Publications by authors named "Michael C Nevitt"

222 Publications

Relationship of Patellofemoral Osteoarthritis to Changes in Performance-Based Physical Function Over 7 Years: The Multicenter Osteoarthritis Study.

J Rheumatol 2021 Sep 1. Epub 2021 Sep 1.

Faculty of Health Sciences and Bone and Joint Institute, Western University, London, Canada; Division of Rheumatology, Boston University School of Medicine, Boston, USA; Department of Biostatistics, Boston University School of Public Health, Boston, USA; Department of Physical Therapy, University of Delaware, Newark, USA; Department of Rheumatology, Massachusetts General Hospital, Boston, USA; Department of Epidemiology and Biostatistics, University of California San Francisco, San Francisco, USA; Department of Epidemiology, The University of Iowa, Iowa City, USA; Department of Epidemiology, University of Alabama at Birmingham, Birmingham, USA; Department of Physical Therapy, Movement, and Rehabilitation Sciences, Northeastern University, Boston, USA. Funding: The Multicenter Osteoarthritis Study was funded by the NIH/NIA UO1 AG18820, UO1 AG18832, UO1 AG18947, and UO1 AG19069. Dr. Hart is funded by a Canadian Institutes of Health Research Fellowship. Dr. Stefanik is supported by NIH/NIAMS K23 AR070913. Dr. Neogi was supported by NIH/NIAMS K24AR070892. This work was also supported by NIH/NIAMS P30AR072571. Funding sources had no role in the study design, collection, analysis, and interpretation of the data or the decision to submit the manuscript for publication. Address correspondence to Joshua J. Stefanik Department of Physical Therapy, Movement, and Rehabilitation Sciences, Boston, MA, United States. E-mail:

Objective: Determine the relationship of patellofemoral osteoarthritis (OA) to changes in performancebased function over 7 years.

Methods: 2666 participants (62.2±8.0 years, BMI 30.6±5.9kg/m; 60% female) from the Multicenter Osteoarthritis Study with knee radiographs at baseline and who completed repeated chair stands and 20- meter walk test at baseline, 2.5, 5, and 7 years were included. Generalized linear models assessed the relation of radiographic patellofemoral OA and radiographic patellofemoral OA with frequent knee pain to longitudinal changes in performance-based function. Analyses were adjusted for age, sex, BMI, tibiofemoral OA, and injury/surgery.

Results: Linear models demonstrated a significant group by time interaction for the repeated chair stands (p=0.04) and the 20-meter walk test (p<0.0001). Those with radiographic patellofemoral OA took 1.01seconds longer on the repeated chair stands (p=0.02) and 1.69seconds longer on the 20-meter walk test (p<0.0001) at 7 years compared with baseline. When examining the relation of radiographic patellofemoral OA with frequent knee pain to performance-based function there was a significant group by time interaction for repeated chair stands (p=0.05) and the 20-meter walk test (p<0.0001). Those with radiographic patellofemoral OA with frequent knee pain increased their time on the repeated chair stands by 1.12seconds (p=0.04) and 1.91seconds (p<0.0001) on the 20-meter walk test over 7 years.

Conclusion: Individuals with radiographic patellofemoral OA and those with radiographic patellofemoral OA with frequent knee pain have worsening of performance-based function over time. This knowledge may present opportunities to plan for early treatment strategies for patellofemoral OA to limit functional decline over time.
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http://dx.doi.org/10.3899/jrheum.210270DOI Listing
September 2021

Sports with a Bat or Racket are Not Associated with Thumb-base Osteoarthritis.

J Athl Train 2021 Aug 17. Epub 2021 Aug 17.

Timothy E. McAlindon, MD, MPH, Chief, Division of Rheumatology, Allergy, & Immunology, Tufts Medical Center, Boston, MA, USA,

Context: Repetitive joint use is a risk factor for osteoarthritis, which is a leading cause of disability. Sports requiring a bat or racket to perform repetitive high-velocity impacts may increase the risk of thumb-base osteoarthritis. However, this hypothesis remains untested.

Objective: To determine if a history of participation in racket or bat sports is associated with the prevalence of thumb-base osteoarthritis.

Design: Descriptive epidemiology study.

Setting: Osteoarthritis Initiative. Four clinical sites in the United States.

Participants: We included men and women from the recruited from the community. Eligible participants had dominant hand radiographic readings, hand symptom assessments, and historical physical activity survey data.

Main Outcome Measures: A history of exposure to racket or bat sports (baseball/softball, racquetball/squash, badminton, table tennis, tennis [doubles/singles]) was based on self-reported recall data covering 3 age ranges (12-18 years, 19-34 years, 35-49 years). Prevalent radiographic thumb-base osteoarthritis was defined as someone with Kellgren-Lawrence grade≥2 in the first carpometacarpal joint or scaphotrapezoidal joint at the OAI baseline visit. Symptomatic thumb-base osteoarthritis was defined as the presence of radiographic osteoarthritis and hand/finger symptoms.

Results: In total, we included 2309 participants. Among 1049 men, 355 (34%) and 56 (5%) had radiographic or symptomatic thumb-base osteoarthritis, respectively; and among 1260 women, 535 (42%) and 170 (13%), respectively. After adjusting for age, race, and education level, we found no statistically significant associations between a history of any racket or bat sport participation and thumb-base osteoarthritis (radiographic or symptomatic; odds ratios range from 0.82 to 1.34).

Conclusions: Within a community-based cohort, a self-reported history of participation in racket or bat sports was not associated with an increased odds of having radiographic or symptomatic thumb-base osteoarthritis in the dominant hand.
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http://dx.doi.org/10.4085/1062-6050-0208.21DOI Listing
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

Opioid users show worse baseline knee osteoarthritis and faster progression of degenerative changes: a retrospective case-control study based on data from the Osteoarthritis Initiative (OAI).

Arthritis Res Ther 2021 05 22;23(1):146. Epub 2021 May 22.

Department of Radiology and Biomedical Imaging, University of California, San Francisco, 185 Berry Street, Lobby 6, Suite 350, San Francisco, CA, 94107, USA.

Background: Opioids are frequently prescribed for pain control in knee osteoarthritis patients, despite recommendations by current guidelines. Previous studies have investigated the chondrotoxicity of different opioid subtypes. However, the impact opioids may have on progression of osteoarthritis in vivo remains unknown. The aim of this study was thus to describe the associations between opioid use and knee structural changes and clinical outcomes, over 4 years.

