Patterns of Comorbidities and Prescribing and Dispensing of Non-steroidal Anti-inflammatory Drugs (NSAIDs) Among Patients with Osteoarthritis in the USA: Real-World Study.

BACKGROUND: Osteoarthritis (OA) is a major cause of chronic pain. Non-steroidal anti-inflammatory drugs (NSAIDs) are analgesics commonly used for musculoskeletal pain; however, NSAIDs can increase the risk of certain adverse events, such as gastrointestinal bleeding, edema, heart failure, and hypertension. OBJECTIVE: The objective of this study was to characterize existing comorbidities among patients with OA. For patients with OA with and without a coexisting medical condition of interest (CMCOI), we estimated the prevalence of prescribing and dispensing NSAIDs pre-OA and post-OA diagnosis. METHODS: Data from three large administrative claims databases were used to construct an OA retrospective cohort. Databases leveraged were IBM MarketScan Medicare Supplemental Database (MDCR), IBM MarketScan Commercial Database (CCAE), and Optum's de-identified Clinformatics® Data Mart Database (Optum CDM). The OA study population was defined to be those patients who had an OA diagnosis from an inpatient or outpatient visit with at least 365 days of prior observation time in the database during January 2000 through May 2021. Asthma, cardiovascular disorders, renal impairment, and gastrointestinal bleeding risks were the CMCOI of interest. Patients with OA were then classified as having or not having evidence of a CMCOI. For both groups, NSAID dispensing patterns pre-OA and post-OA diagnosis were identified. Descriptive analysis was performed within the Observational Health Data Sciences and Informatics framework. RESULTS: In each database, the proportion of the OA population with at least one CMCOI was nearly 50% or more (48.0% CCAE; 74.4% MDCR; 68.6% Optum CDM). Cardiovascular disease was the most commonly observed CMCOI in each database, and in two databases, nearly one in four patients with OA had two or more CMCOI (23.2% MDCR; 22.6% Optum CDM). Among the OA population with CMCOI, NSAID utilization post-OA diagnosis ranged from 33.0 to 46.2%. Following diagnosis of OA, an increase in the prescribing and dispensing of NSAIDs was observed in all databases, regardless of patient CMCOI presence. CONCLUSIONS: This study provides real-world evidence of the pattern of prescribing and dispensing of NSAIDs among patients with OA with and without CMCOI, which indicates that at least half of patients with OA in the USA have a coexisting condition. These conditions may increase the risk of side effects commonly associated with NSAIDs. Yet, at least 32% of these patients were prescribed and dispensed NSAIDs. These data support the importance of shared decision making between healthcare professionals and patients when considering NSAIDs for the treatment of OA in patients with NSAID-relevant coexisting medical conditions.

Evidence-Based Guideline for the management of osteoporosis in men.

Historically, osteoporosis has been viewed as a disease of women, with research, trials of interventions and guidelines predominantly focused as such. It is apparent, however, that this condition causes a substantial health burden in men also, and that its assessment and management must ultimately be addressed across both sexes. In this article, an international multidisciplinary working group of the European Society for Clinical and Economic Aspects of Osteoporosis, Osteoarthritis and Musculoskeletal Diseases presents GRADE-assessed recommendations for the diagnosis, monitoring and treatment of osteoporosis in men. The recommendations are based on a comprehensive review of the latest research related to diagnostic and screening approaches for osteoporosis and its associated high fracture risk in men, covering disease burden, appropriate interpretation of bone densitometry (including the use of a female reference database for densitometric diagnosis in men) and absolute fracture risk, thresholds for treatment, and interventions that can be used therapeutically and their health economic evaluation. Future work should specifically address the efficacy of anti-osteoporosis medications, including denosumab and bone-forming therapies.

Estimating the cost and epidemiology of mild to severe chronic pain associated with osteoarthritis in England: a retrospective analysis of linked primary and secondary care data.

