Faculty Bibliography

OBJECTIVE:This study sought to develop and employ a comprehensive and standardized ultrasound (US) protocol and scoring atlas for the evaluation of features relevant to knee osteoarthritis (KOA) in a community-based cohort in the United States, with the goals of demonstrating feasibility, reliability, and validity. METHODS:We utilized data from the fourth follow-up (2016-2018) of the Johnston County OA Project, which includes individuals with (~50%) and without radiographic KOA. All participants underwent standardized knee radiography and completed standard questionnaires including the Knee Injury and Osteoarthritis Outcome Score (KOOS). Bilateral knee US images were obtained by a trained sonographer using a standardized protocol and scored by trained rheumatologists using an atlas developed for this study. A total of 396 knees were each scored by two readers according to the atlas. Associations between US features, radiographic findings (graded by an expert radiologist), and KOOS scores were assessed. RESULTS:Overall interreader reliability for US scoring was fair to moderate. The strongest correlations between US and radiographic features were seen for osteophytes, and similarly strong correlations were seen between US osteophytes and overall radiographic Kellgren-Lawrence Grade, demonstrating criterion validity. Features of effusion/synovitis and osteophytes were most associated with KOOS pain and impaired function. CONCLUSION/CONCLUSIONS:US is a feasible, reliable, and valid method to assess features relevant to KOA in clinical and research settings. The protocol and atlas developed in this study can be utilized to evaluate KOA in a standardized fashion in future clinical studies, enabling greater utilization of this valuable modality in osteoarthritis.

OBJECTIVE:Musculoskeletal ultrasound (MSUS) in rheumatology in the US has advanced by way of promotion of certifications and standards of use and inclusion of core fellowship curriculum. In order to inform endeavors for curricular integration, the objectives of the present study were to assess current program needs for curricular incorporation and the teaching methods that are being employed. METHODS:A needs-assessment survey (S1) was sent to 113 rheumatology fellowship program directors. For programs that taught MSUS, a curriculum survey (S2) was sent to lead faculty. Programs were stratified according to program size and use of a formal written curriculum. RESULTS:S1 (108 of 113 respondents; response rate 96%) revealed that 94% of programs taught MSUS, with 41% having a curriculum. Curricular implementation was unaffected by program size. Formal curricular adoption of MSUS was favored by 103 directors (95.3%), with 65.7% preferring such adoption to be optional. S2 (74 of 101 respondents; response rate 73%) showed that 41% of programs utilized a formal curriculum. Multiple teaching strategies were used, with content that was generally similar. Use of external courses, including the Ultrasound School of North American Rheumatologists course, was prevalent. Fewer barriers were noted compared to past surveys, but inadequate time, funding, and number of trained faculty still remained. Lack of divisional interest (P = 0.046) and interest of fellows (P = 0.012) were noted among programs without a formal curriculum. CONCLUSION:MSUS is taught by a significantly larger number of rheumatology fellowship programs today. Multiple teaching strategies are used with common content, and barriers still remain for some programs. Most program directors favor inclusion of a standardized MSUS curriculum, with many favoring inclusion to be optional.

Objective/UNASSIGNED:Osteoarthritis is highly prevalent and, on aggregate, is one of the largest contributors to US spending on hospital-based health care. This study sought to examine body mass index (BMI)-related variation in the association of osteoarthritis with healthcare utilization and expenditures. Methods/UNASSIGNED:. Study outcomes and covariates were measured during a 1-year evaluation period spanning 6 months before and after index. Multivariable regression analyses examined the association of BMI with osteoarthritis prevalence, and the combined associations of osteoarthritis and BMI with osteoarthritis-related medication utilization, all-cause hospitalization, and healthcare expenditures. Results/UNASSIGNED:< .01): utilization rates for analgesic medications (41.5-53.5%); rates of all-cause hospitalization (26.3%-32.0%); and total healthcare expenditures ($18 204-$23 372). Conclusion/UNASSIGNED:The prevalence and economic burden of osteoarthritis grow with increasing BMI; primary prevention of weight-related osteoarthritis and secondary weight management may help to alleviate this burden.

