Biomarkers of incident radiographic knee osteoarthritis: Do they vary by chronic knee symptoms?

Objective

To explore the ability of osteoarthritis (OA)–related biomarkers to predict incident radiographic knee OA in a large sample of African American and Caucasian men and women.

Methods

Baseline levels of serum cartilage oligomeric matrix protein (COMP), hyaluronan (HA), high‐sensitivity C‐reactive protein (hsCRP), and keratan sulfate (KS) and baseline and followup radiographs were available for 353 knees without baseline osteophyte formation and for 446 knees without baseline joint space narrowing (JSN). Cox models estimated the hazard ratio (HR) and 95% confidence interval (95% CI) for incident knee OA for a 1‐unit increase in the ln of each biomarker, with adjustment for age, race, sex, body mass index, and knee OA of the contralateral limb. Report of chronic knee symptoms was explored as a modifier of the association.

Results

The hazard of incident knee osteophytes (HR 2.16 [95% CI 1.39–3.37]) and incident JSN (HR 1.82 [95% CI 1.15–2.89]) increased with higher baseline ln(COMP) levels. The hazard of incident knee JSN increased with higher ln(HA) levels (HR 1.46 [95% CI 1.14–1.87]). Baseline ln(hsCRP) and ln(KS) did not predict incident knee outcomes. HRs per unit increase in ln(COMP), ln(HA), and ln(KS) were higher among knees with chronic symptoms than among those without symptoms.

Conclusion

Higher baseline ln(COMP) and ln(HA) levels were associated with incident knee OA over an average followup period of 6.3 years. These results represent detection of a molecular stage of OA prior to radiographic manifestations. Further exploration is needed to determine how chronic knee symptoms modify the biomarker–incident knee OA association.

     

Serum hyaluronan levels and radiographic knee and hip osteoarthritis in African Americans and Caucasians in the Johnston County Osteoarthritis Project

OBJECTIVE: Serum hyaluronan (HA) has been proposed as a potential biomarker of osteoarthritis (OA). We examined associations between serum HA and radiographic OA in an ethnically diverse, population-based sample. METHODS: Participants were selected from the Johnston County Osteoarthritis Project, using stratified simple random sampling to achieve balance according to radiographic knee OA status, ethnic group, sex, and age group. Serum HA was measured by enzyme-linked immunosorbent assay. Radiographic OA variables included knee OA, knee OA laterality, knee OA severity, concomitant knee and hip OA, and total number of OA-affected knee and hip joints. Analysis of covariance was used to assess differences in mean serum levels of natural log-transformed HA (ln serum HA) between groups, adjusting for ethnicity, sex, age, body mass index (BMI), and self-reported comorbidities. RESULTS: Levels of ln serum HA were positively associated with all definitions of radiographic OA (P < 0.0001). Levels of ln serum HA were higher in Caucasians (P = 0.0094) and in men (P = 0.0038) and were moderately correlated with age (r = 0.35, P < 0.0001). The associations with radiographic OA, ethnicity, sex, and age remained statistically significant after adjustment (P < 0.0045). There were no interactions between ethnicity and the other covariates. CONCLUSION: These cross-sectional data support a role for serum HA as a biomarker of radiographic OA. The variations in levels of serum HA attributable to ethnicity, sex, and age were not explained by radiographic OA, BMI, or comorbidities. The lack of strong confounding between serum HA and comorbidities further supports a role for serum HA as a potential biomarker.     

Serum cartilage oligomeric matrix protein reflects osteoarthritis presence and severity: the Johnston County Osteoarthritis Project.

