Pharmaceutical treatment of osteoarthritis.

OBJECTIVE: To review the current state of pharmaceutical treatment recommendations for the management of osteoarthritis. METHOD: A narrative review was drafted to describe treatment guidelines, mechanism of action, pharmacokinetics, and toxicity for nine classes of pharmaceuticals: 1) oral nonsteroidal anti-inflammatory drugs (NSAIDs), 2) topical NSAIDs, 3) COX-2 inhibitors, 4) duloxetine, 5) intra-articular corticosteroids, 6) intra-articular hyaluronic acid, 7) acetaminophen (paracetamol), 8) tramadol, and 9) capsaicin. RESULTS: In general, oral and topical NSAIDs, including COX-2 inhibitors, are strongly recommended first-line treatments for osteoarthritis due to their ability to improve pain and function but are associated with increased risks in patients with certain comorbidities (e.g., heightened cardiovascular risks). Intra-articular corticosteroid injections are generally recommended for osteoarthritis management and have relatively minor adverse effects. Other treatments, such as capsaicin, tramadol, and acetaminophen, are more controversial, and many updated guidelines offer differing recommendations. CONCLUSION: The pharmaceutical management of osteoarthritis is a constantly evolving field. Promising treatments are emerging, and medicines that were once considered conventional (e.g., acetaminophen) are gradually becoming less acceptable based on concerns with efficacy and safety. Clinicians need to consider the latest evidence and recommendations to make an informed decision with their patients about how to optimize treatment plans for patients with knee, hip, polyarticular, or hand osteoarthritis.

Excessive alcohol consumption and the risk of knee osteoarthritis: a prospective study from the Osteoarthritis Initiative.

OBJECTIVE: To examine the association of alcohol consumption with risk of incident knee osteoarthritis (OA) in a large prospective cohort study. DESIGN: In the Osteoarthritis Initiative, 2,846 participants aged 45-79 years and free from radiographic knee OA in at least one knee at baseline were followed up to 96 months. Information on baseline alcohol consumption was obtained from the Block Brief Food Frequency Questionnaire. Incident cases of radiographic knee OA (ROA) were defined as Kellgren-Lawrence grade changing from zero or one to ≥ two during the follow-up time. Incident symptomatic OA (SxOA) was defined as ROA with knee pain worsening. The Cox proportional hazards models were used to assess the independent association between alcohol consumption and risk of knee. RESULTS: During 96 months' follow-up, we identified 691 knees with incident ROA, and 496 knees with incident SxOA among 2,846 subjects. Compared to non-drinkers, excessive alcohol consumption was significantly associated with increased risk of ROA (HR ≥ 30  g/d vs none = 1.93, 95% CI: 1.28-2.89) and SxOA (HR ≥ 30 g/d vs none = 1.61, 95% CI: 1.04-2.48). Similar association was observed for liquor consumption (HR liquor≥15 g/d vs none = 1.71, 95% CI: 1.16-2.52 for ROA; HR liquor≥15 g/d vs none = 1.59, 95% CI: 1.04-2.39 for SxOA). Light to moderate alcohol consumption was not associated with knee OA risk. CONCLUSION: Our results suggest that excessive alcohol drinking was associated with an increased risk of knee OA. Further studies are needed in other populations.

Dietary patterns and risk of developing knee osteoarthritis: data from the osteoarthritis initiative.

OBJECTIVE: Some studies have examined the association between dietary factors and risk of knee osteoarthritis (OA). We aimed to examine the prospective association of major dietary patterns with the risk of developing knee OA. METHOD: We followed 2,842 participants in Osteoarthritis Initiative (OAI) aged 45-79 years and with at least one knee free from radiographic knee OA at baseline for up to 72 months. We defined knee OA incidence as Kellgren and Lawrence grade ≥2 during follow-up visits. Using principal component analysis, Western and prudent dietary patterns were derived. Cox proportional hazards models were used to assess the association between dietary patterns and incident knee OA. RESULTS: Among study participants, 385 (418 knees) developed knee OA within 72 months. Following a Western dietary pattern was associated with an increased risk of knee OA (HR quartile 4 vs 1 = 1.69, 95% CI: 1.13 to 2.52, p trend: 0.03), while adherence to the prudent pattern was associated with a reduced risk of knee OA (HR quartile 4 vs 1 = 0.70, 95% CI: 0.50 to 0.98, p trend: 0.05). The observed associations attenuated after additionally adjusting for body mass index (BMI). The observed associations were mediated through BMI by approximately 30%. CONCLUSION: Following a Western diet was associated with increased risk of knee OA, whereas following a prudent pattern was associated with a reduced risk of knee OA. The associations were partially mediated through BMI.

