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

Advancement in the zone of calcified cartilage in osteoarthritic hands of patients detected by high definition macroradiography

AbstractObjective High definition macroradiography permits the advancement in the zone of calcified cartilage (described as a ZCC step) to be detected in osteoarthritic (OA) hand joints of patients. The pattern of their incidence and distribution was determined and compared to the joint space width (JSW) measurement.Design Macroradiographs, ×5 magnification, were obtained of the OA hands of 44 patients at baseline and at 18 months. The incidence of ZCC steps, identified as an advancement in the mineralized cartilage front into articular cartilage, was assessed at each articular surface. JSW was measured and was used to determine the difference in JSW between hands and groups of joints with and without ZCC steps at both X-ray visits.Results ZCC steps were only found at the convex articular surfaces in 42 (48%) of hand joints in 28 (64%) patients. Here, ZCC steps were present in 36 joints in the non-dominant hand compared to 30 joints in the dominant hand. In the former, they were present in 22 DIP, six PIP and eight MCP joints and in 12 DIP, 8 PIP and 10 MCP joints in the dominant hand. By 18 months new ZCC steps had formed in 15 hands with and 17 hands without previous ZCC steps. At both X-ray visits no statistically significant difference in JSW was found between the hands and joint groups with and without ZCC steps.Conclusion Although ZCC steps and JSW loss were greater at the PIP joints, supporting a mechanical hypothesis for ZCC formation, their presence in joints, where JSW was larger, and their greater incidence in the non-dominant PIP joints, suggest that factors associated with vascular changes, related to subchondral bone remodeling, are responsible.{copy

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

Risedronate decreases biochemical markers of cartilage degradation but does not decrease symptoms or slow radiographic progression in patients with medial compartment osteoarthritis of the knee: Results of the two-year multinational knee osteoarthritis structural arthritis study

Objective Bisphosphonates have slowed the progression of osteoarthritis (OA) in animal models and have decreased pain in states of high bone turnover. The Knee OA Structural Arthritis (KOSTAR) study, which is the largest study to date investigating a potential structure-modifying OA drug, tested the efficacy of risedronate in providing symptom relief and slowing disease progression in patients with knee OA. Methods The study group comprised 2,483 patients with medial compartment knee OA and 2–4 mm of joint space width (JSW), as determined using fluoroscopically positioned, semiflexed-view radiography. Patients were enrolled in 2 parallel 2-year studies in North America and the European Union. These studies evaluated the efficacy of risedronate at dosages of 5 mg/day, 15 mg/day, 35 mg/week (in Europe), and 50 mg/week (in North America) compared with placebo in reducing signs and symptoms, as measured by the Western Ontario and McMaster Universities Osteoarthritis (WOMAC) index and patient global assessment (PGA) scores, and in slowing radiographic progression. Results A reduction of ∼20% in signs and symptoms, as measured by WOMAC subscales and PGA scores, was observed in all groups, with no treatment effect of risedronate demonstrated. Risedronate did not significantly reduce radiographic progression as measured by decreased JSW or using a dichotomous definition of progression (joint space loss of ≥0.6 mm). Thirteen percent of patients receiving placebo demonstrated significant disease progression over 2 years. A dose-dependent reduction in the level of C-terminal crosslinking telopeptide of type II collagen, a cartilage degradation marker associated with progressive OA, was seen in patients who received risedronate. No increase in the number of adverse events was demonstrated for risedronate compared with placebo. Conclusion Although risedronate (compared with placebo) did not improve signs or symptoms of OA, nor did it alter progression of OA, a reduction in the level of a marker of cartilage degradation was observed. A sustained clinically relevant improvement in signs and symptoms was observed in all treatment and placebo groups.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/55858/1/22160_ftp.pd

In vivo microfocal computed tomography and micro–magnetic resonance imaging evaluation of antiresorptive and antiinflammatory drugs as preventive treatments of osteoarthritis in the rat

Objective To determine whether treatment with an antiresorptive drug in combination with an antiinflammatory drug reduces periarticular bone and soft tissue adaptations associated with the progression of posttraumatic secondary osteoarthritis (OA). Methods We used in vivo microfocal computed tomography (micro-CT) to map bony adaptations and in vivo micro–magnetic resonance imaging (micro-MRI) to examine joint inflammation in a rat model of surgically induced OA secondary to knee triad injury. We examined the arthroprotective effects of the bisphosphonates alendronate and risedronate and the nonsteroidal antiinflammatory drug (NSAID) meloxicam. Results Micro-CT revealed reduced levels of periarticular trabecular bone loss in animals with knee triad injury treated with the bisphosphonate drugs alendronate or risedronate, or the NSAID meloxicam, compared with untreated animals. Alendronate treatment reduced bony osteophyte development. While risedronate as a monotherapy did not positively impact osteophytogenesis, combination therapy with risedronate and meloxicam reduced osteophyte severity somewhat. Micro-MRI revealed an increased, diffuse water signal in the epiphyses of untreated rats with knee triad injury 8 weeks after surgery, suggestive of a bone marrow lesion–like stimulus. In contrast, meloxicam-treated rats showed a significant reduction in fluid signal compared with both bisphosphonate-treated groups 8 weeks after surgery. Histologic analysis qualitatively confirmed the chondroprotective effect of both bisphosphonate treatments, showing fewer degradative changes compared with untreated rats with knee triad injury. Conclusion Our findings indicate that select combinations of bisphosphonate and NSAID drug therapy in the early stages of secondary OA preserve trabecular bone mass and reduce the impact of osteophytic bony adaptations and bone marrow lesion–like stimulus. Bisphosphonate and NSAID therapy may be an effective disease-modifying drug regimen if administered early after the initial injury.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/78085/1/27595_ftp.pd

