% female), incidence estimates for knee osteonecrosis were 0.006-0.10%, with incidence rates of 0.01-0.17 per 1000 person-years. Among the 81,807 who had a knee replacement, the incidence of knee osteonecrosis in the year prior to knee replacement was 0.004-0.06%. In Medicare, among 316,593 with knee replacement (mean age 74, 68% female), the incidence of knee osteonecrosis was 0.24-0.7%.

Conclusion: Knee osteonecrosis is rare among people with knee OA, including in the year prior to knee replacement. These data provide context for interpreting osteonecrosis events in NGF trials.
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http://dx.doi.org/10.1016/j.ocarto.2021.100169DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8096165PMC
June 2021

Association of dietary fiber and risk of hip fracture in men from the Framingham Osteoporosis Study and the Concord Health and Ageing in Men Project.

Nutr Health 2021 May 4:2601060211011798. Epub 2021 May 4.

Centre for Health Systems and Safety Research, Australian Institute of Health Innovation Faculty of Medicine, Health and Human Sciences, Macquarie University, NSW 2109, Australia.

Background: Data in the Offspring Framingham Osteoporosis Study (FOS) suggested that higher intake of dietary fiber was modestly protective against loss of bone mineral density at the femoral neck in men but not in women.

Aim: To examine the relationship of fiber intake with risk of hip fractures in men.

Methods: We included 367 men from the FOS Original cohort, 1730 men from the FOS Offspring cohort, and 782 men from the Concord Health and Ageing in Men Project (CHAMP) in the analysis. Incident fractures were defined as medically confirmed first occurrence of osteoporotic fractures at the proximal femur. Fiber intake was estimated via a validated food frequency questionnaire (FFQ) or diet history. Cox proportional hazards models were applied to estimate hazard ratios (HRs) and 95% confidence intervals (CIs). A random-effects model was used to estimate the pooled relative risk in meta-analysis.

Results: Seventy-two incident hip fractures were identified, of which 24 occurred in the FOS Original cohort [mean (SD): age 75.3 (5.1) years; follow-up time: 8.5 (6.2) years; dietary fiber: 19 (8) (g/d)], 19 in the FOS Offspring cohort [58.8 (9.8) years; 11.0 (5.9) years; 19 (8) (g/d)], and 29 in CHAMP [81.4 (4.5) years; 5.2 (1.5) years; 28 (10) (g/d)]. We did not find significant associations within each cohort between fiber intake and risk of hip fractures. The pooled HR (95% CI) was 0.80 (0.39, 1.66) comparing energy-adjusted dietary fiber at tertile 3 vs. tertile 1 (I = 0, = 0.56).

Conclusion: These data suggested that dietary fiber was not associated with risk of incident hip fractures in men.
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http://dx.doi.org/10.1177/02601060211011798DOI Listing
May 2021

Web Exclusive. Annals On Call - Knee Osteoarthritis: Does the Type of Shoe Matter?

Ann Intern Med 2021 04 6;174(4):OC1. Epub 2021 Apr 6.

Boston University, Boston, Massachusetts (D.T.F.).

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http://dx.doi.org/10.7326/A20-0010DOI Listing
April 2021

A Picture Is Worth a Thousand Words, But Only If It Is a Good Picture.

Arthritis Rheumatol 2021 06 15;73(6):912-913. Epub 2021 Apr 15.

Boston Children's Hospital and Brigham and Women's Hospital, Boston, Massachusetts.

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http://dx.doi.org/10.1002/art.41682DOI Listing
June 2021

Quantifying varus thrust in knee osteoarthritis using wearable inertial sensors: A proof of concept.

Clin Biomech (Bristol, Avon) 2020 12 11;80:105232. Epub 2020 Nov 11.

Department of Physical Therapy & Athletic Training, Boston University College of Health & Rehabilitation Sciences: Sargent College, Boston, MA, USA; Division of Rheumatology, Department of Medicine, Boston University School of Medicine, Boston, MA, USA. Electronic address:

Background: Varus thrust during walking, visualized as excessive frontal plane knee motion during weight acceptance, is a modifiable risk factor for progression of knee osteoarthritis. However, visual assessment does not capture thrust severity and quantification with optical motion capture is often not feasible. Inertial sensors may provide a convenient alternative to optical motion capture. This proof-of-concept study sought to compare wearable inertial sensors to optical motion capture for the quantification of varus thrust.

