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.

     

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 ≥3), a summary grade ≥3, or definite osteophytes (grade ≥2) and JSN (grade ≥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.

     

A large Icelandic family with early osteoarthritis of the hip associated with a susceptibility locus on chromosome 16p

Objective

To describe a large kinship with inherited hip osteoarthritis (OA) and its associated susceptibility locus.

Methods

Four generations of a kinship with familial hip OA were identified and characterized by family history and by clinical, radiographic, and histopathologic examination. In the genome‐wide search for a susceptibility locus, OA cases were defined as those who had undergone total hip replacement associated with a clinical and radiographic diagnosis of hip OA. A genome‐wide scan was performed using a framework set of microsatellite markers with an average spacing of 10 cM.

Results

The hip OA of this family was indistinguishable from that of idiopathic, nonfamilial hip OA. There was no apparent evidence of spondyloepiphyseal dysplasia or other dysplasias usually associated with mutations in collagen genes. The genome‐wide scan revealed a locus on chromosome 16p between 28 cM and 47 cM from the telomere, and this locus met the criteria for suggestive linkage (multipoint allele‐sharing logarithm of odds [LOD] score 2.58, P = 1.6 × 10⁻⁴). Two additional regions with LOD scores of >1.5 were obtained.

Conclusion

We have identified and described the largest kinship with familial hip OA reported to date. Evidence for linkage in this family suggests that a gene for susceptibility to hip OA exists on chromosome 16p. This represents an independent identification of a susceptibility locus previously reported for hip OA in this geographic region.

     

Association of the interleukin‐1 gene cluster on chromosome 2q13 with knee osteoarthritis

Objective

To investigate whether the interleukin‐1 (IL‐1) ligand gene cluster at 2q13 encodes for genetic susceptibility to primary osteoarthritis (OA).

Methods

Seven single‐nucleotide polymorphisms (SNPs) and a variable‐number tandem repeat (VNTR) polymorphism from within the IL‐1 ligand genes IL1A, IL1B, and IL1RN were genotyped in a cohort of 557 OA cases and 557 age‐matched controls.

Results

None of the variants demonstrated association in the unstratified data set. However, when cases were stratified according to sex and site of disease (hip or knee), 4 SNPs showed marginal evidence for association (P < 0.1) in knee cases (n = 136) and male knee cases (n = 58). For 2 of these SNPs, evidence for association was enhanced when probands from 60 knee‐only affected sibling pair families were genotyped and combined with the original knee cases (P ≤ 0.05). Further analysis revealed that the associated alleles at 2 of these SNPs were markers for the same haplotype, the frequency of which was significantly elevated when knee cases and knee probands were combined (P = 0.01, odds ratio [OR] 1.4) and when male knee cases and male knee probands were combined (P = 0.009, OR 1.7). Furthermore, linkage analysis of 2q revealed suggestive evidence for linkage to the IL‐1 gene clusters in affected sibling pairs concordant for knee OA but no evidence for linkage in affected sibling pairs concordant for hip OA.

Conclusion

The IL‐1 ligand cluster encodes for susceptibility to knee OA but not to hip OA, highlighting the genetic heterogeneity of this common, complex disease.

     

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.

     

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.

     

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.

     

Evidence for a role of the genomic region of the gene encoding for the alpha1 chain of type IX collagen (COL9A1) in hip osteoarthritis: A population-based study

OBJECTIVE: Type IX collagen proteoglycan is an important protein in collagen networks and has been implicated in hip osteoarthritis (OA). We studied 2 COL9A1 markers (509-8B2 and 509-12B1) in relation to radiographic OA, within the framework of the Rotterdam Study, a population-based study of 7,983 subjects ages 55 years and older. METHODS: We used 2 different designs, as follows: 1) a linkage study of 83 probands with multiple joints affected with radiographic OA and their 221 siblings, yielding 445 sibpairs who participated in the study, and 2) an association study in a series of 71 patients with radiographic hip OA and 269 controls without radiographic OA. All subjects were characterized for the 2 COL9A1 markers, 509-8B2 and 509-12B1. The mean test was used to assess the proportion of alleles shared in concordantly affected and unaffected sibpairs. The chi-square test was used to compare the allele distributions in patients and controls. RESULTS: Affected sibpairs with radiographic hip OA shared alleles identical by descent at markers 8B2 and 12B1 significantly more often than expected (mean +/- SD 0.66 +/- 0.07 and 0.65 +/- 0.08, respectively; P < 0.05). No excess sharing for radiographic OA was observed at other joint sites. When comparing the frequency of marker 8B2 and 12B1 alleles in subjects with radiographic OA and controls, the frequency of 8B2 alleles in subjects with radiographic OA differed significantly(P = 0.01) from that in controls. CONCLUSION: Our data suggest that susceptibility for hip OA is conferred within or close to the COL9A1 gene in linkage disequilibrium with the COL9A1 509-8B2 marker.     

