Setting up distinctive outcome measures for each osteoarthritis phenotype.

Osteoarthritis (OA) is an evolving chronic joint disease with a huge global impact. Given the intricate nature of the etiopathogenesis and subsequent high heterogeneity in the clinical course of OA, it is crucial to discriminate between etiopathogenic endotypes and clinical phenotypes, especially in the early stages of the disease. In this sense, we propose that an OA phenotype should be properly assessed with a set of outcome measures including those specifically related to the main underlying pathophysiological mechanisms.

Targeting chronic innate inflammatory pathways, the main road to prevention of osteoarthritis progression.

Osteoarthritis (OA) is a chronic joint disease characterized by cartilage degradation, osteophyte formation, subchondral bone sclerosis, and synovitis. Systemic factors such as obesity and the components of the metabolic syndrome seem to contribute to its progression. Breakdown of cartilage ensues from an altered balance between mechanical overload and its absorption by this tissue.

Mediators and Patterns of Muscle Loss in Chronic Systemic Inflammation.

Besides its primary function in locomotion, skeletal muscle (SKM), which represents up to half of human's weight, also plays a fundamental homeostatic role. Through the secretion of soluble peptides, or myokines, SKM interacts with major organs involved in metabolic processes. In turn, metabolic cues from these organs are received by muscle cells, which adapt their response accordingly.

Clinical settings in knee osteoarthritis: Pathophysiology guides treatment.

Osteoarthritis (OA) is the most common chronic joint disorder and its prevalence increases rapidly during midlife. Complex interactions of genetic alterations, sex hormone deficit, and aging with mechanical factors and systemic inflammation-associated metabolic syndrome lead to joint damage. Thus, the expression of a clinical phenotype in the early stages of OA relies on the main underlying pathway and predominant joint tissue involved at a given time.

The combined therapy with chondroitin sulfate plus glucosamine sulfate or chondroitin sulfate plus glucosamine hydrochloride does not improve joint damage in an experimental model of knee osteoarthritis in rabbits.

Osteoarthritis is the most common chronic joint disorder especially during aging. Although with controversies, glucosamine, both in its forms of sulfate and hydrochloride, and chondroitin sulfate are commonly employed to treat osteoarthritis. Due to the modest improve in the symptoms observed in patients treated with these drugs alone, a formulation combining both agents has been considered.

Combined Treatment With Chondroitin Sulfate and Glucosamine Sulfate Shows No Superiority Over Placebo for Reduction of Joint Pain and Functional Impairment in Patients With Knee Osteoarthritis: A Six-Month Multicenter, Randomized, Double-Blind, Placebo-Controlled Clinical Trial.

Objective: To assess the efficacy and safety of combination therapy with chondroitin sulfate (CS) and glucosamine sulfate (GS) compared to placebo in patients with symptomatic knee osteoarthritis (OA).

Methods: A multicenter, randomized, double-blind, placebo-controlled study was performed in 164 patients with Kellgren/Lawrence grade 2 or grade 3 radiographic knee OA and moderate-to-severe knee pain (mean ± SD global pain score 62.1 ± 11.

An update on the up and coming therapies to treat osteoarthritis, a multifaceted disease.

Introduction: The lack of a complete understanding of the complex processes involved in the etiopathogenesis and subsequent appropriate phenotyping makes it difficult to find therapies that may be efficacious in most patients with osteoarthritis (OA). Consensus recommendations involve mainly non-pharmacological approaches. Analgesics and NSAIDs are considered second choice options due to their poor efficacy/safety ratios.

Osteoarthritis in Latin America: Study of Demographic and Clinical Characteristics in 3040 Patients.

Background: Latin America is a heterogeneous region made up of different populations, cultures, latitudes, altitudes, and immigrants from different areas and ethnic groups.

Objective: The purpose of this study is to describe the clinical and demographic profile of patients with osteoarthritis (OA) evaluated by a selected group of rheumatologists in 13 Latin American countries.

Methods: A descriptive, observational, cross-sectional study was conducted in 13 Latin American countries of patients with symptomatic OA.

Characterization of multinucleated giant cells in synovium and subchondral bone in knee osteoarthritis and rheumatoid arthritis.

Background: Multinucleated giant cells have been noticed in diverse arthritic conditions since their first description in rheumatoid synovium. However, their role in the pathogenesis of osteoarthritis (OA) or rheumatoid arthritis (RA) still remains broadly unknown. We aimed to study the presence and characteristics of multinucleated giant cells (MGC) both in synovium and in subchondral bone tissues of patients with OA or RA.

DXA in the assessment of subchondral bone mineral density in knee osteoarthritis--A semi-standardized protocol after systematic review.

Introduction: Subchondral bone mineral density (sBMD) contributes to the initiation and progression of knee osteoarthritis (OA). Reliable methods to assess sBMD status may predict the response of specific OA phenotypes to targeted therapies. While dual-energy X-ray absorptiometry (DXA) of the knee can determine sBMD, no consensus exists regarding its methodology.

