L.S. Lohmander

Knee injury and Osteoarthritis Outcome Score (KOOS) ‐ validation of a Swedish version

The Knee injury and Osteoarthritis Outcome Score (KOOS) is a self‐administered instrument measuring outcome after knee injury at impairment, disability, and handicap level in five subscales. Reliability, validity, and responsiveness of a Swedish version was assessed in 142 patients who underwent arthroscopy because of injury to the menisci, anterior cruciate ligament, or cartilage of the knee. The clinimetric properties were found to be good and comparable to the American version of the KOOS. Comparison to the Short Form‐36 and the Lysholm knee scoring scale revealed expected correlations and construct validity. Item by item, symptoms and functional limitations were compared between diagnostic groups. High responsiveness was found three months after arthroscopic partial meniscectomy for all subscales but Activities of Daily Living.

Incidence of severe knee and hip osteoarthritis in relation to different measures of body mass. A population-based prospective cohort study.

OBJECTIVE To determine in a prospective population-based cohort study relationships between different measures of body mass and the incidence of severe knee and hip osteoarthritis defined as arthroplasty of knee or hip due to osteoarthritis. MATERIALS AND METHODS Body mass index (BMI), waist circumference, waist-hip ratio (WHR), weight and percentage of body fat (BF%) were measured at baseline in 11,026 men and 16,934 women from the general population. The incidence of osteoarthritis over 11 years was monitored by linkage with the Swedish hospital discharge register. RESULTS 471 individuals had knee osteoarthritis and 551 had hip osteoarthritis. After adjustment for age, sex, smoking and physical activity, the relative risks (RR) of knee osteoarthritis (fourth vs first quartile) were 8.1 (95% CI 5.3 to 12.4) for BMI, 6.7 (4.5 to 9.9) for waist circumference, 6.5 (4.6 to 9.43) for weight, 3.6 (2.6 to 5.0) for BF% and 2.2 (1.7 to 3.0) for WHR. Corresponding RR for hip osteoarthritis were 2.6 (2.0 to 3.4) for BMI, 3.0 (2.3 to 4.0) for weight, 2.5 (1.9 to 3.3) for waist, 1.3 (0.99 to 1.6) for WHR and 1.5 (1.2 to 2.0) for BF%. CONCLUSION All measures of overweight were associated with the incidence of knee osteoarthritis, with the strongest relative risk gradient observed for BMI. The incidence of hip osteoarthritis showed smaller but significant differences between normal weight and obesity. Our results support a major link between overweight and biomechanics in increasing the risk of knee and hip osteoarthritis in men and women.

WOMAC Osteoarthritis Index: Reliability, validity, and responsiveness in patients with arthroscopically assessed osteoarthritis

OBJECTIVE To validate the WOMAC Osteoarthritis Index for use in Sweden. METHODS Test-retest reliability, internal consistency, validity, and responsiveness was determined in 52 patients (mean age 48 (20-69)) with arthroscopically assessed cartilage damage of the tibio-femoral knee joint. RESULTS All WOMAC scales were internally consistent with Cronbachs alpha coefficients of 0.83, 0.87, and 0.96 pre-operatively. Test-retest reliability was satisfactory with intraclass correlation coefficients of 0.74, 0.58, and 0.92. As hypothesized worse post-operative but not pre-operative outcomes were associated with radiographic OA. In comparison with the SF-36 the expected correlations were found when comparing items measuring similar and dissimilar constructs, supporting the concepts of convergent and divergent construct validity. Three months after arthroscopy significant mean improvement was seen in all WOMAC scales (p<0.0004). CONCLUSION The Swedish version of WOMAC is a reliable, valid, and responsive instrument with metric properties in agreement with the original widely used version.

Predictors of patient relevant outcome after total hip replacement for osteoarthritis: a prospective study

Objectives: To investigate prospectively long term patient relevant outcomes after unilateral total hip replacement (THR) for osteoarthritis (OA). To identify non-responders to this intervention and patient related predictors of unsatisfactory outcome. Methods: A case-control study comparing health related quality of life of 219 patients (mean age 71) after THR with that of a matched reference group of 117 subjects without hip complaints recruited from the community. Patients and reference group answered SF-36 and WOMAC questionnaires preoperatively, at 3, 6, 12 months, and at 3.6 years (range 26–65 months) postoperatively. Supplementary questions were asked at the final follow up. Results: 198/211 (94%) of the patients and 83/109 (76%) of the reference group participated at the final follow up. At follow up, the only difference between the two groups in the SF-36 was physical function, where patients scored worse. Patients also reported worse WOMAC function. 31% of the patients had improved by <10/100 WOMAC score points for pain and/or function at final follow up, compared with preoperatively. More pain preoperatively and higher age and postoperative low back pain predicted a worse outcome in WOMAC function. Conclusion: 3.6 years after THR for OA, health related quality of life was similar for patients and reference group except for function, where patients had worse function. Higher age and more pain preoperatively predicted a poor outcome. Patients with hip OA with musculoskeletal comorbidities, such as low back pain and OA of the non-operated hip, have less long term functional improvement after THR.