OBJECTIVE: Osteoarthritis (OA) affects 10% of adults in the UK. Despite over one-third of people with OA experiencing chronic pain, few studies have examined the population-level impact of chronic pain associated with OA. We compared resource-use and epidemiological outcomes in patients with mild, moderate and severe chronic OA-associated pain and matched controls without known OA. DESIGN: Retrospective, longitudinal, observational cohort study (July 2008 to June 2019). SETTING: Electronic records extracted from Clinical Practice Research Datalink GOLD primary care linked to Hospital Episode Statistics (HES). PARTICIPANTS: Patients (cases; n=23 016) aged ≥18 years with chronic OA-associated pain. Controls (n=23 016) without OA or chronic pain matched on age, sex, comorbidity burden, general practitioner practice and available HES data. INTERVENTIONS: None. PRIMARY AND SECONDARY OUTCOME MEASURES: Total healthcare resource use (HCRU), direct healthcare costs in 0-12, 12-24 and 24-36 months postindex. Secondary outcomes included incidence and prevalence of chronic OA-associated pain and pharmacological management. RESULTS: HCRU was consistently greater in cases versus controls for all resource categories during preindex and postindex periods. Across follow-up periods, resource use was greatest in patients with severe pain. In the first 12 months postindexing, mean total costs incurred by cases were four times higher versus matched controls (£256 vs £62); costs were approximately twice as high in cases vs controls for months 12-24 (£166 vs £86) and 24-36 (£150 vs £81; all p<0.0001). The incidence of new cases of chronic pain associated with OA was 2.64 per 1000 person-years; the prevalence was 1.4%. CONCLUSIONS: This study highlights the real-world cost of chronic pain associated with OA in cases versus matched controls. We included patients with mild, moderate and severe pain associated with OA, and showed HCRU in discrete 1-year time frames. The true economic burden of pain associated with OA is likely to be considerably higher when indirect costs are considered.

Chronic Low Back Pain with and without Concomitant Osteoarthritis: A Retrospective, Longitudinal Cohort Study of Patients in England.

Objective: Despite the high prevalence of chronic low back pain (CLBP) and osteoarthritis (OA), few estimates of the economic cost of these conditions in England have been published. The aim of the present analysis was to characterise the economic burden of moderate-to-severe pain associated with CLBP + OA and CLBP alone compared with general population-matched controls without CLBP or OA. The primary objective was to describe the total healthcare resource use (HCRU) and direct healthcare costs associated with the target patient populations. Secondary objectives were to describe treatment patterns and surgical procedures. Methods: This was a retrospective, observational cohort study of patients receiving healthcare indicative of moderate-to-severe chronic pain associated with CLBP, with or without OA. We used linked longitudinal data from the Clinical Practice Research Datalink GOLD and Hospital Episode Statistics (HES). Patients (cases) were matched 1 : 1 with controls on age, sex, comorbidity burden, GP practice, and HES data availability. Results: The CLBP-alone cohort comprised 13 554 cases with CLBP and 13 554 matched controls; the CLBP + OA cohort comprised 7803 cases with both OA and CLBP and 7803 matched controls. Across all follow-up periods, patients with CLBP alone and those with CLBP + OA had significantly more GP consultations, outpatient attendances, emergency department visits, and inpatient stays than controls (all p < 0.0001). By 36 months after indexing, the mean (SD) per-patient total direct healthcare cost in the CLBP-alone cohort was £5081 (£5905) for cases and £1809 (£4451) for controls (p < 0.0001); in the CLBP + OA cohort, the mean (SD) per-patient total direct healthcare cost was £8819 (£7143) for cases and £2428 (£4280) for controls (p < 0.0001). Conclusion: Moderate-to-severe chronic pain associated with CLBP-with or without OA-has a substantial impact on patients and healthcare providers, leading to higher HCRU and costs versus controls among people with CLBP alone or together with OA.

Prescription opioid utilization patterns, and associated outcomes, among privately insured patients prescribed opioids to manage pain associated with osteoarthritis.

OBJECTIVE: To describe utilization patterns, negative clinical outcomes and economic burden of patients diagnosed with osteoarthritis (OA) of the hip and/or knee who received a prescription for tramadol or non-tramadol opioids vs. non-opioid drugs. METHODS: Optum Healthcare Solutions, Inc. commercial claims data were used (1/2012--3/2017). Adults with ≥2 diagnoses of OA of the hip and/or knee, and ≥30 days supply of pain medications were identified during the three-year period from the date of first prescription (index date) after the first OA diagnosis. Drug utilization statistics in the follow-up period were summarized by initial treatment (i.e. tramadol, non-tramadol opioids, non-opioid drugs). Opioid initiators were matched to those initiated on non-opioid treatments using a propensity score model accounting for baseline characteristics. Matched pairs analysis compared outcomes for these cohorts. RESULTS: Of 62,715 total patients, 15,270 (24.3%) initiated treatment with opioids, including 3,513 (5.6%) on tramadol and 11,757 (18.7%) on non-tramadol opioids. Opioid initiators had more comorbidities, higher baseline healthcare costs, and were more likely to have OA of the hip. Among non-opioid initiators, 27.5% switched to tramadol and 63% switched to non-tramadol opioids. Among tramadol initiators, 71% switched to non-tramadol opioids. Patients initiated on opioids had 20.4% (p < .01) higher all-cause healthcare costs and higher percentages experiencing multiple negative clinical outcomes (all p < .01) compared to matched controls. CONCLUSIONS: Most patients with OA of the hip and/or knee either initiate on or switch to opioids for long-term management of OA-related pain despite known risks. This highlights the need for new treatments that delay or prevent use of opioids.