Methods: Twenty-six participants with medial knee osteoarthritis underwent gait analysis at self-selected and fast speeds. Linear regression with generalized estimating equations assessed associations between peak knee adduction velocity or knee adduction excursion from optical motion capture and peak thigh or shank adduction velocity from two inertial sensors on the lower limb. Relationships between inertial measures and peak external knee adduction moment were assessed as a secondary aim.

Findings: Both thigh and shank inertial sensor measures were associated with the optical motion capture measures for both speeds (P < 0.001 to P = 0.020), with the thigh measures having less variability than the shank. After accounting for age, sex, body mass index, radiographic severity, and limb alignment, thigh adduction velocity was also associated with knee adduction moment at both speeds (both P < 0.001).

Interpretation: An inertial sensor placed on the mid-thigh can quantify varus thrust in people with medial knee osteoarthritis without the need for optical motion capture. This single sensor may be useful for risk screening or evaluating the effects of interventions in large samples.
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http://dx.doi.org/10.1016/j.clinbiomech.2020.105232DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7749075PMC
December 2020

Effect of Vitamin D Supplementation, Omega-3 Fatty Acid Supplementation, or a Strength-Training Exercise Program on Clinical Outcomes in Older Adults: The DO-HEALTH Randomized Clinical Trial.

JAMA 2020 11;324(18):1855-1868

Department of Biostatistics, Harvard T. H. Chan School of Public Health, Boston, Massachusetts.

Importance: The benefits of vitamin D, omega-3 fatty acids, and exercise in disease prevention remain unclear.

Objective: To test whether vitamin D, omega-3s, and a strength-training exercise program, alone or in combination, improved 6 health outcomes among older adults.

Design, Setting, And Participants: Double-blind, placebo-controlled, 2 × 2 × 2 factorial randomized clinical trial among 2157 adults aged 70 years or older who had no major health events in the 5 years prior to enrollment and had sufficient mobility and good cognitive status. Patients were recruited between December 2012 and November 2014, and final follow-up was in November 2017.

Interventions: Participants were randomized to 3 years of intervention in 1 of the following 8 groups: 2000 IU/d of vitamin D3, 1 g/d of omega-3s, and a strength-training exercise program (n = 264); vitamin D3 and omega-3s (n = 265); vitamin D3 and exercise (n = 275); vitamin D3 alone (n = 272); omega-3s and exercise (n = 275); omega-3s alone (n = 269); exercise alone (n = 267); or placebo (n = 270).

Main Outcomes And Measures: The 6 primary outcomes were change in systolic and diastolic blood pressure (BP), Short Physical Performance Battery (SPPB), Montreal Cognitive Assessment (MoCA), and incidence rates (IRs) of nonvertebral fractures and infections over 3 years. Based on multiple comparisons of 6 primary end points, 99% confidence intervals are presented and P < .01 was required for statistical significance.

Results: Among 2157 randomized participants (mean age, 74.9 years; 61.7% women), 1900 (88%) completed the study. Median follow-up was 2.99 years. Overall, there were no statistically significant benefits of any intervention individually or in combination for the 6 end points at 3 years. For instance, the differences in mean change in systolic BP with vitamin D vs no vitamin D and with omega-3s vs no omega-3s were both -0.8 (99% CI, -2.1 to 0.5) mm Hg, with P < .13 and P < .11, respectively; the difference in mean change in diastolic BP with omega-3s vs no omega-3s was -0.5 (99% CI, -1.2 to 0.2) mm Hg; P = .06); and the difference in mean change in IR of infections with omega-3s vs no omega-3s was -0.13 (99% CI, -0.23 to -0.03), with an IR ratio of 0.89 (99% CI, 0.78-1.01; P = .02). No effects were found on the outcomes of SPPB, MoCA, and incidence of nonvertebral fractures). A total of 25 deaths were reported, with similar numbers in all treatment groups.

Conclusions And Relevance: Among adults without major comorbidities aged 70 years or older, treatment with vitamin D3, omega-3s, or a strength-training exercise program did not result in statistically significant differences in improvement in systolic or diastolic blood pressure, nonvertebral fractures, physical performance, infection rates, or cognitive function. These findings do not support the effectiveness of these 3 interventions for these clinical outcomes.