Methods: Participants with baseline opioid use (n=181) and who continued use for ≥1 year between baseline and 4-year follow-up (n=79) were included from the Osteoarthritis Initiative cohort and frequency matched with non-users (controls) (1:2). Whole-Organ Magnetic Resonance Imaging Scores (WORMS) were obtained, including a total summation score (WORMS total, range 0-96) and subscores for cartilage (0-36), menisci (0-24), and bone marrow abnormalities and subchondral cyst-like lesions (0-18, respectively). Knee Injury Osteoarthritis Outcomes score (KOOS) symptoms, quality of life (QOL), and pain were also obtained at baseline and follow-up (range 0-100; lower scores indicate worse outcomes). Using linear regression models, associations between baseline and longitudinal findings were investigated. As pain may modify observations, a sensitivity analysis was performed for longitudinal findings. All analyses were adjusted for sex, BMI, age, race, and Kellgren-Lawrence grade.

Results: Opioid users had greater structural degeneration at baseline (WORMS total: Coef. [95% CI], P; 7.1 [5.5, 8.8], <0.001) and a greater increase over 4 years (4.7 [2.9, 6.5], <0.001), compared to controls. Cartilage and meniscus scores increased greater in opioid users, compared to controls (P≤0.001), and findings withstood the adjustment for baseline pain (P≤0.002). All baseline KOOS scores were lower in opioid users compared to controls (P<0.001). QOL loss was greater, when adjusted for baseline KOOS pain (QOL -6.9 [-11.6, -2.1], 0.005).

Conclusions: Opioid users had worse baseline knee structural degeneration and faster progression. Opioid use was also associated with worse symptoms, pain, and QOL. Furthermore, QOL loss was greater in opioid users compared to controls, when adjusted for baseline KOOS pain, indicating that opioids may not be suited to prevent subjective disease progression in KOA patients.
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http://dx.doi.org/10.1186/s13075-021-02524-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8140460PMC
May 2021

Weight Cycling and Knee Joint Degeneration in Individuals with Overweight or Obesity: Four-Year Magnetic Resonance Imaging Data from the Osteoarthritis Initiative.

Obesity (Silver Spring) 2021 05 1;29(5):909-918. Epub 2021 Apr 1.

Department of Radiology and Biomedical Imaging, University of California, San Francisco, San Francisco, California, USA.

Objective: The aim of this study was to investigate the associations between weight cycling and knee joint degeneration in individuals with overweight or obesity with different patterns of weight change over 4 years.

Methods: A total of 2,271 individuals from the Osteoarthritis Initiative database were assessed (case-control study). Linear regression models using annual BMI measurements over 4 years were used to classify participants as weight cyclers or noncyclers. 3-T magnetic resonance imaging was used to quantify knee cartilage transverse relaxation time (T2) and cartilage thickness annually over 4 years in all subjects. Whole-Organ Magnetic Resonance Imaging Scores (WORMS) were obtained for cartilage, meniscus, and bone-marrow abnormalities in 958 subjects at baseline and at the 4-year follow-up. The longitudinal differences in cartilage T2 and thickness between weight cyclers and noncyclers were assessed using general estimating equations, whereas the differences in WORMS outcomes were compared using general linear models.

Results: No significant differences in the rate of change of cartilage thickness or T2 were found between weight cyclers and noncyclers. However, increases in maximum cartilage WORMS (P = 0.0025) and bone-marrow abnormalities (P = 0.04) were significantly greater in weight cyclers than in noncyclers.

Conclusions: Although participants' intent for weight cycling in this study was unknown, weight cyclers had significantly greater increases in cartilage and bone-marrow abnormalities over 4 years than noncyclers, independent of weight gain and loss.
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http://dx.doi.org/10.1002/oby.23129DOI Listing
May 2021

Joint-adjacent Adipose Tissue by MRI is Associated With Prevalence and Progression of Knee Degenerative Changes: Data from the Osteoarthritis Initiative.

J Magn Reson Imaging 2021 07 28;54(1):155-165. Epub 2021 Feb 28.

Department of Radiology and Biomedical Imaging, University of California, San Francisco, San Francisco, California, USA.

Background: Adipose tissue has recently gained interest as an independent imaging biomarker for osteoarthritis.

Purpose: To explore 1) cross-sectional associations between local subcutaneous fat (SCF) thickness at the knee and the extent of degenerative changes in overweight and obese individuals and 2) associations between local fat distribution and progression of osteoarthritis over 4 years.

Study Type: Retrospective cohort study.

Population: 338 obese and overweight participants from the Osteoarthritis Initiative cohort without radiographic evidence of osteoarthritis.

Field Strength: 3T: 3D-FLASH-WE; 3D-DESS-WE; T1w-SE; MSME.

Assessment: Baseline SCF thickness was measured in standardized locations medial, lateral and anterior to the knee and the average joint-adjacent SCF (ajSCF) was calculated. Right thigh SCF cross-sectional area was assessed. Quantitative cartilage T relaxation times and semi-quantitative whole organ MRI scores (WORMS) were obtained at baseline and 4-year follow-up. WORMS was calculated as sum of cartilage, bone marrow edema, subchondral cyst, and meniscal scores.

Statistical Tests: Associations of SCF measures with baseline, and 4-year change in T and WORMS were analyzed using regression models. SCF measurements were standardized using the equation . Analyses were adjusted for age, sex, physical activity, and BMI.

Results: Cross-sectionally, significant associations between lateral SCF, lateral compartment WORMS and T were found ( , [95% CI]: 0.53, [0.12-0.95], P < 0.05; ΔT : 0.50, [0.02-0.98], P < 0.05). Moreover, greater lateral SCF was associated with faster progression of lateral WORMS gradings (OR = 1.50, [1.05-2.15], P < 0.05). No significant positive associations were found for thigh SCF and WORMS (P = 0.44) or T measurements (medial: P = 0.15, lateral: 0.39, patellar: P = 0.75).

Data Conclusion: Joint-adjacent SCF thickness was associated with imaging parameters of knee osteoarthritis, both cross-sectionally and longitudinally, while thigh SCF was not, suggesting a spatial association of SCF and knee osteoarthritis. Based on these findings, joint-adjacent SCF may play a role in the development and progression of knee osteoarthritis.

Level Of Evidence: 4 TECHNICAL EFFICACY: Stage 5.
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http://dx.doi.org/10.1002/jmri.27574DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8211379PMC
July 2021

Knee osteoarthritis and time-to all-cause mortality in six community-based cohorts: an international meta-analysis of individual participant-level data.

Aging Clin Exp Res 2021 Mar 15;33(3):529-545. Epub 2021 Feb 15.

Nuffield Department of Orthopaedics, Rheumatology and Musculoskeletal Sciences, University of Oxford, Oxford, UK.

Background: Osteoarthritis (OA) is a chronic joint disease, with increasing global burden of disability and healthcare utilisation. Recent meta-analyses have shown a range of effects of OA on mortality, reflecting different OA definitions and study methods. We seek to overcome limitations introduced when using aggregate results by gathering individual participant-level data (IPD) from international observational studies and standardising methods to determine the association of knee OA with mortality in the general population.

