Total Hip Arthroplasty Versus Education and Exercise: A Propensity-Matched Analysis of 266 Patients Who Have Hip Osteoarthritis.

BACKGROUND: Total hip arthroplasty (THA) for osteoarthritis (OA) is a major health system cost. Education and exercise (Edu+Ex) programs may reduce the number of THAs needed, but supporting data is limited. This study aimed to estimate the treatment effect of THA versus Edu+Ex on pain, function, and quality of life outcomes 3- and 12-months after treatment initiation for hip OA. METHODS: Patients who had hip OA who underwent THA or an Edu+Ex program were included in this propensity-matched study. In 778 patients (Edu+Ex n = 303; THA n = 475), propensity scores were based on pre-treatment characteristics, and patients were matched on a 1:1 ratio. Between-group treatment effects (pain, function, and quality of life) were estimated as the mean difference in change from pre-treatment to 3- and 12-month follow-up using linear mixed models. RESULTS: The matched sample consisted of 266 patients (Edu+Ex n = 133; THA n = 133) that were balanced on all pre-treatment characteristics except opioid use. At 12-month follow-up, THA resulted in significantly greater improvements in pain (mean difference [MD] 35.4; 95% CI [confidence interval] 31.4 to 39.4), function (MD 30.5; 95% CI 26.3 to 34.7), and quality of life (MD 33.6; 95% CI 28.8 to 38.4). Between 17 and 30% of patients receiving Edu+Ex experienced a surgical threshold for clinically meaningful improvement in outcomes, compared to 84 and 90% of THA patients. CONCLUSIONS: A THA provides greater improvements in pain, function, and quality of life. A significant proportion of Edu+Ex patients had clinically meaningful improvements, suggesting Edu+Ex may result in THA deferral in some patients, but confirmatory trials are needed.

Age and sex Differences in Pediatric Neuropathic Pain and Complex Regional Pain Syndrome: A Scoping Review.

BACKGROUND: Age and sex differences may exist in the frequency (incidence, prevalence) or symptoms of neuropathic pain (NP) and complex regional pain syndrome (CRPS) due to biopsychosocial factors (e.g., neurodevelopment, physiological and hormonal changes, psychosocial differences) that evolve through childhood and adolescence.2 Age and sex differences may have implications for evaluating screening and diagnostic tools and treatment interventions. OBJECTIVE: To map the existing literature on pediatric NP and CRPS with respect to age and sex distributions, and age and sex differences in symptomology and frequency. METHODS: A scoping literature review was conducted. Databases were searched from inception to January 2023. Data were collected on study design, setting, demographics, and age and sex differences in frequency and symptoms. RESULTS: Eighty-seven studies were included. Distribution of participants with CRPS (n=37 studies) was predominantly early adolescence (10-14 years) and female sex, while NP (n=42 studies) was most commonly reported throughout adolescence (10-19 years) in both sexes. Forty-one studies examined age and sex differences in frequency; 6 studies reported higher frequency in adolescence. Very few studies (n=11) examined differences in symptomology. DISCUSSION: Large epidemiological studies are required to further understand age and sex differences in frequency of pediatric NP and CRPS. Age and sex differences must be considered when evaluating screening and diagnostic tools and treatment interventions to ensure relevance and validity to both sexes and across ages. Validated tools will improve understanding of age- and sex-dependent differences in symptoms, pathophysiology, and psychosocial impact of pediatric NP and CRPS.

The impact of diabetes on physical and mental health status and patient satisfaction after total hip and knee arthroplasty.

OBJECTIVE: To assess the impact of diabetes on physical and mental health status, as well as patient satisfaction, one-year following knee and hip total joint arthroplasty (TJA) for osteoarthritis (OA). METHODS: Participants were 626 hip and 754 knee TJA patients. Pre-surgery data were collected on socio-demographics and health status. The 12-item Short Form Health Survey (SF-12) was collected pre- and one year post-surgery, and physical (PCS) and mental component (MCS) summary scores computed. One-year patient satisfaction was also recorded. Four regression models tested the effect of diabetes on: 1) PCS change score; 2) MCS change score; 3) achieving minimal clinically important improvement (MCII) on PCS; and 4) patient satisfaction ('Somewhat or Very Satisfied' vs. 'Somewhat or Very Dissatisfied'). An interaction between surgical joint and diabetes was tested in each model. RESULTS: Self-reported diabetes prevalence was 13.0% (95% CI: 11.2%-14.7%) and was more common in knee 16.1% (95% CI: 13.4%-18.7%) than hip 9.3% (95% CI: 7.0%-11.5%) patients. In adjusted analyses, change scores were 2.3 units less on the PCS for those with diabetes compared to those without (p = 0.005). Patients with diabetes were about half as likely to achieve MCII as patients without diabetes (p = 0.004). Diabetes was not significantly associated with satisfaction or changes in MCS scores. Diabetes effects did not differ by surgical joint. CONCLUSIONS: Findings support that diabetes has a negative impact on improvements in physical health after TJA. Considering the growing prevalence of OA and diabetes in the population, our findings support the importance of perioperative screening and management of diabetes in patients undergoing TJA.

