Machine-learning, MRI bone shape and important clinical outcomes in osteoarthritis: data from the Osteoarthritis Initiative.

OBJECTIVES: Osteoarthritis (OA) structural status is imperfectly classified using radiographic assessment. Statistical shape modelling (SSM), a form of machine-learning, provides precise quantification of a characteristic 3D OA bone shape. We aimed to determine the benefits of this novel measure of OA status for assessing risks of clinically important outcomes. METHODS: The study used 4796 individuals from the Osteoarthritis Initiative cohort. SSM-derived femur bone shape (B-score) was measured from all 9433 baseline knee MRIs. We examined the relationship between B-score, radiographic Kellgren-Lawrence grade (KLG) and current and future pain and function as well as total knee replacement (TKR) up to 8 years. RESULTS: B-score repeatability supported 40 discrete grades. KLG and B-score were both associated with risk of current and future pain, functional limitation and TKR; logistic regression curves were similar. However, each KLG included a wide range of B-scores. For example, for KLG3, risk of pain was 34.4 (95% CI 31.7 to 37.0)%, but B-scores within KLG3 knees ranged from 0 to 6; for B-score 0, risk was 17.0 (16.1 to 17.9)% while for B-score 6, it was 52.1 (48.8 to 55.4)%. For TKR, KLG3 risk was 15.3 (13.3 to 17.3)%; while B-score 0 had negligible risk, B-score 6 risk was 35.6 (31.8 to 39.6)%. Age, sex and body mass index had negligible effects on association between B-score and symptoms. CONCLUSIONS: B-score provides reader-independent quantification using a single time-point, providing unambiguous OA status with defined clinical risks across the whole range of disease including pre-radiographic OA. B-score heralds a step-change in OA stratification for interventions and improved personalised assessment, analogous to the T-score in osteoporosis.

Investigating the patient acceptable symptom state cut-offs: longitudinal data from a community cohort using the shoulder pain and disability index.

This prospective study aimed to determine the patient acceptable symptom state (PASS) cut-off for the patient reported outcome measure shoulder pain and disability index (SPADI), and evaluate predictors of PASS achievement following standard shoulder care. Patients with shoulder pain, referred for shoulder ultrasound were recruited from a community cohort. Patients completed both SPADI (scored 0-130) and a question on symptom state and followed-up at 6 months. PASS was calculated from Rasch-transformed scores using 2 methods: the 75th percentile of the cumulative response curve and the receiver operating characteristic curve (ROC). Logistic regression was used to identify factors associated with PASS. 304 participants (169 females, mean age 57.2 years) were included. At 6 months, 193 (63%) reported PASS. The association between SPADI at 6 months and PASS depended on baseline SPADI (interaction p = 0.036). Those with higher baseline scores had higher 6 months PASS cut-offs. Using the 75th percentile method, the 6 months total SPADI cut-off was 49.2 in those starting in the highest tertile at baseline compared to 39.4 in the lowest tertile: 46.4 vs. 36.7 for pain, 46.8 vs. 25.1 for disability. The ROC method yielded similar results. We have shown for the first time that the PASS cut-off for SPADI is dependent on baseline severity scores. Understanding the SPADI PASS threshold is important for clinical research to allow standardised reporting of shoulder intervention success at the patient level.

Patellofemoral morphology is not related to pain using three-dimensional quantitative analysis in an older population: data from the Osteoarthritis Initiative.

Objectives: Current structural associations of patellofemoral pain (PFP) are based on 2D imaging methodology with inherent measurement uncertainty due to positioning and rotation. This study employed novel technology to create 3D measures of commonly described patellofemoral joint imaging features and compared these features in people with and without PFP in a large cohort. Methods: We compared two groups from the Osteoarthritis Initiative: one with localized PFP and pain on stairs, and a control group with no knee pain; both groups had no radiographic OA. MRI bone surfaces were automatically segmented and aligned using active appearance models. We applied t-tests, logistic regression and linear discriminant analysis to compare 13 imaging features (including patella position, trochlear morphology, facet area and tilt) converted into 3D equivalents, and a measure of overall 3D shape. Results: One hundred and fifteen knees with PFP (mean age 59.7, BMI 27.5 kg/m2, female 58.2%) and 438 without PFP (mean age 63.6, BMI 26.9 kg/m2, female 52.9%) were included. After correction for multiple testing, no statistically significant differences were found between groups for any of the 3D imaging features or their combinations. A statistically significant discrimination was noted for overall 3D shape between genders, confirming the validity of the 3D measures. Conclusion: Challenging current perceptions, no differences in patellofemoral morphology were found between older people with and without PFP using 3D quantitative imaging analysis. Further work is needed to see if these findings are replicated in a younger PFP population.