Altered mineralization of human osteoarthritic osteoblasts is attributable to abnormal type I collagen production

Objective

Bone tissue in osteoarthritis (OA) is composed of abundant undermineralized osteoid matrix. The aim of this study was to investigate the mechanisms responsible for this abnormal matrix, using in vitro OA subchondral osteoblasts.

Methods

Primary normal and OA osteoblasts were prepared from tibial plateaus. Phenotype was determined by alkaline phosphatase activity, and osteocalcin, osteopontin, prostaglandin E₂ (PGE₂), and transforming growth factor β1 (TGFβ1) were assessed by enzyme‐linked immunosorbent assay. Expression of COL1A1 and COL1A2 was determined by real‐time polymerase chain reaction. The production of type I collagen was determined by the release of its C‐terminal propeptide and Western blot analysis. In vitro mineralization was evaluated by alizarin red staining. Inhibition of TGFβ1 expression was performed using a small interfering RNA technique.

Results

Mineralization of OA osteoblasts was reduced compared with mineralization of normal osteoblasts, even in the presence of bone morphogenetic protein 2 (BMP‐2). Alkaline phosphatase and osteocalcin levels were elevated in OA osteoblasts compared with normal osteoblasts, whereas osteopontin levels were similar. The COL1A1‐to‐COL1A2 messenger RNA ratio was 3‐fold higher in OA osteoblasts compared with normal osteoblasts, and the production of collagen by OA osteoblasts was increased. Because TGFβ1 inhibits BMP‐2–dependent mineralization, and because TGFβ1 levels are ∼4‐fold higher in OA osteoblasts than in normal osteoblasts, inhibiting TGFβ1 levels in OA osteoblasts corrected the abnormal COL1A1‐to‐COL1A2 ratio and increased alizarin red staining.

Conclusion

Elevated TGFβ1 levels in OA osteoblasts are responsible, in part, for the abnormal ratio of COL1A1 to COL1A2 and for the abnormal production of mature type I collagen. This abnormal COL1A1‐to‐COL1A2 ratio generates a matrix that blunts mineralization in OA osteoblasts.

     

Association of 25‐hydroxyvitamin D with prevalent osteoarthritis of the hip in elderly men: The osteoporotic fractures in men study

Objective

To examine the cross‐sectional association of serum levels of 25‐hydroxyvitamin D, or 25(OH)D, with prevalent radiographic hip osteoarthritis (OA) in elderly men.

Methods

In a cohort of 1,104 elderly men from the Osteoporotic Fractures in Men Study, 25(OH)D serum levels were determined by mass spectrometry, followed by pelvic radiographs ∼4.6 years later. Categories of vitamin D levels were defined as follows: deficiency as ≤15 ng/ml, insufficiency as 15.1–30 ng/ml, and sufficiency as >30 ng/ml. Radiographs were assessed for severity of hip OA using a summary grade of 0–4 for individual features of hip OA. Logistic regression was used to assess associations of serum 25(OH)D levels with prevalent radiographic hip OA; covariates included age, clinic site, season at the time of blood withdrawal, self‐reported hip pain for >30 days, timed 6‐meter walk, presence of at least 1 coexisting condition, and self‐rated health status.