Trial Registration: ClinicalTrials.gov Identifier: NCT01745263.
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http://dx.doi.org/10.1001/jama.2020.16909DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7656284PMC
November 2020

Intra-articular Corticosteroid Injections for the Treatment of Hip and Knee Osteoarthritis-related Pain: Considerations and Controversies with a Focus on Imaging- Scientific Expert Panel.

Radiology 2020 12 20;297(3):503-512. Epub 2020 Oct 20.

From the Department of Radiology, VA Boston Healthcare System, Boston University School of Medicine, 1400 VFW Pkwy, Suite 1B105, West Roxbury, MA 02132 (A.G., T.N., D.T.F., F.W.R.); Department of Orthopedic Surgery, Brigham and Women's Hospital, Harvard University, Boston, Mass (J.N.K.); Department of Medicine, University of Arizona Health Sciences Center, Tucson, Ariz (C.K.K.); Leeds Institute of Rheumatic and Musculoskeletal Medicine, University of Leeds, Leeds, England (P.G.C.); and Department of Radiology, University of Erlangen, Erlangen, Germany (F.W.R.).

Current management of osteoarthritis (OA) is primarily focused on symptom control. Intra-articular corticosteroid (IACS) injections are often used for pain management of hip and knee OA in patients who have not responded to oral or topical analgesics. Recent case series suggested that negative structural outcomes including accelerated OA progression, subchondral insufficiency fracture, complications of pre-existing osteonecrosis, and rapid joint destruction (including bone loss) may be observed in patients who received IACS injections. This expert panel report reviews the current understanding of pain in OA, summarizes current international guidelines regarding indications for IACS injection, and considers preinterventional safety measures, including imaging. Potential profiles of those who would likely benefit from IACS injection and a suggestion for an updated patient consent form are presented. As of today, there is no established recommendation or consensus regarding imaging, clinical, or laboratory markers before an IACS injection to screen for OA-related imaging abnormalities. Repeating radiographs before each subsequent IACS injection remains controversial. The true cause and natural history of these complications are unclear and require further study. To determine the cause and natural history, large prospective studies evaluating the risk of accelerated OA or joint destruction after IACS injections are needed. However, given the relatively rare incidence of these adverse outcomes, any clinical trial would be challenging in design and a large number of patients would need to be included.
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http://dx.doi.org/10.1148/radiol.2020200771DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7706887PMC
December 2020

Drs. Dai and Felson reply.

J Rheumatol 2021 02 15;48(2):303. Epub 2020 Oct 15.

Boston University School of Medicine, Department of Medicine, Section of Rheumatology, Boston, Massachusetts, USA.

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http://dx.doi.org/10.3899/jrheum.201222DOI Listing
February 2021

Biomechanical Footwear for Osteoarthritic Knee Pain-Reply.

JAMA 2020 10;324(13):1351-1352

St Michael's Hospital, University of Toronto, Toronto, Ontario, Canada.

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http://dx.doi.org/10.1001/jama.2020.14825DOI Listing
October 2020

Knee Extensor and Flexor Torque Variability During Maximal Strength Testing and Change in Knee Pain and Physical Function at 60-Mo Follow-Up: The Multicenter Osteoarthritis Study (MOST).

Am J Phys Med Rehabil 2021 02;100(2):196-201

From the Department of PM&R, University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania (AS); Biostatistics and Epidemiology Data Analytics Center (BEDAC), Boston University School of Public Health, Boston, Massachusetts (NW); Boston University, Boston, Massachusetts (DTF); University of Alabama at Birmingham, Birmingham, Alabama (CEL); University of California, San Francisco, San Francisco, California (MCN); University of Kansas Medical Center, Kansas City, Kansas (NAS); and The University of Iowa, Iowa City, Iowa (NAS).