OBJECTIVE: To characterize serum cartilage oligomeric matrix protein (COMP) levels by age and gender for a radiographically defined population free of hip and knee osteoarthritis (OA), and to examine the potential utility of COMP as a diagnostic biomarker for knee OA. METHODS: Serum samples and knee and hip radiographs were obtained at a baseline evaluation as part of the Johnston County Osteoarthritis Project, a population-based study of OA in rural North Carolina. A total of 291 Caucasian participants were randomly selected for COMP analysis, 143 patients with radiographic knee OA (Kellgren/Lawrence [K/L] grade > or = 2) and 148 controls with neither hip nor knee OA (K/L grade 0), evenly distributed by age and gender. COMP was quantified by competitive enzyme-linked immunosorbent assay with monoclonal antibody 17-C10. The natural log-transformed COMP data were analyzed using general linear models. RESULTS: Serum COMP levels were significantly elevated (P = 0.0001) in the age > or = 65 group (mean +/- SD 1,302.1 +/- 496.7 ng/ml) versus the age 45-54 and age 55-64 groups (1,058.1 +/- 432.4 and 1,038.6 +/- 313.3, respectively). Serum COMP levels of the OA group were significantly higher than those of the control group (1,208.57 +/- 487.47 ng/ml versus 1,061.83 +/- 370.58 ng/ml; P = 0.0093). Serum COMP levels also increased significantly with knee OA K/L grade (P = 0.0047), knee OA laterality (P = 0.0043), and number of knee and hip joints involved (P = 0.0001). There was no significant difference in serum COMP levels by gender or obesity. CONCLUSION: We demonstrate that in a population-based sample, serum COMP levels can distinguish an OA-affected subgroup from an unaffected subgroup and can reflect disease severity and multiple joint involvement in OA.     

Serum cartilage oligomeric matrix protein (COMP) levels in knee osteoarthritis in a Brazilian population: clinical and radiological correlation

OBJECTIVES: In this study we present data on serum cartilage oligomeric matrix protein (COMP) levels in a Brazilian population with isolated knee osteoarthritis (OA) compared to healthy controls. Clinical and radiological correlations with COMP levels were also evaluated. METHODS: Two hundred and seventy-two patients seen at the Rheumatology Division of the Federal University of S?o Paulo (UNIFESP) with a symptom of 'pain in the knees' for at least 3 months were invited to participate in this study. History and clinical examination were performed in all patients. Eighty-six patients with clinical isolated knee OA according to the American College of Rheumatology (ACR) criteria and without other causes of pain in the knee were included. Fifty-eight healthy individuals were selected, matched for age and sex, and used as controls. OA evaluation included Lequesne and Western Ontario and MacMaster Universities osteoarthritis index (WOMAC) questionnaires, visual analogue scale (VAS) for pain and standard knee X-rays. Blood samples were taken from all participants and serum COMP levels were measured by enzyme-linked immunosorbent assay (ELISA). OA radiological analysis was performed using the Kellgren and Lawrence (K/L) grading scale. RESULTS: Patients with symptomatic knee OA presented significantly higher serum COMP levels compared to healthy controls and to those with non-symptomatic narrowing of the articular space (p<0.001). Patients with clinical evidence of knee OA and without radiological abnormalities (K/L grade 0 or 1) had intermediate serum COMP levels, significantly higher than those observed in healthy controls (p<0.03). CONCLUSIONS: We observed increased serum COMP levels in patients with symptomatic radiological knee OA. High serum COMP levels may also indicate cartilage damage in selected symptomatic patients without significant radiological abnormalities.     

Sex and ethnic differences in the association of ASPN, CALM1, COL2A1, COMP, and FRZB with genetic susceptibility to osteoarthritis of the knee

OBJECTIVE: To assess whether the association of genetic polymorphisms with osteoarthritis (OA) in other populations could be replicated in a large, multicenter, mixed-sex, case-control study of clinical knee OA. METHODS: Genetic polymorphisms in OA candidate genes were genotyped in 298 men and 305 women, ages 50-86 years, all of whom had a diagnosis of knee OA as assessed clinically and radiographically, and in 300 male and 299 female control subjects matched for age and ethnicity. Allele and haplotype frequencies for 5 genes (ASPN, CALM1, COL2A1, COMP, and FRZB) previously tested for association with hip and/or knee OA in other populations were compared between patients and control subjects, analyzing men and women separately. RESULTS: The same FRZB 2-marker single-nucleotide polymorphism (SNP) haplotype associated with hip OA in other populations of Caucasian women was shown to increase the risk of knee OA among the women (but not the men) in the current study (odds ratio [OR] 2.87, P < 0.04). The CALM1 SNP, which affects the risk of hip OA in Japanese individuals, was not shown to be associated with susceptibility to OA in men or women. COL2A1 haplotypes were demonstrated to be associated with a decreased risk of knee OA in men (OR 0.68, P < 0.005) but not in women. COMP haplotypes that were associated with susceptibility to knee OA were different in men and women (P < 0.014 and P < 0.032, respectively). A meta-analysis of these data and those from previously published reports indicated a strong association between the FRZB G324 allele (P < 0.0003) and suggested that an ASPN allele is protective against the risk of knee OA in Caucasians (P < 0.02). CONCLUSION: Our results indicate that genetic polymorphisms affecting knee OA vary between populations (Japanese versus Caucasian) and sexes and indicate a role for ASPN, COMP, FRZB, and COL2A1 in Caucasians.     