Health economic impact of moderate-to-severe chronic pain associated with osteoarthritis in England: a retrospective analysis of linked primary and secondary care data.

OBJECTIVE: Despite the prevalence of osteoarthritis (OA) in England, few studies have examined the health economic impact of chronic pain associated with OA. The aim of this study was to compare outcomes in patients with moderate-to-severe chronic pain associated with OA and matched controls without known OA. DESIGN: Retrospective, longitudinal, observational cohort study. SETTING: Electronic records extracted from the Clinical Practice Research Datalink GOLD primary care database linked to Hospital Episode Statistics (HES) data set. PARTICIPANTS: Patients (cases; n=5931) ≥18 years and with existing diagnosis of OA and moderate-to-severe pain associated with their OA, and controls matched on age, sex, comorbidity burden, general practitioner (GP) practice and availability of HES data. INTERVENTIONS: None. PRIMARY AND SECONDARY OUTCOME MEASURES: Total healthcare resource use (HCRU) and direct healthcare costs during 0-6, 0-12, 0-24 and 0-36 months of follow-up. Secondary outcomes measures included pharmacological management and time to total joint replacement. RESULTS: Patients with moderate-to-severe chronic pain associated with OA used significantly more healthcare services versus matched controls, reflected by higher HCRU and significantly higher direct costs. During the first 12 months' follow-up, cases had significantly more GP consultations, outpatient attendances, emergency department visits and inpatient stays than matched controls (all p<0.0001). Total mean costs incurred by cases during 0-12 months' follow-up were five times higher in cases versus controls (mean (SD): £4199 (£3966) vs £781 (£2073), respectively). Extensive cycling through pharmacological therapies was observed; among cases, 2040 (34.4%), 1340 (22.6%), 841 (14.2%), 459 (7.7%) and 706 (11.9%) received 1-5, 6-10, 11-15, 16-20 and >20 lines of therapy, respectively. CONCLUSIONS: This wide-ranging, longitudinal, observational study of real-world primary and secondary care data demonstrates the impact of moderate-to-severe chronic pain associated with OA in patients compared with matched controls. Further studies are required to fully quantify the health economic burden of moderate-to-severe pain associated with OA.

Update on the clinical use of trabecular bone score (TBS) in the management of osteoporosis: results of an expert group meeting organized by the European Society for Clinical and Economic Aspects of Osteoporosis, Osteoarthritis and Musculoskeletal Diseases (ESCEO), and the International Osteoporosis Foundation (IOF) under the auspices of WHO Collaborating Center for Epidemiology of Musculoskeletal Health and Aging.

PURPOSE: Trabecular bone score (TBS) is a grey-level textural measurement acquired from dual-energy X-ray absorptiometry lumbar spine images and is a validated index of bone microarchitecture. In 2015, a Working Group of the European Society on Clinical and Economic Aspects of Osteoporosis, Osteoarthritis and Musculoskeletal Diseases (ESCEO) published a review of the TBS literature, concluding that TBS predicts hip and major osteoporotic fracture, at least partly independent of bone mineral density (BMD) and clinical risk factors. It was also concluded that TBS is potentially amenable to change as a result of pharmacological therapy. Further evidence on the utility of TBS has since accumulated in both primary and secondary osteoporosis, and the introduction of FRAX and BMD T-score adjustment for TBS has accelerated adoption. This position paper therefore presents a review of the updated scientific literature and provides expert consensus statements and corresponding operational guidelines for the use of TBS. METHODS: An Expert Working Group was convened by the ESCEO and a systematic review of the evidence undertaken, with defined search strategies for four key topics with respect to the potential use of TBS: (1) fracture prediction in men and women; (2) initiating and monitoring treatment in postmenopausal osteoporosis; (3) fracture prediction in secondary osteoporosis; and (4) treatment monitoring in secondary osteoporosis. Statements to guide the clinical use of TBS were derived from the review and graded by consensus using the Grades of Recommendation, Assessment, Development and Evaluation (GRADE) approach. RESULTS: A total of 96 articles were reviewed and included data on the use of TBS for fracture prediction in men and women, from over 20 countries. The updated evidence shows that TBS enhances fracture risk prediction in both primary and secondary osteoporosis, and can, when taken with BMD and clinical risk factors, inform treatment initiation and the choice of antiosteoporosis treatment. Evidence also indicates that TBS provides useful adjunctive information in monitoring treatment with long-term denosumab and anabolic agents. All expert consensus statements were voted as strongly recommended. CONCLUSION: The addition of TBS assessment to FRAX and/or BMD enhances fracture risk prediction in primary and secondary osteoporosis, adding useful information for treatment decision-making and monitoring. The expert consensus statements provided in this paper can be used to guide the integration of TBS in clinical practice for the assessment and management of osteoporosis. An example of an operational approach is provided in the appendix. This position paper presents an up-to-date review of the evidence base, synthesised through expert consensus statements, which informs the implementation of Trabecular Bone Score in clinical practice.