Examining the longitudinal associations between activity limitations, instrumental supports and social participation in osteoarthritis: A CLSA population-based study.

OBJECTIVE: In osteoarthritis (OA) research, disability is largely studied within the context of activities of daily living. Broader consequences for social participation are often overlooked. In prior work, instrumental supports received and their perceived availability were shown to play a role in the maintenance of social participation. Two indicators of social participation were identified, diversity and intensity. The current study extends the findings from this prior cross-sectional work by examining these relationships longitudinally. METHODS: Data are from the baseline and 3-year follow-up questionnaires of the Canadian Longitudinal Study on Aging, a population-based study of people ages 45-85 years at baseline. The sample was restricted to those who at baseline reported a doctor diagnosis of OA (n = 4104). Using structural equation modeling, latent variables were derived at each time point for activity limitations, instrumental supports perceived and received, and social participation diversity and intensity. Longitudinal factorial invariance was assessed. Model covariates included age, sex, education, income, marital status, smoking status, obesity, and number of chronic conditions. RESULTS: For all latent variables, strong factorial longitudinal invariance was found. Activity limitations increased over time. Greater baseline social participation intensity was associated with increases in later intensity and diversity. Increasing activity limitations were associated with decreases in social participation and with increasing receipt of instrumental supports; they were not associated with changes in perceived availability of supports. However, increasing perceived availability was positively associated with social participation intensity. CONCLUSIONS: With a goal of increasing social participation, findings suggest a focus on interventions to reduce activity limitations in OA is necessary. Findings additionally highlight an important role for perceived availability of instrumental supports in maintaining or improving social participation in OA, in addition to current social participation, particularly intensity, for future social participation status.

Total Knee Arthroplasty Versus Education and Exercise for Knee Osteoarthritis: A Propensity-Matched Analysis.

OBJECTIVE: We estimate the treatment effect of total knee arthroplasty (TKA) versus an education and exercise (Edu+Ex) program on pain, function, and quality of life outcomes 3 and 12 months after treatment initiation for knee osteoarthritis (OA). METHODS: Patients with knee OA who had undergone TKA were matched on a 1:1 ratio with participants in an Edu+Ex program based on a propensity score fitted to a range of pretreatment covariates. After matching, between-group differences in improvement (the treatment effect) in Knee Injury and Osteoarthritis Outcome Score 12-item version (0, worst to 100, best) pain, function, and quality of life from baseline to 3 and 12 months were estimated using linear mixed models, adjusting for unbalanced covariates, if any, after matching. RESULTS: The matched sample consisted of 522 patients (Edu+Ex, n = 261; TKA, n = 261) who were balanced on all pretreatment characteristics. At 12-month follow-up, TKA resulted in significantly greater improvements in pain (mean difference [MD] 22.8; 95% confidence interval [95% CI] 19.7-25.8), function (MD 21.2; 95% CI 17.7-24.4), and quality of life (MD 18.3; 15.0-21.6). Even so, at least one-third of patients receiving Edu+Ex had a clinically meaningful improvement in outcomes at 12 months compared with 75% of patients with TKA. CONCLUSION: TKA is associated with greater improvements in pain, function, and quality of life, but these findings also suggest that Edu+Ex may be a viable alternative to TKA in a meaningful proportion of patients, which may reduce overall TKA need. Confirmatory trials are needed.

Association of synovial fluid and urinary C2C-HUSA levels with surgical outcomes post-total knee arthroplasty.