Prevalence of knee symptoms and radiographic and symptomatic knee osteoarthritis in African Americans and Caucasians: the Johnston County Osteoarthritis Project

OBJECTIVE: To report contemporary estimates of the prevalence of knee-related osteoarthritis (OA) outcomes in African Americans and Caucasians aged > or = 45 years. METHODS: Weighted prevalence estimates for knee symptoms, radiographic knee OA, symptomatic knee OA, and severe radiographic knee OA were calculated for age, ethnic, and sex subgroups, in 3018 participants (33% African Americans, 38% men) in the baseline examination (1991-97) of The Johnston County Osteoarthritis Project, a population-based study of OA in North Carolina. Radiographic knee OA was defined as Kellgren-Lawrence radiographic grade > or = 2, severe radiographic knee OA as grades 3 and 4, and symptomatic knee OA as knee symptoms in a knee with radiographic OA. RESULTS: Knee symptoms were present in 43%, 28% had radiographic knee OA, 16% had symptomatic knee OA, and 8% had severe radiographic knee OA. Prevalence was higher in older individuals and women. African Americans had slightly higher prevalence of knee symptoms, radiographic knee OA, and symptomatic knee OA, but significantly higher prevalence of severe radiographic knee OA compared to Caucasians. CONCLUSION: Policy should be directed to increasing education of the public and the medical community about the high prevalence of these conditions, especially in these subgroups, to decrease their impact and ultimately prevent them.     

Changes in cartilage and bone metabolism identified by serum markers in early osteoarthritis of the knee joint

Serum concentrations of two extracellular matrix molecules were determined over a 3 yr period in individuals with chronic knee pain to investigate whether sequential serum measurements of cartilage- and bone-derived molecular fragments reflect early stages of osteoarthritis (OA) of the knee joints. Thirty-eight individuals with chronic knee pain (> 3 months at inclusion) with or without radiographic evidence of knee joint OA at the 3 yr follow-up radiographic examination were studied. Serum concentrations of cartilage oligomeric matrix protein (COMP) and bone sialoprotein (BSP) increased significantly (P < 0.001) in the 23 individuals with radiographic OA at follow-up, while remaining unchanged in the 15 individuals with normal radiographs at follow-up. The baseline concentrations of the two variables did not differ between the groups. These findings suggest that pathological processes in cartilage and subchondral bone coincide in OA, and appear to be reflected by circulating levels of macromolecules released from cartilage and bone. Changes in serum levels of COMP and BSP are potential tools in studies of knee joint OA in subjects with chronic knee pain.      

Racial variations in self-reported osteoarthritis symptom severity among veterans

BACKGROUND AND AIMS: This study aimed at examining factors related to osteoarthritis (OA) symptom severity in African American and Caucasian veterans (n=202). METHODS: OA symptom severity (lower extremity pain, stiffness, and physical function) was measured by the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC). We also examined whether racial differences existed when controlling for other important demographic and clinical variables, including age, gender, income, educational level, employment status, marital status, number of years with OA symptoms, location of arthritic joints (hip, knee, back, foot/ankle), use of exercise, and current use of OA medications. Lastly, we examined whether factors associated with self-reported OA symptom severity differed in African American and Caucasian veterans. RESULTS: The mean WOMAC score for African American veterans (on a scale of 0-96) was 54.6 (SD=17.2), and the mean score for Caucasian veterans was 48.4 (SD=17.6; p=0.02). In a multivariable regression model including demographic and clinical variables, African American veterans had significantly higher WOMAC scores than Caucasians (3=0.185, p=0.009). In Caucasian veterans, greater number of years with OA, presence of hip OA, and a low income were associated with greater WOMAC scores. In African Americans, no use of exercise and the presence of OA in the hip or back were associated with greater WOMAC scores. CONCLUSIONS: Among this sample of veterans, African Americans had significantly higher WOMAC scores than Caucasians after controlling for other important demographic and clinical factors. Different and more intense treatment strategies may be needed for African American veterans with OA.     

