Risk factors for progression of lumbar spine disc degeneration: the Chingford Study

OBJECTIVE: Few data exist concerning the natural history of lumbar spine disc degeneration and associated risk factors. We therefore undertook this study to examine the radiographic progression of lumbar spine disc degeneration over the course of 9 years in a population-based inception cohort of women from the Chingford Study. METHODS: Seven hundred ninety-six paired lumbar spine radiographs were read by a single reader for anterior osteophytes (AO) and disc space narrowing (DSN) using the Lane atlas at each lumbar disc space (L1-5). Disc degeneration was defined using thresholds of AO and DSN grade 1+ in one or more vertebrae (L1-5) within a subject. Progression was defined as an increase in grade in an affected year-1 vertebra. Potential risk factors were assessed using odds ratios and 95% confidence intervals adjusted for age, body mass index (BMI), and other potential confounders in logistic regression models using the STATA statistical package. RESULTS: The mean +/- SD age at baseline was 53.8 +/- 6.0 years, and mean +/- SD BMI was 25.4 +/- 4.1 kg/m(2). Progression rates for AO and DSN were 4% per annum and 3% per annum, respectively. Progression of DSN was predicted by age, back pain, and radiographic hip and knee osteoarthritis (OA). Progression of AO was predicted by age and radiographic hip OA, with borderline significance for BMI >30 kg/m(2). No significant effects were seen for smoking, physical activity, hormone replacement therapy use, multiparity, or hand OA. CONCLUSION: This is the first population-based longitudinal study to assess progression of the individual radiographic features of AO and DSN in lumbar spine disc degeneration. We demonstrated progression rates of 3-4% per annum, with important risk factors for progression, including age, back pain, and radiographic OA at the hip and knee.     

Association of nitrate use with risk of new radiographic features of hip osteoarthritis in elderly white women: the study of osteoporotic fractures

OBJECTIVE: To examine the association between nitrate medication use and the development of new radiographic findings of hip osteoarthritis (OA) in elderly women. METHODS: Pelvic radiographs were obtained at baseline and a mean of 8.3 years later in 5,987 women, age > or =65 years at the baseline examination of the Study of Osteoporotic Fractures. Atlas-standardized individual radiographic features (IRFs) of OA were assessed and minimal joint space was measured on paired films. New radiographic findings of hip OA were defined as the development in hips free of these findings at baseline: 1) joint space narrowing (JSN), which consisted of either a MJS < or =1.5 mm or an IRF score indicating lateral JSN > or =2 or medial JSN > or =3; 2) an IRF score for osteophytes of > or =2 in any location; or 3) a summary grade of 2 or more (at least 2 IRFs present). Nitrate use was recorded by interview at years 6 and 8. Logistic and linear regression analyses were performed to determine the association of nitrate use with new radiographic findings of hip OA, adjusting for age, weight, height, bone mineral density, and estrogen. RESULTS: Compared with no reported use of nitrates, we found significant associations between use of nitrates at 1 clinic visit and new JSN (odds ratio [OR] 1.94, 95% confidence interval [95% CI] 1.18-3.17, P = 0.009), new osteophyte formation (OR 1.70, 95% CI 1.03-2.88, P = 0.04), and any new radiographic finding of hip OA or total hip arthroplasty for OA (OR 1.71, 95% CI 1.16-2.52, P = 0.007). Any nitrate use was associated with an increased risk of developing summary grade 3 or greater hip OA (OR 1.84, 95% CI 1.03-3.31, P = 0.041), but not with any other incident findings of OA. CONCLUSION: Older women using nitrates may have an increased risk of developing new radiographic findings of hip OA.     

Natural history of radiographic hip osteoarthritis: A retrospective cohort study with 11-28 years of followup

Objective

To evaluate the association between radiographic hip osteoarthritis (OA) and future total hip replacement (THR) due to OA or hip fracture.

Methods

We studied a cohort of individuals who had colon radiography from 1980–1997. Minimal joint space (MJS) was measured and each hip was graded for radiographic OA according to the Kellgren/Lawrence scale. Subjects were followed until the end of 2008. A Cox proportional hazards model, adjusted for age and sex, was used to evaluate factors associated with THR and hip fracture.

