Longitudinal study of radiographic spinal osteoarthritis in a macaque model.
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ABSTRACT:
SUBMITTER: Duncan AE
PROVIDER: S-EPMC3241944 | biostudies-literature | 2011 Aug
REPOSITORIES: biostudies-literature
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Longitudinal study of radiographic spinal osteoarthritis in a macaque model.
Duncan Andrea E AE Colman Ricki J RJ Kramer Patricia A PA
Journal of orthopaedic research : official publication of the Orthopaedic Research Society 20110304 8
Cross-sectional analyses of naturally occurring spinal osteoarthritis (OA) in primates have shown that age and body mass are significant predictors, but whether or not these relationships hold true in longitudinal evaluations remains unclear. Because spinal OA manifests similarly in humans and monkeys and macaque monkeys age >3 times the rate of humans, macaque models offer opportunities for longitudinal study that are difficult in humans. Our objective was to characterize the longitudinal devel ...[more]
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Project description:IntroductionPost hoc analyses of osteoporosis trials have suggested that alendronate and strontium ranelate may be associated with a reduction in the progression of spinal radiographic osteoarthritis (OA). We performed an analysis on a subgroup of participants in the horizon PFT trial (a 3-year randomized controlled trial (RCT) of yearly zoledronic acid (ZA) in postmenopausal women with osteoporosis), to evaluate the effect of ZA on the structural progression of spinal osteophytes (OPh) and disk space narrowing (DN).MethodsPaired lateral spinal X-rays (baseline and 36 months) were selected from the horizon PFT trial records restricted to those with radiographic OA at baseline. The X-rays were analyzed by two readers blinded to the treatment allocation. OPh and DN were scored separately using the Lane atlas (0-3 for increasing severity at each vertebral level) at all evaluable levels from T4-12 and L1-5.ResultsA total of 504 sets of paired radiographs were included in the analysis, 245 in the ZA group and 259 in the placebo group. Overall, the rates of change of OPh and DN scores were low, and they were not statistically different between the groups (change in the whole spine OPh ZA 1.0 ± 1.6, placebo 0.8 ± 1.3, p = 0.1; DN ZA 0.3 ± 1.0, placebo 0.3 ± 0.8, p = 0.7).ConclusionYearly ZA for 3 years was not associated with a slowing of progression of OPh or DN in the thoracolumbar spine in patients with pre-existing radiographic OA.
| S-EPMC9283639 | biostudies-literature
Project description:BackgroundThe aim of this study was to identify modifiable clinical factors associated with radiographic osteoarthritis progression over 1 to 2 years in people with painful medial knee osteoarthritis.MethodsA longitudinal study was conducted within a randomised controlled trial, the "Long-term Evaluation of Glucosamine Sulfate" (LEGS study). Recruitment occurred in 2007-2009, with 1- and 2-year follow-up assessments by blinded assessors. Community-dwelling people with chronic knee pain (≥4/10) and medial tibiofemoral narrowing (but retaining >2mm medial joint space width) on radiographs were recruited. From 605 participants, follow-up data were available for 498 (82%, mean [sd] age 60 [8] years). Risk factors evaluated at baseline were pain, physical function, use of non-steroidal anti-inflammatory drugs (NSAIDs), statin use, not meeting physical activity guidelines, presence of Heberden's nodes, history of knee surgery/trauma, and manual occupation. Multivariable logistic regression analysis was conducted adjusting for age, sex, obesity, high blood pressure, allocation to glucosamine and chondroitin treatment, and baseline structural disease severity (Kellgren and Lawrence grade, joint space width, and varus alignment). Radiographic osteoarthritis progression was defined as joint space narrowing ≥0.5mm over 1 to 2 years (latest follow-up used where available).ResultsRadiographic osteoarthritis progression occurred in 58 participants (12%). Clinical factors independently associated with radiographic progression were the use of NSAIDs, adjusted odds ratios (OR) and 95% confidence intervals (CI) 2.05 (95% CI 1.1 to 3.8), and not meeting physical activity guidelines, OR 2.07 (95% CI 0.9 to 4.7).ConclusionsAmong people with mild radiographic knee osteoarthritis, people who use NSAIDs and/or do not meet physical activity guidelines have a greater risk of radiographic osteoarthritis progression.Trial registrationClinicalTrials.gov , NCT00513422 . This original study trial was registered a priori, on August 8, 2007. The current study hypothesis arose before inspection of the data.