Results

Men with radiographic hip OA had a slower 6‐meter walking time (P < 0.0001), reported more hip pain (P = 0.0001), had a lower vitamin D level (P = 0.0002), and had a higher prevalence of vitamin D insufficiency (P = 0.002) and vitamin D deficiency (P = 0.012) compared with controls. Higher 25(OH)D levels were associated with a lower prevalence of radiographic hip OA (odds ratio [OR] 1.39 per 1 SD decrease in 25[OH]D, 95% confidence interval [95% CI] 1.11–1.74) after adjusting for age, season, and clinic site. Men with vitamin D insufficiency had an increased likelihood of prevalent radiographic hip OA (OR 2.19, 95% CI 1.21–3.97) compared with men with sufficient levels of 25(OH)D, and in men with vitamin D deficiency, there was a tendency toward an increased likelihood of radiographic hip OA (OR 1.99, 95% CI 0.83–4.74).

Conclusion

Men with vitamin D deficiencies are twice as likely to have prevalent radiographic hip OA, and therefore vitamin D therapy to augment skeletal health in the elderly is warranted.

     

The association between hip morphology parameters and nineteen‐year risk of end‐stage osteoarthritis of the hip: A nested case–control study

Objective

Subtle deformities of the hip joint are implicated in the etiology of osteoarthritis (OA) of the hip. Parameters that quantify these deformities may aid understanding of these associations. We undertook this study to examine relationships between such parameters and the 19‐year risk of total hip arthroplasty (THA) for end‐stage OA.

Methods

A new software program designed for measuring morphologic parameters around the hip was developed and validated in a reliability study. THA was the outcome measure for end‐stage OA. A nested case–control study was used with individuals from a cohort of 1,003 women who were recruited at year 1 in 1989 and followed up to year 20 (the Chingford Study). All hips with THA by year 20 and 243 randomly selected control hips were studied. Pelvis radiographs obtained at year 2 were analyzed for variations in hip morphology. Measurements were compared between the THA case group and the control group.

Results

Patients with THA had a higher prevalence of cam deformity than did their respective controls (median alpha angle 62.4° versus 45.8° [P = 0.001]; mean modified triangular index height 28.5 mm versus 26.9 mm [P = 0.001]) as well as a higher prevalence of acetabular dysplasia (mean lateral center edge angle 29.5° versus 34.3° [P = 0.001]; median extrusion index 0.25 versus 0.185 [P = 0.009]). Logistic regression analyses clustering by subject and adjusting for radiographic hip OA at year 2 showed that these morphologic parameters were still significantly associated with THA by year 20. The alpha angle and lateral center edge angle predicted the risk of THA independently when included in the same model.

Conclusion

This investigation describes measurements that predict the risk of THA for end‐stage OA by year 20, independently of the presence of radiographic hip OA at year 2. These measurements can be made on an anteroposterior pelvis radiograph, which is an inexpensive and commonly used clinical method of investigation.

     

Nonrandom evolution of end‐stage osteoarthritis of the lower limbs

Objective

Patients with unilateral hip or knee replacements for end‐stage osteoarthritis (OA) are at high risk for future progression of OA in other joints of the lower extremities, often requiring additional joint replacements. Although the risks of future surgery in the contralateral cognate joints (i.e., contralateral hip replacement after an initial hip replacement) have been evaluated, the evolution of end‐stage hip OA to OA involving the knee joints, and vice versa (i.e., noncognate progression) has not been investigated. Because characterization of OA progression in noncognate joints may shed light on the pathogenesis of multijoint OA, we investigated the pattern of evolution of end‐stage lower extremity OA in a large, clinical cohort.

Methods

Total joint replacement (TJR) was selected as a marker of end‐stage OA, and a database comprising all lower extremity TJRs performed at a large referral center between 1981 and 2001 was accessed. Of the 5,894 patients identified, 486 patients with idiopathic OA who underwent hip replacement and 414 who underwent initial knee replacement were analyzed to determine the relative likelihood of subsequent TJRs. Patients with the systemic inflammatory arthropathy, rheumatoid arthritis (RA), were evaluated as a control population because RA progression is not considered to be a primarily mechanically mediated process.

Results

The contralateral cognate joint was the most common second joint to undergo replacement in both the OA and the RA groups. However, in OA patients for whom the second TJR was in a noncognate joint, that joint was >2‐fold more likely to be on the contralateral limb than on the ipsilateral limb (hip to knee P < 0.001; knee to hip P = 0.013). In contrast, among the RA cohort, the evolution was random and no laterality for noncognate TJR was observed at either the hip or the knee (P = 0.782).