Results

A total of 2,953 hips were studied (57% women). The cumulative incidence of THR was 2.5% and the cumulative incidence of hip fracture was 2.6%. For hips with radiographic hip OA (MJS of 2.5 mm or less), the cumulative incidence of THR was 16.9% and the hazard ratio (HR) for THR was 13.2 (95% confidence interval [95% CI] 8.1–21). Using Kellgren/Lawrence grading, the HR for THR was 12.9 (95% CI 7.9–21) for hips with radiographic OA compared to those without. The HR for all types of hip fracture for hips with radiographic OA (MJS of 2.5 mm or less) was 0.47 (95% CI 0.15–1.5), for intracapsular fractures was 0.29 (95% CI 0.04–2.1), and for extracapsular fractures was 0.67 (95% CI 0.16–2.8).

Conclusion

The risk of THR due to OA is substantially increased in patients with radiographic hip OA, regardless of symptoms, and increases with decreasing MJS. However, 11–28 years after having had radiographic hip OA, more than 4 of 5 of those having radiographic signs of hip OA had not had a THR for OA.     

Racial differences in foot disorders and foot type

Objective

To describe racial differences in the frequency of structural foot disorders and pes planus and pes cavus foot types in a large cohort of African American and white men and women ages ≥50 years.

Methods

Of 1,695 Johnston County Osteoarthritis Project participants evaluated for foot disorders/types in 2006–2010, 4 with lower extremity amputation were excluded, leaving 1,691 available for analyses (mean age 69 years, mean body mass index [BMI] 31.5 kg/m², 68% women, 31% African American). The most common foot disorders/types were identified using a validated foot examination. Each foot disorder/type was compared by race using logistic regression, controlling for age, BMI, and sex. Effect modification between race (African American versus white) and age, BMI (categorized as ≥30 kg/m² [obese] or <30 kg/m² [nonobese]), sex, and education was examined.

Results

Hallux valgus (64%), hammer toes (35%), overlapping toes (34%), and pes planus (23%) were common. Compared to whites, African Americans were almost 3 times more likely to have pes planus and were nearly 5 times less likely to have Tailor's bunions or pes cavus. Among the nonobese, African Americans were more likely than whites to have hallux valgus (adjusted odds ratio [OR_adj] 2.01, 95% confidence interval [95% CI] 1.39–2.92), hammer toes (OR_adj 2.64, 95% CI 1.88–3.70), and overlapping toes (OR_adj 1.53, 95% CI 1.09–2.13).

Conclusion

Foot disorders are common among adults ages ≥50 years and differ by race. Future research is needed to determine the etiology of foot problems, especially those with racial differences, in order to inform prevention approaches.     

Self‐reported knee and foot alignments in early adult life and risk of osteoarthritis

Objective

To determine whether self‐reported early adult life malalignment of knees or feet are risk factors for knee or hip osteoarthritis (OA).

Methods

Participants in the Genetics of Osteoarthritis and Lifestyle case–control database were sent a questionnaire (n = 3,022) containing line‐drawing instruments for self‐reported knee and foot alignment at ages 20–29 years. Respondents were categorized as having straight, valgus, or varus knee, and straight, toe‐in, or toe‐out feet. Radiographic criteria were used to define current isolated knee or hip OA, combined knee and hip OA, or non‐OA controls. Odds ratios (ORs), adjusted ORs, and 95% confidence intervals (95% CIs) were calculated and logistic regression was performed.

Results

The response rate was 72%; 87.5% of responders (n = 1,901) completed the alignment questions. Increased risk of isolated knee OA occurred with early adult varus (adjusted OR 5.16, 95% CI 2.87–9.41) and valgus knees (adjusted OR 3.16, 95% CI 1.04–9.64). The positive association between knee OA and toe‐in foot was explained by varus knee. There was an increased risk of combined knee/hip OA from varus (adjusted OR 4.52, 95% CI 2.39–8.53) and valgus knees (adjusted OR 3.07, 95% CI 0.99–9.54). Varus knee was associated with risk of medial tibiofemoral OA, whereas valgus knee was associated with risk of lateral tibiofemoral and lateral patellofemoral OA. Toe‐out foot was associated with reduced medial patellofemoral OA. For knee OA, a multiplicative interaction analysis between occupational risks and varus/valgus yielded an OR_int of 3.20 (95% CI 1.08–9.49).

