Bone - Articles in Press

In situ fatty acid profile of femoral cancellous subchondral bone in osteoarthritic and fragility fracture females: Implications for bone remodelling - Corrected Proof

J.M. Humphries, J.S. Kuliwaba, R.J. Gibson, N.L. Fazzalari — 2012-05-14

Abstract: We report here differences in the fatty acid profile of cancellous bone matrix, including n-3, n-6, mono- and poly-unsaturated, as well as saturated fats, between femoral heads from female OA (n=8, aged 68–88years), fractured neck of femur (#NOF) (n=19, 67–88years) and autopsy controls (CTRL) (n=4, 85–97years). Femoral heads were collected from individuals undergoing orthopaedic surgery for OA or #NOF; the fatty acid profile of sub-samples from the superior principal compressive and superior principal tensile regions were determined by gas chromatography. A total of 42 individual fatty acids were detected at varying concentrations with significant differences between subchondral bone from OA subjects, subchondral bone from #NOF subjects and subchondral bone from CTRL subjects, as well as between the superior principal compressive and superior principal tensile regions (for saturated fats only).Subchondral bone from OA subjects had higher total n-6 (OA=10.89±3.17, #NOF=11.11±1.83, CTRL=8.32±2.05, p=0.008) and total n-3 (OA=1.34±0.38, #NOF=1.19±0.18, CTRL=1.15±0.48, p=0.011) percentages than subchondral bone from #NOF subjects and subchondral bone from CTRL subjects, and there was no difference in the n-6:n-3 ratio, nor within the percentage of n-9 fatty acids. Arachidonic acid (OA=0.42±0.16, #NOF=0.26±0.06, CTRL=0.28±0.06, p=0.01), and γ-linolenic acid (OA=0.11±0.03, #NOF=0.05±0.02, CTRL=0.04±0.02, p<0.001) were higher in subchondral bone from OA subjects than subchondral bone from #NOF subjects and subchondral bone from CTRL subjects. In conclusion, there is a wide diversity of fatty acids in cancellous bone matrix from the femoral heads of OA and #NOF, suggesting they may have regulatory effects on inflammatory processes, and their metabolites.This article is part of a Special Issue entitled Osteoarthritis.Highlights: ► The femoral subchondral bone matrix in situ total fat content of osteoarthritic and non-OA subjects differ. ► n-3, n-6 and n-9 fatty acid profiles differ between OA and non-OA groups. ► Differential fatty acid profiles may modulate inflammatory processes influencing subchondral bone remodelling, hence, the onset and progression of OA.

Peripartum nutrition and adult bone health - Corrected Proof

Andrew Grey — 2012-05-14

In their review of the effects of pre- and peri-natal maternal nutrition on the skeletal health of offspring, Devlin and Bouxsein conclude that “…any imbalance in maternal diet – too few calories, too much fat, too little protein – seems to alter postnatal bone mass …” and call for more research to determine the mechanism(s) by which peri-natal “programming” influences bone mass . However, the evidence that peri-partum influences on adult skeletal health are biologically significant is underwhelming. The suggestions from correlative studies that both maternal undernutrition and overnutrition might be detrimental to the offspring's skeleton should immediately prompt scepticism. Cohort studies suggest that birth weight explains a trivial proportion of the variance in adult bone mineral density (BMD) , and even very substantial reductions in birth weight are associated with small (0.5 SD) decrements in peak BMD that are considerably attenuated by adjustment for adult body weight . Since BMD in turn only explains a proportion of the risk of fragility fracture , it is very likely that alterations in fetal nutrition contribute very little to fracture risk in older adults. Overly enthusiastic interpretation of an extremely limited (in both quantity and quality) dataset is potentially dangerous, in causing undue anxiety among pregnant women about the influence of their diet on the long-term health of their children, and in diverting scarce research funds into attempts to explain a phenomenon for which no consistent or compelling evidence of an important effect exists.