Application of biomarkers in the development of drugs intended for the treatment of osteoarthritis

OBJECTIVE Osteoarthritis (OA) is a chronic and slowly progressive disease for which biomarkers may be able to provide a more rapid indication of therapeutic responses to therapy than is currently available; this could accelerate and facilitate OA drug discovery and development programs. The goal of this document is to provide a summary and guide to the application of in vitro (biochemical and other soluble) biomarkers in the development of drugs for OA and to outline and stimulate a research agenda that will further this goal. METHODS The Biomarkers Working Group representing experts in the field of OA biomarker research from both academia and industry developed this consensus document between 2007 and 2009 at the behest of the Osteoarthritis Research Society International Federal Drug Administration initiative (OARSI FDA initiative). RESULTS This document summarizes definitions and classification systems for biomarkers, the current outcome measures used in OA clinical trials, applications and potential utility of biomarkers for development of OA therapeutics, the current state of qualification of OA-related biomarkers, pathways for biomarker qualification, critical needs to advance the use of biomarkers for drug development, recommendations regarding practices and clinical trials, and a research agenda to advance the science of OA-related biomarkers. CONCLUSIONS Although many OA-related biomarkers are currently available they exist in various states of qualification and validation. The biomarkers that are likely to have the earliest beneficial impact on clinical trials fall into two general categories, those that will allow targeting of subjects most likely to either respond and/or progress (prognostic value) within a reasonable and manageable time frame for a clinical study (for instance within 1-2 years for an OA trial), and those that provide early feedback for preclinical decision-making and for trial organizers that a drug is having the desired biochemical effect. As in vitro biomarkers are increasingly investigated in the context of specific drug treatments, advances in the field can be expected that will lead to rapid expansion of the list of available biomarkers with increasing understanding of the molecular processes that they represent.

Arthroscopic surgery for degenerative knee: systematic review and meta-analysis of benefits and harms

Objective To determine benefits and harms of arthroscopic knee surgery involving partial meniscectomy, debridement, or both for middle aged or older patients with knee pain and degenerative knee disease. Design Systematic review and meta-analysis. Main outcome measures Pain and physical function. Data sources Systematic searches for benefits and harms were carried out in Medline, Embase, CINAHL, Web of Science, and the Cochrane Central Register of Controlled Trials (CENTRAL) up to August 2014. Only studies published in 2000 or later were included for harms. Eligibility criteria for selecting studies Randomised controlled trials assessing benefit of arthroscopic surgery involving partial meniscectomy, debridement, or both for patients with or without radiographic signs of osteoarthritis were included. For harms, cohort studies, register based studies, and case series were also allowed. Results The search identified nine trials assessing the benefits of knee arthroscopic surgery in middle aged and older patients with knee pain and degenerative knee disease. The main analysis, combining the primary endpoints of the individual trials from three to 24 months postoperatively, showed a small difference in favour of interventions including arthroscopic surgery compared with control treatments for pain (effect size 0.14, 95% confidence interval 0.03 to 0.26). This difference corresponds to a benefit of 2.4 (95% confidence interval 0.4 to 4.3) mm on a 0–100 mm visual analogue scale. When analysed over time of follow-up, interventions including arthroscopy showed a small benefit of 3–5 mm for pain at three and six months but not later up to 24 months. No significant benefit on physical function was found (effect size 0.09, −0.05 to 0.24). Nine studies reporting on harms were identified. Harms included symptomatic deep venous thrombosis (4.13 (95% confidence interval 1.78 to 9.60) events per 1000 procedures), pulmonary embolism, infection, and death. Conclusions The small inconsequential benefit seen from interventions that include arthroscopy for the degenerative knee is limited in time and absent at one to two years after surgery. Knee arthroscopy is associated with harms. Taken together, these findings do not support the practise of arthroscopic surgery for middle aged or older patients with knee pain with or without signs of osteoarthritis. Systematic review registration PROSPERO CRD42014009145.

C-reactive protein, metabolic syndrome and incidence of severe hip and knee osteoarthritis. A population-based cohort study.

