Developments in the clinical understanding of osteoarthritis

With the recognition that osteoarthritis is a disease of the whole joint, attention has focused increasingly on features in the joint environment which cause ongoing joint damage and are likely sources of pain. This article reviews current ways of assessing osteoarthritis progression and what factors potentiate it, structural abnormalities that probably produce pain, new understandings of the genetics of osteoarthritis, and evaluations of new and old treatments

A surplus of positive trials: weighing biases and reconsidering equipoise

In this issue, Fries and Krishnan raise provocative new ideas to explain the surfeit of positive industry sponsored trials evaluating new drugs. They suggest that these trials were designed after so much preliminary work that they were bound to be positive (design bias) and that this violates clinical equipoise, which they characterize as an antiquated concept that should be replaced by a focus on subject autonomy in decision making and expected value for all treatments in a trial. We contend that publication bias, more than design bias, could account for the remarkably high prevalence of positive presented trials. Furthermore, even if all new drugs were efficacious, given the likelihood of type 2 errors, not all trials would be positive. We also suggest that clinical equipoise is a nuanced concept dependent on the existence of controversy about the relative value of two treatments being compared. If there were no controversy, then trials would be both unnecessary and unethical. The proposed idea of positive expected value is intriguing, but in the real world such clearly determinable values do not exist. Neither is it clear how investigators and sponsors, who are invested in the success of a proposed therapy, would (or whether they should) develop such a formula

Can health care databases be used to identify incident cases of osteonecrosis?

INTRODUCTION. Osteonecrosis (ON) is a rare disease associated with alcohol and glucocorticoid use. Identifying additional risk factors is difficult as the number of cases at any single center is small. We investigated whether data available in large health care databases can be used to identify incident ON cases. METHODS. Using data from the Boston Veterans Affairs Healthcare system, we identified potential cases of ON. These records, including available radiographs and reports, were reviewed. Using published criteria, we evaluated whether the subjects had confirmed ON (radiographs/reports met criteria), incident ON (onset of symptoms within 6 months of first code), or prevalent ON (onset more than 6 months prior to first code or onset could not be determined). We tested different definitions for incident ON using information derived from administrative data. These were compared to the 'gold standard' (record review) and positive predictive values (PPVs) were derived. Since PPVs for incident cases were low, we found the number of incident cases expected for every 1,000 potential cases identified, using the definitions as an initial screening tool to reduce the number of medical records that required examination. RESULTS. We identified 87 potential cases. No case of jaw ON was identified. Only 15 (17%) incident cases of ON were identified. PPVs never exceed 50% for incident ON. However, if we used the definition '(at least 1 inpatient ON code) and (no prior codes for osteoarthritis)' as an initial screen, then for every 1,000 records, we would need to review only 150 to find 69 incident cases. CONCLUSIONS. Though the precise PPVs we found may not be generalizable to other databases, we believe that administrative data alone should not be used to identify incident cases of ON without confirming the diagnosis through a review of medical records. By applying the above definition, the number of records requiring review can be markedly reduced. This method can be used to find cases for valid case-control studies of risk factors for ON.National Institutes of Health (AR47785, AR07598); Arthritis Foundation Postdoctoral Fellowshi

Rheumatoid arthritis as underlying cause of death in 31 countries, 1987-2011: Trend analysis of WHO mortality database

Objective To examine trends in rheumatoid arthritis (RA) as an underlying cause of death (UCD) in 31 countries across the globe during 1987-2011. Methods Data on mortality and population were collected from the World Health Organization mortality database and the United Nations. Age-standardized mortality rates (ASMR) were calculated by means of direct standardization. We applied joinpoint regression analysis for trend analysis. Between-country disparities were examined using between-country variance, and Gini coefficient. Due to low numbers of deaths, we smoothed our ASMR using a three-year moving average. The changes in number of RA deaths between 1987 and 2011 were decomposed using two counterfactual scenarios. Results The absolute number of deaths with RA registered as UCD declined from 9281 (0.12% of all-cause deaths) in 1987 to 8428 in 2011 (0.09% of all-cause deaths). The mean ASMR declined from 7.1/million person-years in 1987-89 to 3.7 in 2009-11 (48.2% reduction). Reduction of 25% or more in ASMR occurred in 21 countries while a corresponding increase was observed in 3 countries. There was a persistent reduction in RA mortality and, on average, the ASMR declined by 3.0% per year. The absolute and relative between-country disparities declined over the study period.CONCLUSION: Mortality rates attributable to RA have declined globally. However, there were substantial between-country disparities in RA mortality, though the disparities decreased over time. Population aging combined with fall in RA mortality may lead to an increase in the economic burden of disease that should be taken into consideration in policy-making. This article is protected by copyright. All rights reserved