Conclusion

This characterization of end‐stage lower extremity OA demonstrates that the disease evolves nonrandomly; after 1 joint is replaced, the contralateral limb is significantly more likely to show progression of OA than is the ipsilateral limb. Thus, OA in 1 weight‐bearing joint appears to influence the evolution of OA in other joints. The absence of such laterality in RA suggests that OA progression may be mediated by extrinsic factors such as altered joint loading.

     

Impact of type of meniscal tear on radiographic and symptomatic knee osteoarthritis: A sixteen‐year followup of meniscectomy with matched controls

Objective

To investigate long‐term radiographic and patient‐relevant outcome of isolated limited meniscectomy with regard to type of meniscal tear and extent of surgical resection.

Methods

We studied 155 patients with intact cruciate ligaments (mean ± SD age 54 ± 12 years) who had undergone meniscectomy an average of 16 ± 1 years earlier. The patients were examined using standardized radiography and validated self‐administered questionnaires. The Knee Injury and Osteoarthritis Outcome Score (KOOS) was used to quantify knee‐related symptoms, and the definition of a symptomatic knee was determined. We used 68 control subjects matched for age, sex, and body mass index to calculate the relative risks (RRs).

Results

Radiographic tibiofemoral osteoarthritis (OA) (Kellgren/Lawrence grade ≥2) was present in 66 index knees (43%), of which 39 (59%) were considered to be symptomatic according to the KOOS. In total, 77 patients (50%) had a symptomatic index knee. In a multivariate model, degenerative meniscal tears were associated with both radiographic OA (P = 0.030) and combined radiographic and symptomatic OA (P ≤ 0.015). The RRs for combined radiographic and symptomatic OA after degenerative and traumatic types of meniscal tear were 7.0 (95% confidence interval [95% CI] 2.1–23.5) and 2.7 (95% CI 0.9–7.7), respectively, compared with matched controls.

Conclusion

An isolated meniscal tear treated by limited meniscectomy is associated with a high risk of radiographic and symptomatic tibiofemoral OA at 16‐year followup. Factors associated with worse outcome were degenerative meniscal lesions and extensive resections. We suggest that degenerative meniscal tears may be associated with incipient OA, and that the meniscal tear signals the first symptom of the disease.

     

Evaluation of the structure‐modifying effects of diacerein in hip osteoarthritis: ECHODIAH,a three‐year,placebo‐controlled trial

Objective

To evaluate the ability of diacerein, an interleukin‐1β inhibitor, to slow the progressive decrease in joint space width observed in patients with hip osteoarthritis (OA).

Methods

In this randomized, double‐blind, placebo‐controlled 3‐year study, 507 patients with primary OA of the hip (by the American College of Rheumatology criteria) received diacerein (50 mg twice a day) or placebo. The minimal hip joint space width was measured by a central reader on yearly pelvic radiographs, using a 0.1‐mm–graduated magnifying glass.

Results

Baseline characteristics were comparable in the 2 treatment groups (255 patients receiving diacerein, 252 receiving placebo); 238 patients (47%) discontinued the study, mainly because of adverse events in the diacerein group (25% versus 12% with placebo) and because of inefficacy in the placebo group (14% versus 7% with diacerein). The percentage of patients with radiographic progression, defined by a joint space loss of at least 0.5 mm, was significantly lower in patients receiving diacerein than in patients receiving placebo, both in the intent‐to‐treat analysis and in the completer analysis (50.7% versus 60.4% [P = 0.036] and 47.3% versus 62.3% [P = 0.007], respectively). In those patients who completed 3 years of treatment, the rate of joint space narrowing was significantly lower with diacerein (mean ± SD 0.18 ± 0.25 mm/year versus 0.23 ± 0.23 mm/year with placebo; P = 0.042). Diacerein had no evident effect on the symptoms of OA in this study. However, a post hoc covariate analysis that took into account the use of analgesics and antiinflammatory drugs showed an effect of diacerein on the Lequesne functional index. Diacerein was well tolerated during the 3‐year study. The most frequent adverse events were transient changes in bowel habits.

Conclusion

This study confirms previous clinical findings indicating that the demonstration of a structure‐modifying effect in hip OA is feasible, and shows, for the first time, that treatment with diacerein for 3 years has a significant structure‐modifying effect as compared with placebo, coupled with a good safety profile. The clinical relevance of these findings requires further investigation.