| S-EPMC8176608 | biostudies-literature
Project description:OBJECTIVE:To explore whether metabolic syndrome and its components are associated with hand osteoarthritis (OA) using longitudinal data from the Framingham Study. METHODS:Our cross-sectional analyses included 1,089 persons (ages 50-75 years), of whom 785 had longitudinal radiographs obtained 7 years apart. Of these, 586 with no hand OA at baseline were included in analyses of hand OA incidence. We explored associations between metabolic syndrome and its components (central obesity, hypertension, diabetes mellitus, triglyceridemia, and low high-density lipoprotein) and radiographic hand OA (defined as ≥2 interphalangeal joints with a Kellgren/Lawrence [K/L] grade of ≥2) using logistic regression analyses with adjustment for age, sex, and body mass index. In longitudinal analyses, metabolic syndrome was used as a predictor for change in K/L sum score and incident hand OA. RESULTS:Metabolic syndrome was not associated with the presence of hand OA (odds ratio [OR] 1.11 [95% confidence interval (95% CI) 0.78-1.59]), change in K/L sum score (OR 0.83 [95% CI 0.59-1.17]), or incidence of hand OA (OR 0.91 [95% CI 0.58-1.44]). Hypertension was borderline significantly associated with the presence of hand OA (OR 1.25 [95% CI 0.90-1.74]), and a significant association was found between hypertension and change in K/L sum score (OR 1.47 [95% CI 1.08-1.99]). Consistent dose-response relationships were not demonstrated (data not shown). Furthermore, hypertension was not significantly associated with hand OA incidence (OR 1.23 [95% CI 0.82-1.83]). No significant associations were found between metabolic syndrome and erosive hand OA. CONCLUSION:We found no association between metabolic syndrome and hand OA. The role of hypertension in hand OA pathogenesis warrants further investigation.
| S-EPMC5700863 | biostudies-literature
Project description:ObjectiveThe objective of this study was to investigate spinal radiographic progression in specific age ranges of ankylosing spondylitis (AS) patients.MethodsLongitudinal data for 1125 AS patients at a single hospital from 2000 to 2018 were retrospectively reviewed. Radiographic intervals were obtained from patients with consecutive spinal radiographs. The radiographic progression rate was defined as the modified Stoke Ankylosing Spondylitis Spinal Score (mSASSS) change per year within each interval. Using generalized estimating equations (GEEs), estimated marginal means were calculated for the mSASSS progression rate across age groups after adjusting for potential confounders.ResultsWe obtained 4016 radiographic intervals and stratified them into five groups based on patient age at the interval start: <20 (n = 122); 20-29 (n = 1124); 30-39 (n = 1690); 40-49 (n = 794); and ⩾50 years (n = 286). The mean (SD) mSASSS progression rate for all the intervals was 0.8 (1.9). The GEE-estimated mean mSASSS progression rate increased with age, peaking in the 30-39 age group with a value of 1.15 [95% confidence interval (CI) 1.03, 1.27], and decreased slightly thereafter. In the presence of risk factors, rapid progression occurred at earlier ages: the GEE-estimated mean mSASSS progression rate in those with elevated C-reactive protein levels and preexisting syndesmophytes was 2.82 (95% CI 1.93, 3.71) in the 20-29 age group.ConclusionSpinal structural damage in AS seems to progress most rapidly when patients are age 30-39 years. An awareness of the trends in radiographic progression with advancing age could improve understanding of the natural course of AS.
| S-EPMC9131377 | biostudies-literature
Project description:OBJECTIVE:To assess whether foot and/or ankle symptoms are associated with an increased risk of worsening of knee pain and radiographic change in people with knee osteoarthritis (OA). METHODS:The presence and laterality of foot/ankle symptoms were recorded at baseline in 1368 participants from the Osteoarthritis Initiative (OAI) with symptomatic radiographic knee OA. Knee pain severity (measured using the Western Ontario and McMaster Universities Osteoarthritis Index pain subscale) and minimum medial tibiofemoral joint space (minJSW) width measured on X-ray were assessed yearly over the subsequent 4 years. Associations between foot/ankle symptoms and worsening of (1) knee pain, and (2) both knee pain and minJSW (i.e., symptomatic radiographic knee OA) were assessed using logistic regression. RESULTS:Foot/ankle symptoms in either foot/ankle significantly increased the odds of knee pain worsening (adjusted OR 1.54, 95% CI 1.25 to 1.91). Laterality analysis showed ipsilateral (adjusted OR 1.50, 95% CI 1.07 to 2.10), contralateral (adjusted OR 1.44, 95% CI 1.02 to 2.06) and bilateral foot/ankle symptoms (adjusted OR 1.61, 95% CI 1.22 to 2.13) were all associated with knee pain worsening in the follow up period. There was no association between foot/ankle symptoms and worsening of symptomatic radiographic knee OA. CONCLUSION:The presence of foot/ankle symptoms in people with symptomatic radiographic knee OA was associated with increased risk of knee pain worsening, but not worsening of symptomatic radiographic knee OA, over the subsequent 4 years. Future studies should investigate whether treatment of foot/ankle symptoms reduces the risk of knee pain worsening in people with knee OA.