OBJECTIVES: After total knee arthroplasty (TKA), ∼30% of knee osteoarthritis (KOA) patients show little symptomatic improvement. Earlier studies have correlated urinary (u) type 2 collagen C terminal cleavage peptide assay (C2C-HUSA), which detects a fragment of cartilage collagen breakdown, with KOA progression. This study determines whether C2C levels in urine, synovial fluid, or their ratio, are associated with post-surgical outcomes. METHODS: From a large sample of 489 subjects, diagnosed with primary KOA undergoing TKA, Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) pain and function scores were collected at baseline (time of surgery) and one-year post-TKA. Baseline urine (u) and synovial fluid (sf) were analysed using the IBEX-C2C-HUSA assay, with higher values indicating higher amounts of cartilage degradation. For urine, results were normalised to creatinine. Furthermore, subjects' changes in WOMAC scores were categorised based on percent reduction in pain or improvement in function, compared to baseline, such that >66.7%, >33.3 to ≤66.7%, and ≤33.3% denoted "strong", "moderate" and "mild/worse" responses, respectively. Associations of individual biofluid C2C-HUSA levels, or their ratio, with change in WOMAC pain and function scores up to one-year post-TKA, or category of change, were analysed by linear, logistic, or cumulative odds models. RESULTS: Higher baseline uC2C-HUSA levels or a lower ratio of baseline sfC2C-HUSA to uC2C-HUSA were associated with improvements in WOMAC pain by linear multivariable modelling [odds ratio -0.40 (95% confidence interval -0.76, -0.05) p = 0.03; 0.36 (0.01, 0.71), p = 0.04, respectively], while sfC2C-HUSA alone was not. However, lower ratios of sfC2C-HUSA to uC2C-HUSA were associated with improvements in WOMAC function [1.37 (0.18, 2.55), p = 0.02], while sfC2C-HUSA and uC2C-HUSA alone were not. Lower ratios of sfC2C-HUSA to uC2C-HUSA were also associated with an increased likelihood of a subject being categorised in a group where TKA was beneficial in both univariable [pain, 0.81 (0.68, 0.96), p = 0.02; function, 0.92 (0.85, 0.99), p = 0.035] and multivariable [pain, 0.81 (0.68, 0.97) p = 0.02; function, 0.92 (0.85, 1.00), p = 0.043] ordinal modelling, while sfC2C-HUSA and uC2C-HUSA alone were not. CONCLUSIONS: Overall, ratios of baseline sfC2C-HUSA to uC2C-HUSA, and baseline uC2C-HUSA, may play an important role in studying post-TKA surgical outcomes.

Osteoarthritis year in review 2023: Epidemiology & therapy.

OBJECTIVE: To highlight some important findings from osteoarthritis (OA) epidemiology and therapy research undertaken over the past year. METHODS: Search of MEDLINE and EMBASE databases between April 1, 2022 to March 3, 2023 using "exp *Osteoarthritis/" as the preliminary search term. The search was limited to articles published in English and including human subjects. Final inclusions were based on perceived importance and results that may inform improved identification of risk factors or OA treatments, as well as OA subgroups of potential relevance to risk factors or treatment approaches. RESULTS: 3182 studies were screened, leaving 208 eligible for inclusion. This narrative review of thirty-three selected studies was arranged into: a) OA predictors - population-based studies, b) Specific predictors of OA and OA outcome; c) Intra-articular injections, and d) OA phenotypes. There was some suggestion of sex differences in predictors of incidence or outcomes. Body mass index changes appear largely to affect knee OA outcomes. Evidence points to a lack of benefit of viscosupplementation in knee OA; findings were variable for other injectables. Studies of OA phenotypes reveal potentially relevant clinical and pathophysiological differences. CONCLUSIONS: Identifying risk factors for the incidence/progression of OA represents an ongoing and important area of OA research. Sex may play a role in this understanding and bears consideration and further study. For knee injectables other than viscosupplementation, additional high-quality trials appear warranted. Continued investigation and application of phenotyping across the OA disease, illness and care spectrum may be key to developing disease-modifying agents and their appropriate selection for individuals.

High health care use prior to elective surgery for osteoarthritis is associated with poor postoperative outcomes: A Canadian population-based cohort study.