Pain and functional trajectories in symptomatic knee osteoarthritis over up to 12 weeks of exercise exposure.

OBJECTIVE: Exercise is the recommended treatment for knee osteoarthritis (OA). However, heterogeneous patterns in treatment response are poorly understood. Our purpose was to identify pain and functional trajectories from exercise interventions in knee OA, and to determine their association with baseline factors. METHODS: Prospective cohort of 171 participants (mean age 61 years; BMI 32 kg/m2, 71% female; 57% white) with symptomatic knee OA from a randomized trial comparing 12-week Tai Chi and Physical Therapy. We analyzed weekly Western Ontario and McMaster Osteoarthritis Index (WOMAC) pain (0-500) and function (0-1700) scores using group-based trajectory models. Associations between baseline factors and trajectories were examined using multinomial logistic regression. RESULTS: We identified four pain trajectories: Lower-Early Improvement (43%), Moderate-Early Improvement (32%), Higher-Delayed Improvement (15%), and Higher-No Improvement (10%). We found similar trajectories for function, except that the lower function trajectories diverged into gradual (12%) or delayed-improvement (15%). Compared with the Lower-Early Improvement pain trajectory, moderate and higher trajectories were associated with poorer physical and psychosocial health. A similar pattern of associations were found among the function trajectories. CONCLUSIONS: We found four distinct trajectories for pain and function over up to 12-weeks of exercise interventions. While most participants experienced improvements over a short-term exposure, subgroups with greater baseline pain/physical disability had either gradual, delayed, or no improvements. These findings help disentangle the heterogeneity of treatment response and may advance patient-centered care in knee OA.

Patterns of intra-articular injection use after initiation of treatment in patients with knee osteoarthritis: data from the osteoarthritis initiative.

OBJECTIVE: We sought to describe and evaluate longitudinal use of intra-articular injections after treatment initiation among adults with radiographically confirmed knee osteoarthritis (OA). METHOD: Using data from the Osteoarthritis Initiative (OAI), we included participants with radiographically confirmed OA (Kellgren-Lawrence grade (K-L) ≥ 2) in ≥1 knee at baseline. With 9 years of data, 412 participants newly initiating hyaluronic acid or corticosteroid injections with their index visit were identified. For each type of injection initiated, socio-demographic and clinical characteristics were described by patterns of treatments (one-time use, switched, or continued injections). Multinomial logistic models estimated the extent to which patient-reported symptoms (post-initial injection and changes over time) were associated with patterns of injection use. RESULTS: Of those initiating injections, ∼19% switched, ∼21% continued injection type, and ∼60% did not report any additional injections. For participants initiating corticosteroid injections, greater symptoms post-initial injection were associated with lower odds of continued use compared to one-time users (adjusted odds ratio (aOR) for Western Ontario and McMaster Universities Arthritis Index (WOMAC) pain: 0.91; 95%, confidence interval (CI): 0.83 to 0.99; aORstiffness: 0.77; CI: 0.63 to 0.94; aORphysical function: 0.97; CI: 0.94 to 1.00). Symptom changes over time (e.g., worsened or improved) were not associated with patterns of injections use. CONCLUSION: After treatment initiation, the proportion of patients switching injection use and one-time users was substantial. Symptoms post-initial injection appear to be associated with patterns of injection use. The extent to which these patterns are an indication of lack of impact on patient-reported symptoms should be explored.

The relationship between meniscal pathology and osteoarthritis depends on the type of meniscal damage visible on magnetic resonance images: data from the Osteoarthritis Initiative.

