Effects of Denosumab in Japanese Patients With Rheumatoid Arthritis Treated With Conventional Antirheumatic Drugs: 36-month Extension of a Phase III Study.

Objective: To evaluate the safety and efficacy of long-term denosumab 60 mg every 6 months (Q6M) or every 3 months (Q3M) in patients with rheumatoid arthritis (RA).

Methods: This 12-month, randomized, double-blind, placebo-controlled, multicenter, phase III trial with an open-label extension period from 12 to 36 months (DESIRABLE) enrolled Japanese patients with RA treated with placebo (P) for 12 months followed by either denosumab Q6M (P/Q6M) or denosumab Q3M (P/Q3M) for 24 months; denosumab Q6M for 36 months (Q6M/Q6M); or denosumab Q3M for 36 months (Q3M/Q3M). Efficacy was assessed by van der Heijde modified total Sharp score (mTSS), bone erosion score (BES), and joint space narrowing (JSN) score.

Identifying the preferable rheumatoid arthritis subgroups for intervention with the anti-RANKL antibody denosumab to reduce progression of joint destruction.

Objectives: To clarify which rheumatoid arthritis (RA) patients benefit most from the anti-receptor activator of nuclear factor-κB ligand antibody denosumab to reduce the progression of joint destruction.

Methods: We pooled patient data from the 12-month, double-blind, placebo-controlled DRIVE (phase II) and DESIRABLE (phase III) studies. In DRIVE, concomitant treatment was limited to methotrexate, salazosulfapyridine and bucillamine.

History of etidronate.

Etidronate is a non-nitrogen-containing bisphosphonate. Because it binds with calcium and inhibits crystal formation and dissolution, it was considered by Procter & Gamble as an additive to toothpaste (to prevent build-up of tartar) and detergent (to bind calcium and increase sudsing in "hard" water). The first clinical use (1968) was for fibrodysplasia ossificans progressiva.

Effects of the anti-RANKL antibody denosumab on joint structural damage in patients with rheumatoid arthritis treated with conventional synthetic disease-modifying antirheumatic drugs (DESIRABLE study): a randomised, double-blind, placebo-controlled phase 3 trial.

Objective: To evaluate the efficacy of denosumab in suppressing joint destruction when added to conventional synthetic disease-modifying antirheumatic drug (csDMARD) therapy in patients with rheumatoid arthritis (RA).

Methods: This was a multi-centre, randomised, double-blind, parallel-group, placebo-controlled phase 3 study in Japan. Patients with RA aged ≥20 years receiving csDMARDs were randomly assigned (1:1:1) to denosumab 60 mg every 3 months (Q3M), denosumab 60 mg every 6 months (Q6M) or placebo.

Efficacy of denosumab with regard to bone destruction in prognostic subgroups of Japanese rheumatoid arthritis patients from the phase II DRIVE study.

Objectives: To evaluate the efficacy of denosumab for progressive bone erosion in risk factor subgroups of Japanese RA patients.

Methods: This study included 340 RA patients on MTX from the dose-response study of Denosumab in patients with RheumatoId arthritis on methotrexate to Validate inhibitory effect on bone Erosion (DRIVE study-a 12-month, multicentre, randomized, double-blind, placebo-controlled, phase II study). The patients were randomized to receive placebo or denosumab 60 mg every 6 months, 3 months or 2 months.

Non-invasive DXA-derived bone structure assessment of acromegaly patients: a cross-sectional study.

Introduction Impaired bone microarchitecture is involved in vertebral fracture (VF) development among acromegaly patients. Aim of the study Comparison of DXA-derived bone parameters, areal BMD (aBMD), trabecular bone score (TBS) and 3D-SHAPER parameters in acromegaly patients with healthy controls. Methods This cross-sectional study evaluated acromegaly patients and a control group of healthy subjects.

Longitudinal Reliability of the OMERACT Thumb Base Osteoarthritis Magnetic Resonance Imaging Scoring System (TOMS).

Objective: To assess the longitudinal reliability of the Outcome Measures in Rheumatology (OMERACT) Thumb base Osteoarthritis Magnetic resonance imaging (MRI) Scoring system (TOMS).