Association of Osteoarthritis Prevalence With Age and Obesity Factors in Organization for Economic Cooperation and Development Countries: Panel Regression Model.

INTRODUCTION: According to cross-sectional analysis studies supported by microdata, incidence of Osteoarthritis increases in parallel with ageing and obesity, which are common predictors of the disease. The aim of this study is to reveal whether ageing and obesity have an effect on the increase in osteoarthritis prevalence by analyzing cross-country data from Organization for Economic Cooperation and Development countries. METHODS: We used static panel data regression analysis for 36 countries for the period between 2000 and 2017. Along with osteoarthritis prevalence, we used a group of people with a body mass index ≤ 30 within the population as obesity indicator and those older than 65 yrs within the population as ageing indicator. We calculated the effect of ageing and obesity on osteoarthritis prevalence using STATA 13 software. RESULTS: Both variable coefficients, age, and obesity, respectively, were found to be positive and statistically significant at the 1% level. This study shows that both ageing and obesity contribute to an increase in the osteoarthritis prevalence based on macro data from 36 Organization for Economic Cooperation and Development countries. CONCLUSIONS: These findings have significant implications that can be used by both the public and policymakers for preventing the osteoarthritis. Adopting the preventive measures could contribute to decrease in health expenditures.

Hand osteoarthritis is associated with limitations in paid and unpaid work participation and related societal costs: the HOSTAS cohort.

OBJECTIVES: Data on work participation impairment and related societal costs for patients with hand osteoarthritis (OA) are scarce. Therefore, we aimed to investigate the association of hand OA with work limitations and costs of productivity loss in paid and unpaid work. METHODS: We used data from the Hand Osteoarthritis in Secondary Care cohort, including patients with hand OA diagnosed by their treating rheumatologist. Using the validated Health and Labour Questionnaire, we assessed experienced unpaid and paid work restrictions, unpaid work replacement by others and inefficiency and absence during paid work related to hand OA over the last 2 weeks. Societal costs (€) per hour of paid and unpaid work were estimated using Dutch salary data in 2019. RESULTS: 381 patients were included (mean age 61 years, 84% women, 26% high education level, 55% having any comorbidity). Replacement of unpaid work by others due to hand OA was necessary for 171 out of 381 patients (45%). Paid work was reported by 181/381 patients (47%), of whom 13/181 (7%) reported absenteeism, 28/181 (15%) unproductive hours at work and 120/181 (66%) paid work restrictions due to hand OA.Total estimated work-related societal costs per patient with hand OA (381 patients) were €94 (95% CI 59 to 130) per 2 weeks (€2452, 95% CI 1528 to 3377 per year). CONCLUSIONS: Hand OA is associated with impairment in paid and unpaid work participation, which translates into substantial societal costs of lost productivity. These results highlight the importance of adequate hand OA treatment.

Cost-effectiveness of telephone cognitive behavioral therapy for osteoarthritis-related insomnia.

BACKGROUND: Osteoarthritis-related insomnia is the most common form of comorbid insomnia among older Americans. A randomized clinical trial found that six sessions of telephone-delivered cognitive behavioral therapy for insomnia (CBT-I) improved sleep outcomes in this population. Using these data, we evaluated the incremental cost-effectiveness of CBT-I from a healthcare sector perspective. METHODS: The study was based on 325 community-dwelling older adults with insomnia and osteoarthritis pain enrolled with Kaiser Permanente of Washington State. We measured quality-adjusted life years (QALYs) using the EuroQol 5-dimension scale. Arthritis-specific quality of life was measured using the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC). Insomnia-specific quality of life was measured using the Insomnia Severity Index (ISI) and nights without clinical insomnia (i.e., "insomnia-free nights"). Total healthcare costs included intervention and healthcare utilization costs. RESULTS: Over the 12 months after randomization, CBT-I improved ISI and WOMAC by -2.6 points (95% CI: -2.9 to -2.4) and -2.6 points (95% CI: -3.4 to -1.8), respectively. The ISI improvement translated into 89 additional insomnia-free nights (95% CI: 79 to 98) over the 12 months. CBT-I did not significantly reduce total healthcare costs (-$1072 [95% CI: -$1968 to $92]). Improvements in condition-specific measures were not reflected in QALYs gained (-0.01 [95% CI: -0.01 to 0.01]); at a willingness-to-pay of $150,000 per QALY, CBT-I resulted in a positive net monetary benefit of $369 with substantial uncertainty (95% CI: -$1737 to $2270). CONCLUSION: CBT-I improved sleep and arthritis function without increasing costs. These findings support the consideration of telephone CBT-I for treating insomnia among older adults with comorbid OA. Our findings also suggest potential limitations of the general quality of life measures in assessing interventions designed to improve sleep and arthritis outcomes.