OBJECTIVE: To determine the association of different types of meniscal pathology with knee pain, bone marrow lesion (BML) volume, and end-stage knee osteoarthritis (esKOA). DESIGN: Participants were selected from an ancillary project to the Osteoarthritis Initiative (OAI) who had at least one knee with symptomatic osteoarthritis. Baseline magnetic resonance images (MRI) were evaluated for meniscal pathology using a modified International Society of Arthroscopy, Knee Surgery, and Orthopaedic Sports Medicine (ISAKOS) classification system. We collapsed 10 types of meniscal pathology into five categories: normal, intrameniscal signal, morphological deformity/extrusion (altered meniscal shape and/or extrusion but no apparent substance loss), tear, and maceration. Outcomes included Western Ontario and McMaster Universities osteoarthritis index (WOMAC) knee pain and BML volume at baseline and after 2 years. We defined the prevalence of esKOA based on a validated algorithm. We performed logistic regression and adjusted for age, sex, and body mass index (BMI). RESULTS: The 463 participants (53% male) included in the analysis had mean age 63 (9.2) years, BMI 29.6 (4.6) kg/m2, and 71% had Kellgren-Lawrence grade ≥2. Morphological deformity/extrusion and maceration, but no other types of meniscal pathology, were associated with BML volume (morphological deformity/extrusion odds ratio [OR] = 2.47, 95% CI: 1.49, 4.09, maceration OR = 5.85, 95% CI: 3.40, 10.06) and change in BML volume (morphological deformity/extrusion OR = 2.17, 95% CI: 1.37, 3.45, maceration OR = 3.12, 95% CI: 1.87, 5.19). Only maceration was associated with baseline WOMAC knee pain (OR = 2.82, 95% CI: 1.79, 4.43) and prevalence of esKOA (OR = 7.53, 95% CI: 4.25, 13.31). CONCLUSIONS: Based on MRI, morphologic deformity/extrusion and maceration rather than intrameniscal signal or tear were associated with osteoarthritis severity and progression, which highlights the importance of differentiating distinct types of meniscal pathology.

The relationship between smoking and knee osteoarthritis in the Osteoarthritis Initiative.

OBJECTIVE: To estimate the extent that smoking history is associated with symptoms and disease progression among individuals with radiographically confirmed knee Osteoarthritis (OA). METHOD: Both cross-sectional (baseline) and longitudinal studies employed data from the Osteoarthritis Initiative (OAI) (n = 2250 participants). Smoking history was assessed at baseline with 44% current or former smokers. The Western Ontario and McMaster Universities Arthritis Index (WOMAC) was used to measure knee pain, stiffness, and physical function. Disease progression was measured using joint space width (JSW). We used adjusted multivariable linear models to examine the relationship between smoking status and exposure in pack years (PY) with symptoms and JSW at baseline. Changes in symptoms and JSW over time were further assessed. RESULTS: In cross-sectional analyses, compared to never-smokers high PY (≥15 PY) was associated with slightly greater pain (beta 0.36, 95% CI: 0.01-0.71) and stiffness (beta 0.20, 95% CI: 0.03-0.37); and low PY (<15 PY) was associated with better JSW (beta 0.15, 95% CI: 0.02-0.28). Current smoking was associated with greater pain (beta 0.59, 95% CI: 0.04-1.15) compared to never-smokers. These associations were not confirmed in the longitudinal study. Longitudinally, no associations were found between high or low PY or baseline smoking status with changes in symptoms (at 72 months) or JSW (at 48 months). CONCLUSION: Cross-sectional findings are likely due residual confounding. The more robust longitudinal analysis found no associations between smoking status and symptoms or JSW. Long-term smoking provides no benefits to knee OA patients while exposing them to other well-documented serious health risks.

OARSI Clinical Trials Recommendations: Design, conduct, and reporting of clinical trials for knee osteoarthritis.