Serum cartilage oligomeric matrix protein and other biomarker profiles in tibiofemoral and patellofemoral osteoarthritis of the knee

OBJECTIVES: There is some evidence that tibiofemoral osteoarthritis (TFJ OA) and patellofemoral osteoarthritis (PFJ OA) may have different risk factors. To investigate the possibility that these conditions are separate disease entities, we compared biomarker profiles of patients with each disease. METHODS: Serum samples were taken from 222 patients who had knee pain and X-ray signs of knee OA. Eighty-two had only medial TFJ OA and 38 only PFJ OA in one or both knees. The remaining patients had either mixed disease or equivocal radiographic evidence of OA. The following biomarkers were measured in serum samples from baseline and follow-up visits: cartilage oligomeric matrix protein (COMP), glycosaminoglycan, keratan sulphate epitope 5D4, YKL-40, osteocalcin, C-telopeptide of type I collagen, hyaluronan and C-reactive protein. RESULTS: The two subsets of OA (TFJ and PFJ) had similar radiographic disease severity and there were no significant differences in the presence and patterns of pain scores (visual analogue scale and Western Ontario and McMaster Universities Osteoarthritis Index). No difference was found for the biomarkers between the two groups, with one exception. Both baseline and area under the curve per month COMP concentrations were significantly higher in the TFJ than the PFJ group (P<0.01). CONCLUSIONS: The reduced serum COMP in PFJ disease compared with TFJ OA could be due to small articular cartilage volume in the latter or to a qualitative difference in cartilage metabolism.     

The value of cartilage biomarkers in progressive knee osteoarthritis: cross-sectional and 6-year follow-up study in middle-aged subjects

To determine the possible diagnostic and prognostic value of cartilage biomarkers in early-stage progressive and nonprogressive knee osteoarthritis (OA) in a population-based cohort of middle-aged subjects with chronic knee pain. Design tibiofemoral (TF) and patellofemoral (PF) radiographs were graded in 128 subjects (mean age at baseline, 45 ± 6.2 years) in 2002, 2005, and 2008. Cartilage degradation was assessed by urinary C-telopeptide fragments of type II collagen (uCTx-II), synthesis by serum type II A procollagen N-terminal propeptide (sPIIANP), and articular tissue turnover in general by cartilage oligomeric matrix protein (sCOMP). Several diagnostic associations were found between all studied biomarkers and progressive osteophytosis. COMP and CTx-II had a predictive value for subsequent progressive osteophytosis in multiple knee compartments and in case of CTx-II—also for progressive JSN. Over the first 3 years (2002–2005), significant associations were observed between COMP and progressive osteophytosis, whereas 3 years later (2005–2008) between CTx-II and progressive JSN. Thus, the associations between cartilage markers (COMP, CTx-II) and progression of radiographic OA features—osteophytes and JSN—were different between 2002–2005 and 2005–2008. Logistic regression revealed that for every unit increase in COMP level, there was 33 % higher risk for TF osteophyte progression. During early-stage OA, the presence and progression of osteophytosis is accompanied by increased level of cartilage biomarkers. This is the first study to demonstrate biochemical differences over the course of knee OA, illustrating a phasic nonpersistent character of OA with periods of progression and stabilization.     

Characterization of individual radiographic features of hip osteoarthritis in African American and White Women and Men: The Johnston County Osteoarthritis Project

Objective

To describe differences in radiographic features of hip osteoarthritis (OA) between African American and white men and women.

Methods

We conducted a cross‐sectional analysis of radiographic hip OA using baseline data from the Johnston County Osteoarthritis Project, using Kellgren/Lawrence (K/L) grade, and the presence, location, and severity of 4 individual radiographic features (joint space narrowing [JSN], subchondral cysts, sclerosis, and osteophytes). Sex‐specific logistic regression was used to evaluate associations between race and individual radiographic features, adjusting for age, body mass index, education, and prior hip injury. Robust variance estimators via generalized estimating equations were used to account for correlation between hips from the same individual.

Results

The sample (n = 2,739) comprised 57% women and 31% African American participants. Among women, African Americans and whites had a similar prevalence of hip OA, defined as K/L grade ≥2 (23% versus 22%), but African American women were significantly more likely to have superior or medial JSN, moderate or severe axial JSN, medial or lateral osteophytes, and subchondral cysts. Among men, 21% of African Americans and 17% of whites had hip OA; African American men were more likely to have superior or medial JSN and lateral osteophytes, but were less likely to have axial JSN.