BACKGROUND: The characterization and influence of preoperative health care use on quality-of-care indicators (e.g., readmissions) has received limited attention in populations with musculoskeletal disorders. The purpose of this study was to characterize preoperative health care use and examine its effect on quality-of-care indicators among patients undergoing elective surgery for osteoarthritis. METHODS: Data on health care use for 124,750 patients with elective surgery for osteoarthritis in Ontario, Canada, from April 1, 2015 to March 31, 2018 were linked across health administrative databases. Using total health care use one-year previous to surgery, patients were grouped from low to very high users. We used Poisson regression models to estimate rate ratios, while examining the relationship between preoperative health care use and quality-of-care indicators (e.g., extended length of stay, complications, and 90-day hospital readmissions). We controlled for covariates (age, sex, neighborhood income, rural/urban residence, comorbidities, and surgical anatomical site). RESULTS: We found a statistically significant trend of increasing worse outcomes by health care use gradients that persisted after controlling for patient demographics and comorbidities. Findings were consistent across surgical anatomical sites. Moreover, very high users have relatively large numbers of visits to non-musculoskeletal specialists. CONCLUSIONS: Our findings highlight that information on patients' preoperative health care use, together with other risk factors (such as comorbidities), could help decision-making when benchmarking or reimbursing hospitals caring for complex patients undergoing surgery for osteoarthritis.

Time trends and patterns in opioid prescription use following orthopaedic surgery in Ontario, Canada, from 2004/2005 to 2017/2018: a population-based study.

OBJECTIVES: Increased use of opioids and their associated harms have raised concerns around prescription opioid use for pain management following surgery. We examined trends and patterns of opioid prescribing following elective orthopaedic surgery. DESIGN: Population-based study. SETTING: Ontario, Canada. PARTICIPANTS: Ontario residents aged 66+ years who had elective orthopaedic surgery from April 2004 to March 2018. PRIMARY AND SECONDARY OUTCOME MEASURES: Postoperative opioid use (short term: within 90 days of surgery, prolonged: within 180 days and chronic: within 1 year), specific opioids prescribed, average duration (days) and amount (morphine milligram equivalents) of the initial prescription by year of surgery. RESULTS: We included 464 460 elective orthopaedic surgeries in 2004/2005-2017/2018: 80% of patients used opioids within 1 year of surgery-25.1% were chronic users. There was an 8% increase in opioid use within 1 year of surgery, from 75.1% in 2004/2005 to 80.9% in 2017/2018: a 29% increase in short-term use and a decline in prolonged (9%) and chronic (22%) use. After 2014/2015, prescribed opioid amounts initially declined sharply, while the duration of the initial prescription increased substantially. Across categories of use, there was a steady decline in coprescription of benzodiazepines and opioids. CONCLUSIONS: Most patients filled opioid prescriptions after surgery, and many continued filling prescriptions after 3 months. During a period of general increase in awareness of opioid harms and dissemination of guidelines/policies aimed at opioid prescribing for chronic pain, we found changes in prescribing practices following elective orthopaedic surgery. Findings illustrate the potential impact of guidelines/policies on shaping prescription patterns in the surgical population, even in the absence of specific guidelines for surgical prescribing.

Hospital spending and length of stay attributable to perioperative adverse events for inpatient hip, knee, and spine surgery: a retrospective cohort study.

BACKGROUND: The incremental hospital cost and length of stay (LOS) associated with adverse events (AEs) has not been well characterized for planned and unplanned inpatient spine, hip, and knee surgeries. METHODS: Retrospective cohort study of hip, knee, and spine surgeries at an academic hospital in 2011-2012. Adverse events were prospectively collected for 3,063 inpatient cases using the Orthopaedic Surgical AdVerse Event Severity (OrthoSAVES) reporting tool. Case costs were retrospectively obtained and inflated to equivalent 2021 CAD values. Propensity score methodology was used to assess the cost and LOS attributable to AEs, controlling for a variety of patient and procedure factors. RESULTS: The sample was 55% female and average age was 64; 79% of admissions were planned. 30% of cases had one or more AEs (82% had low-severity AEs at worst). The incremental cost and LOS attributable to AEs were $8,500 (95% confidence interval [CI]: 5100-11,800) and 4.7 days (95% CI: 3.4-5.9) per admission. This corresponded to a cumulative $7.8 M (14% of total cohort cost) and 4,290 bed-days (19% of cohort bed-days) attributable to AEs. Incremental estimates varied substantially by (1) admission type (planned: $4,700/2.4 days; unplanned: $20,700/11.5 days), (2) AE severity (low: $4,000/3.1 days; high: $29,500/11.9 days), and (3) anatomical region (spine: $19,800/9 days; hip: $4,900/3.8 days; knee: $1,900/1.5 days). Despite only 21% of admissions being unplanned, adverse events in these admissions cumulatively accounted for 59% of costs and 62% of bed-days attributable to AEs. CONCLUSIONS: This study comprehensively demonstrates the considerable cost and LOS attributable to AEs in orthopaedic and spine admissions. In particular, the incremental cost and LOS attributable to AEs per admission were almost five times as high among unplanned admissions compared to planned admissions. Mitigation strategies focused on unplanned surgeries may result in significant quality improvement and cost savings in the healthcare system.