Abstract: As the population ages, there is a growing burden owing to musculoskeletal diseases, such as knee osteoarthritis, and subsequent functional decline. In the absence of a cure, there is a need to identify factors amenable to intervention to prevent or slow this process. The Multicenter Osteoarthritis Study cohort was developed for this purpose. In this study, associations between variability in peak knee flexor and extensor torque at baseline and worsening of pain and physical function over the subsequent 60 mos were assessed in a cohort of 2680 participants. The highest quartile of baseline knee flexor torque variability was found to be associated longitudinally with worsening pain (fourth quartile ß estimate, mean ± SE, 0.49 ± 0.19; P = 0.0115; with R2 = 0.28 and P for trend across quartiles = 0.0370) and physical function scores (fourth quartile ß estimate, mean ± SE, 1.39 ± 0.64; P = 0.0296; with R2 = 0.25 and P for trend across quartiles = 0.0371), after adjusting for baseline knee osteoarthritis and maximum knee flexor torque. There were no associations between baseline knee extensor torque and worsening pain or physical function by 60 mos. The presence of greater variability in maximum knee flexor strength may identify patients who may benefit from therapies aimed at preventing worsening knee pain and physical function.
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http://dx.doi.org/10.1097/PHM.0000000000001587DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8024112PMC
February 2021

Correction to: Assessment of knee pain from MR imaging using a convolutional Siamese network.

Eur Radiol 2020 Dec;30(12):6968

Section of Computational Biomedicine, Department of Medicine, Boston University School of Medicine, 72 E. Concord Street, Evans 636, Boston, MA, 02118, USA.

The original version of this article, published on 13 February 2020, unfortunately contained a mistake.
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http://dx.doi.org/10.1007/s00330-020-07073-4DOI Listing
December 2020

Which Chronic Low Back Pain Patients Respond Favorably to Yoga, Physical Therapy, and a Self-care Book? Responder Analyses from a Randomized Controlled Trial.

Pain Med 2021 02;22(1):165-180

Department of Family Medicine, Boston University School of Medicine and Boston Medical Center, Boston, Massachusetts, USA.

Purpose: To identify baseline characteristics of adults with chronic low back pain (cLBP) that predict response (i.e., a clinically important improvement) and/or modify treatment effect across three nonpharmacologic interventions.

Design: Secondary analysis of a randomized controlled trial.

Setting: Academic safety net hospital and seven federally qualified community health centers.

Subjects: Adults with cLBP (N = 299).

Methods: We report patient characteristics that were predictors of response and/or modified treatment effect across three 12-week treatments: yoga, physical therapy [PT], and a self-care book. Using preselected characteristics, we used logistic regression to identify predictors of "response," defined as a ≥30% improvement in the Roland Morris Disability Questionnaire. Then, using "response" as our outcome, we identified baseline characteristics that were treatment effect modifiers by testing for statistical interaction (P < 0.05) across two comparisons: 1) yoga-or-PT vs self-care and 2) yoga vs PT.

Results: Overall, 39% (116/299) of participants were responders, with more responders in the yoga-or-PT group (42%) than the self-care (23%) group. There was no difference in proportion responding to yoga (48%) vs PT (37%, odds ratio [OR] = 1.5, 95% confidence interval = 0.88 - 2.6). Predictors of response included having more than a high school education, a higher income, employment, few depressive symptoms, lower perceived stress, few work-related fear avoidance beliefs, high pain self-efficacy, and being a nonsmoker. Effect modifiers included use of pain medication and fear avoidance beliefs related to physical activity (both P = 0.02 for interaction). When comparing yoga or PT with self-care, a greater proportion were responders among those using pain meds (OR = 5.3), which differed from those not taking pain meds (OR = 0.94) at baseline. We also found greater treatment response among those with lower (OR = 7.0), but not high (OR = 1.3), fear avoidance beliefs around physical activity.

Conclusions: Our findings revealed important subgroups for whom referral to yoga or PT may improve cLBP outcomes.
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http://dx.doi.org/10.1093/pm/pnaa153DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7861465PMC
February 2021

Development of classification criteria for hand osteoarthritis: comparative analyses of persons with and without hand osteoarthritis.

RMD Open 2020 06;6(2)

Rheumatology, Leiden University Medical Center, Leiden, Netherlands.

Objectives: Further knowledge about typical hand osteoarthritis (OA) characteristics is needed for the development of new classification criteria for hand OA.

Methods: In a cross-sectional multi-centre international study, a convenience sample of patients from primary and secondary/tertiary care with a physician-based hand OA diagnosis (n = 128) were compared with controls with hand complaints due to inflammatory or non-inflammatory conditions (n = 70). We examined whether self-reported, clinical, radiographic and laboratory findings were associated with hand OA using logistic regression analyses. Discrimination between groups was assessed by calculating the area under receiver operating curves (AUC).