Risk of 30-day Readmission After Knee or Hip Replacement in Rheumatoid Arthritis and Osteoarthritis by Non-Medicare and Medicare Payer Status.

OBJECTIVE: To determine the indication and risk of 30-day rehospitalization after hip or knee replacement among patients with rheumatoid arthritis (RA) and osteoarthritis (OA) by Medicare and non-Medicare status. METHODS: Using the Nationwide Readmission Database (2010-2014), we defined an index hospitalization as an elective hospitalization with a principal procedure of total hip (THR) or knee replacement (TKR) among adults aged ≥ 18 years. Primary payer was categorized as Medicare or non-Medicare. Survey logistic regression provided the odds of 30-day rehospitalization in RA relative to OA. We calculated the rates for principal diagnoses leading to rehospitalization. RESULTS: Overall, 3.53% of 2,190,745 index hospitalization had a 30-day rehospitalization. Patients with RA had a higher adjusted risk of rehospitalization after TKR (OR 1.11, 95% CI 1.02-1.21) and THR (OR 1.39, 95% CI 1.19-1.62). Persons with RA and OA did not differ with respect to rates of infections, cardiac events, or postoperative complications leading to the rehospitalization. After TKR, RA patients with Medicare had a lower venous thromboembolism (VTE) risk (OR 0.58, 95% CI 0.58-0.88), whereas those with RA had a greater VTE risk (OR 2.41, 95% CI 1.04-5.57) after THR. CONCLUSION: Patients with RA had a higher 30-day rehospitalization risk than OA after TKR and THR regardless of payer type. While infections, postoperative complications, and cardiac events did not differ, there was a significant difference in VTE as the principal diagnosis of rehospitalization.

An assessment of the effectiveness of hyaluronic acid and polyacrylamide hydrogel in horses with osteoarthritis: Systematic review and network meta-analysis.

For several years, hyaluronic acid (HyA) and, more recently, polyacrylamide hydrogel (PHyd) have been used to reduce lameness and pain caused by osteoarthritis. However, there is still a lack of scientific evidence of the efficacy of these substances to allow veterinary experts to make decisions about their use in horses. The objective of this study was to evaluate, through a systematic review and network meta-analysis (NMA), the efficacy of HyA, associated or not with other drugs, and PHyd in relieving lameness in horses with osteoarthritis. The searches for primary studies were conducted on four search platforms. The efficacy of HyA and PHyd was estimated through the relative risk difference method. Heterogeneity was observed in the efficacy of HyA, indicating long-term ineffectiveness of this drug when associated or not with anti-inflammatory drugs. In contrast, the results indicate that PHyd is an effective alternative therapy, with a long period of action in reducing lameness in horses with osteoarthritis. This study provides evidence that the application of PHyd and HyA is effective in reducing lameness caused by osteoarthritis in horses at different time periods, where PHyd has a longer time of action.

Voices of African American Older Adults on the Implications of Social and Healthcare-Related Policies for Osteoarthritis Pain Care.

BACKGROUND: Chronic pain is a distressing symptom that older adults with osteoarthritis (OA) seek to minimize through management. Research consistently points out the disparities that older African Americans face when managing chronic pain conditions, but a major gap in the literature is how pain care policy at the federal, state, and local level protects or exposes older African Americans to disadvantaged care. AIMS: The purpose of this original research is to examine policy issues and care enhancement opportunities that emerge from the narratives and personal stories of older African Americans living with chronic OA pain. DESIGN: A secondary qualitative data analysis. METHODS: African Americans (≥50 years) with OA pain living in Louisiana were interviewed to gather global perspectives and specific information about how they manage OA pain. Narrative analytic techniques were applied to 18 individual, semistructured interviews. RESULTS: Three policy-related pain management issues and implications surfaced from the older African Americans' rich narratives: (1) "Access to and navigation of the healthcare system," (2) "Affordability of natural supplements, medications, and treatments," and (3) "Expansion of pain palliative care and community programs." CONCLUSIONS: African American older adults face numerous challenges in managing pain well. Navigating the healthcare system is an abiding issue, and perceived injustice in care was a common thread throughout the narratives. On the positive side, older African Americans also proposed practice- and policy-related solutions to counter the pain treatment challenges. Nurses are natural advocates for patients, and should work to change healthcare policies that unfairly marginalize ethnic/racial older adults' long-term ability to manage chronic pain.

