Rates of medial tibiofemoral joint space narrowing in osteoarthritis studies consistent despite methodological differences

SummaryRationaleMinimum tibiofemoral joint space width in the medial compartment (JSW) is the most well-established structural outcome measure for osteoarthritis (OA) of the knee. Its usefulness as a measure of therapeutic effectiveness in short-term studies is limited by the rate and variability of joint space narrowing (JSN) in the OA population. Microfocal radiography has been shown to improve reproducibility of JSW measurement compared to standard radiography, but measurement of magnification from microfocal knee films has been problematic, and JSN is yet to be investigated in a longitudinal microfocal study.ObjectiveTo establish the effect on JSW reproducibility of a new method of magnification measurement in microfocal radiographs. To report on and compare rates of medial tibiofemoral JSN and their variations in the placebo arms of microfocal and standard radiographic clinical trials in OA, using fluoroscopic semi-flexed (SF) knee positioning. To place in the context of published estimates of rates of JSN from comparable studies.MethodsUsing microfocal radiography, 36 patients were followed at a single centre for 2 years. Using standard radiography, 86 patients were followed for 1 year at a single centre, and 549 for 2 years in a multi-centre international study. Computerised JSW measurement was undertaken using enhanced and automated versions of existing algorithms. Rates of JSN were examined in the context of a review of published rates of JSN using a variety of techniques.ResultsReproducibility of JSW measurement from microfocal radiographs was improved by the new magnification measurement. Rates of JSN were similar across the studies, but more variable when using standard radiography. The rates of JSN were also consistent with those from previously published investigations; all estimates since 2000, bar one, being consistent with the value 0.05mm/year.ConclusionMicrofocal radiography using the new method lowered the variability of the rate of JSN, but the high cost and low availability of microfocal equipment remains a barrier to its more widespread use. The consistently low but highly variable rates of JSN seen in the review suggest that continued attempts to improve radiographic and mensural techniques are unlikely to significantly reduce required sample sizes

Effect of risedronate on joint structure and symptoms of knee osteoarthritis: results of the BRISK randomized, controlled trial [ISRCTN01928173]

To determine the efficacy and safety of risedronate in patients with knee osteoarthritis (OA), the British study of risedronate in structure and symptoms of knee OA (BRISK), a 1-year prospective, double-blind, placebo-controlled study, enrolled patients (40–80 years of age) with mild to moderate OA of the medial compartment of the knee. The primary aims were to detect differences in symptoms and function. Patients were randomized to once-daily risedronate (5 mg or 15 mg) or placebo. Radiographs were taken at baseline and 1 year for assessment of joint-space width using a standardized radiographic method with fluoroscopic positioning of the joint. Pain, function, and stiffness were assessed using the Western Ontario and McMaster Universities (WOMAC) OA index. The patient global assessment and use of walking aids were measured and bone and cartilage markers were assessed. The intention-to-treat population consisted of 284 patients. Those receiving risedronate at 15 mg showed improvement of the WOMAC index, particularly of physical function, significant improvement of the patient global assessment (P < 0.001), and decreased use of walking aids relative to patients receiving the placebo (P = 0.009). A trend towards attenuation of joint-space narrowing was observed in the group receiving 15 mg risedronate. Eight percent (n = 7) of patients receiving placebo and 4% (n = 4) of patients receiving 5 mg risedronate exhibited detectable progression of disease (joint-space width ≥ 25% or ≥ 0.75 mm) versus 1% (n = 1) of patients receiving 15 mg risedronate (P = 0.067). Risedronate (15 mg) significantly reduced markers of cartilage degradation and bone resorption. Both doses of risedronate were well tolerated. In this study, clear trends towards improvement were observed in both joint structure and symptoms in patients with primary knee OA treated with risedronate

Assessment of the role of sutures in a lizard skull: a computer modelling study

Sutures form an integral part of the functioning skull, but their role has long been debated among vertebrate morphologists and palaeontologists. Furthermore, the relationship between typical skull sutures, and those involved in cranial kinesis, is poorly understood. In a series of computational modelling studies, complex loading conditions obtained through multibody dynamics analysis were imposed on a finite element model of the skull of Uromastyx hardwickii, an akinetic herbivorous lizard. A finite element analysis (FEA) of a skull with no sutures revealed higher patterns of strain in regions where cranial sutures are located in the skull. From these findings, FEAs were performed on skulls with sutures (individual and groups of sutures) to investigate their role and function more thoroughly. Our results showed that individual sutures relieved strain locally, but only at the expense of elevated strain in other regions of the skull. These findings provide an insight into the behaviour of sutures and show how they are adapted to work together to distribute strain around the skull. Premature fusion of one suture could therefore lead to increased abnormal loading on other regions of the skull causing irregular bone growth and deformities. This detailed investigation also revealed that the frontal–parietal suture of the Uromastyx skull played a substantial role in relieving strain compared with the other sutures. This raises questions about the original role of mesokinesis in squamate evolution