The relationship between three-dimensional knee MRI bone shape and total knee replacement-a case control study: data from the Osteoarthritis Initiative.

OBJECTIVE: There is growing understanding of the importance of bone in OA. Our aim was to determine the relationship between 3D MRI bone shape and total knee replacement (TKR). METHODS: A nested case-control study within the Osteoarthritis Initiative cohort identified case knees with confirmed TKR for OA and controls that were matched using propensity scores. Active appearance modelling quantification of the bone shape of all knee bones identified vectors between knees having or not having OA. Vectors were scaled such that -1 and +1 represented the mean non-OA and mean OA shapes. RESULTS: Compared to controls (n = 310), TKR cases (n = 310) had a more positive mean baseline 3D bone shape vector, indicating more advanced structural OA, for the femur [mean 0.98 vs -0.11; difference (95% CI) 1.10 (0.88, 1.31)], tibia [mean 0.86 vs -0.07; difference (95% CI) 0.94 (0.72, 1.16)] and patella [mean 0.95 vs 0.03; difference (95% CI) 0.92 (0.65, 1.20)]. Odds ratios (95% CI) for TKR per normalized unit of 3D bone shape vector for the femur, tibia and patella were: 1.85 (1.59, 2.16), 1.64 (1.42, 1.89) and 1.36 (1.22, 1.50), respectively, all P < 0.001. After including Kellgren-Lawrence grade in a multivariable analysis, only the femur 3D shape vector remained significantly associated with TKR [odds ratio 1.24 (1.02, 1.51)]. CONCLUSION: 3D bone shape was associated with the endpoint of this study, TKR, with femoral shape being most associated. This study contributes to the validation of quantitative MRI bone biomarkers for OA structure-modification trials.

The clinical characteristics of older people with chronic multiple-site joint pains and their utilisation of therapeutic interventions: data from a prospective cohort study.

BACKGROUND: Chronic multiple-site joint pain (MSJP) is common in older people and associated with poor outcomes, yet under-researched. Our aim was to detail the clinical characteristics of people with MSJP and their utilisation of therapies. METHODS: MSJP was defined as pain in at least one large joint and one other joint for >6 weeks in the last three months. A mixed community, primary and secondary care cohort of people >50 years old underwent detailed history and examination by a single clinician. Treatment utilisation was recorded comprehensively. RESULTS: 201 adults were recruited, 82% women, mean age 63, BMI 31 kg/m(2). Median number of painful joints per patient was 6 (IQR 4-9; range 2-17); most common painful sites were knee (84%), lower back (62%) and shoulder (47%). 194/201 (96%) had an osteoarthritis (OA) diagnosis, 155/194 (80%) also had soft tissue pathology and 72% had back problems. 85% had OA at multiple sites. Upper and lower limb weakness was common (90 and 77% respectively). Lower limb weakness was significantly associated with obesity. Only 26% had received written information about their joints. Though 79% had attended physiotherapy, the majority (93%) had muscle weakness. Only 36 % of overweight participants had accessed weight-loss support. Half of those with foot pain had seen a podiatrist or used appliances. Multiple concurrent pharmacological therapies were used by 47%. CONCLUSION: MSJP represents a combination of OA, back pain and soft tissue disorders; muscle weakness is extremely common. Therapies appear underutilised in people with MJSP. Identifying the reasons for this should guide effective intervention research.

Shoulder symptoms trajectories over four years: data from a longitudinal study on osteoarthritis.