Conclusion

Constitutional alignment of the leg in terms of varus or valgus knee or foot rotation may be a significant factor in determining development and distribution of knee but not hip OA.     

Association of the interleukin‐1 gene cluster with radiographic signs of osteoarthritis of the hip

Objective

To study the role of the interleukin‐1β gene (IL1B) and the IL‐1 receptor antagonist gene (IL1RN) in relation to the occurrence of radiographic osteoarthritis (ROA) in the hip, knee, and hand and disc degeneration of the spine.

Methods

The study population consisted of a random sample of 886 subjects (ages 55–65 years) from a population‐based cohort (the Rotterdam study). Two polymorphisms within IL1B (3953C>T and −511C>T) and one within IL1RN (the variable‐number tandem repeat [VNTR]) were analyzed and used in an association study of the occurrence of ROA. Haplotyping and simultaneous logistic regression analysis were performed to investigate whether the associations observed were independent.

Results

Associations with a predisposition for hip ROA were observed for heterozygous and homozygous carriers of the rare IL1B allele −511T (crude odds ratio [OR] 1.8, 95% confidence interval [95% CI] 1.0–3.4 and OR 2.9, 95% CI 1.4–6.3, respectively) and of the IL1RN VNTR allele 2 (crude OR 2.0, 95% CI 1.1–3.4 and OR 3.3, 95% CI 1.4–7.8, respectively). An additive effect was observed for carriers of risk alleles of both polymorphisms, with a significant linear‐by‐linear association (P = 0.00022).

Conclusion

Our findings suggest that the IL‐1 gene cluster polymorphisms may play a significant role in the pathogenesis of OA of the hip.

     

Prevalence and factors associated with uveitis in spondylarthritis patients in France: Results from an observational survey

Objective

To accurately estimate the prevalence of and the factors associated with uveitis in spondylarthritis (SpA) patients in France.

Methods

In an observational survey of SpA patients (diagnosis confirmed by the European Spondylarthropathy Study Group and/or Amor's criteria) consulting their rheumatologist for routine followup, we collected information regarding present/past history of uveitis, as well as detailed characteristics of the disease. Factors independently associated with uveitis were determined.

Results

From September 2008 to January 2009, 202 rheumatologists participated in the survey and recruited 902 patients (61% men) with a mean ± SD age of 45.3 ± 13.4 years and a mean ± SD disease duration of 10.4 ± 9.6 years. The SpA diagnoses were ankylosing spondylitis (71%), psoriatic arthritis (18%), or other SpA (11%). The HLA–B27 positivity rate was 76%. Uveitis prevalence was 32.2% (95% confidence interval [95% CI] 29.1–35.3%) since psoriasis and inflammatory bowel disease were 22.3% (95% CI 19.5–25.0%) and 8.6% (95% CI 6.7–10.5%), respectively. Recurrence of uveitis occurred in 52.3% and complications occurred in 11.7% of patients. Factors independently associated with uveitis were HLA–B27 positivity (adjusted odds ratio [OR_adj] 2.97 [95% CI 1.83–4.81], P < 0.0001) and disease duration (OR_adj 1.28 [95% CI 1.16–1.41], P < 0.0001 for ≥10 years).

Conclusion

Results indicate that uveitis is the most common extraarticular feature of SpA, occurring preferentially in HLA–B27–positive patients over the entire course of the disease.     