Background: Osteoarthritis (OA) is the most common form of arthritis, and knee OA is highly prevalent among older adults. Our objective was to evaluate the relationships between ultrasound (US) features and knee symptoms.
Method(s): Our sample (n=203) consisted of cross-sectional data from participants attending the fourth follow-up (2016-2018) of the Johnston County OA Project-a longitudinal population-based prospective cohort study in North Carolina. An US-trained radiology technologist scanned all participants' bilateral knees using a written protocol; the images were scored using a standardized atlas. Logistic regression modeling, using generalized estimating equations to account for correlation between knees, was used to evaluate the associations between the presence of various US features and self-reported knee symptoms and produce adjusted odds ratios and 95% confidence intervals. Each model was adjusted for sex, race, BMI, education, comorbidities, other symptomatic joints, and increasing age.
Result(s): The strongest association between knee symptoms and US features was seen for severe medial osteophytes which increased the odds of reporting knee symptoms by 11 times. Severe lateral osteophytes increased the odds of knee symptoms by over 6 times. Both medial and lateral cartilage damage more than doubled the odds of knee symptoms. Both popliteal cysts and severe effusion/synovitis tripled the odds of reporting at least mild knee symptoms; synovitis was more strongly associated with knee symptoms than effusion. The association between osteophytes and symptoms varied by age, such that participants at age 65 had four times the odds of symptoms in the presence of severe medial osteophytes, increasing to 10 times at age 75.
Conclusion(s): Older participants had significantly higher odds of knee symptoms in the presence of medial osteophytes-a key feature of OA-which clinicians may use to initiate early symptom management. Further studies are needed to evaluate the temporal relationships between US features and knee symptoms throughout the aging process

OBJECTIVE:To develop an evidence-based guideline for the comprehensive management of osteoarthritis (OA) as a collaboration between the American College of Rheumatology (ACR) and the Arthritis Foundation, updating the 2012 ACR recommendations for the management of hand, hip, and knee OA. METHODS:We identified clinically relevant population, intervention, comparator, outcomes questions and critical outcomes in OA. A Literature Review Team performed a systematic literature review to summarize evidence supporting the benefits and harms of available educational, behavioral, psychosocial, physical, mind-body, and pharmacologic therapies for OA. Grading of Recommendations Assessment, Development and Evaluation methodology was used to rate the quality of the evidence. A Voting Panel, including rheumatologists, an internist, physical and occupational therapists, and patients, achieved consensus on the recommendations. RESULTS:Based on the available evidence, either strong or conditional recommendations were made for or against the approaches evaluated. Strong recommendations were made for exercise, weight loss in patients with knee and/or hip OA who are overweight or obese, self-efficacy and self-management programs, tai chi, cane use, hand orthoses for first carpometacarpal (CMC) joint OA, tibiofemoral bracing for tibiofemoral knee OA, topical nonsteroidal antiinflammatory drugs (NSAIDs) for knee OA, oral NSAIDs, and intraarticular glucocorticoid injections for knee OA. Conditional recommendations were made for balance exercises, yoga, cognitive behavioral therapy, kinesiotaping for first CMC OA, orthoses for hand joints other than the first CMC joint, patellofemoral bracing for patellofemoral knee OA, acupuncture, thermal modalities, radiofrequency ablation for knee OA, topical NSAIDs, intraarticular steroid injections and chondroitin sulfate for hand OA, topical capsaicin for knee OA, acetaminophen, duloxetine, and tramadol. CONCLUSION/CONCLUSIONS:This guideline provides direction for clinicians and patients making treatment decisions for the management of OA. Clinicians and patients should engage in shared decision-making that accounts for patients' values, preferences, and comorbidities. These recommendations should not be used to limit or deny access to therapies.