Methods: Seven community-based cohorts were identified containing knee OA-related pain, radiographs, and time-to-mortality, six of which were available for analysis. A two-stage IPD meta-analysis framework was applied: (1) Cox proportional hazard models assessed time-to-mortality of participants with radiographic OA (ROA), OA-related pain (POA), and a combination of pain and ROA (PROA) against pain and ROA-free participants; (2) hazard ratios (HR) were then pooled using the Hartung-Knapp modification for random-effects meta-analysis.

Findings: 10,723 participants in six cohorts from four countries were included in the analyses. Multivariable models (adjusting for age, sex, race, BMI, smoking, alcohol consumption, cardiovascular disease, and diabetes) showed a pooled HR, compared to pain and ROA-free participants, of 1.03 (0.83, 1.28) for ROA, 1.35 (1.12, 1.63) for POA, and 1.37 (1.22, 1.54) for PROA.

Discussion: Participants with POA or PROA had a 35-37% increased association with reduced time-to-mortality, independent of confounders. ROA showed no association with mortality, suggesting that OA-related knee pain may be driving the association with time-to-mortality.

Funding: Versus Arthritis Centre for Sport, Exercise and Osteoarthritis and Osteoarthritis Research Society International.
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http://dx.doi.org/10.1007/s40520-020-01762-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7943431PMC
March 2021

Multivariable modeling of biomarker data from the phase 1 Foundation for the NIH Osteoarthritis Biomarkers Consortium.

Arthritis Care Res (Hoboken) 2021 Jan 9. Epub 2021 Jan 9.

Duke Molecular Physiology Institute and Division of Rheumatology, Department of Medicine, Duke University School of Medicine, Durham, NC, 27701, USA.

Objective: To determine the optimal combination of imaging and biochemical biomarkers to predict knee osteoarthritis (OA) progression.

Methods: Nested case-control study from the FNIH OA Biomarkers Consortium of participants with Kellgren-Lawrence grade 1-3 and complete biomarker data (n=539 to 550). Cases were knees with radiographic and pain progression between 24-48 months from baseline. Radiographic progression only was assessed in secondary analyses. Biomarkers (baseline and 24-month changes) with p<0.10 in univariate analysis were selected, including MRI (quantitative (Q) cartilage thickness and volume; semi-quantitative (SQ) MRI markers; bone shape and area; Q meniscal volume), radiographic (trabecular bone texture (TBT)), and serum and/or urine biochemical markers. Multivariable logistic regression models were built using three different step-wise selection methods (complex vs. parsimonious models).

Results: Among baseline biomarkers, the number of locations affected by osteophytes (SQ), Q central medial femoral and central lateral femoral cartilage thickness, patellar bone shape, and SQ Hoffa-synovitis predicted progression in most models (C-statistics 0.641-0.671). 24-month changes in SQ MRI markers (effusion-synovitis, meniscal morphology, and cartilage damage), Q central medial femoral cartilage thickness, Q medial tibial cartilage volume, Q lateral patellofemoral bone area, horizontal TBT (intercept term), and urine NTX-I predicted progression in most models (C-statistics 0.680-0.724). A different combination of imaging and biochemical biomarkers (baseline and 24-month change) predicted radiographic progression only, with higher C-statistics (0.716-0.832).

Conclusion: This study highlights the combination of biomarkers with potential prognostic utility in OA disease-modifying trials. Properly qualified, these biomarkers could be used to enrich future trials with participants likely to progress.
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http://dx.doi.org/10.1002/acr.24557DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8267050PMC
January 2021

The Longitudinal Relationship Between Physical Activity and Joint Space Narrowing: 48-Month Follow-Up Data from the Osteoarthritis Initiative.

Arthritis Care Res (Hoboken) 2021 Jan 7. Epub 2021 Jan 7.

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

Objective: To determine whether amount of physical activity (PA) is a determinant of joint space narrowing (JSN) worsening over 48-months in participants with knee osteoarthritis (OA).

Methods: Data were obtained from the Osteoarthritis Initiative. PA, measured using the Physical Activity Scale for the Elderly (PASE), was defined as the mean value of the annual measurements conducted prior to development of worsening JSN. Worsening JSN was defined as at least a partial grade increase in OARSI JSN score over 48 months, in comparison with baseline. Restricted cubic spline (RCS) function was used to group participants based on the linear association between PA and JSN worsening. A pooled logistic regression model was used to evaluate the association between PA and JSN worsening adjusted for confounders.

Results: 2,167 participants were included. In total, 625 (28.8%) participants had JSN worsening over 48 months. Compared with PASE score of 140-180, PASE scores of 100-140 and >220 associated with an increased risk of JSN worsening in men with OR (95% CI) of 1.73 (1.07, 2.81) and 1.83 (1.14, 2.93) respectively. Similarly, in participants with Kellgren and Lawrence grade 2, compared with a PASE score of 140-180, PASE score of <100 and >220 were associated with increased risks of JSN worsening, with OR (95% CIs) of 1.69 (1.13, 2.54) and 1.64 (1.05, 2.56) respectively.

Conclusion: Compared to moderate PA, higher or lower amounts of PA are associated with elevated risk for JSN worsening in men and in participants with KL grade 2 knees.
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http://dx.doi.org/10.1002/acr.24554DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8260605PMC
January 2021

Occupation and risk of knee osteoarthritis and knee replacement: A longitudinal, multiple-cohort study.

Semin Arthritis Rheum 2020 10 8;50(5):1006-1014. Epub 2020 Aug 8.

Centre for Sport, Exercise and Osteoarthritis Versus Arthritis, Nuffield Department of Orthopaedics, Rheumatology and Musculoskeletal Sciences, University of Oxford, Oxford, United Kingdom; MRC Lifecourse Epidemiology Unit, Southampton General Hospital, University of Southampton, Southampton, United Kingdom. Electronic address:

Objectives: To examine the effect of occupation on knee osteoarthritis (OA) and total knee replacement (TKR) in working-aged adults.

Methods: We used longitudinal data from the Chingford, Osteoarthritis Initiative (OAI) and Multicentre Osteoarthritis (MOST) studies. Participants with musculoskeletal disorders and/or a history of knee-related surgery were excluded. Participants were followed for up to 19-years (Chingford), 96-months (OAI) and 60-months (MOST) for incident outcomes including radiographic knee OA (RKOA), symptomatic RKOA and TKR. In those with baseline RKOA, progression was defined as the time from RKOA incidence to primary TKR. Occupational job categories and work-place physical activities were assigned to levels of workload. Logistic regression was used to examine the relationship between workload and incident outcomes with survival analyses used to assess progression (reference group: sedentary occupations).

Results: Heavy manual occupations were associated with a 2-fold increased risk (OR: 2.07, 95% CI 1.03 to 4.15) of incident RKOA in the OAI only. Men working in heavy manual occupations in MOST (2.7, 95% CI 1.17 to 6.26) and light manual occupations in OAI (2.00, 95% CI 1.09 to 3.68) had a 2-fold increased risk of incident RKOA. No association was observed among women. Increasing workload was associated with an increased risk of symptomatic RKOA in the OAI and MOST. Light work may be associated with a decreased risk of incident TKR and disease progression.