Methods: Paired MRI of patients with hand osteoarthritis were scored in 2 exercises (6-mo and 2-yr followup) for synovitis, subchondral bone defects (SBD), osteophytes, cartilage assessment, bone marrow lesions (BML), and subluxation. Interreader reliability of delta scores was assessed.

Atlas for the OMERACT thumb base osteoarthritis MRI scoring system (TOMS).

This paper presents an atlas for the Outcome Measures in Rheumatology Clinical Trials (OMERACT) thumb base osteoarthritis MRI scoring system (TOMS). The atlas includes reference images of each grade of each feature that is assessed in TOMS (synovitis grade 0-3, subchondral bone defects grade 0-3, osteophytes grade 0-3, cartilage assessment grade 0-3, subluxation and bone marrow lesions grade 0-3) in the first carpometacarpal and scapho-trapezio-trapezoid joint. The presented reference images can be used to guide scoring of thumb base MRIs in patients with hand osteoarthritis according to the OMERACT TOMS.

The OMERACT Rheumatoid Arthritis Magnetic Resonance Imaging (MRI) Scoring System: Updated Recommendations by the OMERACT MRI in Arthritis Working Group.

Objective: The Outcome Measures in Rheumatology (OMERACT) Rheumatoid Arthritis (RA) Magnetic Resonance Imaging (MRI) scoring system (RAMRIS), evaluating bone erosion, bone marrow edema/osteitis, and synovitis, was introduced in 2002, and is now the standard method of objectively quantifying inflammation and damage by MRI in RA trials. The objective of this paper was to identify subsequent advances and based on them, to provide updated recommendations for the RAMRIS.

Methods: MRI studies relevant for RAMRIS and technical and scientific advances were analyzed by the OMERACT MRI in Arthritis Working Group, which used these data to provide updated considerations on image acquisition, RAMRIS definitions, and scoring systems for the original and new RA pathologies.

Romosozumab (sclerostin monoclonal antibody) versus teriparatide in postmenopausal women with osteoporosis transitioning from oral bisphosphonate therapy: a randomised, open-label, phase 3 trial.

Background: Previous bisphosphonate treatment attenuates the bone-forming effect of teriparatide. We compared the effects of 12 months of romosozumab (AMG 785), a sclerostin monoclonal antibody, versus teriparatide on bone mineral density (BMD) in women with postmenopausal osteoporosis transitioning from bisphosphonate therapy.

Methods: This randomised, phase 3, open-label, active-controlled study was done at 46 sites in North America, Latin America, and Europe.

Evaluating Atypical Features of Femur Fractures: How Change in Radiological Criteria Influenced Incidence and Demography of Atypical Femur Fractures in a Community Setting.

Identification of atypical femoral fractures (AFFs) can be challenging. To assist in the radiological assessment, an American Society for Bone and Mineral Research (ASBMR) Task Force developed a case definition for AFFs in 2010, revising it in 2013. How the revised definition performs in a community setting compared with the 2010 definition is unknown.

Greater Gains in Spine and Hip Strength for Romosozumab Compared With Teriparatide in Postmenopausal Women With Low Bone Mass.

Romosozumab is a monoclonal antibody that inhibits sclerostin and has been shown to reduce the risk of fractures within 12 months. In a phase II, randomized, placebo-controlled clinical trial of treatment-naïve postmenopausal women with low bone mass, romosozumab increased bone mineral density (BMD) at the hip and spine by the dual effect of increasing bone formation and decreasing bone resorption. In a substudy of that trial, which included placebo and teriparatide arms, here we investigated whether those observed increases in BMD also resulted in improvements in estimated strength, as assessed by finite element analysis.

Development and Reliability of the OMERACT Thumb Base Osteoarthritis Magnetic Resonance Imaging Scoring System.

Objective: To develop the Outcome Measures in Rheumatology (OMERACT) thumb base osteoarthritis (OA) magnetic resonance imaging (MRI) scoring system (TOMS) for the assessment of inflammatory and structural abnormalities in this hand OA subset, and test its cross-sectional reliability.

Methods: Included features and their scaling were agreed upon by members of the OMERACT MRI Task Force using the Hand OA MRI scoring system as a template. A reliability exercise was performed in which 3 readers participated, using a preliminary atlas with examples to facilitate reading.