OBJECTIVE:To develop an evidence-based guideline for the comprehensive management of osteoarthritis (OA) as a collaboration between the American College of Rheumatology (ACR) and the Arthritis Foundation, updating the 2012 ACR recommendations for the management of hand, hip, and knee OA. METHODS:We identified clinically relevant population, intervention, comparator, outcomes questions and critical outcomes in OA. A Literature Review Team performed a systematic literature review to summarize evidence supporting the benefits and harms of available educational, behavioral, psychosocial, physical, mind-body, and pharmacologic therapies for OA. Grading of Recommendations Assessment, Development and Evaluation methodology was used to rate the quality of the evidence. A Voting Panel, including rheumatologists, an internist, physical and occupational therapists, and patients, achieved consensus on the recommendations. RESULTS:Based on the available evidence, either strong or conditional recommendations were made for or against the approaches evaluated. Strong recommendations were made for exercise, weight loss in patients with knee and/or hip OA who are overweight or obese, self-efficacy and self-management programs, tai chi, cane use, hand orthoses for first carpometacarpal (CMC) joint OA, tibiofemoral bracing for tibiofemoral knee OA, topical nonsteroidal antiinflammatory drugs (NSAIDs) for knee OA, oral NSAIDs, and intraarticular glucocorticoid injections for knee OA. Conditional recommendations were made for balance exercises, yoga, cognitive behavioral therapy, kinesiotaping for first CMC OA, orthoses for hand joints other than the first CMC joint, patellofemoral bracing for patellofemoral knee OA, acupuncture, thermal modalities, radiofrequency ablation for knee OA, topical NSAIDs, intraarticular steroid injections and chondroitin sulfate for hand OA, topical capsaicin for knee OA, acetaminophen, duloxetine, and tramadol. CONCLUSION/CONCLUSIONS:This guideline provides direction for clinicians and patients making treatment decisions for the management of OA. Clinicians and patients should engage in shared decision-making that accounts for patients' values, preferences, and comorbidities. These recommendations should not be used to limit or deny access to therapies.

Background/Purpose : Weight loss in obese patients can reduce knee osteoarthritis (OA) pain, even when physical therapy and intra-articular injections have failed. The impacts of either non-surgical or surgical weight loss on knee OA pain have been reported separately, but few studies have assessed them conjointly. While the decrease in mechanical load helps, the contribution of metabolic changes is less clear. We aimed to compare biomarker changes with weight loss as predictors of knee pain improvement, and consider a threshold of total weight loss necessary for these changes. Methods : Patients from the NYU Langone Weight Management program were screened for knee pain prior to bariatric surgery or the start of a medical weight loss (MWL) regimen. We excluded patients with autoimmune disease, recent malignancy, recent intra-articular knee injections, and lack of OA by Kellgren-Lawrence (KL) x-ray grading. The BMI, Knee Injury and Osteoarthritis Outcome Score (KOOS) for pain, and blood samples were obtained at baseline and 1, 3, 6 and 12 months for evaluation of pain and biomarker levels. Results : Of 140 patients screened, 81 were eligible and enrolled (82.7% female; BMI 45.2+/-9.6 kg/m2, 31-74; age 52+/-12 years, 30-80). A total of 49 patients had surgery (10 bypass, 30 sleeve, 9 LapBand) and 24 medical weight loss. 33 patients completed visits up to 6 months (2 bypass, 18 sleeve, 6 LapBand, 7 MWL). By 1 month, the surgical patients had lost much more total weight than the MWL group (9.8% vs 4.1 %, p=0.001), and realized marked pain relief (p< 0.001). By 6 months both groups had continued to lose weight, proportionately greater for surgical patients with further pain improvement. (Figure 1) Leptin levels dropped at 1 and then 6 months with both methods of weight loss. The pro-inflammatory protein IL-1Ra decreased significantly by 6 months in the bariatric patients, but increased with the medical regimen across both time points. Soluble vascular adhesion protein 1 (sVAP-1), another pro-inflammatory protein that facilitates leukocyte infiltration, decreased at both the 1 and 6 month intervals -but much more in MWL than in surgical patients. Consistent with the literature, the anti-inflammatory soluble receptor for advanced glycation endproducts (sRAGE) mirrored KOOS pain improvement only in surgical patients and stabilized after 1 month, but did not change in the MWL group. (Table 1) In a subgroup analysis, the 14 surgical patients who lost at least 10% of Figure 1. Surgical and medical outcomes for % total weight loss (TWL), knee pain and biomarkers Table 1. total weight by 1 month had significantly less pain at 6 months than the 12 who did not meet the threshold (DELTAKOOS 47.5 vs 29.9) but the biomarker levels were similar. (Figure 2) Conclusion : Surgical and medically supervised weight loss both lead to significant decreases in adiposity, but only those having bariatric surgery realize significant pain relief. The anatomical changes of surgical (vs. medical) weight loss result in different metabolic cascades given divergent biomarker trends. Bariatric patients who lose more than 10 percent of total body weight within the first month are more likely to have better pain relief by 6 months, but the biomarker changes reflect anatomic intervention -and are not dependent on the degree of surgical weight loss