     

Risk factors for symptomatic knee osteoarthritis fifteen to twenty‐two years after meniscectomy

Objective

To evaluate the influence of age, sex, body mass index (BMI), extent of meniscal resection, cartilage status, and knee load on the development of radiographically evident osteoarthritis (OA) of the knee and knee symptoms after meniscal resection.

Methods

We evaluated 317 patients with no cruciate ligament injury (mean ± SD age 54 ± 11 years) who had undergone meniscal resection 15–22 years earlier (followup rate 70%), with radiographic and clinical examination. The Knee injury and Osteoarthritis Outcome Score was used to quantify knee‐related symptoms. Sixty‐eight unoperated subjects identified from national population records were included as a reference group.

Results

Symptomatic radiographic OA (corresponding to Kellgren/Lawrence grade ≥2) was present in 83 of 305 operated knees (27%) and 7 of 68 control knees (10%) (relative risk 2.6, 95% confidence interval [95% CI] 1.3–6.1). Patients who had undergone total meniscectomy and subjects with obesity (BMI ≥30) had a greater likelihood of tibiofemoral radiographic OA than those who had undergone partial meniscal resection and those with a BMI <25, respectively. Furthermore, degenerative meniscal tear, intraoperative cartilage changes, and lateral meniscectomy were associated with radiographic OA more frequently than were longitudinal tear, absence of cartilage changes, and medial meniscectomy, respectively. Symptomatic tibiofemoral or patellofemoral radiographic OA was associated with obesity, female sex, and degenerative meniscal tear.

Conclusion

Contributing risk factors for OA development after meniscal resection are similar to risk factors for common knee OA. Systemic factors and local biomechanical factors interact. Obesity, female sex, and preexisting early‐stage OA are features associated with poor self‐reported and radiographic outcome. Partial meniscal resection is associated with less radiographic OA over time than is total meniscectomy.

     

Very low prevalence of hip osteoarthritis among Chinese elderly in Beijing,China, compared with whites in the United States: The Beijing osteoarthritis study

Objective

To compare the prevalence of osteoarthritis (OA) of the hip among elderly persons in China and the US.

Methods

We recruited a population‐based sample of 1,506 persons (82% of those enumerated) ages ≥60 years living in Beijing, China. Subjects answered questions about joint symptoms and underwent radiography of the pelvis. Radiographs of the Beijing subjects were intermingled with hip radiographs of white women ages ≥65 years from the Study of Osteoporotic Fractures (SOF) and white men and women ages 60–74 years from the First National Health and Nutrition Examination Survey (NHANES‐I) and were then interpreted. Radiographic hip OA was defined as the presence of 1 of the following 3 findings in either hip: minimum joint space of ≤1.5 mm, definite osteophytes and joint space narrowing, or ≥3 radiographic features of OA. Symptomatic hip OA was defined as both radiographic OA and hip pain.

Results

The crude prevalence of radiographic hip OA in Chinese ages 60–89 years was 0.9% in women and 1.1% in men; it did not increase with age. Chinese women had a lower age‐standardized prevalence of radiographic hip OA compared with white women in the SOF (age‐standardized prevalence ratio 0.07) and the NHANES‐I (prevalence ratio 0.22). Chinese men had a lower prevalence of radiographic hip OA compared with white men of the same age in the NHANES‐I (prevalence ratio 0.19). There were no cases of symptomatic hip OA in the Chinese men and only 1 case in the Chinese women; 35 cases were expected in both sexes.

Conclusion

This is the first population‐based study of hip OA in China to use standardized radiographic methods and definitions. We found that hip OA was 80–90% less frequent than in white persons in the US. Identification of the genetic and environmental factors that underlie these differences may help elucidate the etiology and prevention of hip OA.

     

A randomized controlled trial to evaluate the slow‐acting symptom‐modifying effects of colchicine in osteoarthritis of the knee: A preliminary report

Objective

To determine if colchicine added to nimesulide may have a beneficial effect on osteoarthritis (OA) of the knee.

Methods

Colchicine 0.5 mg twice daily or placebo was added to nimesulide (a nonsteroidal antiinflammatory drug) in 36 patients with OA of the knee in a randomized, double‐blind, placebo‐controlled trial over a 5‐month period.