Pain severity and healthcare resource utilization in patients with osteoarthritis in the United States.

OBJECTIVE: To evaluate healthcare resource utilization (HCRU) by osteoarthritis (OA) pain severity. METHODS: Cross-sectional surveys of US physicians and their patients were conducted between February and May 2017. Using the Numeric Rating Scale, patients were classified by self-reported pain intensity in the last week into mild (0-3), moderate (4-6), and severe (7-10) cohorts. Parameters assessed included clinical characteristics, HCRU, and current caregiver support. Descriptive statistics were obtained, and analysis of variance and chi-square tests were performed. RESULTS: Patients (n = 841) were mostly female (60.9%) and white (77.8%), with mean age of 64.6 years. Patients reported mild (45.4%), moderate (35.9%), and severe (18.7%) OA pain. Mean number of affected joints varied by pain severity (range mild: 2.7 to severe: 3.6; p < 0.0001). Pain severity was associated with an increased number of physician-reported and patient-reported overall healthcare provider visits (HCPs; both p < 0.001). As pain increased, patients reported an increased need for mobility aids, accessibility modifications to homes, and help with daily activities due to functional disability. The number of imaging tests used to diagnose OA was similar across pain severity but varied when used for monitoring (X-rays: p < 0.0001; computerized tomography scans: p < 0.0447). Hospitalization rates for OA were low but were significantly associated with pain severity (mild: 4.9%; severe: 11.5%). Emergency department visits were infrequent but increasing pain severity was associated with more prior and planned surgeries. CONCLUSION: Greater current pain was associated with more prior HCRU including imaging for monitoring progression, HCP visits including more specialty care, hospitalizations, surgery/planned surgery, and loss of independence due to functional disability. Yet rates of hospitalizations and X-ray use were still sizable even among patients with mild pain. These cross-sectional findings warrant longitudinal assessment to further elucidate the impact of pain on HCRU.

Emerging pharmaceutical therapies for osteoarthritis.

The prevalence of osteoarthritis (OA) and the burden associated with the disease are steadily increasing worldwide, representing a major public health challenge for the coming decades. The lack of specific treatments for OA has led to it being recognized as a serious disease that has an unmet medical need. Advances in the understanding of OA pathophysiology have enabled the identification of a variety of potential therapeutic targets involved in the structural progression of OA, some of which are promising and under clinical investigation in randomized controlled trials. Emerging therapies include those targeting matrix-degrading proteases or senescent chondrocytes, promoting cartilage repair or limiting bone remodelling, local low-grade inflammation or Wnt signalling. In addition to these potentially disease-modifying OA drugs (DMOADs), several targets are being explored for the treatment of OA-related pain, such as nerve growth factor inhibitors. The results of these studies are expected to considerably reshape the landscape of OA management over the next few years. This Review describes the pathophysiological processes targeted by emerging therapies for OA, along with relevant clinical data and discussion of the main challenges for the further development of these therapies, to provide context for the latest advances in the field of pharmaceutical therapies for OA.

Diagnosis and management of osteoporosis in postmenopausal women in Gulf Cooperation Council (GCC) countries: consensus statement of the GCC countries' osteoporosis societies under the auspices of the European Society for Clinical and Economic Aspects of Osteoporosis and Osteoarthritis (ESCEO).

