Optimizing fracture prevention: the fracture liaison service, an observational study.

Unlabelled: The response rate to the invitation to the fracture liaison service and reasons for non-response were evaluated in 2,207 fragility fracture patients. Fifty-one percent responded; non-responders were most often not interested (38 %) or were hip fracture patients. After 1 year of treatment, 88 % was still persistent and 2 % had a new fracture.

An OA phenotype may obtain major benefit from bone-acting agents.

Background: Osteoarthritis (OA) joints display relevant microstructure alterations associated to an increase in remodeling at subchondral bone, which supports its crucial role in OA pathogenesis. Despite this, the treatment of knee OA patients with antiresorptive drugs has given discordant results, suggesting the existence of a particular patient subset with good response to halting high subchondral remodeling.

Objective: To identify an OA phenotype that may obtain major benefit from therapy with bone-acting agents.

Increased progression of carotid intima media thickness in thyroid peroxidase antibodies-positive rheumatoid arthritis patients.

Objective: Autoimmune diseases such as rheumatoid arthritis (RA) and hypothyroidism tend to cluster, and this coexistence amplifies the elevated cardiovascular risk in RA. Whether thyroid peroxidase antibodies (TPOabs) are associated with increased cardiovascular disease (CVD) risk has not been studied extensively. Therefore, this study determined firstly the prevalence of TPOabs in RA and secondly whether TPOabs were associated with CVD.

Methotrexate analogues display enhanced inhibition of TNF-α production in whole blood from RA patients.

Objectives: Although methotrexate (MTX) is the anchor drug in the treatment of rheumatoid arthritis (RA), patients experience clinical resistance to MTX upon prolonged treatment. We explored whether new-generation antifolates elicit superior anti-inflammatory properties when compared to MTX, based on their capacity to inhibit tumour necrosis factor (TNF)-α production.

Method: T cells in whole blood from 18 RA patients (including MTX-naïve, MTX- responsive, and MTX non-responsive patients) and seven healthy volunteers were stimulated with αCD3/αCD28 antibodies and incubated ex vivo for 72 h with MTX and eight novel antifolate drugs with potentially favourable biochemical and pharmacological properties.

Is the severity of knee osteoarthritis on magnetic resonance imaging associated with outcome of exercise therapy?

Objective: To evaluate associations between severity of knee osteoarthritis (OA) on magnetic resonance imaging (MRI) and treatment outcomes in knee OA patients treated with exercise therapy in an exploratory study.

Methods: Ninety-five participants with knee OA in a 12-week exercise program had obtained 3.0T MRI scans of the knee joint prior to treatment.

Effective osteoporosis treatment with teriparatide is associated with enhanced quality of life in postmenopausal women with osteoporosis: the European Forsteo Observational Study.

Background: To describe changes in health-related quality of life (HRQoL) of postmenopausal women with osteoporosis treated with teriparatide for up to 18 months and followed-up for a further 18 months, and to assess the influence of recent prior and incident fractures.

Methods: The European Forsteo Observational Study (EFOS) is an observational, prospective, multinational study measuring HRQoL using the EQ-5D. The primary objective was to assess changes in HRQoL during 36 months in the whole study population.

Value of biomarkers in osteoarthritis: current status and perspectives.

Osteoarthritis affects the whole joint structure with progressive changes in cartilage, menisci, ligaments and subchondral bone, and synovial inflammation. Biomarkers are being developed to quantify joint remodelling and disease progression. This article was prepared following a working meeting of the European Society for Clinical and Economic Aspects of Osteoporosis and Osteoarthritis convened to discuss the value of biochemical markers of matrix metabolism in drug development in osteoarthritis.

Methotrexate normalizes up-regulated folate pathway genes in rheumatoid arthritis.

Objective: The folate antagonist methotrexate (MTX) is an anchor drug in the treatment of rheumatoid arthritis (RA), but its mechanism of action with regard to the impact on folate metabolism remains elusive. The aim of the present study was to investigate the cellular pharmacologic impact of MTX on peripheral blood cells, by comparing MTX-treated RA patients to MTX-naive RA patients and healthy controls.

Methods: Gene expression microarray data were used to investigate the expression of 17 folate pathway genes by peripheral blood cells from a cohort of 25 RA patients treated with MTX, 10 MTX-naive RA patients starting treatment with MTX, and 15 healthy controls (test cohort).

Can bone loss in rheumatoid arthritis be prevented?