Frequency of multisite non-hand joint involvement in patients with thumb-base osteoarthritis, and associations with functional and patient-reported outcomes.

Purpose: In OA studies, the focus often is on an index-joint; other affected joint sites are often overlooked. In this thumb-base OA study, we documented the frequency of symptomatic non-hand joint sites and investigated whether their count was associated with thumb-specific functional and patient-reported outcome measures. Design: Patients seeking care for thumb-base OA (conservative or surgical) were included. A patient-completed questionnaire captured sociodemographic and health characteristics, symptomatic hand and non-hand joint sites, and outcome measures (thumb-base pain intensity, symptoms and disability (TASD) and upper-extremity disability/symptoms (quickDASH)). Grip and pinch strength were measured. Linear regressions examined the association between each outcome and symptomatic joint site count, adjusted for several covariates. Results: The mean age of the 145 patients was 62 years, 72% were female. Mean symptomatic non-hand joint site count was 3.6. Ten percent reported only their hands as symptomatic; 30% reported 2-3 other symptomatic sites, and 49% reported 4+. From cross-sectional multivariable analyses, a higher symptomatic non-hand joint site count was associated with worse scores for all patient-reported outcomes and grip strength. Every unit increase in joint site count (49% had a 4+ count) was associated with a 2.1-3.3 unit increase (worse) in patient-reported outcome scores (all p â€‹< â€‹0.02). Conclusions: In this sample, nearly 80% of patients had 2+ symptomatic non-hand joint sites. These symptoms were associated with worse thumb- and hand-specific outcomes, suggesting a need for awareness of whole body OA burden, with implications for outcome score interpretations, study designs, and provision of care in thumb-base OA.

The GLA:D® Canada program for knee and hip osteoarthritis: A comprehensive profile of program participants from 2017 to 2022.

BACKGROUND: The Good Life with osteoArthritis in Denmark (GLA:D®) program was implemented in Canada in 2017 with the aim of making treatment guideline-recommended care available to the 4 million Canadians with knee and hip osteoarthritis (OA). This report describes the GLA:D® Canada program, registry and data collection procedures, and summarizes the sociodemographic and clinical profile of participants with knee and hip OA to inform the scientific research community of the availability of these data for future investigations and collaborations. METHODS: The GLA:D® program consists of three standardized components: a training course for health care providers, a group-based patient education and exercise therapy program, and a participant data registry. Patients seeking care for knee or hip OA symptoms and enrolling in GLA:D® are given the option to provide data to the GLA:D® Canada registry. Participants agreeing to provide data complete a pre-program survey and are followed up after 3-, and 12-months. Data collected on the pre-program and follow-up surveys include sociodemographic factors, clinical characteristics, health status measures, and objective physical function tests. These variables were selected to capture information across relevant health constructs and for future research investigations. RESULTS: At 2022 year-end, a total of 15,193 (11,228 knee; 3,965 hip) participants were included in the GLA:D® Canada registry with 7,527 (knee; 67.0%) and 2,798 (hip; 70.6%) providing pre-program data. Participants were 66 years of age on average, predominately female, and overweight or obese. Typically, participants had knee or hip problems for multiple years prior to initiating GLA:D®, multiple symptomatic knee and hip joints, and at least one medical comorbidity. Before starting the program, the average pain intensity was 5 out of 10, with approximately 2 out of 3 participants using pain medication and 1 in 3 participants reporting a desire to have joint surgery. Likewise, 9 out 10 participants report having previously been given a diagnosis of OA, with 9 out 10 also reporting having had a radiograph, of which approximately 87% reported the radiograph showed signs of OA. CONCLUSION: We have described the GLA:D® Canada program, registry and data collection procedures, and provided a detailed summary to date of the profiles of participants with knee and hip OA. These individual participant data have the potential to be linked with local health administrative data registries and comparatively assessed with other international GLA:D® registries. Researchers are invited to make use of these rich datasets and participate in collaborative endeavours to tackle questions of Canadian and global importance for a large and growing clinical population of individuals with hip and knee OA.