Conclusion

Individual radiographic features and patterns of hip OA differed by race among women and men, suggesting the possibility of anatomic and/or developmental variation in the hip joint. African Americans have an increased frequency of features that have been predictive of hip replacement in other populations, a finding worthy of further study.     

Suggestion of nonlinear or phasic progression of knee osteoarthritis based on measurements of serum cartilage oligomeric matrix protein levels over five years

OBJECTIVE: In many patients with knee osteoarthritis (OA), the disease progresses, and there is loss of cartilage; in others, the disease stabilizes with time. Previous studies have demonstrated that concentrations of serum proteins that reflect joint tissue metabolism can identify knees that will deteriorate, leading to the suggestion that OA disease activity is phasic or cyclical. The aim of the current study was to determine whether longitudinal measurements of one such protein, serum cartilage oligomeric matrix protein (COMP), are related to disease outcome over a 5-year period. METHODS: Serum COMP levels were measured by enzyme-linked immunosorbent assay at study entry and every 6 months thereafter in 115 patients with knee pain and OA of mainly the tibiofemoral joint. Cartilage loss was determined from knee radiographs taken at entry and at 24, 36, and 60 months. Disease progression was defined as either a reduction in the tibiofemoral joint space width by at least 2 mm or total knee replacement (TKR) in either knee at followup. COMP concentrations at baseline and the area under the curve (AUC) of measurements obtained over 5 years were compared between progressors and nonprogressors by Student's 2-tailed t-test. The patterns and probability of progression according to TKR or > or =2 mm of narrowing of the tibiofemoral joint space were analyzed by logistic regression models. RESULTS: The mean +/- SD ages of the progressors and nonprogressors were 64.2 +/- 7.8 years and 63.3 +/- 10.6 years, respectively, and the proportion of females was 51% and 56%, respectively. Of the 37 patients whose OA progressed (22 by TKR and 15 by > or =2-mm reduction in tibiofemoral joint space), 13 lost cartilage during the first 2 years, and 18 lost cartilage during the last 2 years. The mean +/- SD serum COMP concentration at baseline was significantly higher in the progressors compared with the nonprogressors (14.12 +/- 3.39 units/liter versus 12.62 +/- 3.25 units/liter; P < 0.036). Serum COMP levels rose significantly after TKR; however, after allowing for the effect of TKR, the AUC/month was significantly higher in the progressors compared with the nonprogressors (12.52 +/- 2.71 versus 10.82 +/- 2.71; P < 0.003). Serum COMP concentrations were higher during periods of radiographic progression and identified periods of progression that were nonlinear. Logistic regression analysis showed that on average, a 1-unit increase in serum COMP levels increased the probability of radiographic progression by 15%. CONCLUSION: The data suggest that serum COMP is related to progressive joint damage in knee OA. The patterns of progression for the early and late progressors are consistent with the hypothesis that knee OA progression is episodic or phasic. Large between-subject variation precludes the use of individual values to predict progression with confidence. However, sequential measurements of serum COMP levels may identify patients whose OA is likely to progress over the next year or two.     

Diurnal variation of serum and urine biomarkers in patients with radiographic knee osteoarthritis

OBJECTIVE: To evaluate diurnal variation of biomarkers in subjects with osteoarthritis (OA) of the knee. METHODS: Twenty subjects with radiographic knee OA were admitted to the General Clinical Research Center of Duke University for an overnight stay to undergo serial blood and urine sampling. Biomarkers measured included serum hyaluronan (HA), cartilage oligomeric matrix protein (COMP), keratan sulfate (KS-5D4), aggrecan neoepitope (CS846), high-sensitivity C-reactive protein (hsCRP), osteocalcin, transforming growth factor beta1 (TGFbeta1), and type II collagen (CII)-related epitopes (neoepitope from cleavage of CII [C2C], carboxy-terminus of three-quarter peptide from cleavage of CI and CII [C1,2C], and type II procollagen carboxy-propeptide [CPII] in serum, and C-terminal telopeptides of CII [CTX-II] and C2C in urine). RESULTS: Levels of serum HA, COMP, KS-5D4, and TGFbeta1 increased significantly from T0 (before arising from bed) to T1 (1 hour after arising). More diurnal variation in HA was observed in patients with higher daily mean HA concentrations. CPII increased significantly from T0 to T2 (4 hours after arising). Urinary concentrations of CTX-II were also found to vary with morning activity, decreasing significantly from T0 to T2. Urinary C2C concentrations increased significantly from T0 until T3 (early evening). No diurnal variations in CS846, hsCRP, osteocalcin, serum C2C, or C1,2C were observed. Six biomarkers (serum C2C, C1,2C, COMP, KS-5D4, TGFbeta1, and urinary CTX-II) were associated with radiographic knee OA (expressed as the sum of Kellgren/Lawrence radiographic severity grades), with the strongest correlations observed with measurements obtained at later time points (either T2 or T3). CONCLUSION: Our study results suggest that serum and urine sampling for HA, COMP, KS-5D4, TGFbeta1, CPII, urinary CTX-II, and urinary C2C should be standardized in future OA clinical trials. Serum and urine sampling at late midday time points may be the optimal approach for OA studies, although this result should be validated in a larger cohort.     