Biological markers in osteoarthritis - Corrected Proof

J.Ch. Rousseau, P. Garnero — 2012-05-03

Abstract: Osteoarthritis (OA) is considered as a chronic disease with a long “silent” period. The diagnosis is generally based on clinical symptoms and radiographic changes. However X-ray has a poor sensitivity and a relatively large precision error that does not allow an early detection of OA or the monitoring of joint damage progression. The limitations of the tools that are currently available for OA assessment have been the impetus to identify specific biological markers that reflect quantitative and dynamic variations in joint remodeling. Research has focused on the structural components of cartilage matrix, especially type II collagen degradation markers. In spite of a significant increase of some markers in individuals with early stage of OA, the large overlap with control subjects indicates that the current biomarkers used alone have limited diagnostic potential. However, the combination of specific markers seems to improve the prediction of disease progression at the individual level. Several types of treatment have been investigated but the lack of medications with definitively demonstrated chondroprotective activity has limited the assessment of the potential role of biomarkers for monitoring patients' responses to the treatment of OA. In this review, we will use the BIPED classification that appeared in 2006 for OA markers to describe the potential usage of a given marker [5].This article is part of a Special Issue entitled Osteoarthritis.Highlights: ► At individual level, the current markers have limited diagnostic potential. ► Several markers have been shown to correlate with the burden of disease. ► The combined used of markers could assist the prediction of disease progression. ► For monitoring patients' responses to treatment markers might provide relevant information.

Effects of aging on articular cartilage homeostasis - Corrected Proof

Martin Lotz, Richard F. Loeser — 2012-04-30

Abstract: This review is focused on aging-related changes in cells and extracellular matrix of the articular cartilage. Major extracellular matrix changes are a reduced thickness of cartilage, proteolysis, advanced glycation and calcification. The cellular changes include reduced cell density, cellular senescence with abnormal secretory profiles, and impaired cellular defense mechanisms and anabolic responses. The extracellular and cellular changes compound each other, leading to biomechanical dysfunction and tissue destruction. The consequences of aging-related changes for joint homeostasis and risk for osteoarthritis are discussed.This article is part of a Special Issue entitled “Osteoarthritis”.

Vascular tissues are a primary source of BMP2 expression during bone formation induced by distraction osteogenesis - Corrected Proof

2012-04-27

Abstract: Prior studies showed that bone regeneration during distraction osteogenesis (DO) was dependent on vascular tissue development and that inhibition of VEGFR signaling diminished the expression of BMP2. A combination of micro-computed tomography (μCT) analysis of vascular and skeletal tissues, immunohistological and histological analysis of transgenic mice containing a BAC transgene in which β-galactosidase had been inserted into the coding region of BMP2 and qRT-PCR analysis, was used to examine how the spatial temporal expression of the morphogenetic signals that drive skeletal and vascular tissue development is coordinated during DO. These results showed that BMP2 expression was induced in smooth muscle and vascular endothelial cells of arteries and veins, capillary endothelial cells, hypertrophic chondrocytes and osteocytes. BMP2 was not expressed by lymphatic vessels or macrophages. Separate peaks of BMP2 mRNA expression were induced in the surrounding muscular tissues and the distraction gap and corresponded first with large vessel collateralization and arteriole remodeling followed by periods of angiogenesis in the gap region. Immunohistological and qRT-PCR analysis of VEGF receptors and ligands showed that mesenchymal cells, lining cells and chondrocytes, expressed VEGFA, although PlGF expression was only seen in mesenchymal cells within the gap region. On the other hand VEGFR2 appeared to be predominantly expressed by vascular endothelial and hematopoietic cells. These results suggest that bone and vascular tissue formation is coordinated via a mutually supporting set of paracrine loops in which blood vessels primarily synthesize the morphogens that promote bone formation while mesenchymal cells primarily synthesize the morphogens that promote vascular tissue formation.Highlights: ► Vascular smooth muscle and endothelia cells express BMP2 during osteogenesis. ► Mesenchymal cells and skeletal cells express VEGFA and PlGF during osteogenesis. ► Lymphatic vessels and macrophages do not express BMP.

Clinical correlates of atypical femoral fracture - Corrected Proof

2012-04-16

Abstract: Background: Reports of atypical femur fracture in bisphosphonate-exposed women have prompted interest in characterizing the clinical profiles of these patients.Methods: Among women age ≥60years with hip or femur fracture during 2007–2008, we identified 79 with low-trauma subtrochanteric or femoral shaft fracture. Radiographic images were reviewed to assign fracture pattern and distinguish atypical femur fracture from non-atypical femur fracture. Differences in clinical characteristics and pharmacologic exposures were compared.Results: Among 79 women (38 subtrochanteric and 41 femoral shaft fracture), 38 had an atypical femur fracture. Compared to those with a non-atypical femur fracture, women with atypical femur fracture were significantly younger (74.0 vs 81.0years), more likely to be Asian (50.0 vs 2.4%) and to have received bisphosphonate therapy (97.4 vs 41.5%). Similarly, the contralateral femur showed a stress or complete fracture in 39.5% of atypical femur fractures vs 2.4% non-atypical femur fracture, and focal cortical hypertrophy of the contralateral femur in an additional 21.1% of atypical cases.Conclusions: Women suffering atypical femur fractures have a markedly different clinical profile from those sustaining typical fractures. Women with atypical femur fracture tend to be younger, Asian, and bisphosphonate-exposed. The high frequency of contralateral femur findings suggests a generalized process.