A new approach to numerical characterisation of wear particle surfaces in three-dimensions for wear study

In the wear and tear process of synovial joints, wear particles generated and released from articular cartilage within the joints have surface topography and mechanical property which can be used to reveal wear conditions. Three-dimensional (3D) particle images acquired using laser scanning confocal microscopy (LSCM) contain appropriate surface information for quantitatively characterizing the surface morphology and changes to seek a further understanding of the wear process and wear features. This paper presents a new attempt on the 3D numerical characterisation of wear particle surfaces using the field and feature parameter sets which are defined in ISO/FDIS 25178-2. Based on the innovative pattern recognition capability, the feature parameters are, for the first time, employed for quantitative analysis of wear debris surface textures. Through performing parameter classification, ANOVA analysis and correlation analysis, typical changing trends of the surface transformation of the wear particles along with the severity of wear conditions and osteoarthritis (OA) have been observed. Moreover, the feature parameters have shown a significant sensitivity with the wear particle surfaces texture evolution under OA development. A correlation analysis of the numerical analysis results of cartilage surface texture variations and that of their wear particles has been conducted in this study. Key surface descriptors have been determined. Further research is needed to verify the above outcomes using clinic samples

'For me it's about not feeling like I'm on a diet':a thematic analysis of women's experiences of an intermittent energy restricted diet to reduce breast cancer risk

BACKGROUND: Weight-loss programmes requiring intermittent energy restriction offer an alternative to continuous energy restriction programmes that typically have low adherence. We reported greater weight loss, better adherence and spontaneous reduced energy intake on healthy eating days with intermittent as opposed to continuous energy restriction. The present study aims to explore why intermittent energy restriction diets exert these positive effects. METHODS: Semi-structured interviews were carried out with 13 women aged 39-62 years, who followed a 4-month intermittent energy restriction (2 days of low energy/low carbohydrate, 5 days of healthy eating). Nine of the 13 women successfully lost >5% of their total body weight. Data were analysed using thematic analysis. RESULTS: The intermittent regimen redefined the meaning of dieting and normal eating. Women reconceptualised dieting as only two low energy days per week, even though this often differed from their pre-diet eating patterns. Women reported that they could adhere more closely to the rules of the intermittent diet compared to previously attempted continuous diets. They found that the intermittent diet was less cognitively demanding because the restrictive and clear rules of the intermittent diet were easier to understand and easier to follow than with continuous dieting. CONCLUSIONS: Many participants found intermittent dieting preferable to previous experiences of continuous dieting. The findings provide some insight into the ways in which intermittent dieting is successful, and why it could be considered a viable alternative to continuous energy restriction for weight loss

Bone and cartilage in osteoarthritis: is what's best for one good or bad for the other?

The interest in the relationship between articular cartilage and the structural and functional properties of peri-articular bone relates to the intimate contact that exists between these tissues in joints that are susceptible to the development of osteoarthritis (OA). The demonstration in several animal models that osteoporosis and decreased bone tissue modulus leads to an increased propensity for the development of post-traumatic OA is paradoxical in light of the extensive epidemiological literature indicating that individuals with high systemic bone mass, assessed by bone mineral density, are at increased risk for OA. These observations underscore the need for further studies to define the pathophysiological mechanisms involved in the interaction between subchondral bone and articular cartilage and for applying this information to the development of therapeutic interventions to improve the outcomes in patients with OA

Are bisphosphonates effective in the treatment of osteoarthritis pain? A meta-analysis and systematic review.

Osteoarthritis (OA) is the most common form of arthritis worldwide. Pain and reduced function are the main symptoms in this prevalent disease. There are currently no treatments for OA that modify disease progression; therefore analgesic drugs and joint replacement for larger joints are the standard of care. In light of several recent studies reporting the use of bisphosphonates for OA treatment, our work aimed to evaluate published literature to assess the effectiveness of bisphosphonates in OA treatment

British Lung Foundation/United Kingdom primary immunodeficiency network consensus statement on the definition, diagnosis, and management of granulomatous-lymphocytic interstitial lung disease in common variable immunodeficiency disorders

A proportion of people living with common variable immunodeficiency disorders develop granulomatous-lymphocytic interstitial lung disease (GLILD). We aimed to develop a consensus statement on the definition, diagnosis, and management of GLILD. All UK specialist centers were contacted and relevant physicians were invited to take part in a 3-round online Delphi process. Responses were graded as Strongly Agree, Tend to Agree, Neither Agree nor Disagree, Tend to Disagree, and Strongly Disagree, scored +1, +0.5, 0, −0.5, and −1, respectively. Agreement was defined as greater than or equal to 80% consensus. Scores are reported as mean ± SD. There was 100% agreement (score, 0.92 ± 0.19) for the following definition: “GLILD is a distinct clinico-radio-pathological ILD occurring in patients with [common variable immunodeficiency disorders], associated with a lymphocytic infiltrate and/or granuloma in the lung, and in whom other conditions have been considered and where possible excluded.” There was consensus that the workup of suspected GLILD requires chest computed tomography (CT) (0.98 ± 0.01), lung function tests (eg, gas transfer, 0.94 ± 0.17), bronchoscopy to exclude infection (0.63 ± 0.50), and lung biopsy (0.58 ± 0.40). There was no consensus on whether expectant management following optimization of immunoglobulin therapy was acceptable: 67% agreed, 25% disagreed, score 0.38 ± 0.59; 90% agreed that when treatment was required, first-line treatment should be with corticosteroids alone (score, 0.55 ± 0.51)