Conclusion: Heavy manual work carries an increased risk of incident knee OA; particularly among men. Workload may influence the occurrence of TKR and disease progression.
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http://dx.doi.org/10.1016/j.semarthrit.2020.08.003DOI Listing
October 2020

Is there an association of serum low density lipoprotein, high density lipoprotein or total cholesterol with development of knee osteoarthritis?

Arthritis Care Res (Hoboken) 2020 Sep 22. Epub 2020 Sep 22.

Boston University, School of Medicine, United States, Boston.

Objectives: Studies suggest an association between elevated total serum cholesterol (TC), particularly low-density lipoprotein (LDL), and osteoarthritis (OA). We evaluated the association between total cholesterol, LDL, and high-density lipoprotein (HDL) and risk of knee OA.

Methods: We studied participants from the Multicenter Osteoarthritis study (MOST) cohort at risk of developing knee OA. From baseline through 7 years, repeated knee x-rays and MRIs were obtained and knee symptoms were queried. From baseline fasting blood samples, lipids and lipoproteins were analyzed using standard assays. After excluding participants with baseline OA, we defined two sets of cases: those developing radiographic OA and those developing symptomatic OA (knee pain and radiographic OA). Controls did not develop these outcomes. Additionally, we examined worsening of: cartilage loss and synovitis on MRI and of knee pain using the WOMAC scale. We carried out logistic regression adjusting for age, sex, BMI, education, baseline pain, and depressive symptoms, testing total cholesterol and lipoproteins as continuous measures and did sensitivity analyses examining whether commonly used thresholds for high cholesterol, LDL or low HDL increased risk.

Results: We studied 337 cases with incident symptomatic OA and 283 cases with incident radiographic OA. Mean age at baseline was 62 years (55% women). Neither total cholesterol, LDL nor HDL showed a significant association with radiographic or symptomatic OA. Additionally, we found no association of these lipid measures with cartilage loss, worsening synovitis or worsening knee pain.

Conclusion: Our data do not support an association between total cholesterol, LDL or HDL with OA outcomes.
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http://dx.doi.org/10.1002/acr.24455DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8054264PMC
September 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

Determining a Threshold of Medial Meniscal Extrusion for Prediction of Knee Pain and Cartilage Damage Progression Over 4 Years: Data From the Osteoarthritis Initiative.

AJR Am J Roentgenol 2021 05 29;216(5):1318-1328. Epub 2020 Jul 29.

Department of Radiology and Biomedical Imaging, Musculoskeletal Quantitative Imaging Research Group, University of California San Francisco, 185 Berry St, Ste 350, San Francisco, CA 94107.

The extent of medial meniscal extrusion (MME) that is associated with structural and symptomatic progression of knee osteoarthritis has not been defined yet. The purpose of our study was to investigate MRI-based thresholds of MME that are associated with structural progression of knee degenerative disease and symptoms over a period of 4 years. We studied 328 knees of 235 participants that were randomly selected from the Osteoarthritis Initiative cohort. MME was quantified on coronal sections of intermediate-weighted MRI sequences obtained at 3 T. Knee pain and cartilage abnormalities were measured using the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) pain scale and the cartilage whole-organ MRI score (WORMS). General estimating equations with logistic regression models were used to correlate baseline MME and changes in pain (WOMAC) and cartilage damage (WORMS). ROC analyses were performed to determine the area under the ROC curve (AUROC). Individual thresholds were determined by maximizing the product of sensitivity and specificity. The AUROC for predicting progression of knee pain, medial compartment cartilage damage, and medial tibial cartilage damage were 0.71, 0.70, and 0.72, respectively, and the individual thresholds for MME were 2.5, 2.7, and 2.8 mm. A single threshold of 2.5 mm was determined by maximizing the mean of the product of sensitivity and specificity of the three outcome variables (knee pain progression, medial compartmental cartilage damage progression, and medial tibial cartilage damage progression). MME was associated with knee pain and cartilage damage progression over 4 years. A single threshold of 2.5 mm was found to be the most useful threshold for predicting knee pain, medial compartment cartilage damage progression, and tibial cartilage damage progression over 4 years. This threshold could be used to standardize the diagnostic criterion of extrusion and to better characterize the risk for subsequent structural and symptomatic progression of knee osteoarthritis.
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http://dx.doi.org/10.2214/AJR.20.23864DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8183109PMC
May 2021

Natural history of new horizontal meniscal tears in individuals at risk for and with mild to moderate osteoarthritis: data from osteoarthritis initiative.

Eur Radiol 2020 Nov 22;30(11):5971-5980. Epub 2020 Jun 22.

Department of Radiology and Biomedical Imaging, University of California San Francisco, 185 Berry Street, Lobby 6, Suite 350, San Francisco, CA, 94107, USA.

Objectives: To study the natural history of new horizontal meniscal tears and their association with progression of cartilage degeneration in individuals at risk for or with mild to moderate knee osteoarthritis over 4 years.

Methods: Individuals who developed a new meniscal tear in the right knee over 2 years were selected from the Osteoarthritis Initiative 3T MRI studies. Knee structural changes were analyzed at the time of tear appearance (baseline), and after 4 years using a modified Whole-Organ Magnetic Resonance Imaging Score (WORMS). Meniscal tears were classified as either horizontal tears or non-horizontal tears. Individuals without a meniscal tear were 1:3 frequency matched according to BMI, gender, race, and age and served as the control group. Linear regression analysis was used to compare cross-sectional and longitudinal changes in cartilage WORMS scores.

Results: Forty-one subjects developed horizontal tears, including one indiviudal who developed a tear in both menisci, and 34 developed non-horizonal tears. We found that (29/41 (70.7%)) of horizontal and (20/34 (58.8%)) of non-horizonatal tears were stable during follow-up (p = 0.281). Although knees with an incident tear had higher than controls WORMS MAX total knee scores at baseline (coef. = 0.47, p = 0.044, 95% CI = 0.01 to 0.93), there were no significant differences between the horizontal subgroup and knees without tears in overall cartilage scores at baseline and in progression over 4 years of follow-up.

Conclusions: New horizontal meniscal tears tended to be stable over 4 years and presented no significant differences in progression of cartilage degeneration when compared with knees without tears.

Key Points: • Most of horizonal meniscal tears were stable over 4 years. • There were no statistically significant differences in overall progression of cartilage degenerative changes between knees with horizonal meniscal tears and control knees without tears • Horizontal tears most often occurred at the posterior horn of the medial meniscus and at the body of the lateral meniscus.
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http://dx.doi.org/10.1007/s00330-020-06960-0DOI Listing
November 2020

Meniscal Root Tears and Extrusion Are Significantly Associated with the Development of Accelerated Knee Osteoarthritis: Data from the Osteoarthritis Initiative.