Functional characterization of normal and degraded bovine meniscus: Rate-dependent indentation and friction studies - Corrected Proof

2012-04-06

Abstract: The menisci are known to play important roles in normal joint function and the development of diseases such as osteoarthritis. However, our understanding of meniscus' load bearing and lubrication properties at the tissue level remains limited. The objective of this investigation was to characterize the site- and rate-dependency of the compressive and frictional responses of the meniscus under a spherical contact load. Using a custom testing device, indentation tests with rates of 1, 10, 25, 50, and 100μm/s were performed on bovine medial meniscus explants, which were harvested from five locations including the femoral apposing surface at the anterior, central, and posterior locations and the central portion at the deep layer and at the tibial apposing surface (n=5 per location). Sliding tests with rates of 0.05, 0.25, 1, and 5mm/s were performed on the central femoral aspect and central tibial aspect superficial samples (n=6 per location). A separate set of superficial samples were subjected to papain digestion and tested prior to and post treatment. Our findings are: i) the Hertz contact model can be used to fit the force responses of meniscus under the conditions tested; ii) the anterior region is significantly stiffer than the posterior region and tissue modulus does not vary with tissue depth at the central region; iii) the friction coefficient of the meniscus is on the order of 0.02 under migratory contacts and the femoral apposing surface tends to show lower friction than the tibial apposing surface; iv) the meniscus exhibits increased modulus and lubrication with increased indentation and sliding rates; v) matrix degradation impedes the functional load support and lubrication properties of the tissue. The site- and rate-dependent properties of the meniscus may be attributed to spatial variations of the tissue's biphasic structure. These properties substantiate the role of the meniscus as one of the important bearing surfaces of the knee. These data contribute to an improved understanding of meniscus function, and its role in degenerative joint diseases. In addition, the results provide functional metrics for developing engineered tissue replacements. This article is part of a Special Issue entitled Osteoarthritis.Highlights: ► Measured site- and rate-dependent load support and lubrication characteristics of normal and degraded meniscus. ► Stiffness and lubrication increased with increased rates. ► Load support and lubrication varied spatially along and throughout the meniscus. ► Papain digestion reduced load capacity and lubrication.

The role of synovitis in osteoarthritis pathogenesis - Corrected Proof

Carla R. Scanzello, Steven R. Goldring — 2012-03-15

Abstract: Research into the pathophysiology of osteoarthritis (OA) has focused on cartilage and peri-articular bone, but there is increasing recognition that OA affects all of the joint tissues, including the synovium (SM). Under normal physiological conditions the synovial lining consists of a thin layer of cells with phenotypic features of macrophages and fibroblasts. These cells and the underlying vascularized connective tissue stroma form a complex structure that is an important source of synovial fluid (SF) components that are essential for normal cartilage and joint function. The histological changes observed in the SM in OA generally include features indicative of an inflammatory “synovitis”; specifically they encompass a range of abnormalities, such as synovial lining hyperplasia, infiltration of macrophages and lymphocytes, neoangiogenesis and fibrosis. The pattern of synovial reaction varies with disease duration and associated metabolic and structural changes in other joint tissues. Imaging modalities including magnetic resonance (MRI) and ultrasound (US) have proved useful in detecting and quantifying synovial abnormalities, but individual studies have varied in their methods of evaluation. Despite these differences, most studies have concluded that the presence of synovitis in OA is associated with more severe pain and joint dysfunction. In addition, synovitis may be predictive of faster rates of cartilage loss in certain patient populations. Recent studies have provided insights into the pathogenic mechanisms underlying the development of synovitis in OA. Available evidence suggests that the inflammatory process involves engagement of Toll-like receptors and activation of the complement cascade by degradation products of extracellular matrices of cartilage and other joint tissues. The ensuing synovial reaction can lead to synthesis and release of a wide variety of cytokines and chemokines. Some of these inflammatory mediators are detected in joint tissues and SF in OA and have catabolic effects on chondrocytes. These inflammatory mediators represent potential targets for therapeutic interventions designed to reduce both symptoms and structural joint damage in OA. This article is part of a Special Issue entitled: Osteoarthritis.