Association between spine disc degeneration and type II collagen degradation in postmenopausal women: the OFELY study

OBJECTIVE: To investigate whether radiologic spine disc degeneration is associated with increased type II collagen (CII) degradation products in the urine of postmenopausal women, independently of radiologic knee osteoarthritis (OA) and clinical hand OA. METHODS: The study group comprised 324 postmenopausal women ages 58-94 years who had no treatment or disease that could alter bone metabolism. Lateral radiographs of the thoracic and lumbar spine were obtained in each woman and scored for disc space narrowing (DSN) and osteophytes. Fixed-flexion posteroanterior radiographs of the knee were obtained to assess femorotibial knee OA. In all women, hand OA was assessed by clinical examination, and the level of urinary C-terminal crosslinking telopeptide of CII (CTX-II), a biologic marker of CII degradation, was measured. RESULTS: The prevalences of radiographic lumbar and thoracic spine disc degeneration, knee OA, and clinical hand OA were 84%, 88%, 35%, and 58%, respectively. After adjustment for age and body mass index (BMI), patients with lumbar spine DSN grade > or = 1 had, on average, 34% higher CTX-II levels compared with the other women (P = 0.0005), whereas no association was observed with lumbar spine osteophytes. No significant association between thoracic spine DSN or osteophytes and urinary CTX-II levels was observed. Multivariate analysis of variance showed that, after adjustment for age and BMI, lumbar spine DSN (P = 0.0049), knee OA (P = 0.0055), and clinical hand OA (P = 0.0060) were, independently of each other, associated with CTX-II levels. Thus, patients with lumbar spine DSN, knee OA, and clinical hand OA had CTX-II levels 80% higher (P < 0.0001 after adjustment for age and BMI) than those of patients with no lumbar spine DSN, no radiologic knee OA, and no clinical hand OA. CONCLUSION: Postmenopausal women with lumbar spine disc degeneration are characterized by increased CII degradation. The contribution of lumbar spine DSN to CII degradation was similar to, and independent of, the contribution of radiologic knee OA or clinical hand OA. Lumbar spine disc degeneration in elderly patients should be assessed when analyzing levels of CTX-II in studies of knee, hip, and hand OA.     

Does hand osteoarthritis predict future hip or knee osteoarthritis?

Objective

To evaluate the risk of future hip or knee osteoarthritis (OA) in subjects with hand OA at baseline and to evaluate whether the concurrent presence of hand OA, other risk factors for OA, or an OA biomarker (type II collagen C‐telopeptide degradation product [CTX‐II]) further increases the risk.

Methods

Radiographs of the hands (baseline) and the hips and knees (baseline and 6.6 years later) were obtained in a randomly selected subset of participants in the Rotterdam Study who were ages 55 years and older. Radiographs were scored for the presence of OA using the Kellgren/Lawrence (K/L) system. A total of 1,235 subjects without OA of the hip/knee (K/L score 0–1) at baseline were included in the study. CTX‐II levels were measured at baseline. The independent risk of future hip/knee OA in subjects with hand OA at baseline was assessed by logistic regression, as stratified for age, sex, body mass index, family history of OA, and heavy workload.

Results

Overall 12.1% of the participants (19.7% of those with hand OA versus 10.0% of those without) developed hip or knee OA (odds ratio [OR] 2.1 [95% confidence interval (95% CI) 1.3–3.1]). Subjects with hand OA had an increased risk of future hip OA (OR 3.0 [95% CI 1.6–5.4]), which was further increased in those with a family history of OA. Subjects with hand OA had an OR of 1.6 [95% CI 1.0–2.8) for the future development of knee OA, which was further increased in those who were overweight. Concurrent hand OA and high levels of CTX‐II further increased the risk of having hip or knee OA at followup (OR 4.2 [95% CI 2.3–7.8]).

Conclusion

The presence of hand OA at baseline showed an increased risk of future hip/knee OA (higher for hip OA than for knee OA). The concurrent presence of hand OA and other OA risk factors or high CTX‐II levels further increased the risk of future hip/knee OA.

     

Are tall people at higher risk of low back pain surgery? A discussion on the results of a multipurpose cohort

Objective

To investigate whether height is associated with low back pain (LBP) and surgery, taking into account personal and socioeconomic risk factors in a general population.

Methods

In 2001, 13,680 participants of the Gazel cohort completed a self‐reported questionnaire on LBP and surgery interventions. Three groups were compared according to their body height: no LBP (reference group, participants who declared they never had LBP), LBP without surgery (participants who ever had LBP but without surgery), and back surgery (participants who ever had surgery for LBP). Adjusted variables were sex, age, educational level, marital status, height, and body mass index.