Rheumatoid arthritis (RA) is a systemic inflammatory disease that can lead to local joint deformations (bone erosions and joint space narrowing) and to extra-articular phenomena, including generalized osteoporosis. In addition, in patients with RA, the risk of vertebral and nonvertebral fractures is doubled. High disease activity (inflammation), immobility, and glucocorticoid use are common factors that substantially increase fracture risk in these patients, on top of the background fracture risk based on classical risk factors such as high age, low body mass, and female gender.

Established and forthcoming drugs for the treatment of osteoporosis.

Nowadays, effective drugs are available to prevent fractures in patients at high risk for osteoporotic fractures. The generic bisphosphonates alendronate and risedronate are first choice, because of their effectiveness and tolerability in the majority of patients, while they also have a low cost price. However, the use of bisphosphonates can be associated with side effects: not only the well-known (upper) gastrointestinal side effects, but also (spontaneous) atypical fractures of the femur and aseptic necrosis of the jaw.

Knee joint stabilization therapy in patients with osteoarthritis of the knee: a randomized, controlled trial.

Objective: To investigate whether an exercise program, initially focusing on knee stabilization and subsequently on muscle strength and performance of daily activities is more effective than an exercise program focusing on muscle strength and performance of daily activities only, in reducing activity limitations in patients with knee osteoarthritis (OA) and instability of the knee joint.

Design: A single-blind, randomized, controlled trial involving 159 knee OA patients with self-reported and/or biomechanically assessed knee instability, randomly assigned to two treatment groups. Both groups received a supervised exercise program for 12 weeks, consisting of muscle strengthening exercises and training of daily activities, but only in the experimental group specific knee joint stabilization training was provided.

Three trajectories of activity limitations in early symptomatic knee osteoarthritis: a 5-year follow-up study.

Objectives: Knee osteoarthritis (OA) is a leading cause of activity limitations. The knee OA population is likely to consist of subgroups. The aim of the present study was to identify homogeneous subgroups with distinct trajectories of activity limitations in patients with early symptomatic knee OA and to describe characteristics of these subgroups.

A non-inferiority trial of an attenuated combination strategy ('COBRA-light') compared to the original COBRA strategy: clinical results after 26 weeks.

Background: Early, intensive treatment of rheumatoid arthritis (RA) with the combination of (initially high dose) prednisolone, methotrexate and sulfasalazine (COBRA therapy) considerably lowers disease activity and suppresses radiological progression, but is infrequently prescribed in daily practice. Attenuating the COBRA regimen might lessen concerns about side effects, but the efficacy of such strategies is unknown.

Objective: To compare the 'COBRA-light' strategy with only two drugs, comprising a lower dose of prednisolone (starting at 30 mg/day, tapered to 7.

How to define responders in osteoarthritis.

Background: Osteoarthritis is a clinical syndrome of failure of the joint accompanied by varying degrees of joint pain, functional limitation, and reduced quality of life due to deterioration of articular cartilage and involvement of other joint structures.

Scope: Regulatory agencies require relevant clinical benefit on symptoms and structure modification for registration of a new therapy as a disease-modifying osteoarthritis drug (DMOAD). An international Working Group of the European Society on Clinical and Economic Aspects of Osteoporosis and Osteoarthritis (ESCEO) and International Osteoporosis Foundation was convened to explore the current burden of osteoarthritis, review current regulatory guidelines for the conduct of clinical trials, and examine the concept of responder analyses for improving drug evaluation in osteoarthritis.

Early local swelling and tenderness are associated with large-joint damage after 8 years of treatment to target in patients with recent-onset rheumatoid arthritis.

Objective: To assess whether early swelling and tenderness in large joints in patients with rheumatoid arthritis (RA) is predictive of later local damage and whether this leads to functional disability.

Methods: Two-year clinical and 8-year radiological followup data from the BeSt study (trial numbers NTR262 and NTR265), a randomized controlled treat-to-target trial, were used. The association between early local joint swelling and/or tenderness (at least once, or for ≥ 2 consecutive visits) and later large-joint damage (Larsen score ≥ 1) was assessed using generalized estimating equations.

Osteoarthritis and osteoporosis: what is the overlap?

Osteoarthritis (OA) and osteoporosis (OP) are highly prevalent health problems, associated with considerable morbidity. In the past, attention was focused on a supposed inverse relationship between OA and OP, since both disorders usually affect the elderly, but were regarded to rarely coexist in a single person. However, recent studies have revealed several factors which contribute to the pathogenesis of both disorders.

The association between reduced knee joint proprioception and medial meniscal abnormalities using MRI in knee osteoarthritis: results from the Amsterdam osteoarthritis cohort.