Frizzled-related protein variants are risk factors for hip osteoarthritis

OBJECTIVE: To examine the association of the Arg200Trp and Arg324Gly variants of FRZB with the risk and phenotype of radiographic osteoarthritis (OA) of the hip and serum levels of Frizzled-related protein (FRP) in a prospective cohort of elderly Caucasian women. METHODS: Radiographic hip OA status of patients was defined by the presence of severe joint space narrowing (JSN) (feature grade>or=3), a summary grade>or=3, or definite osteophytes (grade>or=2) and JSN (grade>or=2) in the same hip. Genotypes were obtained in 569 patients with radiographic OA of the hip and in 1,317 and 4,136 controls for the Arg200Trp and Arg324Gly variants, respectively. Serum FRP levels were measured by enzyme-linked immunosorbent assay. Multivariate logistic regression was performed. RESULTS: The minor allele frequency for the Arg200Trp polymorphism was 0.12 in the control group compared with 0.14 in the group with radiographic OA of the hip (P=0.12), and the minor allele frequency for the Arg324Gly variant was 0.083 in the control group compared with 0.088 in the group with radiographic OA of the hip (P=0.63). The multilocus genotypes available in 1,886 subjects suggested that inheritance of both minor alleles was a risk factor for developing OA characterized by JSN (P<0.01). Patients with radiographic OA of the hip who were homozygous for the Arg200Trp minor allele had higher serum FRP levels than controls who were homozygous for the major allele. CONCLUSION: Our data confirm findings of another study, that a rare haplotype with both Arg200Trp and Arg324Gly FRZB variants contributes to the genetic susceptibility to hip OA among Caucasian women, and that these polymorphisms may contribute to increased serum levels of proteins as biomarkers of OA.     

High prevalence of lateral knee osteoarthritis in Beijing Chinese compared with Framingham Caucasian subjects

OBJECTIVE: We recently reported that, despite their thinness, elderly subjects in Beijing, China had an equal prevalence (in men) or higher prevalence (in women) of both radiographic and symptomatic knee osteoarthritis (OA) compared with that in the Framingham, Massachusetts cohort of elderly subjects. Our objective was to evaluate whether Chinese subjects might have more medial disease than do Caucasians, given a report of varus alignment in the knee joints of Chinese elderly. METHODS: We compared the prevalence of medial and lateral radiographic knee OA and measured anatomic alignment in the knees of elderly subjects from the Beijing and Framingham cohorts. Both studies recruited a random sample of the population. The Beijing OA Study used the Framingham OA Study protocol for radiographs. Anteroposterior weight-bearing films were read for Kellgren and Lawrence (K/L) grade and joint space narrowing (JSN; 0-3 scale) in each compartment. Medial disease was defined when radiographs showed a K/L grade >or=2 and medial JSN >or=1, and lateral disease was assessed in a comparable manner. Using knee-specific analyses, we compared the prevalence of medial and lateral knee OA after adjusting for age, body mass index, and the correlation between the 2 knees. Restricting the analyses to knees with JSN >or=2 and comparing the proportion of OA knees with medial disease and lateral disease yielded similar results. We assessed alignment in knees from 100 persons without OA, measuring the angle subtended by the femoral and tibial anatomic axes. RESULTS: We studied 1,781 Chinese subjects ages 60-88 years, and 1,084 Framingham subjects ages 63-93 years. Whereas medial OA was less prevalent among the Beijing men, lateral OA was more than twice as prevalent among the Beijing men and women, compared with that in the Framingham elderly. For example, of all knees with radiographic OA, 28.5% of Beijing women's knees had lateral OA versus 11% of Framingham women's knees (P < 0.001), and among men, 32.3% of Beijing men's knees versus 8.8% of Framingham men's knees (P < 0.001) had lateral OA. Alignment was more valgus in the Beijing men than in the Framingham men (mean 4.5 degrees versus 2.7 degrees valgus, respectively; P < 0.001), but no differences in alignment were evident in the women. CONCLUSION: In this first attempt to compare the characteristics of OA in different racial groups, we conclude that, opposite to expectations, Chinese subjects have much more lateral OA than do Caucasian subjects in the Framingham cohort, a predilection possibly explained in the men by differences in anatomic alignment.     