Results

Mean height was significantly higher in men in the back surgery group than in the reference group and the LBP group. The proportion of surgically‐treated LBP was higher for people whose height was ≥4th quartile (P < 0.0001). Being in the highest quartile for height was a stronger risk factor for surgery (adjusted odds ratio [OR_adj] = 2.01, 95% confidence interval [95% CI] 1.61–2.51) than for LBP without surgery (OR_adj = 1.29, 95% CI 1.18–1.40).

Conclusion

The results suggest that being tall is a predictor for back surgery.     

IL28B polymorphism is associated with fatty change in the liver of chronic hepatitis C patients

Background

Several single nucleotide polymorphisms (SNPs) within the interleukin 28B (IL28B) locus are associated with sustained viral response in chronic hepatitis C (HCV) patients who were treated with pegylated interferon (PEG-IFN) plus ribavirin (RBV) combination therapy. Recently, an association between γ-GTP level and IL28B genotype was identified. In this study, the relationship between IL28B genotype and liver steatosis was analyzed.

Methods

One hundred fifty-three patients who underwent liver biopsy before PEG-IFN plus RBV combination therapy were enrolled. The level of liver steatosis was measured using a BIOREVO BZ-9000 microscope, and the proportion of fatty change and clear cell change were calculated using Dynamic cell count BZ-H1C software. IL28B SNP genotype (rs8099917) was determined using the Invader Assay.

Results

Vesicular change was significantly associated with body mass index (BMI), HCV RNA titer, serum aspartate aminotransferase, γ-GTP, IL28B genotype and liver fibrosis level (P?P?adj?=?8.158; 95% CI 2.412–27.589), liver fibrosis (OR_adj?=?2.541; 95% CI 1.040–6.207) and BMI (OR_adj?=?1.147; 95% CI 1.011–1.301) were significant independent factors for vesicular change and IL28B genotype (OR_adj?=?3.000; 95% CI 1.282–7.019) for clear cell change.

Conclusion

In this study, a new quantitative method to objectively evaluate hepatic steatosis was described. IL28B genotypes were significantly associated with both vesicular and clear cell changes of livers in chronic hepatitis C patients.     

Bone Mineral Density and the Risk of Hip and Knee Osteoarthritis: The Johnston County Osteoarthritis Project

Objective

To address knowledge gaps regarding the relationship between bone mineral density (BMD) and incident hip or knee osteoarthritis (OA); specifically, lack of information regarding hip OA or symptomatic outcomes.

Methods

Using data (n = 1,474) from the Johnston County Osteoarthritis Project's first (1999–2004) and second (2005–2010) followup of participants ages ≥45 years, we examined the association between total hip BMD and both hip and knee OA. Total hip BMD was measured using dual x‐ray absorptiometry, and participants were classified into sex‐specific quartiles (low, intermediate low, intermediate high, and high). Radiographic OA (ROA) was defined as development of Kellgren/Lawrence grade ≥2. Symptomatic ROA (sROA) was defined as onset of both ROA and symptoms. Weibull regression modeling was used to estimate hazard ratios (HRs) and 95% confidence intervals (95% CIs).

Results

Median followup time was 6.5 years (range 4.0–10.2 years). In multivariate models, and compared with participants with low BMD, those with intermediate high and high BMD were less likely to develop hip sROA (HR 0.52 [95% CI 0.31–0.86] and 0.56 [95% CI 0.31–0.86], respectively; P = 0.024 for trend); high BMD was not associated (HR 0.69 [95% CI 0.45–1.06]) with risk of hip ROA. Compared with participants with low BMD, those with intermediate low and intermediate high total hip BMD were more likely to develop knee sROA (HR 2.15 [95% CI 1.40–3.30] and 1.65 [95% CI 1.02–2.67], respectively; P = 0.325 for trend); similar associations were seen with knee ROA.

Conclusion

Our findings suggest that higher BMD may reduce the risk of hip sROA, while intermediate levels may increase the risk of both knee sROA and ROA.

     

Economic burden of knee and hip osteoarthritis in spain

Objective

To estimate the direct and indirect osteoarthritis (OA)–attributable costs and predictors of costs of knee and hip OA in Spain.