| S-EPMC5565691 | biostudies-literature
Project description:ObjectivesTo evaluate spinal radiographic damage over time and to explore the associations of radiographic progression with patient characteristics and clinical assessments including disease activity in ankylosing spondylitis (AS) patients treated with tumor necrosis factor-alpha (TNF-α) blocking therapy in daily clinical practice.MethodsConsecutive outpatients from the Groningen Leeuwarden AS (GLAS) cohort were included based on the availability of cervical and lumbar radiographs before start of TNF-α blocking therapy and after 2, 4, and/or 6 years of follow-up. Clinical data were assessed at the same time points. Radiographs were scored by two independent readers using the modified Stoke AS Spine Score (mSASSS). Spinal radiographic progression in relation to clinical assessments was analyzed using generalized estimating equations.Results176 AS patients were included, 58% had syndesmophytes at baseline. Median mSASSS increased significantly from 10.7 (IQR: 4.6-24.0) at baseline to 14.8 (IQR: 7.9-32.8) at 6 years. At the group level, spinal radiographic progression was linear with a mean progression rate of 1.3 mSASSS units per 2 years. Both spinal radiographic damage at baseline and radiographic progression were highly variable between AS patients. Male gender, older age, longer disease duration, higher BMI, longer smoking duration, high CRP, and high ASDAS were significantly associated with syndesmophytes at baseline. Significantly more radiographic progression was seen in patients with versus without syndesmophytes (2.0 vs. 0.5 mSASSS units per 2 years) and in patients >40 versus ≤40 years of age (1.8 vs. 0.7 mSASSS units per 2 years). No longitudinal associations between radiographic progression and clinical assessments were found.ConclusionsThis prospective longitudinal observational cohort study in daily clinical practice shows overall slow and linear spinal radiographic progression in AS patients treated with TNF-α blocking therapy. At the individual level, progression was highly variable. Patients with syndesmophytes at baseline showed a 4-fold higher radiographic progression rate than patients without syndesmophytes.
| S-EPMC4400173 | biostudies-literature
Project description:ObjectiveTo investigate whether tumor necrosis factor inhibitors (TNFi) impact spinal radiographic progression in patients with axial spondyloarthritis (SpA) and whether this is coupled to their effect on inflammation.MethodsPatients with axial SpA fulfilling the modified New York criteria were included in a prospective cohort (the ALBERTA Follow Up Research Cohort in Ankylosing Spondylitis Treatment). Spine radiographs, performed every 2 years for up to 10 years, were scored by 2 central readers, using the modified Stoke Ankylosing Spondylitis Spine Score (mSASSS). The indirect effect of TNFi on mSASSS was evaluated with generalized estimating equations by testing the interaction between TNFi and Ankylosing Spondylitis Disease Activity Score (ASDAS) at the start of each 2-year interval (t). If significant, the association between ASDAS at t and mSASSS at the end of the interval (t+1) was assessed in 1) patients treated with TNFi at all visits, 2) patients treated with TNFi at some visits, and 3) patients who were never treated with TNFi. In addition, the association between TNFi at t and mSASSS at t+1 (adjusting for ASDAS at t) was also tested (direct effect).ResultsIn total, 314 patients were included. A gradient was seen for the effect of ASDAS at t on mSASSS at t+1 (interaction P = 0.10), with a higher progression in patients never treated with TNFi (β = 0.41 [95% confidence interval (95% CI) 0.13, 0.68]) compared to those continuously treated (β = 0.16 [95% CI 0.00, 0.31]) (indirect effect). However, TNFi also directly slowed progression, as treated patients had on average an mSASSS 0.85 units lower at t+1 compared to untreated patients (β = -0.85 [95% CI -1.35, -0.35]).ConclusionOur findings indicate that TNFi reduce spinal radiographic progression in patients with radiographic axial SpA, which might be partially uncoupled from their effects on inflammation as measured by the ASDAS.