Determining minimal clinically important difference estimates following surgery for degenerative conditions of the lumbar spine: analysis of the Canadian Spine Outcomes and Research Network (CSORN) registry.

BACKGROUND CONTEXT: There is significant variability in minimal clinically important difference (MCID) criteria for lumbar spine surgery that suggests population and primary pathology specific thresholds may be required to help determine surgical success when using patient reported outcome measures (PROMs). PURPOSE: The purpose of this study was to estimate MCID thresholds for 3 commonly used PROMs after surgical intervention for each of 4 common lumbar spine pathologies. STUDY DESIGN/SETTING: Observational longitudinal study of patients from the Canadian Spine Outcomes and Research Network (CSORN) national registry. PATIENT SAMPLE: Patients undergoing surgery from 2015 to 2018 for lumbar spinal stenosis (LSS; n = 856), degenerative spondylolisthesis (DS; n = 591), disc herniation (DH; n = 520) or degenerative disc disease (DDD n = 185) were included. OUTCOME MEASURES: PROMs were collected presurgery and 1-year postsurgery: the Oswestry Disability Index (ODI), and back and leg Numeric Pain Rating Scales (NPRS). At 1-year, patients reported whether they were 'Much better'/'Better'/'Same'/'Worse'/'Much worse' compared to before their surgery. Responses to this item were used as the anchor in analyses to determine surgical MCIDs for benefit ('Much better'/'Better') and substantial benefit ('Much better'). METHODS: MCIDs for absolute and percentage change for each of the 3 PROMs were estimated using a receiving operating curve (ROC) approach, with maximization of Youden's index as primary criterion. Area under the curve (AUC) estimates, sensitivity, specificity and correct classification rates were determined. All analyses were conducted separately by pathology group. RESULTS: MCIDs for ODI change ranged from -10.0 (DDD) to -16.9 (DH) for benefit, and -13.8 (LSS) to -22.0 (DS,DH) for substantial benefit. MCID for back and leg NPRS change were -2 to -3 for each group for benefit and -4.0 for substantial benefit for all groups on back NPRS. MCID estimates for percentage change varied by PROM and pathology group, ranging from -11.1% (ODI for DDD) to -50.0% (leg NPRS for DH) for benefit and from -40.0% (ODI for DDD) to -66.6% (leg NPRS for DH) for substantial benefit. Correct classification rates for all MCID thresholds ranged from 71% to 89% and were relatively lower for absolute vs percent change for those with high or low presurgical scores. CONCLUSIONS: Our findings suggest that the use of generic MCID thresholds across pathologies in lumbar spine surgery is not recommended. For patients with relatively low or high presurgery PROM scores, MCIDs based on percentage change, rather than absolute change, appear generally preferable. These findings have applicability in clinical and research settings, and are important for future surgical prognostic work.

Examination of the Increased Risk for Falls Among Individuals With Knee Osteoarthritis: A Canadian Longitudinal Study on Aging Population-Based Study.

OBJECTIVE: To characterize the profile of individuals with and without knee osteoarthritis (OA) who fell, and to identify factors contributing to an individual with knee OA experiencing 1 or multiple injurious falls. METHODS: Data are from the baseline and 3-year follow-up questionnaires of the Canadian Longitudinal Study on Aging, a population-based study of people ages 45-85 years at baseline. Analyses were limited to individuals either reporting knee OA or no arthritis at baseline (n = 21,710). Differences between falling patterns among those with and without knee OA were tested using chi-square tests and multivariable-adjusted logistic regression models. An ordinal logistic regression model examined predictors of experiencing 1 or more injurious falls among individuals with knee OA. RESULTS: Among individuals reporting knee OA, 10% reported 1 or more injurious falls; 6% reported 1 fall, and 4% reported 2+ falls. Having knee OA significantly contributed to the risk of falling (odds ratio [OR] 1.33 [95% confidence interval (95% CI) 1.14-1.56]), and individuals with knee OA were more likely to report having a fall indoors while standing or walking. Among individuals with knee OA, reporting a previous fall (OR 1.75 [95% CI 1.22-2.52]), previous fracture (OR 1.42 [95% CI 1.12-1.80]), and having urinary incontinence (OR 1.38 [95% CI 1.01-1.88]) were significant predictors of falling. CONCLUSION: Our findings support the idea that knee OA is an independent risk factor for falls. The circumstances in which falls occur differ from those for individuals without knee OA. The risk factors and environments that are associated with falling may provide opportunities for clinical intervention and fall prevention strategies.