Methods

This study included consecutive patients age ≥50 years with symptomatic and radiologic knee and/or hip OA who were seen at primary care centers in all provinces of Spain. Information on demographics, health status (Short Form 12 Health Survey), comorbidities (Charlson Index), clinical (Western Ontario and McMaster Universities Osteoarthritis Index [WOMAC]) and radiologic OA severity (Kellgren/Lawrence [K/L] scale), data related to OA health resources utilization (medical and nonmedical), and subjects' and caregivers' expenses and time lost in the previous 6 months were collected in 2 separate, structured, and detailed interviews. Costs in euros were assigned using market prices and official sources if available, and were annualized (to 2007). The predictors of costs were assessed in multivariate regression models. Costs were log‐transformed before being modeled.

Results

A total of 1,071 subjects were analyzed (74% women, mean ± SD age 71 ± 9 years). Average total annual costs were €1,502 per patient. Direct costs accounted for 86% of the total cost. We estimated a national cost of €4,738 million, representing 0.5% of the gross national product. Higher total costs were associated with comorbidity (Charlson Index odds ratio [OR] 1.27, 95% confidence interval [95% CI] 1.03–1.58), poorer health status (P < 0.050), worse WOMAC scores (OR 1.05, 95% CI 1.03–1.08), and grade 4 K/L scores (OR 1.76, 95% CI 1.15–2.69).

Conclusion

The economic burden of knee and hip OA is substantial. Costs increased with comorbidity, poorer health status, and clinical and radiologic OA severity.     

Association of clinical findings with pre–radiographic and radiographic knee osteoarthritis in a population‐based study

Objective

To determine the prevalence of pre–radiographic osteoarthritis (ROA) and ROA of the knee in a symptomatic population‐based cohort, and to evaluate the clinical correlates of pre‐ROA and ROA.

Methods

Subjects ages 40–79 years with knee pain were recruited as a random population sample and classified using magnetic resonance cartilage (MRC) scores (range 0–4) and Kellgren/Lawrence (K/L) scale grades (range 0–4) as no OA (MRC score <2, K/L grade <2), pre‐ROA (MRC score ≥2, K/L grade <2), and ROA (MRC score ≥2, K/L grade ≥2). Logistic regression was used to evaluate the association of clinical variables with cartilage defects, comparing subjects with any cartilage defects (pre‐ROA/ROA) with those without, and to determine associations with individual OA subgroups.

Results

Of 255 symptomatic subjects, no OA, pre‐ROA, and ROA were seen in 13%, 49%, and 38%, respectively. The prevalence of pre‐ROA/ROA compared with no OA was associated with age (odds ratio [OR] 2.89, 95% confidence interval [95% CI] 1.59–5.26), sports activity (OR 1.35, 95% CI 1.07–1.70), abnormal gait (OR 10.86, 95% CI 1.46–1,388.4), effusion (OR 16.58, 95% CI 2.22–2,120.5), and flexion contracture (OR 2.37, 95% CI 1.50–3.73). The prevalence of ROA versus no OA was significantly associated with age, body mass index, pain frequency, pain duration, severe knee injury, sports activity, gait, effusion, bony swelling, crepitus, flexion contracture, and flexion. The prevalence of pre‐ROA versus no OA was increased with age, sports activity, effusion, and flexion contracture, and reduced with valgus malalignment.

Conclusion

Cartilage defects were highly prevalent in this symptomatic population‐based cohort, with 49% of subjects having pre‐ROA and 38% having ROA. Prevalent cartilage defects were significantly associated with age, sports activity, abnormal gait, effusion, and flexion contracture.     

Association of the frizzled‐related protein gene with symptomatic osteoarthritis at multiple sites

Objective

To confirm the association of 2 variants of the Frizzled‐related protein gene (FRZB) with osteoarthritis (OA) of the hip, and to investigate whether these variants also associate with other heritable generalized OA phenotypes.

Methods

An association analysis of 2 variants (R200W and R324G) of FRZB was performed in a random sample of 1,369 subjects (ages 55–70 years) from a population‐based cohort (the Rotterdam Study) scored for radiographic characteristics of OA in the hip, hand, spine, and knee and in a patient population of Caucasian probands (ages 40–70 years) and their siblings selected for the presence of primary symptomatic OA at multiple sites.