| S-EPMC8361759 | biostudies-literature
Project description:ObjectiveA major barrier to genetic studies of osteoarthritis (OA) is the need to obtain large numbers of individuals with standardized radiographic evaluations for OA. To address this gap, we performed a genome-wide association study (GWAS) of radiographically defined tibiofemoral knee OA in 3,898 cases and 3,168 controls from 4 well-characterized North American cohorts, and we performed replication analysis of previously reported OA loci.MethodsWe performed meta-analysis using a 2-stage design. Stage 1 (discovery) consisted of a GWAS meta-analysis of radiographic knee OA carried out in the Osteoarthritis Initiative and the Johnston County Osteoarthritis Project. Knee OA was defined as definite osteophytes and possible joint space narrowing or total joint replacement in one or both knees. Stage 2 (validation) was performed in the Multicenter Osteoarthritis Study and the Genetics of Osteoarthritis study. We genotyped lead meta-analysis variants (P ≤ 1 × 10-4 ) from stage 1 and tested the association between these variants and knee OA. We then combined results from all cohorts in a meta-analysis.ResultsLead variants from stage 1, representing 49 unique loci, were analyzed in stage 2; none met genome-wide significance in the combined analysis of stage 1 and stage 2. We validated 1 locus (rs4867568 near LSP1P3) with nominal significance (P < 0.05), which was also our top finding in the combined meta-analysis (odds ratio [OR] 0.84 [95% confidence interval (95% CI) 0.79-0.91], P = 3.02 × 10-6 ). We observed nominally significant associations (P < 0.05) with 3 previously reported OA loci: rs143383 in GDF5 (OR 1.12 [95% CI 1.04-1.21], P = 2.13 × 10-3 ), rs835487 in CHST11 (OR 0.93 [95% CI 0.85-0.99], P = 0.03), and rs8044769 in FTO (OR 1.10 [95% CI 1.03-1.19], P = 6.13 × 10-3 ).ConclusionThese findings provide suggestive evidence of a novel knee OA locus and confirm previously reported associations in GDF5, CHST11, and FTO.
| S-EPMC5274579 | biostudies-literature
Project description:ObjectiveTo identify plasma markers associated with an increased risk of radiographic knee osteoarthritis(OA) progression using a metabolomics approach.MethodsStudy participants were from the Multicenter Osteoarthritis Study (MOST) and were categorized into 2 groups based on the presence of baseline radiographic OA. Subjects in group 1 had unilateral knee OA and subjects in group 2 had bilateral knee OA. Progression was defined as a half-grade or greater worsening in joint space width at 30-month follow-up. For group 1, a participant progressed when their OA knee showed radiographic progression and the contralateral knee developed OA; for group 2, a participant progressed when both knees with OA showed radiographic progression. Metabolomic profiling was performed on plasma samples collected at baseline and logistic regression was performed to test the association between each metabolite and knee OA progression after adjustment for age, sex, BMI, and clinic site. Significance was defined as P ≤ 0.0003 in the combined analysis.ResultsThere were 234 progressors (57 in group 1 and 177 in group 2) and 322 nonprogressors (206 in group 1 and 116 in group 2) included in the analyses. Among 157 metabolites studied, we found that odds of progression were 1.46 times higher per SD increase of phenylalanine level (95% CI 1.20-1.77, P = 0.0001) in the combined analysis. Sex-specific analysis showed that an association was seen in women (P = 0.0002) but not in men.ConclusionOur data suggest that phenylalanine might be a novel plasma marker for higher risk of bilateral radiographic knee OA progression in women.
| S-EPMC8039838 | biostudies-literature
Project description:BackgroundA newly-described syndrome called Aneurysm-Osteoarthritis Syndrome (AOS) was recently reported. AOS presents with early onset osteoarthritis (OA) in multiple joints, together with aneurysms in major arteries, and is caused by rare mutations in SMAD3. Because of the similarity of AOS to idiopathic generalized OA (GOA), we hypothesized that SMAD3 is also associated with GOA and tested the hypothesis in a population-based cohort.MethodsStudy participants were derived from the Chingford study. Kellgren-Lawrence (KL) grades and the individual features of osteophytes and joint space narrowing (JSN) were scored from radiographs of hands, knees, hips, and lumbar spines. The total KL score, osteophyte score, and JSN score were calculated and used as indicators of the total burden of radiographic OA. Forty-one common SNPs within SMAD3 were genotyped using the Illumina HumanHap610Q array. Linear regression modelling was used to test the association between the total KL score, osteophyte score, and JSN score and each of the 41 SNPs, with adjustment for patient age and BMI. Permutation testing was used to control the false positive rate.ResultsA total of 609 individuals were included in the analysis. All were Caucasian females with a mean age of 60.9±5.8. We found that rs3825977, with a minor allele (T) frequency of 20%, in the last intron of SMAD3, was significantly associated with total KL score (β = 0.14, Ppermutation = 0.002). This association was stronger for the total JSN score (β = 0.19, Ppermutation = 0.002) than for total osteophyte score (β = 0.11, Ppermutation = 0.02). The T allele is associated with a 1.47-fold increased odds for people with 5 or more joints to be affected by radiographic OA (Ppermutation = 0.046).ConclusionWe found that SMAD3 is significantly associated with the total burden of radiographic OA. Further studies are required to reveal the mechanism of the association.
| S-EPMC4031234 | biostudies-literature