The goal of this document is to update the original OARSI recommendations specifically for the design, conduct, and reporting of clinical trials that target symptom or structure modification among individuals with knee osteoarthritis (OA). To develop recommendations for the design, conduct, and reporting of clinical trials for knee OA we initially drafted recommendations through an iterative process. Members of the working group included representatives from industry and academia. After the working group members reviewed a final draft, they scored the appropriateness for recommendations. After the members voted we calculated the median score among the nine members of the working group who completed the score. The document includes 25 recommendations regarding randomization, blocking and stratification, blinding, enhancing accuracy of patient-reported outcomes (PRO), selecting a study population and index knee, describing interventions, patient-reported and physical performance measures, structural outcome measures, biochemical biomarkers, and reporting recommendations. In summary, the working group identified 25 recommendations that represent the current best practices regarding clinical trials that target symptom or structure modification among individuals with knee OA. These updated recommendations incorporate novel technologies (e.g., magnetic resonance imaging (MRI)) and strategies to address the heterogeneity of knee OA.

Osteoarthritis-related biomarkers following anterior cruciate ligament injury and reconstruction: a systematic review.

OBJECTIVE: There is an increased risk of developing knee osteoarthritis (OA) following anterior cruciate ligament (ACL) injury. Biomarkers may provide diagnostic, prognostic, or burden of disease indicators of OA before radiographic changes become apparent. Unfortunately, there has been no systematic review to clarify which biomarkers may be most informative following injury. Therefore, this review critically investigated existing studies of OA-related biomarkers in ACL-deficient (ACL-D) and reconstructed (ACL-R) patients to summarize the current evidence and identify knowledge gaps. DESIGN: A systematic review of the literature in Web of Science and PubMed databases (1960-June 2014) was performed. All English-language case-control and longitudinal studies assessing OA-related biomarkers in ACL-D and ACL-R patients were considered. Data regarding biomarker changes over time within ACL-D and ACL-R patients as well as differences in ACL-D/ACL-R patients compared with a control group were extracted from pertinent studies. RESULTS: A descriptive summary of 20 included studies was produced. In ACL-D patients compared with controls, synovial fluid biomarkers indicated elevated collagen turnover, while the inflammatory cytokine response was inconclusive. In ACL-R patients, serum concentrations indicated decreased collagen breakdown, but urine concentrations were indicative of greater collagen breakdown when compared to controls. Compared to preoperative values, the overall inflammatory cytokine response measured with synovial fluid biomarkers increased while plasma biomarkers did not change following reconstruction. CONCLUSION: Patients with ACL-D or ACL-R have altered biomarkers indicative of OA. More research with standardized reporting is needed to effectively determine which biomarkers are the most indicative for OA development and progression following ACL injury.

Bone marrow lesions are associated with altered trabecular morphometry.

OBJECTIVE: Bone marrow lesions (BMLs) are a common magnetic resonance (MR) feature in patients with osteoarthritis, however their pathological basis remains poorly understood and has not been evaluated in vivo. Our aim was to evaluate the trabecular structure associated with the presence and size of BMLs present in the same regions of interest (ROI) using quantitative MR-based trabecular morphometry. DESIGN: 158 participants in the Osteoarthritis Initiative (OAI) were imaged with a coronal 3D fast imaging with steady state precession (FISP) sequence for trabecular morphometry in the same session as the OAI 3 T MR knee evaluation. The proximal medial tibial subchondral bone in the central weight-bearing ROI on these knee 3D FISP images were quantitatively evaluated for apparent bone volume fraction, trabecular number, spacing, and thickness. BMLs were also evaluated in the subchondral bone immediately adjacent to the articular cartilage. BML volume was also evaluated within the same trabecular morphometry ROI and semi-quantitatively classified as none, small, or large. Kruskal-Wallis test was used to determine if mean apparent bone volume fraction, trabecular number, spacing, or thickness differed by BML score. RESULTS: Compared to knees with ROIs containing no BMLs, knees with small or large BMLs had statistically higher apparent bone volume fraction (P < 0.01), trabecular number (P < 0.01), and thickness (P = 0.02), and lower trabecular spacing (P < 0.01). CONCLUSIONS: Compared to knees with ROIs containing no BMLs, knees with ROIs containing small or large BMLs had higher apparent bone volume fraction, trabecular number and thickness, but lower trabecular spacing. These findings may represent areas of locally increased bone remodeling or compression.

Cross-sectional DXA and MR measures of tibial periarticular bone associate with radiographic knee osteoarthritis severity.