Results: Strong associations with hand OA were observed for radiographic osteophytes (OR = 1.62, 95% CI 1.40 to 1.88) and joint space narrowing (JSN) (OR = 1.57, 95% CI 1.36 to 1.82) in the distal interphalangeal (DIP) joints with excellent discrimination (AUC = 0.82 for both). For osteophytes and JSN, we found acceptable discrimination between groups in the proximal interphalangeal joints (AUC = 0.77 and 0.78, respectively), but poorer discrimination in the first carpometacarpal joints (AUC = 0.67 and 0.63, respectively). Painful DIP joints were associated with hand OA, but were less able to discriminate between groups (AUC = 0.67). Age and family history of OA were positively associated with hand OA, whereas negative associations were found for pain, stiffness and soft tissue swelling in metacarpophalangeal joints, pain and marginal erosions in wrists, longer morning stiffness, inflammatory biomarkers and autoantibodies.

Conclusions: Differences in symptoms, clinical findings, radiographic changes and laboratory tests were found in patients with hand OA versus controls. Radiographic OA features, especially in DIP joints, were best suited to discriminate between groups.
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http://dx.doi.org/10.1136/rmdopen-2020-001265DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7425183PMC
June 2020

Effect of Biomechanical Footwear on Knee Pain in People With Knee Osteoarthritis: The BIOTOK Randomized Clinical Trial.

JAMA 2020 May;323(18):1802-1812

Applied Health Research Centre, Li Ka Shing Knowledge Institute, St Michael's Hospital, Toronto, Ontario, Canada.

Importance: Individually calibrated biomechanical footwear therapy may improve pain and physical function in people with symptomatic knee osteoarthritis, but the benefits of this therapy are unclear.

Objective: To assess the effect of a biomechanical footwear therapy vs control footwear over 24 weeks of follow-up.

Design, Setting, And Participants: Randomized clinical trial conducted at a Swiss university hospital. Participants (N = 220) with symptomatic, radiologically confirmed knee osteoarthritis were recruited between April 20, 2015, and January 10, 2017. The last participant visit occurred on August 15, 2017.

Interventions: Participants were randomized to biomechanical footwear involving shoes with individually adjustable external convex pods attached to the outsole (n = 111) or to control footwear (n = 109) that had visible outsole pods that were not adjustable and did not create a convex walking surface.

Main Outcomes And Measures: The primary outcome was knee pain at 24 weeks of follow-up assessed with the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) pain subscore standardized to range from 0 (no symptoms) to 10 (extreme symptoms). The secondary outcomes included WOMAC physical function and stiffness subscores and the WOMAC global score, all ranging from 0 (no symptoms) to 10 (extreme symptoms) at 24 weeks of follow-up, and serious adverse events.

Results: Among the 220 randomized participants (mean age, 65.2 years [SD, 9.3 years]; 104 women [47.3%]), 219 received the allocated treatment and 213 (96.8%) completed follow-up. At 24 weeks of follow-up, the mean standardized WOMAC pain subscore improved from 4.3 to 1.3 in the biomechanical footwear group and from 4.0 to 2.6 in the control footwear group (between-group difference in scores at 24 weeks of follow-up, -1.3 [95% CI, -1.8 to -0.9]; P < .001). The results were consistent for WOMAC physical function subscore (between-group difference, -1.1 [95% CI, -1.5 to -0.7]), WOMAC stiffness subscore (between-group difference, -1.4 [95% CI, -1.9 to -0.9]), and WOMAC global score (between-group difference, -1.2 [95% CI, -1.6 to -0.8]) at 24 weeks of follow-up. Three serious adverse events occurred in the biomechanical footwear group compared with 9 in the control footwear group (2.7% vs 8.3%, respectively); none were related to treatment.

Conclusions And Relevance: Among participants with knee pain from osteoarthritis, use of biomechanical footwear compared with control footwear resulted in an improvement in pain at 24 weeks of follow-up that was statistically significant but of uncertain clinical importance. Further research would be needed to assess long-term efficacy and safety, as well as replication, before reaching conclusions about the clinical value of this device.

Trial Registration: ClinicalTrials.gov Identifier: NCT02363712.
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http://dx.doi.org/10.1001/jama.2020.3565DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7218497PMC
May 2020

Phenylalanine Is a Novel Marker for Radiographic Knee Osteoarthritis Progression: The MOST Study.

J Rheumatol 2021 01 1;48(1):123-128. Epub 2020 May 1.