Hypothalamic-pituitary-adrenal axis activity during exercise in African American and Caucasian women

African American women have a greater prevalence of obesity than Caucasian women, but the reasons for this difference are not known. We have investigated whether activity of the hypothalamic-pituitary adrenal axis plays a role in this phenomenon. Previous studies have shown that plasma ACTH immunoreactivity (ACTH-IR) of African American women, measured after ovine CRH (oCRH) stimulation, is significantly greater than ACTH-IR of Caucasian women, but is not accompanied by greater plasma cortisol concentrations. Analysis by high pressure liquid chromatography has demonstrated that after oCRH stimulation, the plasma ACTH-IR of African American women contains many nonintact ACTH fragments not found in Caucasians. To determine whether these racial differences in ACTH-IR secretion are an artifact of exogenous oCRH administration or are also found after a physiological stimulus for ACTH secretion, we measured hormones of the hypothalamic-pituitary adrenal axis before and after a standardized, maximal exercise treadmill test in 16 African American and 19 Caucasian healthy women matched for age, socioeconomic status, and body mass index. The intensity of exercise performed was similar in the two groups, as determined by duration of exercise, perceived intensity of exertion, plasma lactate, maximal heart rate, and maximum oxygen uptake. Basal ACTH-IR measured by RIA or immunoradiometric assay and cortisol were similar in African Americans and Caucasians. Plasma ACTH-IR, measured 10 min after completion of exercise, was significantly greater in African Americans than in Caucasians [by RIA: mean +/- SD ACTH-IR, 47.1 +/- 30.9 vs. 25.4 +/- 16.7 pmol/L (P < 0.01); by immunoradiometric assay: ACTH-IR, 45.9 +/- 43.2 vs. 21.1 +/- 14.6 pmol/L (P < 0.05)]. However, plasma cortisol after exercise was not different (450.2 +/- 157.7 vs. 483.6 +/- 180.4 nmol/L; P = 0.57). We conclude that ACTH-IR is significantly greater in African American than in Caucasian women after intense exercise. The ACTH-IR of African Americans and Caucasians does not appear to be equipotent at adrenal melanocortin-2 receptors, because the greater ACTH-IR of African Americans does not lead to greater cortisol secretion. Whether some components of the ACTH-IR detected in African Americans affect signal transduction of the hypothalamic melanocortin-4 receptors implicated in body weight regulation and thus predispose African American women to weight gain without altering plasma cortisol remains to be determined.     

Prevalence of falls and the association with knee osteoarthritis and lumbar spondylosis as well as knee and lower back pain in Japanese men and women

Objective

There is little information on falls by sex and age strata in Japan, and few factors associated with falls have been established. However, the association between bone and joint diseases and falls remains unclear. We examined prevalence of falls by sex and age strata, determined its association with radiographic osteoarthritis (OA) of the knee and lumbar spine, and determined knee and lower back pain after single and multiple falls.

Methods

A questionnaire assessed the number of falls during 12 months preceding baseline. Knee and lumbar spine radiographs were read by Kellgren/Lawrence (K/L) grade; radiographic knee OA and lumbar spondylosis were defined as a K/L grade of 3 or 4. Knee and lower back pain were estimated by an interview.

Results

A total of 587 men and 1,088 women (mean ± SD age 65.3 ± 12.0 years) were analyzed. During 1 year, 79 (13.5%) men and 207 (19.0%) women reported at least 1 fall. With increasing age, the prevalence of multiple falls was higher in women, but lower in elderly men age >60 years. In men, few factors were significantly associated with falls. In women, radiographic knee OA and lumbar spondylosis, as well as knee and lower back pain, were significantly associated with multiple falls without adjustment. Lower back pain and knee pain were independently associated with multiple falls in women after adjustment.

