Pathophysiology of peri-articular bone changes in osteoarthritis

Weinans, Harrie; Siebelt, Michiel; Agricola, Rintje; Botter, Sander M.; Piscaer, T.M.; Waarsing, J.H.

doi:10.1016/j.bone.2012.02.002

Cited by 58 publications

(45 citation statements)

References 75 publications

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“…Numerous clinical and experimental studies have confirmed that increased bone volume and changes in bone quality of the tibial subchondral bone of the knee are related to loss of cartilage integrity [7,8,36-38]. Goldring and Goldring have pointed out that subchondral bone responds more rapidly to adverse loading and events than cartilage [5].…”

Section: Discussionmentioning

confidence: 99%

Genome-wide expression profiles of subchondral bone in osteoarthritis

et al. 2013

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IntroductionThe aim of this study was to evaluate, for the first time, the differences in gene expression profiles of normal and osteoarthritic (OA) subchondral bone in human subjects.MethodsFollowing histological assessment of the integrity of overlying cartilage and the severity of bone abnormality by micro-computed tomography, we isolated total RNA from regions of interest from human OA (n = 20) and non-OA (n = 5) knee lateral tibial (LT) and medial tibial (MT) plateaus. A whole-genome profiling study was performed on an Agilent microarray platform and analyzed using Agilent GeneSpring GX11.5. Confirmatory quantitative reverse-transcription polymerase chain reaction (qRT-PCR) analysis was performed on samples from 9 OA individuals to confirm differential expression of 85 genes identified by microarray. Ingenuity Pathway Analysis (IPA) was used to investigate canonical pathways and immunohistochemical staining was performed to validate protein expression levels in samples.ResultsA total of 972 differentially expressed genes were identified (fold change ≥ ± 2, P ≤0.05) between LT (minimal degeneration) and MT (significant degeneration) regions from OA samples; these data implicated 279 canonical pathways in IPA. The qRT-PCR data strongly confirmed the accuracy of microarray results (R2 = 0.58, P <0.0001). Novel pathways were identified in this study including Periostin (POSTN) and Leptin (LEP), which are implicated in bone remodeling by osteoblasts.ConclusionsTo the best of our knowledge, this study represents the most comprehensive direct assessment to date of gene expression profiling in OA subchondral bone. This study provides insights that could contribute to the development of new biomarkers and therapeutic strategies for OA.

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Section: Discussionmentioning

confidence: 99%

Genome-wide expression profiles of subchondral bone in osteoarthritis

et al. 2013

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“…Inflammation can be caused by a variety of cytokines such as Interleukins (ILs) [51], Tumor Necrosis Factors (TNFs), and Nitric Oxide (NO) [52], whereas, cartilage degradation is mainly caused by enzymes, such as Matrix Metalloproteinases (MMPs) and a disintegrin and metalloproteinase with thrombospondin motifs (ADAMTS) [52]. Furthermore, a strong correlation between subchondral bone changes and OA development has been described [53,54].…”

Section: Dmoadsmentioning

confidence: 99%

Drugs and Polymers for Delivery Systems in OA Joints: Clinical Needs and Opportunities

et al. 2014

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Osteoarthritis (OA) is a big burden of disease worldwide and one of the most common causes of disability in the adult population. Currently applied therapies consist of physical therapy, oral medication, intra-articular injections, and surgical interventions, with the main goal being to reduce pain and improve function and quality of life. Intra-articular (IA) administration of drugs has potential benefits in OA treatment because it minimizes systemic bioavailability and side effects associated with oral administration of drugs without compromising the therapeutic effect in the joint. However, IA drug residence time is short and there is a clinical need for a vehicle that is able to provide a sustained release long enough for IA therapy to fulfill its promise. This review summarizes the use of different polymeric systems and the incorporated drugs for IA drug delivery in the osteoarthritic joint with a primary focus on clinical needs and opportunities.

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“…Emergent evidence suggests that vitamin D plays an important role in immune regulation, and epidemiological data suggest that vitamin D deficiency may be a risk factor for development of autoimmune and chronic diseases [16–17]. Vitamin D has been found to play a role in multiple articular structures, including cartilage, subchondral bone and periarticular muscle, which are risk factors for the progression of knee osteoarthritis [18–19]. Studies have shown that lower serum levels of vitamin D associated with greater knee pain, higher prevalence of radiographic osteoarthritis (OA), incidence of knee pain, progression of radiographic OA, loss of joint space, and osteophyte growth [20–22].…”

Section: Introductionmentioning

confidence: 99%

Association of arthritis and vitamin D insufficiency with physical disability in Mexican older adults: findings from the Mexican Health and Aging Study

et al. 2016

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Objective Arthritis and vitamin D insufficiency are prevalent in older adults and are risk factors for disability. The objective of this study was to examine the effect of co-ocurring arthritis and vitamin D defficiency on upper-lower extremity functional limitations and disability in older adults. Methods We examined 1,533 participants aged ≥50 years from a subsample of the Mexican Health and Aging Study. Measures included sociodemographics, body mass index, comorbid conditions, falls, physical activity, physical function tests, functional limitations, activities of daily living (ADL), and vitamin D. Participants were categorized into four groups according to arthritis and vitamin D status: no vitamin D insufficiency and no arthritis (58.80%), vitamin D insufficiency only (27.49%), arthritis only (8.47%), and arthritis and vitamin D insufficiency (5.24%). Results Fourteen percent reported arthritis and 31.2% had vitamin D insufficiency. The arthritis and vitamin D insufficiency group was associated with upper-lower extremity functional limitations (odds ratio [OR] =1.82, 95% Confidence Interval[CI]=1.06-3.15, and OR=1.90, 95%CI=1.00-3.62, respectively) and ADL disability (OR=3.00, 95%CI=1.63-5.51) when compared with the no vitamin D insufficiency and no arthritis group (reference group). The arthritis only group was three times more likely to report upper-lower extremity functional limitations and ADL disability. The vitamin D insufficiency only group was not significantly associated with functional limitations nor ADL disability. Conclusion Arthritis and vitamin D insufficiency increased the risk of ADL disability in this population. However, the effect of arthritis and vitamin D insufficiency on upper- lower extremity functional limitations was not higher than the effect of arthritis only, but higher than the effect on vitamin D insufficiency alone.

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Pathophysiology of peri-articular bone changes in osteoarthritis

Cited by 58 publications

References 75 publications

Genome-wide expression profiles of subchondral bone in osteoarthritis

Genome-wide expression profiles of subchondral bone in osteoarthritis

Drugs and Polymers for Delivery Systems in OA Joints: Clinical Needs and Opportunities

Association of arthritis and vitamin D insufficiency with physical disability in Mexican older adults: findings from the Mexican Health and Aging Study

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