Role of bone architecture and anatomy in osteoarthritis - Corrected Proof

Julie C. Baker-LePain, Nancy E. Lane — 2012-03-09

Abstract: When considering the pathogenesis of osteoarthritis (OA), it is important to review the contribution of bone in addition to the contribution of cartilage and synovium. Although bone clearly plays a role in determining the distribution of biomechanical forces across joints, which in turn plays a role in the initiation of OA, it has also more recently been appreciated that bone may contribute in a biological sense to the pathogenesis of OA. Far from being a static structure, bone is a dynamic tissue undergoing constant remodeling, and it is clear from a number of radiographic and biochemical studies that bone and cartilage degradation occurs hand in hand. Whether the initial instigating event in OA occurs in cartilage or bone is not known, but it is clear that bony changes occur very early in the pathogenesis of OA and often predate radiographic appearance of the disease. This review focuses on the structural variants of both hip and knee that have been associated with OA and the ultrastructural bone changes in these sites occurring in early OA pathogenesis.This article is part of a Special Issue entitled Osteoarthritis.

Pathophysiology of peri-articular bone changes in osteoarthritis - Corrected Proof

H. Weinans, M. Siebelt, R. Agricola, S.M. Botter, T.M. Piscaer, J.H. Waarsing — 2012-03-09

Abstract: Osteoarthritis (OA) is a disease that involves the entire joint, but its pathophysiology is not well described. Alterations in peri-articular bone are an integral part of the OA disease process and different aspects of bone changes have been described in different patient (sub)groups and animal models. In this review we will discuss the osteoarthritis pathophysiology from the perspective of periarticular bone changes, which can be considered at three hierarchical levels: the bone (or joint) shape, the subchondral bone architecture and its cellular and molecular phenotype. In this review we try to provide an overview of the current knowledge of peri-articular bone changes in OA and what it could possibly imply for the initiation of OA and its progression.This article is part of a Special Issue entitled “Osteoarthritis”.

Elevated cross-talk between subchondral bone and cartilage in osteoarthritic joints - Corrected Proof

2012-01-13

Abstract: Osteoarthritis (OA) is a degenerative joint disease and one of the leading causes of disability in the United States and across the world. As a disease of the whole joint, OA exhibits a complicated etiology with risk factors including, but not limited to, ageing, altered joint loading, and injury. Subchondral bone is hypothesized to be involved in OA development. However, direct evidence supporting this is lacking. We previously detected measurable transport of solute across the mineralized calcified cartilage in normal joints, suggesting a potential cross-talk between subchondral bone and cartilage. Whether this cross-talk exists in OA has not been established yet. Using two models that induced OA by either ageing or surgery (destabilization of medial meniscus, DMM), we tested the hypothesis that increased cross-talk occurs in OA. We quantified the diffusivity of sodium fluorescein (mol. wt. 376Da), a marker of small-sized signaling molecules, within calcified joint matrix using our newly developed fluorescence loss induced by photobleaching (FLIP) method. Tracer diffusivity was found to be 0.30±0.17 and 0.33±0.20μm2/s within the calcified cartilage and 0.12±0.04 and 0.07±0.03μm2/s across the osteochondral interface in the aged (20–24-month-old, n=4) and DMM OA joints (5-month-old, n=5), respectively, which were comparable to the control values for the contralateral non-operated joints in the DMM mice (0.48±0.13 and 0.12±0.06μm2/s). Although we did not detect significant changes in tissue matrix permeability in OA joints, we found i) an increased number of vessels invading the calcified cartilage (and sometimes approaching the tidemark) in the aged (+100%) and DMM (+50%) joints relative to the normal age controls; and ii) a 60% thinning of the subchondral bone and calcified cartilage layers in the aged joints (with no significant changes detected in the DMM joints). These results suggested that the capacity for cross-talk between subchondral bone and articular cartilage could be elevated in OA. Further studies are needed to identify the direction of the cross-talk, the signaling molecules involved, and to test whether subchondral bone initiates OA development and could serve as a pharmaceutical target for OA treatment.This article is part of a Special Issue entitled “Osteoarthritis”.Highlights: ► Bone-cartilage cross-talk examined in two models (surgical DMM and ageing) of OA. ► Decreased (but not significant) tissue permeability in mineralized ECM of OA joints. ► Increased vessels invasion in aged (+100%) and DMM (+50%) joints vs. controls. ► 60% thinning of thickness in aged joints and no changes in DMM joints vs. controls. ► Bone-cartilage cross-talk elevated in the two OA models via different mechanisms.