The association between patellar alignment on magnetic resonance imaging and radiographic manifestations of knee osteoarthritis

The aim of our study was to evaluate the association between patellar alignment by using magnetic resonance imaging images and radiographic manifestations of patello-femoral osteoarthritis (OA). Subjects were recruited to participate in a natural history study of symptomatic knee OA. We examined the relation of patellar alignment in the sagittal plane (patellar length ratio (PLR)) and the transverse plane (sulcus angle (SA), lateral patellar tilt angle (LPTA), and bisect offset (BO)) to radiographic features of patello-femoral OA, namely joint space narrowing and patellar osteophytes, using a proportional odds logistic regression model while adjusting for age, sex, and bone mass index (BMI). The study sample consisted of 126 males (average age 68.0 years, BMI 31.2) and 87 females (average age 64.7 years, BMI 31.6), 75% of whom had tibiofemoral OA (a Kellgren-Lawrence score of 2 or more). PLR showed a statistically significant association with joint space narrowing and osteophytosis in the lateral compartment. SA showed significant association with medial joint space narrowing and with lateral and medial patellar osteophytosis. LPTA and BO showed significant association with both radiographic indices of the lateral compartment. Clear linear trends were found in association between PLR, LPTA and BO, and with outcomes associated with lateral patello-femoral OA. SA, LPTA, and BO showed linear trends of association with medial joint space narrowing. Results of our study clearly suggest the association between indices of patellar alignment and such features of patello-femoral OA as osteophytosis and joint space narrowing. Additional studies will be required to establish the normal and abnormal ranges of patellar alignment indices and their longitudinal relation to patello-femoral OA

Epidemiologic studies for osteoarthritis: new versus conventional study design approaches

Current insights into osteoarthritis epidemiology Osteoarthritis (OA) is the most common form of arthritis. Symptomatic knee OA occurs in approximately 13% of persons who are aged 60 and older Epidemiology is the study of the occurrence of disease in populations and its association with characteristics of people and their environments. Epidemiologic studies have provided much information about the occurrence of OA. Disease in the knee is common, especially among the aged; hip OA is less prevalent in most populations than disease in the knee; and for disease in the hand, radiographic OA is nearly universal in older people, whereas symptoms are less frequent. Studies have also shown that, for most joints, women who are olde

Cartilage markers and their association with cartilage loss on magnetic resonance imaging in knee osteoarthritis: the Boston Osteoarthritis Knee Study

We used data from a longitudinal observation study to determine whether markers of cartilage turnover could serve as predictors of cartilage loss on magnetic resonance imaging (MRI). We conducted a study of data from the Boston Osteoarthritis of the Knee Study (BOKS), a completed natural history study of knee osteoarthritis (OA). All subjects in the study met American College of Rheumatology criteria for knee OA. Baseline and follow-up knee magnetic resonance images were scored for cartilage loss by means of the WORMS (Whole Organ Magnetic Resonance Imaging Score) semiquantitative grading scheme. Within the BOKS population, 80 subjects who experienced cartilage loss and 80 subjects who did not were selected for the purposes of this nested case control study. We assessed the baseline levels of cartilage degradation and synthesis products by means of assays for type I and II cleavage by collagenases (Col2:3/4Cshort or C1,2C), type II cleavage only with Col2:3/4Clongmono (C2C), type II synthesis (C-propeptide), the C-telopeptide of type II (Col2CTx), aggrecan 846 epitope, and cartilage oligomeric matrix protein (COMP). We performed a logistic regression to examine the relation of levels of each biomarker to the risk of cartilage loss in any knee. All analyses were adjusted for gender, age, and body mass index (BMI); results stratified by gender gave similar results. One hundred thirty-seven patients with symptomatic knee OA were assessed. At baseline, the mean (standard deviation) age was 67 (9) years and 54% were male. Seventy-six percent of the subjects had radiographic tibiofemoral OA (Kellgren & Lawrence grade of greater than or equal to 2) and the remainder had patellofemoral OA. With the exception of COMP, none of the other biomarkers was a statistically significant predictor of cartilage loss. For a 1-unit increase in COMP, the odds of cartilage loss increased 6.09 times (95% confidence interval [CI] 1.34 to 27.67). After the analysis of COMP was adjusted for age, gender, and BMI, the risk for cartilage loss was 6.35 (95% CI 1.36 to 29.65). Among subjects with symptomatic knee OA, a single measurement of increased COMP predicted subsequent cartilage loss on MRI. The other biochemical markers of cartilage synthesis and degradation do not facilitate prediction of cartilage loss. With the exception of COMP, if changes in cartilage turnover in patients with symptomatic knee OA are associated with cartilage loss, they do not appear to affect systemic biomarker levels