Results

The 30% improvement rate at 20 weeks was higher in the colchicine group than in the control group receiving placebo, as measured by total Western Ontario and McMaster University Osteoarthritis scores (57.9% versus 23.5%) and visual analog scale for index knee pain (52.6% versus 17.6%) (primary measures of response). The significance persisted on combined analysis by Mantel‐Haenszel test (P = 0.062). Comparison of means also showed significant improvement in the colchicine group versus the control group in a multivariate analysis performed using T² test (P = 0.0115).

Conclusion

Among patients with OA of the knee, the group receiving colchicine plus nimesulide exhibited significantly greater symptomatic benefit at 20 weeks than did the control group receiving nimesulide plus placebo.

     

Femorotibial subchondral bone area and regional cartilage thickness: A cross‐sectional description in healthy reference cases and various radiographic stages of osteoarthritis in 1,003 knees from the Osteoarthritis Initiative

Objective

To identify structural differences in total subchondral bone area (tAB) and cartilage thickness between healthy reference knees and knees with radiographic osteoarthritis (OA).

Methods

Baseline magnetic resonance images from 1 knee of 1,003 Osteoarthritis Initiative participants were studied: 112 healthy reference knees without radiographic OA, symptoms, or risk factors; 70 preradiographic OA knees (calculated Kellgren/Lawrence [K/L] grade 0/1); and 821 radiographic OA knees (calculated K/L grade ≥2). Means and standard (Z) scores (SD unit differences compared with normal subjects) of the tAB and regional cartilage thickness were assessed in the weight‐bearing femorotibial joint and compared between groups.

Results

In men, tAB was 8.2% larger in preradiographic OA knees and 6.6%, 8.1%, and 8.5% larger in calculated K/L grade 2, 3, and 4 radiographic OA knees, respectively, than in reference knees. In women, the differences were +6.8%, +7.3%, +9.9%, and +8.1%, respectively. The external medial tibia showed the greatest reduction in cartilage thickness (Z scores ?5.1/?5.6 in men/women) with Osteoarthritis Research Society International medial joint space narrowing (JSN) grade 3, and the external lateral tibia (Z scores ?6.0 for both sexes) showed the greatest reduction with lateral JSN grade 3. In all subregions of end‐stage radiographic OA knees, ≥25% of the average normal cartilage thickness was maintained. An overall trend toward thicker cartilage was found in preradiographic OA and calculated K/L grade 2 knees, especially in the external central medial femur.

Conclusion

tABs were larger in preradiographic OA and radiographic OA knees than in healthy reference knees, and the difference did not become larger with higher calculated K/L grades. Specific subregions with substantial cartilage thickening or thinning were identified in pre‐, early, and late radiographic OA.

     

Problems in the development and validation of questionnaire‐based screening instruments for ascertaining cases with symptomatic knee osteoarthritis: The Framingham Study

Objective

To determine if screening for symptomatic knee osteoarthritis (OA) for clinical trials and epidemiologic studies could be satisfactorily done without performing knee radiographs and to develop efficient screening instruments for symptomatic knee OA based on self‐reported symptoms and functional limitations.

Methods

We administered a mailed questionnaire containing many different questions on knee symptoms and functional limitations to 1,921 participants of the Framingham Study who had previously been screened for symptomatic OA with a history and knee radiographs. Recursive partitioning methods (using the Classification and Regression Trees [CART] program) were used to create a set of screening instruments for symptomatic knee OA, which was defined as knee symptoms on most days and radiographic evidence of OA. Three screening instruments were developed to maximize the sensitivity, specificity, and efficiency.

Results

The sensitive instrument had 84% sensitivity and 73% specificity. The specific instrument had 46% sensitivity and 94% specificity. The efficient instrument had 56% sensitivity and 85% specificity. Sensitivity was lower and specificity was higher when these instruments were used to screen for radiographic OA. All instruments had higher sensitivity but lower specificity when used for older subjects (age >60) with greater disease prevalence. However, using any of these instruments as a single‐step screening mechanism resulted in considerable misclassification.

Conclusion

We conclude that none of these instruments has adequate diagnostic test performance to serve as a single‐step evaluation of the presence or absence of symptomatic knee OA.