OBJECTIVE: Limited data exist on the natural history of shoulder symptoms. We aimed to describe longitudinal patterns of shoulder symptoms and determine risk factors for incidence and persistence. METHODS: Data from Osteoarthritis Initiative participants followed annually for 4 years were used to describe shoulder symptom (yes/no, side) incidence and prevalence using descriptive analyses. Regression analyses investigated the association between three shoulder symptoms outcomes (persistent, incident and intermittent) and clinical factors. Latent Class Growth Analysis (LCGA) identified trajectories in those reporting pain at ≥1 timepoint. RESULTS: 4796 participants (58% females, mean age 61.2 years) were included. Baseline shoulder symptom prevalence was 22%; 32% of these reported bilateral symptoms. In those reporting right symptoms, 260/1886 (14%) had persistent symptoms. Those with persistent symptoms had worse baseline and 4-year clinical status (poorer function, mental health and quality of life). In regression analysis, persistent symptoms were associated with: adjusted OR (95% CI): sleep disturbance (1.97 (1.49, 2.62), work absenteeism (2.16 (1.38, 2.62), lower limb weakness (1.76 (1.37, 2.27), multiple-site joint symptoms (≥3 joints excluding shoulders) 4.90 (2.79, 8.58) and white ethnicity (1.39 (1.04, 1.88). Lower limb weakness was also associated with incident symptoms; no variables were associated with intermittent symptoms. LCGA identified two trajectories: the trajectory with high probability for symptoms (9% of LCGA analysis cohort) showed similar relationships to clinical variables as in the persistent symptoms group. CONCLUSION: In this large, 4-year study, persistent shoulder symptoms were common and associated with worse clinical outcomes. At least one risk factor for incident symptoms is modifiable.

Toward the Development of Data-Driven Diagnostic Subgroups for People With Patellofemoral Pain Using Modifiable Clinical, Biomechanical, and Imaging Features.

BACKGROUND: Unfavorable treatment outcomes for people with patellofemoral pain (PFP) have been attributed to the potential existence of subgroups that respond differently to treatment. OBJECTIVES: This study aimed to identify subgroups within PFP by combining modifiable clinical, biomechanical, and imaging features and exploring the prognosis of these subgroups. METHODS: This was a longitudinal cohort study, with baseline cluster analyses. Baseline data were analyzed using a 2-stage cluster analysis; 10 features were analyzed within 4 health domains before being combined at the second stage. Prognosis of the subgroups was assessed at 12 months, with subgroup differences reported as global rating of change and analyzed with an exploratory logistic regression adjusted for known confounders. RESULTS: Seventy participants were included (mean age, 31 years; 43 [61%] female). Cluster analysis revealed 4 subgroups: "strong," "pronation and malalignment," "weak," and "active and flexible." Descriptively, compared to the strong subgroup (55% favorable), the odds of a favorable outcome were lower in the weak subgroup (31% favorable; adjusted odds ratio [OR] = 0.30; 95% confidence interval [CI]: 0.07, 1.36) and the pronation and malalignment subgroup (50%; OR = 0.64; 95% CI: 0.11, 3.66), and higher in the active and flexible subgroup (63%; OR = 1.24; 95% CI: 0.20, 7.51). After adjustment, compared to the strong subgroup, differences between some subgroups remained substantive, but none were statistically significant. CONCLUSION: In this relatively small cohort, 4 PFP subgroups were identified that show potentially different outcomes at 12 months. Further research is required to determine whether a stratified treatment approach using these subgroups would improve outcomes for people with PFP. LEVEL OF EVIDENCE: Diagnosis, level 2b. J Orthop Sports Phys Ther 2019;49(7):536-547. doi:10.2519/jospt.2019.8607.

Toward a clinical definition of early osteoarthritis: onset of patient-reported knee pain begins on stairs. Data from the osteoarthritis initiative.

OBJECTIVE: Early detection of osteoarthritis (OA) would increase the chances of effective intervention. We aimed to investigate which patient-reported activity is first associated with knee pain. We hypothesized that pain would occur first during activities requiring weight bearing and knee bending. METHODS: Data were obtained from the Osteoarthritis Initiative (OAI), a multicenter, longitudinal prospective observational cohort of people who have or are at high risk of OA. Participants completed the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC; Likert scale) annually for up to 7 years. Rasch analysis was used to rank the WOMAC pain questions (activities) in order of affirmation as the pain score increased from 0. For each total WOMAC score category (0-20) we selected 25 individuals at random based on their maximum score across all visits. Fit to the Rasch model was assessed in this subset; stability of question ranking over successive visits was confirmed in the full OAI. RESULTS: WOMAC data on 4,673 people were included, with 491 selected for subset analysis. The subset data showed good fit to the Rasch model (χ(2) = 43.31, P = 0.332). In the full OAI, the "using stairs" question was the first to score points as the total pain score increased from 0 (baseline logit score ± 95% confidence interval -4.74 ± 0.07), then "walking" (-2.94 ± 0.07), "standing" (-2.65 ± 0.07), "lying/sitting" (-2.00 ± 0.08), and finally "in bed" (-1.32 ± 0.09). This ordering was consistent over successive visits. CONCLUSION: Knee pain is most likely to first appear during weight-bearing activities involving bending of the knee, such as using stairs. First appearance of this symptom may identify a group suitable for early intervention strategies.