Results

The allele frequency of the 2 variants was not significantly different between subjects with hip radiographic OA (ROA) and controls. The frequency of the G allele of the R324G variant was significantly increased in subjects with generalized ROA from the Rotterdam Study (0.10) and in subjects from the Genetics, osteoARthritis and Progression study (0.11) compared with that in controls from the Rotterdam Study (0.08). Carriers of this G allele had increased susceptibility for generalized ROA (odds ratio [OR] 1.4, 95% confidence interval [95% CI] 0.9–1.9, P = 0.10) or familial symptomatic OA at multiple sites (OR 1.6, 95% CI 1.1–2.3, P = 0.02).

Conclusion

Our results confirm that the R324G variant of the FRZB gene is involved in OA and indicate a role of this variant in several generalized OA phenotypes. A more extended OA phenotype may indeed be expected from genetic variation in an essential pathway of skeletal development such as Wnt signaling.

     

Predictors of change in bodily pain in early rheumatoid arthritis: An inception cohort study

Objective

To investigate possible predictors for lack of pain improvement after 1 year of treatment for early rheumatoid arthritis (RA).

Methods

The Early Rheumatoid Arthritis Network (ERAN) database was used for analysis of baseline and 1‐year pain data. The ERAN is a hospital‐based inception cohort of 1,189 people. Short Form 36 questionnaire bodily pain scores were used to calculate change in pain at 1 year as the outcome. The proportion of the Disease Activity Score in 28 joints (DAS28) attributable to patient‐reported components (joint tenderness and visual analog scale score; DAS28‐P) at baseline was derived as a predictor. Predictors of less improvement in pain were investigated using adjusted odds ratios (OR_adj) generated by logistic regression, adjusting for 14 additional clinical and demographic covariates.

Results

Greater pain at baseline was associated with sex, high DAS28, worse mental health, and smoking. Most patients with early RA reported incomplete improvement in bodily pain after 1 year. The DAS28‐P index did not significantly change in the patients whose disease remained active. Less improvement in pain was predicted by female sex (OR_adj 3.41, 95% confidence interval [95% CI] 1.35–8.64) and a high DAS28‐P index at baseline (OR_adj for tertiles 2.09, 95% CI 1.24–3.55). Other conventional RA risk factors did not predict pain changes.

Conclusion

The factors most likely to predict less improvement in pain in early RA are female sex and a high DAS28‐P index. A high DAS28‐P index may reflect greater contributions of noninflammatory factors, such as central sensitization, to pain. Strategies in addition to inflammatory disease suppression may be required to adequately treat pain.     

A new marker for osteoarthritis: Cross‐sectional and longitudinal approach

Objective

To investigate the association between urinary concentrations of C‐telopeptide fragments of type II collagen (CTX‐II) and the prevalence and progression of radiographic osteoarthritis (OA) of the knee and hip.

Methods

The study population consisted of a sample of 1,235 men and women ages ≥55 years who were enrolled in the Rotterdam Study (a population‐based cohort study) and who were followed up for a mean of 6.6 years. Prevalent radiographic OA was defined as a Kellgren/Lawrence score ≥2; progression of radiographic OA was defined as a decrease in joint space width.

Results

Subjects with a CTX‐II level in the highest quartile had a 4.2‐fold increased risk of having radiographic OA of the knee (95% confidence interval [95% CI] 2.5–7.0) and of the hip (95% CI 2.2–7.8) compared with subjects with a CTX‐II level in the lowest quartile. We observed a substantially stronger association between CTX‐II levels and radiographic OA for subjects with hip pain (odds ratio [OR] 20.4, 95% CI 2.3–185.2) than for those without hip pain (OR 3.0, 95% CI 1.5–6.0). Subjects with a CTX‐II level in the highest quartile had a 6.0‐fold increased risk for progression of radiographic OA at the knee (95% CI 1.2–30.8) and an 8.4‐fold increased risk for progression of radiographic OA at the hip (95% CI 1.0–72.9). All of these associations were found to be independent of known risk factors for OA, such as age, sex, and body mass index.