D.T. Felson, MD, MPH, Department of Rheumatology, Boston University School of Medicine, Boston, USA, and NIHR Manchester Biomedical Research Centre, Manchester Academic Health Science Centre, Manchester University NHS Foundation Trust, Manchester, UK.

Objective: To identify plasma markers associated with an increased risk of radiographic knee osteoarthritis(OA) progression using a metabolomics approach.

Methods: Study participants were from the Multicenter Osteoarthritis Study (MOST) and were categorized into 2 groups based on the presence of baseline radiographic OA. Subjects in group 1 had unilateral knee OA and subjects in group 2 had bilateral knee OA. Progression was defined as a half-grade or greater worsening in joint space width at 30-month follow-up. For group 1, a participant progressed when their OA knee showed radiographic progression and the contralateral knee developed OA; for group 2, a participant progressed when both knees with OA showed radiographic progression. Metabolomic profiling was performed on plasma samples collected at baseline and logistic regression was performed to test the association between each metabolite and knee OA progression after adjustment for age, sex, BMI, and clinic site. Significance was defined as ≤ 0.0003 in the combined analysis.

Results: There were 234 progressors (57 in group 1 and 177 in group 2) and 322 nonprogressors (206 in group 1 and 116 in group 2) included in the analyses. Among 157 metabolites studied, we found that odds of progression were 1.46 times higher per SD increase of phenylalanine level (95% CI 1.20-1.77, = 0.0001) in the combined analysis. Sex-specific analysis showed that an association was seen in women ( = 0.0002) but not in men.

Conclusion: Our data suggest that phenylalanine might be a novel plasma marker for higher risk of bilateral radiographic knee OA progression in women.
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http://dx.doi.org/10.3899/jrheum.200054DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8039838PMC
January 2021

Assessment of knee pain from MR imaging using a convolutional Siamese network.

Eur Radiol 2020 Jun 13;30(6):3538-3548. Epub 2020 Feb 13.

Section of Computational Biomedicine, Department of Medicine, Boston University School of Medicine, 72 E. Concord Street, Evans 636, Boston, MA, 02118, USA.

Objectives: It remains difficult to characterize the source of pain in knee joints either using radiographs or magnetic resonance imaging (MRI). We sought to determine if advanced machine learning methods such as deep neural networks could distinguish knees with pain from those without it and identify the structural features that are associated with knee pain.

Methods: We constructed a convolutional Siamese network to associate MRI scans obtained on subjects from the Osteoarthritis Initiative (OAI) with frequent unilateral knee pain comparing the knee with frequent pain to the contralateral knee without pain. The Siamese network architecture enabled pairwise learning of information from two-dimensional (2D) sagittal intermediate-weighted turbo spin echo slices obtained from similar locations on both knees. Class activation mapping (CAM) was utilized to create saliency maps, which highlighted the regions most associated with knee pain. The MRI scans and the CAMs of each subject were reviewed by an expert radiologist to identify the presence of abnormalities within the model-predicted regions of high association.

Results: Using 10-fold cross-validation, our model achieved an area under curve (AUC) value of 0.808. When individuals whose knee WOMAC pain scores were not discordant were excluded, model performance increased to 0.853. The radiologist review revealed that about 86% of the cases that were predicted correctly had effusion-synovitis within the regions that were most associated with pain.

Conclusions: This study demonstrates a proof of principle that deep learning can be applied to assess knee pain from MRI scans.

Key Points: • Our article is the first to leverage a deep learning framework to associate MR images of the knee with knee pain. • We developed a convolutional Siamese network that had the ability to fuse information from multiple two-dimensional (2D) MRI slices from the knee with pain and the contralateral knee of the same individual without pain to predict unilateral knee pain. • Our model achieved an area under curve (AUC) value of 0.808. When individuals who had WOMAC pain scores that were not discordant for knees (pain discordance < 3) were excluded, model performance increased to 0.853.
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http://dx.doi.org/10.1007/s00330-020-06658-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7786238PMC
June 2020

Determinants of generalized fatigue in individuals with symptomatic knee osteoarthritis: The MOST Study.

Int J Rheum Dis 2020 Apr 28;23(4):559-568. Epub 2020 Jan 28.

Centre for Living, School of Health and Life Sciences, Glasgow Caledonian University, Glasgow, UK.