A Functional Difficulty and Functional Pain Instrument for Hip and Knee Osteoarthritis

Introduction: The objectives of this study were to develop a functional outcome instrument for hip and knee osteoarthritis research (OA-FUNCTION-CAT) using item response theory (IRT) and computer adaptive test (CAT) methods and to assess its psychometric performance compared to the current standard in the field. Methods: We conducted an extensive literature review, focus groups, and cognitive testing to guide the construction of an item bank consisting of 125 functional activities commonly affected by hip and knee osteoarthritis. We recruited a convenience sample of 328 adults with confirmed hip and/or knee osteoarthritis. Subjects reported their degree of functional difficulty and functional pain in performing each activity in the item bank and completed the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC). Confirmatory factor analyses were conducted to assess scale uni-dimensionality, and IRT methods were used to calibrate the items and examine the fit of the data. We assessed the performance of OA-FUNCTION-CATs of different lengths relative to the full item bank and WOMAC using CAT simulation analyses. Results: Confirmatory factor analyses revealed distinct functional difficulty and functional pain domains. Descriptive statistics for scores from 5-, 10-, and 15-item CATs were similar to those for the full item bank. The 10-item OA-FUNCTION-CAT scales demonstrated a high degree of accuracy compared with the item bank (r = 0.96 and 0.89, respectively). Compared to the WOMAC, both scales covered a broader score range and demonstrated a higher degree of precision at the ceiling and reliability across the range of scores. Conclusions: The OA-FUNCTION-CAT provided superior reliability throughout the score range and improved breadth and precision at the ceiling compared with the WOMAC. Further research is needed to assess whether these improvements carry over into superior ability to measure change

Leg-length inequality is not associated with greater trochanteric pain syndrome

INTRODUCTION. Greater trochanteric pain syndrome (GTPS) is a common condition, the pathogenesis of which is incompletely understood. Although leg-length inequality has been suggested as a potential risk factor for GTPS, this widely held assumption has not been tested. METHODS. A cross-sectional analysis of greater trochanteric tenderness to palpation was performed in subjects with complaints of hip pain and no signs of hip osteoarthritis or generalized myofascial tenderness. Subjects were recruited from one clinical center of the Multicenter Osteoarthritis Study, a multicenter population-based study of community-dwelling adults aged 50 to 79 years. Diagnosis of GTPS was based on a standardized physical examination performed by trained examiners, and technicians measured leg length on full-limb anteroposterior radiographs. RESULTS. A total of 1,482 subjects were eligible for analysis of GTPS and leg length. Subjects' mean ± standard deviation age was 62.4 ± 8.2 years, and 59.8% were female. A total of 372 lower limbs from 271 subjects met the definition for having GTPS. Leg-length inequality (difference ≥ 1 cm) was present in 37 subjects with GTPS and in 163 subjects without GTPS (P = 0.86). Using a variety of definitions of leg-length inequality, including categorical and continuous measures, there was no association of this parameter with the occurrence of GTPS (for example, for ≥ 1 cm leg-length inequality, odds ratio = 1.17 (95% confidence interval = 0.79 to 1.73)). In adjusted analyses, female sex was significantly associated with the presence of GTPS, with an adjusted odds ratio of 3.04 (95% confidence interval = 2.07 to 4.47). CONCLUSION. The present study found no evidence to support an association between leg-length inequality and greater trochanteric pain syndrome.National Institutes of Health and National Institute of Child Health and Human Development (5K12HD001097-08); National Insititues of Health and National Institue on Aging (1 U01 AG18832; 1 U01 AG18820; 1 U01 AG19069, 1 U01 AG18947