OBJECTIVE To explore the relationships between C-reactive protein (CRP), metabolic syndrome (MetS) and incidence of severe knee or hip osteoarthritis (OA) in a prospective study. METHODS A population-based cohort (n=5171, mean age 57.5+/-5.9 years) was examined between 1991 and 1994. Data was collected on lifestyle habits, measures of overweight, blood pressure as well as high-density lipoprotein (HDL) cholesterol, triglycerides, glucose and CRP measured with high-sensitive methods. Incidence of severe OA, defined as arthroplasty due to knee or hip OA, was monitored over 12 years of follow-up, in relation to CRP levels and presence of the MetS according to the adult treatment panel III-national cholesterol education program (ATPIII-NCEP) definition. RESULTS A total of 120 participants had severe hip OA and 89 had knee OA during the follow-up. After adjustment for age, sex, smoking, physical activity and CRP, presence of MetS was associated with significantly increased risk of knee OA (relative risk [RR]: 2.1, 95% confidence interval [CI]: 1.3-3.3). However, this relationship was attenuated and non-significant after adjustment for body mass index (BMI) (RR: 1.1, 95% CI: 0.7-1.8). MetS was not significantly associated with incidence of hip OA. In women, CRP was associated with knee OA in the age-adjusted analysis. However, there was no significant relationship between CRP and incidence of knee or hip OA after risk factor adjustments. CONCLUSION The increased incidence of knee OA in participants with the MetS was largely explained by increased BMI. CRP was not associated with incidence of knee or hip OA when possible confounding factors were taken into account.

Acute rotational trauma to the knee: poor agreement between clinical assessment and magnetic resonance imaging findings

Objectives: To determine the incidence of anterior cruciate ligament (ACL) injuries in the general population; the pathology associated with a knee sprain verified by magnetic resonance imaging (MRI); and the agreement between clinical findings and MRI.

The acutely ACL injured knee assessed by MRI: changes in joint fluid, bone marrow lesions, and cartilage during the first year

OBJECTIVES To investigate changes in the knee during the first year after acute rupture of the anterior cruciate ligament (ACL) of volumes of joint fluid (JF), bone marrow lesions (BMLs), and cartilage volume (VC), and cartilage thickness (ThCcAB) and cartilage surface area (AC). To identify factors associated with these changes. METHODS Fifty-eight subjects (mean age 26 years, 16 women) with an ACL rupture to a previously un-injured knee were followed prospectively using a 1.5T MR imager at baseline (within 5 weeks from injury), 3 months, 6 months, and 1 year. Thirty-four subjects were treated with ACL reconstruction followed by a structured rehabilitation program and 24 subjects were treated with structured rehabilitation only. Morphometric data were acquired from computer-assisted segmentation of MR images. Morphometric cartilage change was reported as mean change divided by the standard deviation of change (standard response mean, SRM). RESULTS JF and BML volumes gradually decreased over the first year, although BML persisted in 62% of the knees after 1 year. One year after the ACL injury, a reduction of VC, AC and ThCcAB (SRM -0.440 or greater) was found in the trochlea femur (TrF), while an increase of VC and ThCcAB was found in the central medial femur (cMF) (SRM greater than 0.477). ACL reconstruction was directly and significantly related to increased JF volume at 3 and 6 months (P<0.001), BML volume at 6 months (P=0.031), VC and ThCcAB in cMF (P<0.002) and decreased cartilage area in TrF (P=0.010) at 12 months. CONCLUSION Following an acute ACL tear, cMF and TrF showed the greatest consistent changes of cartilage morphometry. An ACL reconstruction performed within a mean of 6 weeks from injury was associated with increased ThCcAB and VC in cMF and decreased AC in TrF, compared to knees treated without reconstruction. This may suggest a delayed structural restitution in ACL reconstructed knees.

Call for standardized definitions of osteoarthritis and risk stratification for clinical trials and clinical use.

Osteoarthritis (OA) is a heterogeneous disorder. The goals of this review are (1) To stimulate use of standardized nomenclature for OA that could serve as building blocks for describing OA and defining OA phenotypes, in short to provide unifying disease concepts for a heterogeneous disorder; and (2) To stimulate establishment of ROAD (Risk of OA Development) and ROAP (Risk of OA Progression) tools analogous to the FRAX™ instrument for predicting risk of fracture in osteoporosis; and (3) To stimulate formulation of tools for identifying disease in its early preradiographic and/or molecular stages - REDI (Reliable Early Disease Identification). Consensus around more sensitive and specific diagnostic criteria for OA could spur development of disease modifying therapies for this entity that has proved so recalcitrant to date. We fully acknowledge that as we move forward, we expect to develop more sophisticated definitions, terminology and tools.