Aim: The aim of the study was to identify sociodemographic, disease-related, physical and mental health-related determinants of fatigue at 2-year follow-up in individuals with symptomatic knee osteoarthritis (OA).

Methods: A longitudinal analysis of participants with symptomatic knee OA from the Multicenter Osteoarthritis Study (MOST) was conducted to identify predictors of fatigue at 2-year follow-up. Participants self-reported fatigue at baseline for the first time in the MOST cohort and at follow-up using a 0-10 visual analog scale. At baseline, questionnaires on sociodemographics, disease-related symptoms, physical and mental health factors were completed. Data were analyzed using linear regressions with a backwards elimination approach.

Results: Of the 2330 individuals in the MOST cohort at baseline, 576 had symptomatic knee OA and of these, 449 with complete fatigue values at baseline and follow-up were included in this analysis. Minimally important fatigue change (ie, worsening [≥1.13], no change [<0.82 or <1.13] and improvement [≥-0.82]) from baseline to follow-up were unequal within the population (34.5%, 26.9%, 38.5%; χ [2, N = 449] = 9.32, P = .009). The multiple linear regression showed that baseline fatigue (unstandardized coefficient [Β] = 0.435; 95% confidence interval [CI] 0.348-0.523, P < .001), slow gait speed (Β = -1.124; 95% CI -1.962 to -0.285, P = .009), depressive symptoms (Β = 0.049; 95% CI 0.024-0.075, P < .001) and higher numbers of comorbidities (Β = 0.242; 95% CI 0.045-0.439, P = .016) were significant predictors of greater fatigue at follow-up.

Conclusion: Fatigue is strongly associated with physical- and mental-related health factors. Individualized treatments that include combined psychological and physical function rehabilitation might be modalities for fatigue management.
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http://dx.doi.org/10.1111/1756-185X.13797DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7160026PMC
April 2020

Sleep Quality Is Related to Worsening Knee Pain in Those with Widespread Pain: The Multicenter Osteoarthritis Study.

J Rheumatol 2020 07 15;47(7):1019-1025. Epub 2019 Nov 15.

From the Boston University School of Medicine, Department of Medicine, Section of Rheumatology, Boston, Massachusetts, USA; Epidemiology and Biostatistics, University of California, San Francisco, California; Department of Epidemiology, School of Public Health, University of Alabama at Birmingham, Birmingham, Alabama; Department of Epidemiology and the Institute for Clinical and Translational Science, The University of Iowa, Iowa, USA; The University of Sydney, Faculty of Medicine and Health, School of Pharmacy, Sydney, Australia; Centre for Epidemiology, University of Manchester and the National Institute for Health Research (NIHR) Manchester Biomedical Research Centre (BRC), Manchester University National Health Service (NHS) Trust, Manchester, UK.

Objective: We examined the association between sleep and odds of developing knee pain, and whether this relationship varied by status of widespread pain (WSP).

Methods: At the 60-month visit of the Multicenter Osteoarthritis Study, sleep quality and restless sleep were each assessed by using a single item from 2 validated questionnaires. Each sleep measure was categorized into 3 levels, with poor/most restless sleep as the reference. WSP was defined as pain above and below the waist on both sides of the body and axially using a standard homunculus, based on the American College of Rheumatology criteria. Outcomes from 60-84 months included (1) knee pain worsening (KPW; defined as minimal clinically important difference in WOMAC pain), (2) prevalent, and (3) incident consistent frequent knee pain. We applied generalized estimating equations in multivariable logistic regression models.

Results: We studied 2329 participants (4658 knees; 67.9 yrs, body mass index 30.9]. We found that WSP modified the relationship between sleep quality and KPW (p = 0.002 for interaction). Among persons with WSP, OR (95% CI) for KPW was 0.53 (0.35-0.78) for those with very good sleep quality (p trend < 0.001); additionally, we found the strongest association of sleep quality in persons with > 8 painful joint sites (p trend < 0.01), but not in those with ≤ 2 painful joint sites. Similar results were observed using restless sleep, in the presence of WSP. The cross-sectional relationship between sleep and prevalence of consistent frequent knee pain was significant.

Conclusion: Better sleep was related to less KPW with coexisting widespread pain.
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http://dx.doi.org/10.3899/jrheum.181365DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7225049PMC
July 2020

Influence of Antagonistic Hamstring Coactivation on Measurement of Quadriceps Strength in Older Adults.