Cartilage 2020 Jun 21:1947603520934525. Epub 2020 Jun 21.

Department of Radiology and Biomedical Imaging, University of California, San Francisco, CA, USA.

Objective: To identify joint structural risk factors, measured using quantitative compositional and semiquantitative magnetic resonance imaging (MRI) scoring, associated with the development of accelerated knee osteoarthritis (AKOA) compared with a more normal rate of knee osteoarthritis (OA) development.

Design: From the Osteoarthritis Initiative we selected knees with no radiographic OA (Kellgren-Lawrence grade [KL] 0/1) that developed advanced-stage OA (KL 3/4; AKOA) within a 4-year timeframe and a comparison group with a more normal rate of OA development (KL 0/1 to KL 2 in 4 years). MRIs at the beginning of the 4-year timeframe were assessed for cartilage T2 values and structural abnormalities using a modified Whole-Organ Magnetic Resonance Imaging Score (WORMS). Associations of MRI findings with AKOA versus normal OA were assessed using multivariable logistic regression models.

Results: A total of 106 AKOA and 168 subjects with normal OA development were included. Mean cartilage T2 values were not significantly associated with AKOA (odds ratio [OR] 1.06; 95% confidence interval [CI] 0.82-1.36). Risk factors for AKOA development included higher meniscus maximum scores (OR 1.37; 95% CI 1.11-1.68), presence of meniscal extrusion (OR 6.30; 95% CI 2.57-15.49), presence of root tears (OR 4.64; 95% CI 1.61-13.34), and higher medial tibia cartilage lesion scores (OR 1.96; 95% CI 1.19-3.24).

Conclusions: We identified meniscal damage, especially meniscal extrusion and meniscal root tears as risk factors for AKOA development. These findings contribute to identifying subjects at risk of AKOA at an early stage when preventative measures targeting modifiable risk factors such as meniscal repair surgery could still be effective.
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http://dx.doi.org/10.1177/1947603520934525DOI Listing
June 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

The Association of Parity with Greater Dynamic Pronation of the Feet.

PM R 2021 02 11;13(2):144-152. Epub 2020 May 11.

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

Background: Postpartum women are at increased risk for lower limb musculoskeletal disorders. Foot arch collapse following pregnancy has been reported as a mechanism for this increased risk. However, dynamic changes during gait in postpartum women have not been reported. Therefore, we assessed the association between parity and dynamic foot pronation during gait.

Objective: To determine (1) if there is an association between parity and dynamic foot pronation (center of pressure excursion index, CPEI) during gait; and (2) the extent to which there is a dose-effect of parity on foot pronation.

Design: The Multicenter Osteoarthritis Study (MOST) Study is a longitudinal cohort study of adults with or at risk for knee osteoarthritis (OA).

Setting: Two communities in the United States, Birmingham, Alabama and Iowa City, Iowa.

Interventions: Not applicable PARTICIPANTS: A population-based sample of 1177 MOST participants who were female, had complete CPEI and parity data and completed the baseline, 30- and 60-month visits.

Main Outcome Measures: Odds of a one quintile decrease in CPEI by parity group and mean CPEI by parity group.

Results: In 1177 women, mean age was 67.7 years and mean body mass index (BMI) was 30.6 kg/m . As parity increased, there was significantly greater foot pronation, lower mean CPEI: 19.1 (18.2-20.1), 18.9 (18.4-19.4), 18 (17.5-18.6) to 17.5 (16.4-18.6) in the 0 to 4 and >5 children groups, respectively; (P = .002), which remained significant after adjusting for race and clinic site (P = .005). There was a positive linear trend (β = 1.08, 1.03-1.14) in odds ratios of a one quintile decrease in CPEI (greater pronation) with increasing parity level (P = .004), which remained significant after adjusting for race and clinic site (P = .01). After adjusting for age and BMI, these two associations were no longer statistically significant.

Conclusions: This study indicates a positive correlation between parity and greater dynamic pronation of the feet.
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http://dx.doi.org/10.1002/pmrj.12381DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7554144PMC
February 2021

Association of blood pressure with knee cartilage composition and structural knee abnormalities: data from the osteoarthritis initiative.

Skeletal Radiol 2020 Sep 7;49(9):1359-1368. Epub 2020 Mar 7.

Department of Radiology and Biomedical Imaging, University of California, San Francisco, 185 Berry Street, Suite 350, San Francisco, CA, 94107, USA.

Objective: To investigate the associations of systolic blood pressure (SBP) and diastolic blood pressure (DBP) with changes in knee cartilage composition and joint structure over 48 months, using magnetic resonance imaging (MRI) data from the Osteoarthritis Initiative (OAI).

Materials And Methods: A total of 1126 participants with right knee Kellgren-Lawrence (KL) score 0-2 at baseline, no history of rheumatoid arthritis, blood pressure measurements at baseline, and cartilage T2 measurements at baseline and 48 months were selected from the OAI. Cartilage composition was assessed using MRI T2 measurements, including laminar and gray-level co-occurrence matrix texture analyses. Structural knee abnormalities were graded using the whole-organ magnetic resonance imaging score (WORMS). We performed linear regression, adjusting for age, sex, body mass index, physical activity, smoking status, alcohol use, KL score, number of anti-hypertensive medications, and number of nonsteroidal anti-inflammatory drugs.

Results: Higher baseline DBP was associated with greater increases in global T2 (coefficient 0.22 (95% CI 0.09, 0.34), P = 0.004), global superficial layer T2 (coefficient 0.39 (95% CI 0.20, 0.58), P = 0.001), global contrast (coefficient 15.67 (95% CI 8.81, 22.53), P < 0.001), global entropy (coefficient 0.02 (95% CI 0.01, 0.03) P = 0.011), and global variance (coefficient 9.14 (95% CI 5.18, 13.09), P < 0.001). Compared with DBP, the associations of SBP with change in cartilage T2 parameters and WORMS subscores showed estimates of smaller magnitude.

Conclusion: Higher baseline DBP was associated with higher and more heterogenous cartilage T2 values over 48 months, indicating increased cartilage matrix degenerative changes.
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http://dx.doi.org/10.1007/s00256-020-03409-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7365750PMC
September 2020

Psychological and Pain Sensitization Characteristics Are Associated With Patellofemoral Osteoarthritis Symptoms: The Multicenter Osteoarthritis Study.

J Rheumatol 2020 11 1;47(11):1696-1703. Epub 2020 Mar 1.

J.J. Stefanik, PT, PhD, Department of Physical Therapy, Movement and Rehabilitation Sciences, Northeastern University, Boston, Massachusetts, USA.