Background/Purpose : Osteoarthritis (OA) is a highly heterogeneous disease, which suggest that multiple endotypes exist. Identification and characterization of such endotypes may assist in precision medicine for identification of faster progressors whom may benefit from a given type of intervention. Recent published data have shown that SNPs in growth factors such as TGFbeta and GDF are associated with OA, which indicate that cartilage formation and repair play an important role in progression of OA. The aim was to determine whether a biomarker of type II collagen formation measured in serum, as a potential surrogate measure of cartilage formation, could predict radiographic progression in knee OA population. Subsequently, we investigated if such a proposed low cartilage formation/repair endotype was more responsive to a potential treatment of OA. Methods : hsPRO-C2, a measurement of the type II collagen pro-peptide, was measured in blood samples of two independent knee OA cohorts: 106 recruited at New York University (NYU cohort) and 147 from the phase III OA trial SMC021-2301 (clinicaltrial.gov: NCT00486434) evaluating the efficacy and safety of oral salmon calcitonin. Patients were dichotomized based on their baseline level of hsPRO-C2 and the mean difference in two-year radiographic progression (joint space narrowing (JSN)) was analyzed using ANCOVA adjusting for baseline demographics and clinical characteristics. Results : In the NYU cohort, baseline plasma hsPRO-C2 levels were negatively correlated with the progression of radiographic JSN (r = -0.26, p = 0.009). Quartile analysis demonstrated a significant difference in mean JSN from quartile 1 to 4 (0.51 mm versus -0.07 mm, p = 0.036, fig. 1). Knee OA patients with low hsPRO-C2 levels (<= 1.48 ng/mL) revealed significantly larger JSN compared to the individuals with high hsPRO-C2 levels ( > 1.48 ng/ mL) at 24 months (0.37 mm vs 0.02 mm, p = 0.042). In the SMC cohort, there was no significant treatment effect on the medial JSN over 2 years before stratification by hsPRO-C2; however, as observed in the NYU cohort, JSN was on average higher in the low hsPRO-C2 (<= 1.96 ng/mL) group compared to the high group ( > 1.96 ng/ mL). Furthermore, in the low baseline hsPRO-C2 subgroup, sCT-treated patients on average had a lower JSN compared to placebo patients (p < 0.05, fig. 2). The opposite trend was observed in patients with high baseline hsPRO-C2. Conclusion : Here we show that low levels of cartilage formation, measured by PRO-C2, were associated with radiographic progression and greater likelihood of response to a salmon calcitonin. Low PRO-C2 may provide a measure of an OA endotype with low background cartilage formation (at baseline) and higher capacity for repair when treated with a potential cartilage anabolic drug