PM R 2020 05 25;12(5):470-478. Epub 2019 Nov 25.

Department of Rehabilitation Medicine, The University of Kansas, Kansas City, KS.

Background: There is limited understanding of how antagonist muscle coactivation relates to measurement of strength in both individuals with and without knee osteoarthritis (KOA).

Objective: This study sought to determine whether hamstring coactivation during a maximal quadriceps activation task attenuates net quadriceps strength.

Design: Cross-sectional cohort analysis was conducted using data from the 60-month visit of the Multicenter Osteoarthritis Study (MOST).

Setting: Laboratory.

Participants: A sample of 2328 community-dwelling MOST participants between the ages of 55 and 84 years, with or at elevated risk for KOA, completed the 60-month MOST follow-up visit. Of these, 1666 met inclusion criteria for the current study.

Interventions: Not applicable.

Main Outcome Measure(s): Quadriceps strength; percentage of combined hamstring coactivation (HC), medial HC, and lateral HC. Quadriceps and hamstring strength were assessed using an isokinetic dynamometer. Surface electromyography was used to assess muscle activation patterns. General linear models, adjusted for age, BMI, Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC), Kellgren-Lawrence (KL) grade and study site, modeled the relationship between antagonist hamstring coactivation and quadriceps strength.

Results: Men had significantly greater quadriceps strength (P < .001), history of knee injury (P < .001) and surgery (P = .002), and greater presence of varus malalignment (P < .001). Women had greater pain (P < .001) and proportion of KL grade ≥2 (P = .017). Gender-specific analyses revealed combined HC (P = .013) and lateral HC inversely associated with quadriceps strength in women (P = .023) but not in men (combined HC P = .320, lateral HC P = .755). A nonlinear association was detected between quadriceps strength and medial HC. Assessment of quartiles of medial HC revealed the third quartile had reduced quadriceps strength when compared to the lowest quartile of coactivation in both men and women.

Conclusions: Hamstring coactivation attenuates measured quadriceps strength in women with or at elevated risk for KOA.

Level Of Evidence: II.
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http://dx.doi.org/10.1002/pmrj.12253DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8016551PMC
May 2020

Mediating Role of Bone Marrow Lesions, Synovitis, Pain Sensitization, and Depressive Symptoms on Knee Pain Improvement Following Substantial Weight Loss.

Arthritis Rheumatol 2020 03 22;72(3):420-427. Epub 2020 Jan 22.

Boston University School of Medicine, Boston, Massachusetts, and University of Manchester, NIHR Manchester Biomedical Research Centre, and Manchester University NHS Foundation Trust, Manchester, UK.

Objective: Massive weight loss leads to marked knee pain reduction in individuals with knee pain, but the reason for the reduction in pain is unknown. This study was undertaken to quantify the contribution of magnetic resonance imaging (MRI)-evidenced changes in pain-sensitive structures, bone marrow lesions (BMLs), and synovitis, and changes in pain sensitization or depressive symptoms, to knee pain improvement after substantial weight loss.

Methods: Morbidly obese patients with knee pain on most days were evaluated before bariatric surgery or medical weight management and at 1-year follow-up for BMLs and synovitis seen on MRI, the pressure pain threshold (PPT) at the patella and the right wrist, depressive symptoms (using the Center for Epidemiologic Studies Depression scale [CES-D]), and Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) pain survey. Natural-effects models were used to quantify the extent that achieving a minimum clinically important difference (MCID) of ≥18% on the WOMAC pain scale could be mediated by weight loss-induced changes in BMLs, synovitis, PPT, and depressive symptoms.

Results: Of 75 participants, 53.3% lost ≥20% of weight by 1 year. Of these, 75% attained the MCID for pain improvement, compared with 34.3% in those who had <20% weight loss. Mediation analyses suggested that, in those with at least 20% weight loss, the odds of pain improvement increased by 62%, 15%, and 22% through changes in patella PPT, wrist PPT, and CES-D, respectively, but pain improvement was not mediated by MRI changes in BMLs or synovitis.

Conclusion: Weight loss-induced knee pain improvement is partially mediated by changes in pain sensitization and depressive symptoms but is independent of MRI changes in BMLs and synovitis.
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http://dx.doi.org/10.1002/art.41125DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7050338PMC
March 2020
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