Background: Osteoarthritis (OA) of the knee is characterized by pain and activity limitations. In knee OA, proprioceptive accuracy is reduced and might be associated with pain and activity limitations. Although causes of reduced proprioceptive accuracy are divergent, medial meniscal abnormalities, which are highly prevalent in knee OA, have been suggested to play an important role.

Association of high body mass index with decreased treatment response to combination therapy in recent-onset rheumatoid arthritis patients.

Objective: To assess the association between high body mass index (BMI) and treatment response in recent-onset rheumatoid arthritis.

Methods: In the Behandelstrategieën voor Reumatoide Artritis (Treatment Strategies for Rheumatoid Arthritis) study, 508 patients were randomized to initial monotherapy or combination therapy with prednisone or infliximab (IFX). The response to Disease Activity Score (DAS) ≤2.

A multi-biomarker score measures rheumatoid arthritis disease activity in the BeSt study.

Objective: To evaluate a multi-biomarker disease activity (MBDA) score, a novel index based on 12 serum proteins, as a tool to guide management of RA patients.

Methods: A total of 125 patients with RA from the Behandel Strategieën study were studied. Clinical data and serum samples were available from 179 visits, 91 at baseline and 88 at year 1.

Glucocorticoid-induced osteoporosis: an update on current pharmacotherapy and future directions.

Introduction: Glucocorticoid-induced osteoporosis (GIOP) is one of the most devastating side-effects of glucocorticoid (GC) use, as it is associated with an increased fracture risk. The importance of GIOP as a health problem is underlined by the frequent use of GC treatment in patients with various chronic diseases and by the high rates of osteoporosis found in these patient groups.

Areas Covered: Recent studies on bone metabolism and the influence of GCs have contributed to a better understanding of the pathogenesis of GIOP.

Overcoming bortezomib resistance in human B cells by anti-CD20/rituximab-mediated complement-dependent cytotoxicity and epoxyketone-based irreversible proteasome inhibitors.

Background: In clinical and experimental settings, antibody-based anti-CD20/rituximab and small molecule proteasome inhibitor (PI) bortezomib (BTZ) treatment proved effective modalities for B cell depletion in lymphoproliferative disorders as well as autoimmune diseases. However, the chronic nature of these diseases requires either prolonged or re-treatment, often with acquired resistance as a consequence.

Methods: Here we studied the molecular basis of acquired resistance to BTZ in JY human B lymphoblastic cells following prolonged exposure to this drug and examined possibilities to overcome resistance by next generation PIs and anti-CD20/rituximab-mediated complement-dependent cytotoxicity (CDC).

Association of serum C-reactive protein and erythrocyte sedimentation rate with muscle strength in patients with knee osteoarthritis.

Objective: To examine the association of serum CRP and ESR with muscle strength in patients with knee OA.

Methods: Cross-sectional data from 285 patients with knee OA from the Amsterdam Osteoarthritis (AMS-OA) cohort were analysed. CRP (mg/l) and ESR (mm/l) were measured in serum from patients' blood samples and the values were dichotomized for the analyses.

Risk of alanine transferase (ALT) elevation in patients with rheumatoid arthritis treated with methotrexate in a DAS-steered strategy.

Objective: To determine incidence of increased levels of alanine transferase (ALT) >2× upper limit of normal (ULN) in patients receiving methotrexate (MTX), treated according to a dynamic strategy, and to identify predictors of ALT of >2× ULN.

Methods: Data of 508 recent-onset rheumatoid arthritis (RA) patients from the BeSt study, randomized to initial monotherapy or combination therapy, were used. Treatment was dynamic, aiming at a disease activity score = ≤ 2.

Association of postural control with muscle strength, proprioception, self-reported knee instability and activity limitations in patients with knee osteoarthritis.

Objective: To determine the association of postural control with muscle strength, proprioception, self-reported knee instability and activity limitations in patients with knee osteoarthritis.

Methods: A total of 284 patients with knee osteoarthritis from the Amsterdam Osteoarthritis cohort were included. Postural control was assessed using the One-Leg Stand Test (OLST), in which the patients were asked to stand on one leg for 30 s.

Changes in bone mineral density during long-term treatment with adalimumab in patients with rheumatoid arthritis: a cohort study.

Objective: To investigate the effect of long-term adalimumab treatment on BMD of the lumbar spine, total hip and hands in patients with RA.

Methods: In 184 established RA patients treated with adalimumab for at least 1 year, BMD measurements of the total hip and lumbar spine were performed using dual-energy X-ray absorptiometry. Metacarpal cortex BMD was measured using digital X-ray radiogrammetry.