Conclusion

This study shows that CTX‐II is associated with both the prevalence and the progression of radiographic OA at the knee and hip. Importantly, this association is independent of known clinical risk factors for OA and seems stronger in subjects with joint pain.

     

Demographic and Clinical Factors Associated With Nonsurgical Osteoarthritis Treatment Among Patients in Outpatient Clinics

Objective

To identify patient demographic and clinical characteristics associated with osteoarthritis (OA) treatment use.

Methods

This was a secondary data analysis of 3 clinical trials among patients with hip or knee OA conducted in Duke Primary Care practices, the Durham Veterans Affairs (VA) Health Care System, and the University of North Carolina–Chapel Hill (UNC). At baseline, participants reported sociodemographic characteristics, OA‐related pain and function, and OA treatment use, including oral analgesics, topical creams, joint injections, and physical therapy. Separate, multivariable logistic models (adjusted for clustering of clinics and providers for the Duke and VA cohorts) were used to estimate odds ratios (ORs) and 95% confidence intervals (95% CIs) for the associations between participant characteristics and each type of OA treatment.

Results

Oral analgesic use was reported by 70–82% of participants across the 3 cohorts. Physical therapy, knee injections, and topical creams were used by 39–52%, 55–60%, and 25–39% of Duke, VA, and UNC participants, respectively. In multivariable models, worse pain, stiffness, and function, per 5‐unit increase, were associated with greater odds of using any oral analgesic for the cohorts from Duke (OR 1.18 [95% CI 1.08–1.28]) and UNC (OR 1.14 [95% CI 1.05–1.24]), but not for the VA cohort (OR 1.04 [95% CI 0.95–1.14]). For all 3 cohorts, nonwhites had higher odds of using topical creams compared to whites.

Conclusion

Results suggest potential underutilization of therapies other than oral analgesics. Patient characteristics may affect OA treatment use, and understanding the relationship between these factors and OA treatment preferences may improve adherence to OA treatment guidelines.     

Type I collagen α1 Sp1 transcription factor binding site polymorphism is associated with reduced risk of hip osteoarthritis defined by severe joint space narrowing in elderly women

Objective

A common G/T substitution at an Sp1 binding site in intron 1 of the COL1A1 gene has been reported to be associated with reduced bone mineral density and increased risk of osteoporotic fracture. The purpose of this study was to examine whether there is an association between COL1A1 Sp1 polymorphism and radiographic osteoarthritis (OA) of the hip in elderly women in the Study of Osteoporotic Fractures.

Methods

Radiographic hip OA status of subjects was defined by the presence of 1 of the following criteria in either hip: a joint space narrowing (JSN) score of ≥3, a Croft summary grade of ≥3, or both definite (score ≥2) osteophytes and JSN in the same hip. Cases of radiographic OA of the hip were further subdivided into those with JSN score ≥3 and those with a femoral osteophyte score ≥2 and JSN score ≤2. The COL1A1 Sp1 polymorphism was genotyped using allele‐specific kinetic polymerase chain reaction in 4,746 women. Multivariate logistic regression was performed to estimate odds ratios (ORs) and 95% confidence intervals (95% CIs).

Results

Radiographic OA of the hip was present in 571 women (12%). Of these patients, 325 (57%) had severe JSN (score ≥3), and 131 (23%) had moderate or moderate‐to‐severe femoral osteophytosis (score ≥2). There was no association of the T/T genotype with either radiographic hip OA or radiographic hip OA characterized by osteophytosis. For radiographic OA of the hip characterized by moderate‐to‐severe JSN, the odds of disease were significantly reduced among subjects with the T/T compared with the G/G genotype (OR 0.30, 95% CI 0.11–0.81, P = 0.02) and did not change after adjustment for potential confounders (OR 0.36, 95% CI 0.13–0.99, P = 0.048).

Conclusion

The T/T genotype of the COL1A1 Sp1 polymorphism was associated with a reduced risk of radiographic OA of the hip characterized by JSN. This association should be confirmed in other populations to determine if mechanistic studies are warranted.