Objective: Determine the relation of symptomatic and structural features of patellofemoral osteoarthritis (PFOA) to psychological characteristics and measures of pain sensitization, in older adults with or at risk of knee osteoarthritis (OA).

Methods: This study included 1112 participants from the Multicenter Osteoarthritis Study (713 females, mean age 66.8 ± SD 7.6 yrs, body mass index 29.5 ± 4.8 kg/m). Participants were grouped based on the presence of PFOA symptoms (anterior knee pain and pain on stairs) and magnetic resonance imaging (MRI) PFOA (full-thickness cartilage lesion with bone marrow lesion): (1) patellofemoral (PF) symptoms with MRI PFOA; (2) PF symptoms without MRI PFOA; (3) MRI PFOA without PF symptoms; and (4) no PF symptoms or MRI PFOA (no PFOA). Relation of PFOA classification to depressive symptoms, catastrophizing, temporal summation (TS) and pressure pain thresholds (PPT) was evaluated using logistic (categorical variables) and linear regression (continuous variables).

Results: Compared with no PFOA, those with PF symptoms with or without MRI PFOA had significantly greater odds of depressive symptoms, catastrophizing, and patellar TS (OR range 1.5-2.01), and those with PF symptoms without MRI PFOA had significantly greater odds of wrist TS (OR 1.66). Males with PF symptoms without MRI PFOA had significantly lower pressure PPT at the patella compared with no PFOA and those with MRI PFOA only (no symptoms). There were no significant differences at the wrist for males, or the patella or wrist for females.

Conclusion: Persons with PFOA symptoms, regardless of MRI PFOA status, are more likely to demonstrate depressive symptoms, catastrophizing, and TS. Males with PFOA symptoms without MRI PFOA demonstrate local hyperalgesia.
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http://dx.doi.org/10.3899/jrheum.190981DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8005266PMC
November 2020

Development and Validation of a Multitask Deep Learning Model for Severity Grading of Hip Osteoarthritis Features on Radiographs.

Radiology 2020 04 4;295(1):136-145. Epub 2020 Feb 4.

From the Department of Radiology and Biomedical Imaging (C.E.v.S., J.H.S., E.O., P.M.J., M.P., S.C.F., T.M.L., V.P.) and Department of Epidemiology and Biostatistics (F.L., M.C.N.), University of California, San Francisco, 185 Berry St, Suite 350, San Francisco, CA 94107; Department of Diagnostic and Interventional Radiology, Technische Universität München, Munich, Germany (C.E.v.S., S.C.F.); Department of Diagnostic and Interventional Radiology, Medical Center-University of Freiburg, Faculty of Medicine, Freiburg, Germany (P.M.J.); and Department of Radiology, University of California Davis Health, Sacramento, Calif (L.N.).

Background A multitask deep learning model might be useful in large epidemiologic studies wherein detailed structural assessment of osteoarthritis still relies on expert radiologists' readings. The potential of such a model in clinical routine should be investigated. Purpose To develop a multitask deep learning model for grading radiographic hip osteoarthritis features on radiographs and compare its performance to that of attending-level radiologists. Materials and Methods This retrospective study analyzed hip joints seen on weight-bearing anterior-posterior pelvic radiographs from participants in the Osteoarthritis Initiative (OAI). Participants were recruited from February 2004 to May 2006 for baseline measurements, and follow-up was performed 48 months later. Femoral osteophytes (FOs), acetabular osteophytes (AOs), and joint-space narrowing (JSN) were graded as absent, mild, moderate, or severe according to the Osteoarthritis Research Society International atlas. Subchondral sclerosis and subchondral cysts were graded as present or absent. The participants were split at 80% ( = 3494), 10% ( = 437), and 10% ( = 437) by using split-sample validation into training, validation, and testing sets, respectively. The multitask neural network was based on DenseNet-161, a shared convolutional features extractor trained with multitask loss function. Model performance was evaluated in the internal test set from the OAI and in an external test set by using temporal and geographic validation consisting of routine clinical radiographs. Results A total of 4368 participants (mean age, 61.0 years ± 9.2 [standard deviation]; 2538 women) were evaluated (15 364 hip joints on 7738 weight-bearing anterior-posterior pelvic radiographs). The accuracy of the model for assessing these five features was 86.7% (1333 of 1538) for FOs, 69.9% (1075 of 1538) for AOs, 81.7% (1257 of 1538) for JSN, 95.8% (1473 of 1538) for subchondral sclerosis, and 97.6% (1501 of 1538) for subchondral cysts in the internal test set, and 82.7% (86 of 104) for FOS, 65.4% (68 of 104) for AOs, 80.8% (84 of 104) for JSN, 88.5% (92 of 104) for subchondral sclerosis, and 91.3% (95 of 104) for subchondral cysts in the external test set. Conclusion A multitask deep learning model is a feasible approach to reliably assess radiographic features of hip osteoarthritis. © RSNA, 2020
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http://dx.doi.org/10.1148/radiol.2020190925DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7104703PMC
April 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

The Relationship of Three-Dimensional Joint Space Width on Weight Bearing CT With Pain and Physical Function.

J Orthop Res 2019 Dec 16. Epub 2019 Dec 16.

The University of Kansas, Kansas City, 3901 Rainbow Boulevard, Mailstop 1046; KUMC Department of Rehabilitation Medicine, Kansas City, KS, 66160.

Limitations of plain radiographs may contribute to poor sensitivity in the detection of knee osteoarthritis and poor correlation with pain and physical function. 3D joint space width, measured from weight bearing CT images, may yield a more accurate correlation with patients' symptoms. We assessed the cross-sectional association between 3D joint space width and self-reported pain and physical function. 528 knees (57% women) were analyzed from Multicenter Osteoarthritis Study participants. An upright weight bearing CT scanner was used to acquire bilateral, weight-bearing fixed-flexion images of the knees. A 3D dataset was reconstructed from cone beam projections and joint space width was calculated across the joint surface. The percentages of the apposed medial tibiofemoral joint surface with joint space width <2.0mm and <2.5mm respectively were calculated. Pain and physical function were measured using Western Ontario and McMaster Universities Osteoarthritis Index. Participants who reported greater pain severity tended to have a greater joint area with joint space width <2.0mm (p=.07 for the highest vs. the lowest tertile). Participants who reported greater functional limitations had a greater joint area with joint space width <2.0mm (p=.02 for the highest vs. the lowest tertile). There appears to be an association between the medial tibiofemoral area with joint space width <2.0mm and pain and physical function. This article is protected by copyright. All rights reserved.
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http://dx.doi.org/10.1002/jor.24566DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8016550PMC
December 2019

Using Cumulative Load to Explain How Body Mass Index and Daily Walking Relate to Worsening Knee Cartilage Damage Over Two Years: The MOST Study.

Arthritis Rheumatol 2020 06 2;72(6):957-965. Epub 2020 May 2.

University of Delaware, Newark.