Intervertebral disc degeneration and osteoarthritis: a common molecular disease spectrum.

Intervertebral disc degeneration (IDD) and osteoarthritis (OA) affecting the facet joint of the spine are biomechanically interdependent, typically occur in tandem, and have considerable epidemiological and pathophysiological overlap. Historically, the distinctions between these degenerative diseases have been emphasized. Therefore, research in the two fields often occurs independently without adequate consideration of the co-dependence of the two sites, which reside within the same functional spinal unit. Emerging evidence from animal models of spine degeneration highlight the interdependence of IDD and facet joint OA, warranting a review of the parallels between these two degenerative phenomena for the benefit of both clinicians and research scientists. This Review discusses the pathophysiological aspects of IDD and OA, with an emphasis on tissue, cellular and molecular pathways of degeneration. Although the intervertebral disc and synovial facet joint are biologically distinct structures that are amenable to reductive scientific consideration, substantial overlap exists between the molecular pathways and processes of degeneration (including cartilage destruction, extracellular matrix degeneration and osteophyte formation) that occur at these sites. Thus, researchers, clinicians, advocates and policy-makers should consider viewing the burden and management of spinal degeneration holistically as part of the OA disease continuum.

Cardiovascular Risk Profile and Osteoarthritis-Considering Sex and Multisite Joint Involvement: A Canadian Longitudinal Study on Aging.

OBJECTIVE: The objective of this study was to investigate a profile of cardiovascular disease (CVD) risk factors by sex among individuals with and without osteoarthritis (OA) and to consider single-site and multisite joint OA. METHODS: Data were sourced from Cycle 1, Comprehensive Cohort, Canadian Longitudinal Study on Aging, a national sample of individuals ages 45 to 85 years. Systemic inflammatory/metabolic CVD risk factors collected were high-sensitivity C-reactive protein (hsCRP) level, high-density lipoprotein, triglycerides, total cholesterol, body mass index (BMI), systolic blood pressure, and hemoglobin A1c. Smoking history was also collected. Respondents indicated doctor-diagnosed OA in the knees, hips, and/or hands and were characterized as yes/no OA and single site/multisite OA. Individuals with OA were age- and sex-matched to non-OA controls. Covariates were age, sex, education, income, physical activity, timed up and go test findings, and comorbidities. A latent CVD risk variable was derived in women and men; standardized scores were categorized as follows: lowest, mid-low, mid-high, and highest risk. Associations with OA were quantified using ordinal logistic regressions. RESULTS: A total of 6,098 respondents (3,049 with OA) had a median age of 63 years, and 55.8% were women. One-third of OA respondents were in the highest risk category versus one-fifth of non-OA respondents. Apart from BMI (the largest contributor in both sexes), hsCRP level (an inflammation marker) was predominant in women, and metabolic factors and smoking were predominant in men. Overall, OA was associated with worse CVD risk quartiles compared with non-OA. OA was increasingly associated with worse CVD risk quartiles with increasing risk thresholds among women with multisite OA, but not men. CONCLUSION: Findings suggest unique CVD risks by sex/multisite subgroups and point to a potentially important role for inflammation in OA over and above traditional CVD risk factors.

Factors Influencing Pain Response Following Patient Education and Supervised Exercise in Male and Female Subjects With Hip Osteoarthritis.

OBJECTIVE: To understand factors associated with pain intensity responder status following nonsurgical hip osteoarthritis (OA) intervention, according to sex. METHODS: Data were from individuals with hip OA participating in the Danish Good Life With Osteoarthritis in Denmark 8-week education and exercise program. The following factors were recorded at program entry: age; education; mental well-being; comorbidities; body mass index; symptoms in hip, knee, and low back; and program-specific factors including education sessions, former participant lectures, and supervised exercise sessions. Pain intensity was recorded at baseline and at month 3 (post-program) on a 0-100-mm visual analog scale. Response was defined as pain intensity improvement of ≥30% from baseline to post-program. Logistic regression was used and conducted separately in male and female subjects. RESULTS: The sample included 791 men and 2,253 women. Female subjects had a mean baseline pain score of 47.2 of 100 (95% confidence interval [95% CI] 46.4-48.1) and male subjects had a score of 41.7 (95% CI 40.3-43.1). By post-program, the proportion of pain responders was 50.4% among women and 45.8% among men (difference P = 0.025). Among women, program-specific factors (attending former participant lectures and more supervised exercise sessions) were positively associated with pain response, as were better mental well-being and fewer comorbidities, while symptoms in other joints/sites were associated with a decreased likelihood of response. Among men, program-specific factors were not associated with response, while better mental well-being and fewer comorbidities were associated with being a responder. CONCLUSION: Findings suggest that the influence of some factors on pain response differ for male and female subjects and point to a potential need for targeted approaches for men and women who may require different key messages/approaches from health care providers.