Background/Purpose : To evaluate the frequency and associations of osteoarthritis (KOA) features on knee ultrasound (KUS) in a community-based cohort study with radiographic and symptomatic data in the same knees. Methods : A radiology technologist trained in standardized KUS imaging (SSG) scanned both knees in consecutive individuals enrolled in the Johnston County OA Project, using a written protocol. The KUS protocol included 7 views per knee: longitudinal and transverse suprapatellar in 30 degrees flexion (grading for effusion, gray scale synovitis and color power Doppler [CPD]), medial and lateral longitudinal (for osteophytes, meniscal damage, calcium deposition), maximally flexed suprapatellar transverse (for cartilage damage, calcium deposition) and posterior transverse (for popliteal cysts). Each set of images was scored using an atlas by 2 readers (previously shown to be reliable) whose scores were averaged. Radiographs (XR) were scored separately by an expert radiologist (JBR); all readers were blinded to other imaging and clinical data. Radiographic KOA (rKOA) was defined as a Kellgren-Lawrence grade (KLG) of 2 or more; osteophytes and joint space narrowing (JSN) were scored 0-3 using the OARSI atlas. Symptomatic KOA (sxKOA) was defined as rKOA with symptoms experienced in the same knee. Pain was assessed via the Knee Injury and OA Outcome Score (KOOS) pain subscale for each knee. We produced unadjusted Spearman correlations and additionally tested for nonzero correlation using the Cochran-Mantel-Haenszel statistic to describe associations with each KUS and XR feature and pain. All results shown are for right knees; left knees demonstrated similar patterns. Results : Participants (n=203) had a mean (+/-SD) age of 73 +/- 8 years and a mean BMI of 29.4 +/- 7 kg/m2; about 1/3 were male and 1/3 were African-American. About a third of knees had symptoms and 5% had a history of knee injury. About half of knees met the above definition for rKOA, while almost a quarter met the sxKOA definition. The majority of knees had US evidence (score >0) of at least one of the following: effusion/synovitis, osteophytes, and/ or cartilage damage (data not shown). Correlations between US and XR features are shown in Table 1. The strongest correlations were seen for osteophytes (r=0.6); similar correlations were seen between US osteophytes and XR KLG. Correlations for calcium deposition detected by each modality (r=0.2-0.3) were significant. Non-identical constructs such as medial US meniscal extrusion and XR JSN (r=0.4) were also significantly correlated. Medial XR JSN was more closely related to US meniscal extrusion (r=0.4) than to US cartilage damage (r=0.1). Osteophytes by US, compared with XR, had slightly stronger correlations with KOOS pain (Table 2). Medial meniscal extrusion and cartilage damage by US were significantly correlated with KOOS pain while medial JSN by XR was not; all three were correlated with presence of sxKOA. Conclusion : US assessment of KOA is accessible and reliable and provides information complementary to XR; KUS may provide increased sensitivity for early KOA changes. Future work will further examine the associations between US and radiographic features, including effect modification by key covariates. (Table Presented)

Background: There is a lack of objective diagnostic modalities that identify patients at risk for severe osteoarthritis (OA), which complicates the development of disease-modifying OA drugs. The biochemical marker, high-sensitive PRO-C2 (hsPRO-C2)¹, is a measure of the propeptide of type IIB collagen and a blood measure of cartilage formation.
Objective(s): The aim of this study was to determine whether hsPRO-C2 could predict radiographic progression in a knee OA population and stratify patients into high and low risk for joint destruction.
Method(s): Subjects with varying degrees of symptomatic knee OA (n=106) were included from a New York University (NYU) progression cohort. Radiographic progression was assessed by medial joint space narrowing (JSN), based on the change in joint space width (JSW), of the signal knee at baseline and at 24months. Baseline plasma type II collagen formation biomarker (hsPRO-C2) levels were measured. Association between baseline hsPRO-C2 and JSN was analyzed by Pearson's correlation, corrected for age, sex, BMI, race, baseline JSW, and non-steroids antiinflammatory drugs (NSAID) use. Subjects were divided into quartiles of equal size depending on the hsPRO-C2 levels, and the difference in JSN was investigated. The median level of baseline hsPRO-C2 (1.48 ng/ml) was used as a cut-off for stratifying all the subjects. The difference in JSN over 24 months was investigated in patients dichotomized based on median level. The values were compared with two-way analysis of covariates (ANCOVA).
Result(s): Baseline plasma hsPRO-C2 levels were negatively correlated with the progression of radiographic joint space narrowing over 24 months (r =-0.26, p = 0.009) after adjustment for confounders (Figure 1A). Quartile analysis demonstrated a decreasing trend of hsPRO-C2 in the radiographic progression from quartile 1 to 4 (Figure 1B). One-way ANOVA revealed a significant difference in mean JSN between quartiles 1 and 4 (0.5073 mm versus-0.0691 mm, p = 0.036, Figure 1B). JSN was significantly larger in the low hsPRO-C2 patients (0.3710 mm) com pared to the high hsPRO-C2 patients (0.0195 mm) (Figure 2).
Conclusion(s): These data suggest that symptomatic knee OA subjects with lower levels of hsPRO-C2 at baseline presented more radiographic medial JSN progression as compared to the subjects with higher levels of hsPRO-C2. The biomarker hsPRO-C2 may be useful for predicting OA progression