Objective: Knee cartilage damage is often linked to mechanical overloading. However, cartilage requires mechanical load to remain healthy, suggesting that underloading may be detrimental. This study was undertaken to examine knee overloading and underloading by defining cumulative load as the joint effects of body mass index (BMI) and daily walking, and examine the relationship between cumulative load and worsening cartilage damage over 2 years.

Methods: We used data from the Multicenter Osteoarthritis Study. Steps/day, measured by accelerometry, and BMI were calculated at the 60-month visit. Cartilage damage on magnetic resonance imaging was semiquantitatively scored using the Whole-Organ Magnetic Resonance Imaging Score (WORMS) at the 60-month and 84-month visits; worsening damage was defined as increased WORMS between visits. Risk ratios (RRs) and 95% confidence intervals (95% CIs) were calculated using binomial regression, with adjustment for potential confounders.

Results: Our study included 964 participants, 62% of whom were female, with a mean ± SD age of 66.9 ± 7.5 years. Participants had a mean ± SD BMI of 29.7 ± 4.8 kg/m and walked a mean ± SD of 7,153 ± 2,591 steps/day. Participants who walked a moderate number of steps/day (6,000-7,900) or a high number of steps/day (>7,900) and had a high BMI (>31 kg/m ) had a greater risk of worsening medial tibiofemoral (TF) damage (RR 2.83 [95% CI 1.46-5.48] and RR 2.61 [95% CI 1.50-4.54], respectively) compared with those who walked similar steps/day and had a low BMI (18-27 kg/m ). Participants with a low number of steps/day (<6,000) and a low BMI had a greater risk of worsening medial TF and lateral patellofemoral (PF) damage (RR 2.03 [95% CI 1.06-3.92] and RR 2.28 [95% CI 1.06-4.85], respectively) compared with those who walked a high number of steps/day and had a low BMI. Effect estimates for other compartments of the knee did not reach statistical significance.

Conclusion: This study provides preliminary evidence that both overloading and underloading may be detrimental to medial TF cartilage, and underloading may be detrimental to lateral PF cartilage.
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http://dx.doi.org/10.1002/art.41181DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8020569PMC
June 2020

A pilot study of peripheral blood DNA methylation models as predictors of knee osteoarthritis radiographic progression: data from the Osteoarthritis Initiative (OAI).

Sci Rep 2019 11 14;9(1):16880. Epub 2019 Nov 14.

University of Oklahoma Health Sciences Center, Department of Internal Medicine, Division of Rheumatology, Immunology, and Allergy, Oklahoma City, OK, USA.

Knee osteoarthritis (OA) is a leading cause of chronic disability worldwide, but no diagnostic or prognostic biomarkers are available. Increasing evidence supports epigenetic dysregulation as a contributor to OA pathogenesis. In this pilot study, we investigated epigenetic patterns in peripheral blood mononuclear cells (PBMCs) as models to predict future radiographic progression in OA patients enrolled in the longitudinal Osteoarthritis Initiative (OAI) study. PBMC DNA was analyzed from baseline OAI visits in 58 future radiographic progressors (joint space narrowing at 24 months, sustained at 48 months) compared to 58 non-progressors. DNA methylation was quantified via Illumina microarrays and beta- and M-values were used to generate linear classification models. Data were randomly split into a 60% development and 40% validation subsets, models developed and tested, and cross-validated in a total of 40 cycles. M-value based models outperformed beta-value based models (ROC-AUC 0.81 ± 0.01 vs. 0.73 ± 0.02, mean ± SEM, comparison p = 0.002), with a mean classification accuracy of 73 ± 1% (mean ± SEM) for M- and 69 ± 1% for beta-based models. Adjusting for covariates did not significantly alter model performance. Our findings suggest that PBMC DNA methylation-based models may be useful as biomarkers of OA progression and warrant additional evaluation in larger patient cohorts.
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http://dx.doi.org/10.1038/s41598-019-53298-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6856188PMC
November 2019

Football Increases Future Risk of Symptomatic Radiographic Knee Osteoarthritis.

Med Sci Sports Exerc 2020 04;52(4):795-800

Division of Rheumatology, Tufts Medical Center, Boston, MA.

Introduction: Male youth in the United States commonly participate in gridiron (American) football. There are little data substantiating current popular opinion that it is associated with knee pain or osteoarthritis (OA) later in life. We aimed to evaluate the relationship of football with these outcomes in the Osteoarthritis Initiative (OAI).

Methods: This is a study of male OAI participants with knee x-ray readings, symptom assessments, and completed surveys on lifetime physical activity. The OAI is a multicenter, observational cohort recruited from the community not based on football participation status. A history of exposure to American football was ascertained via self-report. Knee radiographs were scored for Kellgren-Lawrence grade (0-4). Radiographic OA (ROA) was defined as Kellgren-Lawrence ≥ 2 in at least one knee. Frequent knee pain meant at least one knee with frequent knee pain. Symptomatic ROA required at least one knee with both ROA and frequent knee pain.

Results: A total of 1166 men had a mean age of 63.7 (SD, 9.2) yr and body mass index of 28.6 (SD, 4.2) kg·m. Thirty-one percent (365/1166) played football at some point in their lives, 95% of whom participated from ages 12 to 18 yr. The ORs for symptomatic ROA from the lowest to highest football participation were 1.2, 1.5, and 2.2, respectively (P for trend = 0.004). Findings were similar for football from ages 12 to 18 yr and for outcomes of knee pain and ROA.

Conclusion: This is the first large epidemiologic study to suggest that football participation, including in the teen years, may be detrimental toward knee health. Prospective studies evaluating football players are warranted.
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http://dx.doi.org/10.1249/MSS.0000000000002189DOI Listing
April 2020

Evidence that Swimming May Be Protective of Knee Osteoarthritis: Data from the Osteoarthritis Initiative.

PM R 2020 06 4;12(6):529-537. Epub 2019 Dec 4.

Department of General Internal Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX.

Background: To date, there have not been any epidemiologic studies that have evaluated the association between swimming over a lifetime and knee health.

Objective: The study aimed to evaluate the relationship of a history of swimming with knee pain, radiographic knee OA (ROA), and symptomatic knee OA (SOA).

Design: Cross-sectional retrospective study.

Setting: Four academic centers in the United States.

Participants: Respondents to the historical physical activity survey within the Osteoarthritis Initiative with knee radiographs and symptom assessments.

Methods: In this retrospective study nested within the Osteoarthritis Initiative, researchers performed logistic regression with the predictor being swimming over a lifetime and over particular age ranges.

Main Outcome Measurements: Person-based definitions of frequent knee pain, ROA, and SOA.