Genetic factors in OA pathogenesis - Corrected Proof

Kay Chapman, Ana M. Valdes — 2012-01-04

Abstract: Osteoarthritis (OA) is known to have an important genetic component and human genetic studies can help unravel the molecular mechanisms responsible for joint damage and nociception involved in OA. Genetic studies in humans have identified molecules involved in signaling cascades that are important for the pathology of the joint components such as the bone morphogenetic protein growth differentiation factor 5 (GDF5). Genomewide association scans (GWAS) in Asians have uncovered a likely role for structural extracellular matrix components (DVWA), and for molecules involved in immune response (HLA class II DQB1 and BTNL2) but these genes are not associated in Caucasian patients. In Caucasians a ~300 kilobase region in chromosome 7q22 containing several genes has been found to be reproducibly associated with OA. A recent European GWAS taking advantage of imputation techniques has uncovered a variant in the MCF2L gene as significantly associated with large joint OA. MCF2L is involved in neurotrophin mediated regulation of cell motility in the peripheral nervous system, and thus potentially implicated in nociception in OA. As the number of OA cases with genomewide genotyping increases it is expected that many more reproducible variants implicated in OA will be reported.This article is part of a Special Issue entitled Osteoarthritis.Highlights: ► We review the genetic associations reported to date with knee and hip osteoarthritis. ► Different genetic associations are seen in Asian populations from those of European descent. ► In European-descent populations three genetic variants have been reported to be associated with genome-wide significance with OA. ► These variants map to the GDF5 and MCF2L genes, and the COG5/GRP22 cluster (function as yet unknown). ► GDF5 is a chondroprotective growth factor. MCF2L is involved in neurotrophin regulated cell motility and potentially in nociception.

Diagnosis of osteoarthritis: Imaging - Corrected Proof

Hillary J. Braun, Garry E. Gold — 2011-12-30

Abstract: Osteoarthritis (OA) is a chronic, debilitating joint disease characterized by degenerative changes to the bones, cartilage, menisci, ligaments, and synovial tissue. Imaging modalities such as radiography, magnetic resonance imaging (MRI), optical coherence tomography (OCT), and ultrasound (US) permit visualization of these structures and can evaluate disease onset and progression. Radiography is primarily useful for the assessment of bony structures, while OCT is used for evaluation of articular cartilage and US for ligaments and the synovium. MRI permits visualization of all intraarticular structures and pathologies, though US or OCT may be preferential in some circumstances. As OA is a disease of the whole joint, a combination of imaging techniques may be necessary in order to gain the most comprehensive picture of the disease state.This article is part of a Special Issue entitled Osteoarthritis.

Serum xylosyltransferase 1 level increases during early posttraumatic osteoarthritis in mice with high bone forming potential - Corrected Proof

2011-12-19

Abstract: Increased proteoglycan (PG) synthesis is essential for the stimulation of cartilage repair processes that take place during the reversible phase of osteoarthritis (OA). In articular cartilage, xylosyltransferase 1 (Xylt1) is the key enzyme that initiates glycosaminoglycan (GAG) chain synthesis by transferring the first sugar residue to the PG core protein. Biological activity of PGs is closely linked to GAG biosynthesis since their polyanionic nature directly contributes to the proper hydration and elastic properties of the cartilage tissue present at the articular interface. The aim of this study was to investigate whether variations in the level of Xylt1 present in serum can be used to predict OA disease progression. The influence of bone forming activity on the systemic release of this enzyme was addressed by experimentally-inducing OA in mice of two different genetic backgrounds that were previously characterized for their distinct bone metabolism: C57BL/6J (B6, high bone remodelers) or C3H/HeJ (C3H, high bone formers). Serum was collected after medial meniscectomy or sham surgeries in young adult mice of these two strains over a period of 3.5months at which point knee histopathology was assessed. A significant increase in serum Xylt1 levels observed shortly after meniscectomy positively correlated with severe cartilage damage evaluated by histological assessment at later time points in mice of the C3H background. In contrast, no temporal regulation of Xylt1 level was found between meniscectomies and control surgeries in B6 mice, which developed OA at a slower rate. Additionally, longitudinal evaluation of the serum levels of other markers of cartilage/bone metabolism (C1,2C, osteocalcin) did not reveal any association with late knee damages. Our results strongly support the idea that serum Xylt1 has a clinical value for monitoring risk of OA progression in young adults with high bone forming potential. Ultimately, the understanding of posttraumatic mechanisms regulating PG synthesis and their modification by GAG will be essential so that interventions that stimulate cartilage regrowth can be undertaken prior to irreversible destruction of the joint tissue. This article is part of a Special Issue entitled .Highlights: ► Serum level of xylosyltransferases is an indicator of proteoglycan synthesis rate. ► Serum Xylt1 level transiently increases following meniscectomy only in C3H/HeJ mice. ► Meniscectomy induces faster OA progression in C3H/HeJ mice than in C57BL/6J mice. ► Early increase in serum Xylt1 correlates with later cartilage damage in C3H/HeJ. ► Serum levels of Xylt1 may be used as a biomarker to predict OA.