Conclusion

Lower back pain and knee pain were significantly associated with multiple falls in women.     

Association of radiographic features of osteoarthritis of the knee with knee pain: Data from the baltimore longitudinal study of aging

Objective. To examine the association between selfreported knee pain and radiographic features of osteoarthritis (OA) of the knee. Methods. A sample of participants in the Baltimore Longitudinal Study of Aging (452 Caucasian males and 223 Caucasian females) completed questionnaires and underwent a standing radiograph of both knees at the same biennial visit between 1984 and 1989. Radiographs were interpreted using both the Kellgren-Lawrence and individual features scales. Odds ratios were calculated for the association of radiographic features with knee pain after adjustment for age, sex, and body mass index. Results. Overall, 156 (23%) persons reported ever having knee pain, and 104 (15%) reported current knee pain (within the previous year). Both ever knee pain and current knee pain were significantly associated with the presence of definite knee OA (Kellgren-Lawrence grade ≥2) and with the presence of all individual features. There was a direct relationship between all measures of severity of radiographic OA and knee pain. Conclusion. These data demonstrate that radiographic features of knee OA are significantly associated with knee pain. The data also support the continued use of the Kellgren-Lawrence grading scale for defining knee OA in population studies.     

Association of dietary magnesium intake with radiographic knee osteoarthritis: Results from a population‐based study

Objective

To examine the cross‐sectional association between dietary magnesium intake and radiographic knee osteoarthritis (OA) among African American and white men and women.

Methods

The presence of radiographic knee OA was examined among participants from the Johnston County Osteoarthritis Project and was defined as a Kellgren/Lawrence grade of at least 2 in at least 1 knee. The Block Food Frequency Questionnaire was used to assess magnesium intake. Effect modifiers were explored by testing interactions of magnesium intake and selected factors based on previous studies. The multivariable logistic regression model with standard energy adjustment method was used to estimate the relationship between magnesium intake and radiographic knee OA.

Results

The prevalence of knee OA was 36.27% among the 2,112 participants. The relationship between magnesium intake and radiographic knee OA was found to be modified by race (P for interaction = 0.03). An inverse threshold association was observed among whites. Compared to participants in the lowest quintile, the relative odds of radiographic knee OA were cut by one‐half for participants in the second quintile of magnesium intake (odds ratio 0.52, 95% confidence interval 0.34–0.79); further magnesium intake did not provide further benefits (P for trend = 0.51). A statistically significant association was not observed among African Americans.

Conclusion

A modest inverse threshold association was found between dietary magnesium intake and knee OA in whites, but not in African Americans. Further studies are needed to confirm these results and to elucidate the possible mechanisms of action for the racial modification.     

The association of race and ethnicity with disease expression in male US veterans with rheumatoid arthritis

OBJECTIVE: To examine the association of race/ethnicity with measures of disease activity and severity among male US veterans with rheumatoid arthritis (RA). METHODS: Measures of disease activity and severity were examined in a group of US veterans (n = 573) with RA, comparing measures in African American men (n = 79) with Caucasian men (n = 494). Dichotomous variables were compared using logistic regression while continuous variables were examined using linear regression, adjusting for the effects of age, disease duration, and smoking status. RESULTS: Compared to Caucasians, African Americans were slightly younger (65.0 vs 67.1 yrs; p = 0.09) at enrollment and had a similar age at disease onset (50.5 vs 50.6 years; p = 0.98). After adjusting for age, disease duration, and smoking status, there were no differences based on race/ethnicity in rheumatoid factor positivity, the presence of radiographic changes, physical functioning, swollen joint counts, Disease Activity Score (DAS28), or global well-being scores. In contrast, African Americans were about 50% less likely than Caucasians with RA to have subcutaneous nodules (adjusted OR 0.51, 95% CI 0.30-0.86) and had lower tender joint counts (p = 0.007), associations that were attenuated and not significant with further adjustment for collection site. CONCLUSION: With the possible exception of lower rates of rheumatoid nodules and lower tender joint counts in African Americans, there is little evidence to support the existence of important racial/ethnic differences in RA disease expression between African American and Caucasian men.