Targeting subchondral bone in osteoporotic osteoarthritis.

The identification of well-defined phenotypes along the course of the disease may open new avenues for personalized management in osteoarthritis (OA). In vivo research carried out in various animal models as well as epidemiological and clinical data support the existence of a particular phenotype - osteoporotic OA. In fact, subchondral bone has become a potential therapeutic target in OA.

SDF-1 signaling: a promising target in rheumatic diseases.

Introduction: Stromal cell-derived factor 1 (SDF-1) is a potent chemoattractant cytokine with various biological functions such as stem cell mobilization, inflammatory cell infiltration and angiogenesis. Therefore, it has also been implicated in several pathological processes, from ischemic conditions to cancer. Remarkably, SDF-1 and its receptors, CXCR4 and CXCR7, are also present in joint tissues, where they play a role in the pathogenesis of rheumatoid arthritis (RA) and osteoarthritis (OA).

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.

Osteoarthritis: Osteoporotic OA: a reasonable target for bone-acting agents.

Beneficial effects of bone-acting drugs in osteoarthritis (OA) are increasingly reported, but reliable conclusions regarding their efficacy are hindered by methodological drawbacks in study design. Identifying patients with osteoporotic OA, a phenotype defined by decreased density associated with high remodelling in subchondral bone, might improve the success of bone-directed agents.

RANKL synthesized by articular chondrocytes contributes to juxta-articular bone loss in chronic arthritis.

Introduction: The receptor activator nuclear factor-kappaB ligand (RANKL) diffuses from articular cartilage to subchondral bone. However, the role of chondrocyte-synthesized RANKL in rheumatoid arthritis-associated juxta-articular bone loss has not yet been explored. This study aimed to determine whether RANKL produced by chondrocytes induces osteoclastogenesis and juxta-articular bone loss associated with chronic arthritis.

PTH [1-34] enhances bone response around titanium implants in a rabbit model of osteoporosis.

Introduction: Dental implant osseointegration can be impaired in medical conditions with low bone mass, such as glucocorticoid-induced osteoporosis. Intermittent human parathyroid hormone (PTH) [1-34] administration has shown relevant anabolic bone activity in various animal models of osteoporosis. Therefore, we studied the effects of intermittent PTH [1-34] on bone response around titanium implants in experimental osteoporosis induced by ovariectomy and glucocorticoid administration.

Subchondral bone as a key target for osteoarthritis treatment.

Osteoarthritis (OA), the most common form of arthritis, is a debilitating and progressive disease that has become a major cause of disability and impaired quality of life in the elderly. OA is considered an organ disease that affects the whole joint, where the subchondral bone (SB) plays a crucial role. Regardless of whether SB alterations precede cartilage damage or appear during the evolution of the disease, SB is currently recognised as a key target in OA treatment.

Bone mineral density and joint cartilage: four clinical settings of a complex relationship in osteoarthritis.

Experimental and clinical data support the hypothesis that both high and low bone mineral density (BMD) conditions, including osteoporosis, may induce osteoarthritis. However, these conditions do not always predispose to osteoarthritis progression. Four clinical settings could arise from this relationship, and furthermore two phenotypes may be identified whether early osteoarthritis coexists with high or low BMD.

Subchondral bone microstructural damage by increased remodelling aggravates experimental osteoarthritis preceded by osteoporosis.

Introduction: Osteoporosis (OP) increases cartilage damage in a combined rabbit model of OP and osteoarthritis (OA). Accordingly, we assessed whether microstructure impairment at subchondral bone aggravates cartilage damage in this experimental model.

Methods: OP was induced in 20 female rabbits, by ovariectomy and intramuscular injections of methylprednisolone hemisuccinate for four weeks.

Efficacy and safety of a selective estrogen receptor β agonist, ERB-041, in patients with rheumatoid arthritis: a 12-week, randomized, placebo-controlled, phase II study.

Objective: Selective estrogen receptor β (ERβ) agonists have demonstrated relevant antiinflammatory effects in different animal models. This study aimed to compare the efficacy and safety of one of these agonists, ERB-041, in subjects with rheumatoid arthritis (RA).

Methods: A total of 291 patients with active RA receiving stable doses of methotrexate were randomized to receive 5, 25, or 75 mg of ERB-041 or placebo for 12 weeks.

Osteoarthritis associated with estrogen deficiency.

Osteoarthritis (OA) affects all articular tissues and finally leads to joint failure. Although articular tissues have long been considered unresponsive to estrogens or their deficiency, there is now increasing evidence that estrogens influence the activity of joint tissues through complex molecular pathways that act at multiple levels. Indeed, we are only just beginning to understand the effects of estrogen deficiency on articular tissues during OA development and progression, as well as on the association between OA and osteoporosis.