Effects of Romosozumab Compared With Teriparatide on Bone Density and Mass at the Spine and Hip in Postmenopausal Women With Low Bone Mass.

Romosozumab, a monoclonal antibody that binds sclerostin, has a dual effect on bone by increasing bone formation and reducing bone resorption, and thus has favorable effects in both aspects of bone volume regulation. In a phase 2 study, romosozumab increased areal BMD at the lumbar spine and total hip as measured by DXA compared with placebo, alendronate, and teriparatide in postmenopausal women with low bone mass. In additional analyses from this international, randomized study, we now describe the effect of romosozumab on lumbar spine and hip volumetric BMD (vBMD) and BMC at month 12 as assessed by QCT in the subset of participants receiving placebo, s.

High Kellgren-Lawrence Grade and Bone Marrow Lesions Predict Worsening Rates of Radiographic Joint Space Narrowing; The SEKOIA Study.

Objective: Determinants of radiographic progression in osteoarthritis (OA) are poorly understood. We investigated which features on baseline magnetic resonance imaging (MRI) acted as predictors of change in joint space width (JSW).

Methods: A total of 559 men and women over the age of 50 years with clinical knee OA [Kellgren-Lawrence (KL) grade 2-3] were recruited to the placebo arm of the SEKOIA study (98 centers; 18 countries).

Effect of denosumab on Japanese patients with rheumatoid arthritis: a dose-response study of AMG 162 (Denosumab) in patients with RheumatoId arthritis on methotrexate to Validate inhibitory effect on bone Erosion (DRIVE)-a 12-month, multicentre, randomised, double-blind, placebo-controlled, phase II clinical trial.

Objectives: To evaluate efficacy and safety of three different regimens of denosumab, a fully human monoclonal antibody to receptor activator of nuclear factor kappa B (RANK) ligand (RANKL), for Japanese patients with rheumatoid arthritis (RA).

Methods: In this multicentre, randomised, placebo-controlled phase II study, 350 Japanese patients with RA between 6 months and <5 years, stratified by glucocorticoid use and rheumatoid factor status, were randomly assigned to subcutaneous injections of placebo or denosumab 60 mg every 6 months (Q6M), every 3 months (Q3M) or every 2 months (Q2M). All patients basically continued methotrexate treatment and had a supplement of calcium and vitamin D throughout the study.

The Longitudinal Reliability and Responsiveness of the OMERACT Hand Osteoarthritis Magnetic Resonance Imaging Scoring System (HOAMRIS).

Objective: To evaluate the interreader reliability of change scores and the responsiveness of the OMERACT Hand Osteoarthritis (OA) Magnetic Resonance Image (MRI) Scoring System (HOAMRIS).

Methods: Paired MRI (baseline and 5-yr followup) from 20 patients with hand OA were scored with known time sequence by 3 readers according to the HOAMRIS: Synovitis, erosive damage, cysts, osteophytes, cartilage space loss, malalignment, and bone marrow lesions (BML; 0-3 scales with 0.5 increments for synovitis, erosive damage, and BML).

Comparison of proximal femur and vertebral body strength improvements in the FREEDOM trial using an alternative finite element methodology.

Denosumab reduced the incidence of new fractures in postmenopausal women with osteoporosis by 68% at the spine and 40% at the hip over 36 months compared with placebo in the FREEDOM study. This efficacy was supported by improvements from baseline in vertebral (18.2%) strength in axial compression and femoral (8.

Relationship Between Vertebral Fracture Burden, Height Loss, and Pulmonary Function in Postmenopausal Women With Osteoporosis.

The purpose of this analysis was to assess the association of osteoporosis-related vertebral fracture burden and pulmonary function. This study also examined the relationship between vertebral fracture burden and height loss, estimated by arm span - height. This was a single-site and single-visit study.

Reduced Bone Density and Vertebral Fractures in Smokers. Men and COPD Patients at Increased Risk.

Rationale: Former smoking history and chronic obstructive pulmonary disease (COPD) are potential risk factors for osteoporosis and fractures. Under existing guidelines for osteoporosis screening, women are included but men are not, and only current smoking is considered.

Objectives: To demonstrate the impact of COPD and smoking history on the risk of osteoporosis and vertebral fracture in men and women.