OBJECTIVE: We evaluated the relationship of medial proximal tibial periarticular areal bone mineral density (paBMD) and trabecular morphometry and determined whether these bone measures differed across radiographic medial joint space narrowing (JSN) scores. METHODS: 482 participants of the Osteoarthritis Initiative (OAI) Bone Ancillary Study had knee dual X-ray absorptiometry (DXA) and trabecular bone 3T magnetic resonance imaging (MRI) exams assessed at the same visit. Medial proximal tibial paBMD was measured on DXA and apparent trabecular bone volume fraction (aBV/TV), thickness (aTb.Th), number (aTb.N), and spacing (aTb.Sp) were determined from MR images. Radiographs were assessed for medial JSN scores (0-3). We evaluated associations between medial paBMD and trabecular morphometry. Whisker plots with notches of these measures versus medial JSN scores were generated and presented. RESULTS: Mean age was 63.9 (9.2) years, BMI 29.6 (4.8) kg/m(2), and 53% were male. The Spearman correlation coefficients between DXA-measured medial paBMD and aBV/TV was 0.61 [95% confidence interval (CI) 0.55-0.66]; between paBMD and aTb.Th was 0.38 (95%CI 0.30-0.46); paBMD and aTb.N was 0.65 (95%CI 0.60-0.70); paBMD and aTb.Sp was -0.65 (95%CI -0.70 to -0.59). paBMD and the trabecular metrics were associated with medial JSN scores. CONCLUSION: The moderate associations between periarticular trabecular bone density and morphometry and their relationship with greater severity of knee OA support hypotheses of remodeling and/or microscopic compression fractures in the natural history of OA. Longitudinal studies are needed to assess whether knee DXA will be a predictor of OA progression. Further characterization of the periarticular bone in OA utilizing complementary imaging modalities will help clarify OA pathophysiology.

Osteoarthritis year 2011 in review: clinical.

The purpose of this narrative year in review of clinical studies was to highlight a few publications related to obesity and weight loss, physical activity, and synovitis as well as disease modifying interventions that were published between September 2010 and September 2011. This year clinical research highlighted the extent to which obesity and osteoarthritis (OA) are impacting quality of life among adults in the United States and that reducing excessive body weight or becoming more physically active may be beneficial. In addition to weight loss and physical activity and synovitis, research over the past year has highlighted the diverse methods being pursued for structural modification interventions. In addition to chondroitin sulfate there were interesting preliminary findings that meniscal implants and joint distractions may modify OA progression.

Characterization of posture and comfort in laptop users in non-desk settings.

Laptop computers may be used in a variety of postures not coupled to the office workstation. Using passive motion analysis, this study examined mean joint angles during a short typing/editing task in college students (n=20), in up to seven positions. Comfort was assessed after task execution through a body map. For three required postures, joint angles in a prone posture were different than those while seated at a couch with feet either on floor or on ottoman. Specifically, the prone posture was characterized by comparatively non-neutral shoulders, elbows and wrists, and pronounced neck extension. Significantly greater intensity and more regions of discomfort were marked for the prone posture than for the seated postures. It is recommended that the prone posture only be assumed briefly during laptop use. Exposure to laptops outside of the office setting should be assessed in future epidemiologic studies of musculoskeletal complaints and computer use.

Postures, typing strategies, and gender differences in mobile device usage: an observational study.

Mobile device text messaging and other typing is rapidly increasing worldwide. A checklist was utilized to characterize joint postures and typing styles in individuals appearing to be of college age (n = 859) while typing on their mobile devices in public. Gender differences were also ascertained. Almost universally, observed subjects had a flexed neck (91.0%, n = 782), and a non-neutral typing-side wrist (90.3%, n = 776). A greater proportion of males had protracted shoulders (p < 0.01, χ(2) test), while a greater proportion of females had a typing-side inner elbow angle of <90°, particularly while standing (p = 0.03, χ(2) test). 46.1% of subjects typed with both thumbs (two hands holding the mobile device). Just over one-third typed with their right thumb (right hand holding the mobile device). No difference in typing styles between genders was found. Future research should determine whether the non-neutral postures identified may be associated with musculoskeletal disorders.