A consensus platform is provided by the experts of the Gulf Cooperation Council (GCC) countries' respective osteoporosis societies, on which specific guidelines can be developed further for regional use on the assessment and treatment of postmenopausal women at risk from fractures due to osteoporosis. INTRODUCTION: Guidance is provided in a Gulf Cooperation Council (GCC) country setting on the assessment and treatment of postmenopausal women at risk from fractures due to osteoporosis, which is an adaptation of the European guidance by Kanis et al., jointly published by the International Osteoporosis Foundation and the European Society for Clinical and Economic Aspects of Osteoporosis and Osteoarthritis (ESCEO). The respective osteoporosis societies of the Gulf Cooperation Council (GCC) countries assembled for a unifying consensus on the diagnosis and management of osteoporosis in postmenopausal women for the region. METHODS: The Chair for Biomarkers of Chronic Diseases (CBCD) in King Saud University (KSU), Riyadh, Kingdom of Saudi Arabia (KSA), in cooperation with the Saudi Osteoporosis Society (SOS), hosted regional experts and respective leaders from different GCC osteoporosis societies, together with an adviser from the ESCEO. An assembly of experts representing the different osteoporosis societies from Saudi Arabia, the UAE, Bahrain, Oman, and Kuwait gathered on February 15-16, 2019 in Riyadh, KSA for the formulation of a general osteoporosis consensus for the region. RESULTS: The following areas were covered: diagnosis of osteoporosis and assessment of fracture risk; general and pharmacological management of osteoporosis; and hip fractures, vitamin D, recommendation on which FRAX tool to follow, and the importance of country-specific FRAX® and fracture liaison services for secondary fracture prevention. CONCLUSIONS: A platform is provided on which specific guidelines can be developed for regional use in GCC.

Assessment of structural lesions, synovitis and bone marrow lesions in erosive hand osteoarthritis on MRI (0.3T) compared to the radiographic anatomical Verbruggen-Veys score.

OBJECTIVE: To evaluate prevalence of structural lesions, synovitis and bone marrow lesions (BMLs) on MRI performed with a 0.3T imaging system in patients with erosive hand osteoarthritis (EHOA) and to compare them to the anatomic radiographic Verbruggen-Veys score (VV). DESIGN: For this Cross-sectional study, fifty-five EHOA patients were studied with 0.3T contrast-enhanced MRI and radiography (RX) of their dominant hand. Structural lesions were scored according to the OMERACT Hand Osteoarthritis MRI Scoring System as follows: osteophytes and erosions were graded from 0 to 3. On joint destruction lesion synovitis and BMLs were graded from 0 to 1. And on MRI, we evaluated the presence of several structural features: N: normal, O: osteophytic lesions, E: erosive lesions, E/O: osteophytic and erosive lesions and D: joint destruction. RX was scored according to the VV system. Relations between MRI features and VV stages were analysed. RESULTS: MRI identified more structural lesions than RX (77.3% versus 74.8%) and particularly more erosive lesions (E or E/O) than VV Phase E (33.5% versus 20.2%). E/O and D were mostly found on MRI. Synovitis and BMLs were significantly associated with E/O and D with the following odds ratios (ORs): 8.4 (95% CI 1.8-13.6); OR: 13.7 (95% CI 2.9-21.0); OR: 15.7 (95% CI 3.2-23.5); OR: 38.5 (95% CI 9.5-57.0), respectively. CONCLUSION: MRI 0.3T appears completely relevant for EHOA lesion analysis. First, MRI shows more erosive lesions than RX in EHOA; second, it allows for the analysis of synovitis and BMLs to be associated with more specific structural MRI features (E/O and D).

The Association of Osteoarthritis and Related Pain Burden to Incident Alzheimer's Disease and Related Dementias: A Retrospective Cohort Study of U.S. Medicare Beneficiaries.

BACKGROUND: Emerging evidence suggests osteoarthritis (OA) and related symptom burden may increase risk for Alzheimer's disease and related dementias (ADRD). However, longitudinal studies are sparse, and none have examined the potential mediating effects of mood or sleep disorders. OBJECTIVE: To determine the association of OA and related pain to incident ADRD in U.S. elders. METHODS: In this retrospective cohort study, we used baseline and two-year follow-up data from linked Medicare claims and Medicare Current Beneficiary Survey files (11 pooled cohorts, 2001-2013). The study sample comprised 16,934 community-dwelling adults≥65 years, ADRD-free at baseline and enrolled in fee-for-service Medicare. Logistic regression was used to assess the association of OA and related pain (back, neck, joint, neuropathic) to incident ADRD, explore the mediating inlfuence of mood and insomnia-related sleep disorders, and (sensitivity analyses) account for potential survival bias. RESULTS: Overall, 25.5% of beneficiaries had OA at baseline (21.0% with OA and pain); 1149 elders (5.7%) were subsequently diagnosed with ADRD. Compared to beneficiaries without OA, those with OA were significantly more likely to receive a diagnosis of incident ADRD after adjustment for sociodemographics, lifestyle characteristics, comorbidities, and medications (adjusted odds ratio (AOR) = 1.23 (95% confidence interval (CI) 1.06, 1.42). Elders with OA and pain at baseline were significantly more likely to be diagnosed with incident ADRD than were those without OA or pain (AOR = 1.31, CI 1.08, 1.58). Sensitivity analyses yielded similar findings. Inclusion of depression/anxiety, but not sleep disorders, substantially attenuated these associations. CONCLUSION: Findings of this study suggest that: OA is associated with elevated ADRD risk, this association is particularly pronounced in those with OA and pain, and mood disorders may partially mediate this relationship.