Osteochondral alterations in osteoarthritis - Corrected Proof

Sunita Suri, David A. Walsh — 2011-11-18

Abstract: Osteoarthritis (OA) is a major cause of pain and disability in the aging population, but its pathogenesis remains incompletely understood. Alterations beneath the articular cartilage at the osteochondral junction are attracting interest as possible mediators of pain and structural progression in OA. Osteochondral changes occur early during the development of OA and may aggravate pathology elsewhere in the joint. Loss of osteochondral integrity removes the barrier between intra-articular and subchondral compartments, exposing subchondral bone and its nerves to abnormal chemical and biomechanical influence. Osteochondral plasticity results in a merging of tissue compartments across the junction. Loss of the clearly differentiated demarcation between bone and articular cartilage is associated with invasion of articular cartilage by blood vessels and sensory nerves, and advancing endochondral ossification. Increased subchondral bone turnover is intimately associated with these alterations at the osteochondral junction. Cells signal across the osteochondral junction, and this cross-talk may be both a consequence of, and contribute to these pathological changes. Bone turnover, angiogenesis and nerve growth are also features of other diseases such as osteoporosis and cancers, for which therapeutic interventions are already advanced in their development. Here we review pathological changes at the osteochondral junction and explore their potential therapeutic implications for OA. This article is part of a Special Issue entitled .

Tissue engineering approaches for osteoarthritis - Corrected Proof

Frank P. Luyten, Johan Vanlauwe — 2011-11-14

Abstract: With the ageing of the population and the major advances in targeted drug treatments, there is in medicine a shift in attention from survival towards quality of life. Therefore new challenges are emerging in modern health care. Preventive and personalized medicine have been identified as key steps in this context. New targeted biologicals for musculoskeletal diseases such as chronic arthritis have entered daily clinical practice, thereby not only controlling symptoms and signs, inflammation and destruction, but also maintaining function of the joints. The last aspect is essential for the independence of the individual and critical for the quality of life. Since the lifespan of prosthetic devices will always remain limited, new treatment approaches to repair skeletal structures need to be devised for the young and middle aged individuals with skeletal and joint damage caused by either congenital, traumatic, or inflammatory conditions. It is believed that regenerative medicine and more specifically tissue engineering may fill this void to some extent. Indeed, recent cellular therapeutics and combination products, now resorting under a new regulatory class of Advanced Medicinal Therapeutic Products, provide indications that progress is being made with clinically relevant outcomes in well-defined patient populations. For osteoarthritis, a joint disease leading to joint decompensation, novel tissue engineering therapies are being explored and, although most of the developments are still in early phase clinical studies, there are sufficient positive signals to pursue these novel therapeutic approaches in clinics. This article is part of a Special Issue entitled “Osteoarthritis”.

Future therapeutics for osteoarthritis - Corrected Proof

Johanne Martel-Pelletier, Lukas M. Wildi, Jean-Pierre Pelletier — 2011-11-14

Abstract: Osteoarthritis (OA) is a disease of the joints that affects several million individuals worldwide. This disease, which involves mainly the diarthrodial joints, is chronic and develops slowly over decades, making it very difficult to precisely identify the different etiological and risk factors that influence its onset. At present, most therapies for OA are symptomatic. This review will focus on new OA therapeutics in development that are directed toward pain relief as well as others with the potential to reduce or stop the progression of the disease (DMOADs).This article is part of a Special Issue entitled “Osteoarthritis”.

50 Withdrawn - Corrected Proof

2006-02-17