Individual participant data meta-analysis of metabolomics on sustained knee pain in primary osteoarthritis patients.

OBJECTIVES: Knee pain is the major driver for OA patients to seek healthcare, but after pursuing both conservative and surgical pain interventions, ∼20% of patients continue to report long-term pain following total knee arthroplasty (TKA). This study aimed to identify a metabolomic signature for sustained knee pain after TKA to elucidate possible underlying mechanisms. METHODS: Two independent cohorts from St John's, NL, Canada (n = 430), and Toronto, ON, Canada (n = 495) were included in the study. Sustained knee pain was assessed using the WOMAC pain subscale (five questions) at least 1 year after TKA for primary OA. Those reporting any pain on all five questions were considered to have sustained knee pain. Metabolomic profiling was performed on fasted pre-operative plasma samples using the Biocrates Absolute IDQ p180 kit. Associations between metabolites and pair-wise metabolite ratios with sustained knee pain in each individual cohort were assessed using logistic regression with adjustment for age, sex and BMI. Random-effects meta-analysis using inverse variance as weights was performed on summary statistics from both cohorts. RESULTS: One metabolite, phosphatidylcholine (PC) diacyl (aa) C28:1 (odds ratio = 0.66, P = 0.00026), and three metabolite ratios, PC aa C32:0 to PC aa C28:1, PC aa C28:1 to PC aa C32:0, and tetradecadienylcarnitine (C14:2) to sphingomyelin C20:2 (odds ratios = 1.59, 0.60 and 1.59, respectively; all P < 2 × 10-5), were significantly associated with sustained knee pain. CONCLUSIONS: Though further investigations are needed, our results provide potential predictive biomarkers and drug targets that could serve as a marker for poor response and be modified pre-operatively to improve knee pain and surgical response to TKA.

Association of presurgical circulating MicroRNAs with 1-year postsurgical pain reduction in spine facet osteoarthritis patients with lumbar spinal stenosis.

Purpose: Up to 30% of spine facet osteoarthritis patients with lumbar spinal stenosis (SF-OA â€‹+ â€‹LSS) have little to no improvement in their pain after surgery. Lack of meaningful improvement in pain following surgery provides a unique opportunity to identify specific predictive biomarker signatures that might be associated with the outcomes of surgical treatment. The objective of the present study was to determine whether a microRNA (miRNA) biomarker signature could be identified in presurgical blood plasma that corresponded with levels of SF-OA â€‹+ â€‹LSS patient post-surgical pain intensity one year later. Methods: RNA was extracted from baseline plasma of SF-OA â€‹+ â€‹LSS patients and prepared for miRNA sequencing. Statistical approaches were performed to identify differentially expressed miRNAs associated with reduced 1-year postsurgical pain (n â€‹= â€‹56). Using an integrated computational approach, we further created predicted gene and pathway networks for each identified miRNA. Results: We identified a panel of 4 circulating candidate miRNAs (hsa-miR-155-5p, hsa-let-7e-5p, hsa-miR-125a-5p, hsa-miR-99b-5p) with higher levels at presurgical baseline that were associated with greater changes in % NPRS20Δ, reflecting reduced pain intensity levels at one year. Genes encoding hsa-let-7e-5p, hsa-miR-125a-5p, and hsa-miR-99b-5p are part of an evolutionarily conserved miRNA cluster. Using integrated computational analyses, we showed that mammalian target of rapamycin, transforming growth factor-ß1 receptor, Wnt signaling, epithelial-mesenchymal transition regulators, and cholecystokinin signaling were enriched pathways of predicted gene targets. Conclusions: Taken together, our findings suggest that 4 presurgical baseline circulating miRNAs correlate with 1-year postsurgical SF-OA â€‹+ â€‹LSS patient pain intensity and represent possible candidate biomarker signature of surgical pain response.