Results: A total of 2637 participants were included, with a mean age of 64.3 years (SD 8.9), body mass index of 28.4 kg/m (SD 4.9), and 44.2% male. Over a lifetime, the adjusted prevalence measures for frequent knee pain, ROA, and SOA for any versus no history of swimming were 36.4% (33.4% - 39.5%) v. 39.9% (37.4% - 42.5%), 54.3% (51.0% - 57.6%) v. 61.1% (58.4% - 63.7%), and 21.9% (19.4% - 24.7%) v. 27.0% (24.7% - 29.4%) respectively.

Conclusions: This is the first epidemiologic study to indicate that swimming is potentially beneficial toward knee health, particularly when performed earlier in life (before age 35). Future prospective studies are needed to confirm these findings and to better scrutinize the associations in older age groups.
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http://dx.doi.org/10.1002/pmrj.12267DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7166141PMC
June 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

Cartilage degeneration post-meniscectomy performed for degenerative disease versus trauma: data from the Osteoarthritis Initiative.

Skeletal Radiol 2020 Feb 9;49(2):231-240. Epub 2019 Jul 9.

Musculoskeletal Quantitative Imaging Research Group, Department of Radiology & Biomedical Imaging, University of California San Francisco, 185 Berry St, Suite 350, San Francisco, CA, 94107, USA.

Objective: To compare the extent of cartilage deterioration in knees with prior meniscal resection related to trauma versus knees with resection related to degenerative disease, and to compare cartilage deterioration in knees with meniscal surgery to knees without meniscal surgery, controlling for prior knee trauma.

Materials And Methods: In this cross-sectional study, we assessed cartilage deterioration in right knees of Osteoarthritis Initiative participants: (i) with meniscal surgery due to injury (n = 79); (ii) matched control knees with a prior injury but without meniscal surgery (n = 79); (iii) with meniscal surgery but without preceding injury (n = 36); and (iv) matched control knees without meniscal surgery or prior knee injury (n = 36). Cartilage composition was measured using T2 measurements derived using semi-automatic cartilage segmentation of the right. Linear regression analysis was used to compare compartmental values of T2 between groups.

Results: Comparing the mean T2 values in surgical cases with and without injury our results did not show significant differences (group i vs. iii, p > 0.05). However, knees with previous meniscal surgery showed significantly (p < 0.001) higher mean T2 values across all compartments (i.e., global T2) when compared to those without meniscal surgery for both knees with a history of trauma (group i vs. ii) and knees without prior trauma (group iii vs. iv). Similar results were obtained when analyzing the compartments separately.

Conclusions: Cartilage deterioration, assessed by T2, is similar in knees undergoing meniscal surgery after trauma and for degenerative conditions. Both groups demonstrated greater cartilage deterioration than nonsurgical knees, controlling for prior knee injury.
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http://dx.doi.org/10.1007/s00256-019-03267-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8172084PMC
February 2020

Associations Between Vitamins C and D Intake and Cartilage Composition and Knee Joint Morphology Over 4 Years: Data From the Osteoarthritis Initiative.

Arthritis Care Res (Hoboken) 2020 09;72(9):1239-1247

University of California, San Francisco.

Objective: To determine the cross-sectional and longitudinal associations of vitamin C and D intake with magnetic resonance imaging (MRI) measures of cartilage composition (T2) and joint structure (cartilage, meniscus, and bone marrow) using data from the Osteoarthritis Initiative (OAI) cohort.

Methods: A total of 1,785 subjects with radiographic Kellgren/Lawrence knee grades 0-3 in the right knee were selected from the OAI database. Vitamins C and vitamin D intake (diet, supplements, and total) were assessed using the Block Brief 2000 Food Frequency Questionnaire at baseline. The MRI analysis protocol included 3T cartilage T2 quantification and semiquantitative joint morphology gradings (Whole-Organ Magnetic Resonance Imaging Score [WORMS]) at baseline and 4 years. Linear regression was used to assess the association between standardized baseline vitamin intake and both baseline WORMS scores and standardized cartilage T2 values.

Results: Higher vitamin C intake was associated with lower average cartilage T2 values, medial tibia T2 values, and medial tibia WORMS scores (standardized coefficient range -0.07 to -0.05, P < 0.05). Higher vitamin D intake was associated with a lower cartilage WORMS sum score and medial femur WORMS score (standardized coefficient range -0.24 to -0.09, P < 0.05). Consistent use of vitamin D supplements of 400 IU at least once a week over 4 years was associated with significantly less worsening of cartilage, meniscus, and bone marrow abnormalities (odds ratio range 0.40-0.56, P < 0.05).

Conclusion: Supplementation with vitamin D over 4 years was associated with significantly less progression of knee joint abnormalities. Given the observational nature of this study, future longitudinal randomized controlled trials of vitamin D supplementation are warranted.
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http://dx.doi.org/10.1002/acr.24021DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6946891PMC
September 2020

Longitudinal MRI structural findings observed in accelerated knee osteoarthritis: data from the Osteoarthritis Initiative.

Skeletal Radiol 2019 Dec 17;48(12):1949-1959. Epub 2019 Jun 17.

Department of Radiology and Biomedical Imaging, University of California, San Francisco, 185 Berry Street, Lobby 6, Suite 350, San Francisco, CA, 94107, USA.

Objective: To analyze structural, longitudinal MRI findings during the development of accelerated knee osteoarthritis (AKOA) over 4 years.

Materials And Methods: From the Osteoarthritis Initiative (OAI), knees with no radiographic osteoarthritis (KL 0/1) developing advanced-stage osteoarthritis (KL 3/4; AKOA) within a 4-year (y) timeframe were selected. MRIs were graded using the modified Whole-Organ Magnetic Resonance Imaging Score (WORMS) at the beginning of the 4-year timeframe (index visit), at 2-year, and 4-year follow-up. Morphological and clinical findings associated with KL 3/4 onset within 2 years compared to 4 years were assessed using generalized estimating equations.

Results: AKOA was found in 162 knees of 149 subjects (age 63.25 ± 8.3; 103 females; BMI 29.4 ± 3.9). Moderate to severe meniscal lesions WORMS ≥ 3 were present in 25% (41/162) at the index visit, 64% (104/162) at 2-year and 93% (151/162) at 4-year follow-up. Meniscal extrusion was the most prevalent finding (ranging from 18% at the index visit, 45% at 2-year and 94% at 4-year follow-up) and root tears were the most common types of tears (9% at the index visit; 22% at 2 years and 38% at 4 years). Risk factors associated with KL 3/4 onset within 2 years included root tears at the index visit (adjusted OR, 2.82; 95% CI: 1.33, 6.00; p = 0.007) and incident knee injury (42%, 49/116 vs. 24%, 11/46, p = 0.032).

Conclusions: Meniscal abnormalities, in particular extrusion and root tears, were the most prevalent morphological features found in subjects with AKOA. These results suggest that meniscal abnormalities have a significant role in accelerated progression of OA.
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http://dx.doi.org/10.1007/s00256-019-03242-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6814533PMC
December 2019
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