Current diagnosis-related group-based bundling for upper-extremity arthroplasty: a case of insufficient risk adjustment and misaligned incentives.

BACKGROUND: The current Centers for Medicare & Medicaid Services diagnosis-related group (DRG) bundled-payment model for upper-extremity arthroplasty does not differentiate between the type of arthroplasty (anatomic total shoulder arthroplasty [ATSA] vs. reverse total shoulder arthroplasty vs. total elbow arthroplasty [TEA] vs. total wrist arthroplasty) or the diagnosis and indication for surgery (fracture vs. degenerative osteoarthritis vs. inflammatory arthritis). METHODS: The 2011-2014 Medicare 5% Standard Analytical Files (SAF5) database was queried to identify patients undergoing upper-extremity arthroplasty under DRG-483 and -484. Multivariate linear regression modeling was used to assess the marginal cost impact of patient-, procedure-, diagnosis-, and state-level factors on 90-day reimbursements. RESULTS: Of 6101 patients undergoing upper-extremity arthroplasty, 3851 (63.1%) fell under DRG-484 and 2250 (36.9%) were classified under DRG-483. The 90-day risk-adjusted cost of an ATSA for degenerative osteoarthritis was $14,704 ± $655. Patient-level factors associated with higher 90-day reimbursements were male sex (+$777), age 75-79 years (+$740), age 80-84 years (+$1140), and age 85 years or older (+$984). Undergoing a TEA (+$2175) was associated with higher reimbursements, whereas undergoing a shoulder hemiarthroplasty (-$1000) was associated with lower reimbursements. Surgery for a fracture (+$2354) had higher 90-day reimbursements. Malnutrition (+$10,673), alcohol use or dependence (+$6273), Parkinson disease (+$4892), cerebrovascular accident or stroke (+$4637), and hyper-coagulopathy (+$4463) had the highest reimbursements. In general, states in the South and Midwest had lower 90-day reimbursements associated with upper-extremity arthroplasty. CONCLUSIONS: Under the DRG-based model piloted by the Centers for Medicare & Medicaid Services, providers and hospitals would be reimbursed the same amount regardless of the type of surgery (ATSA vs. hemiarthroplasty vs. TEA), patient comorbidity burden, and diagnosis and indication for surgery (fracture vs. degenerative pathology), despite each of these factors having different resource utilization and associated reimbursements. Lack of risk adjustment for fracture indications leads to strong financial disincentives within this model.

Efficacy assessment of radiosynoviorthesis on the progression of radiological osteoarthritic features of hip and ankle joint in patients with osteoarthritis and rheumatoid arthritis.

OBJECTIVE: The study objective was to evaluate the long-term effect of radiosynoviorthesis (RSO) on the progression of radiological and nuclear-medical osteoarthritic features of hip and ankle joint in patients with osteoarthritis and rheumatoid arthritis. PATIENTS AND METHODS: The study included 89 hip joints of 81 patients, of which 48 had osteoarthritis (OA) and 33 had rheumatoid arthritis (RA). In terms of ankle joints, 64 patients were included of which 43 suffered from OA and 21 from RA. The mean follow-up time was 9.2 years for OA and 8.9 years for RA patients. Patients with RA were the active control group. Structural alterations of the hip joints were evaluated following Kellgren-Lawrence score and of ankle joint following Takakura score for both disease entities. For the evaluation of synovitis 2-phase bone scintigraphy was performed. RESULTS: RSO could prevent radiologic status deterioration among 70.6 % of hip osteoarthritic patients and 73.7 % among the hip RA patients. No structural progression was observed in 79.1 % of the treated ankle joints in patients with OA and in 85.7 % of the ankle joints in patients with RA.The scintigraphic response rate for the hip joints of OA patients was 68.6 %, 76.3 % for hip joints of RA patients, 83.1 %, ankle joints of OA patients, and 90.4 % ankle joints of RA patients.The radiographic and scintigraphic RSO response rates were not significantly higher for both joints in RA than OA patients. CONCLUSION: RSO can be a good alternative in the treatment of synovitis and prevention of deterioration of inflammatory and radiographic features even in patients suffering from osteoarthritis and rheumatoid arthritis. RSO may have also a long-term effect to stop or delay progression of both diseases.