Objective:Cartilage morphology displays sensitivity to change in osteoarthritis (OA) with quantitative MRI (qMRI). However, (sub)regional cartilage thickness change at 3.0 Tesla (T) has not been ...directly compared with radiographic progression of joint space narrowing in OA participants and non-arthritic controls.Methods:A total of 145 women were imaged at 7 clinical centres: 86 were non-obese and asymptomatic without radiographic OA and 55 were obese with symptomatic and radiographic OA (27 Kellgren–Lawrence grade (KLG)2 and 28 KLG3). Lyon–Schuss (LS) and fixed flexion (FF) radiographs were obtained at baseline, 12 and 24 months, and coronal spoiled gradient echo MRI sequences at 3.0 T at baseline, 6, 12 and 24 months. (Sub)regional, femorotibial cartilage thickness and minimum joint space width (mJSW) in the medial femorotibial compartment were measured and the standardised response means (SRMs) determined.Results:At 6 months, qMRI demonstrated a −3.7% “annualised” change in cartilage thickness (SRM −0.33) in the central medial femorotibial compartment (cMFTC) of KLG3 subjects, but no change in KLG2 subjects. The SRM for mJSW in 12-month LS/FF radiographs of KLG3 participants was −0.68/−0.13 and at 24 months was −0.62/−0.20. The SRM for cMFTC changes measured with qMRI was −0.32 (12 months; −2.0%) and −0.48 (24 months; −2.2%), respectively.Conclusions:qMRI and LS radiography detected significant change in KLG3 participants at high risk of progression, but not in KLG2 participants, and only small changes in controls. At 12 and 24 months, LS displayed greater, and FF less, sensitivity to change in KLG3 participants than qMRI.
Objective: To evaluate risk factors for progressive radiographic changes of knee osteoarthritis using a standardised fluoroscopically assisted protocol for knee radiography. Methods: Subjects (n = ...319) with unilateral or bilateral knee osteoarthritis underwent a fluoroscopically standardised x ray examination of the knees (semiflexed AP view) and assessment with the Western Ontario and McMaster Universities (WOMAC) osteoarthritis index at baseline and at 30 months. Tibiofemoral joint space narrowing and osteophytosis were graded in randomly ordered serial radiographs by consensus of two readers using standard pictorial atlases. Results: Progression of joint space narrowing was inversely related to baseline joint space width (odds ratio (OR) = 0.67/1.4 mm (95% confidence interval (CI), 0.49 to 0.91)) and positively associated with patellofemoral osteoarthritis (OR = 3.36 (1.83 to 6.18)). Osteophyte growth was inversely related to overall severity (number and size) of osteophytosis at baseline (OR = 0.47/1.8 points on a 12 point osteophyte severity scale (95% CI, 0.33 to 0.66)), and directly related to baseline stiffness (OR = 1.39/2.1 WOMAC scale points (95% CI, 1.09 to 1.77)) and the presence of patellofemoral osteoarthritis at baseline (OR = 2.31 (1.37 to 3.88)). Conclusions: Progression of both joint space narrowing and osteophyte growth are predicted by the severity of the respective radiographic features of osteoarthritis at baseline and by the presence of patellofemoral osteoarthritis. In addition, knee stiffness is a risk factor for progressive osteophyte growth.
To explore the relationship between lower extremity weakness and the progression of established radiographic changes of knee osteoarthritis (OA).
The study cohort of 342 elderly subjects was ...recruited from central Indiana by random digit dialing. We analyzed 79 subjects who had definite radiographic changes of unilateral or bilateral knee OA at baseline and for whom baseline data for lower extremity muscle strength and lean tissue mass and baseline and followup assessments of knee pain were available. Radiographs were graded for severity of OA at baseline and again about 2.5 years later (mean 31.5 months). Knee pain was evaluated at the same examination. Strength of the knee flexors and extensors was assessed bilaterally at baseline by isokinetic dynamometry and lower extremity muscle mass by dual energy x-ray absorptiometry.
Mean peak knee extensor strength of women with progressive OA, before and after adjustment for lower extremity muscle mass, was about 9% lower than that in those with stable radiographic changes, but this difference was not statistically significant. No difference was apparent between the 2 groups with respect to knee flexor (hamstring) strength. The decrease in quadriceps strength among women with progressive OA, relative to those with stable OA, did not appear to be attributable to knee pain, and knee extensor strength at baseline bore no apparent relationship to the development or progression of knee pain among those with OA.
We have shown previously that quadriceps weakness may be of etiologic importance in development of knee OA. The absence of a significant difference in quadriceps strength between subjects with radiographically stable OA and those whose joint damage progressed suggests that factors other than quadriceps weakness are more important determinants of OA progression.
The C/T-13910 mutation is the major factor responsible for the persistence of the lactase-phlorizin hydrolase (LCT) gene expression. Mutation G/A-22018 appears to be only in co-segregation with ...C/T-13910. The objective of the present study was to assess the presence of these two mutations in Brazilian individuals with and without lactose malabsorption diagnosed by the hydrogen breath test (HBT). Ten milk-tolerant and 10 milk-intolerant individuals underwent the HBT after oral ingestion of 50 g lactose (equivalent to 1 L of milk). Analyses for C/T-13910 and G/A-22018 mutations were performed using a PCR-based method. Primers were designed for this study based on the GenBank sequence. The CT/GA, CT/AA, and TT/AA genotypes (lactase persistence) were found in 10 individuals with negative HBT. The CC/GG genotype (lactase non-persistence) was found in 10 individuals, 9 of them with positive HBT results. There was a significant agreement between the presence of mutations in the LCT gene promoter and HBT results (kappa = -0.9, P < 0.001). The CT/AA genotype has not been described previously and seems to be related to lactase persistence. The present study showed a significant agreement between the occurrence of mutations G/A-22018 and C/T-13910 and lactose absorption in Brazilian subjects, suggesting that the molecular test used here could be proposed for the laboratory diagnosis of adult-type primary hypolactasia.
Objective:Given that obesity is a risk factor for osteoarthritis (OA) of the knee, a study was undertaken to determine whether progressively higher body mass index (BMI) among obese women is ...associated with progressive increases in joint space narrowing (JSN).Methods:Medial compartment JSN over 12 months in Lyon Schuss radiographs of 60 obese women (BMI 30.0–50.5 kg/m2) with radiographic and symptomatic OA was compared with that in 81 non-obese women (BMI <28 kg/m2) with normal radiographs and minimal or no symptoms of knee OA.Results:Among the patients with OA, higher BMI tended to be associated with a higher Kellgren and Lawrence (KL) grade of OA severity. JSN in the non-obese controls was negligible, but in the 30 patients with KL grade 2 and KL grade 3 knees, mean (SD) JSN was 0.12 (0.31) mm and 0.32 (0.50) mm, respectively (p<0.005 and p<0.001). No association was seen between baseline BMI and 12-month JSN in patients with OA; indeed, the regression plot suggested a slight inverse relationship between the two.Conclusions:In obese patients with OA, progressively higher BMI values were not accompanied by a progressively increasing rate of JSN. Joint loading was not evaluated, but it is possible that marked obesity limited the functional capacity of some subjects with OA, protecting their knees from loading. For investigators considering eligibility criteria for a trial of a structure-modifying OA drug, these data suggest that recruitment of patients with a BMI much higher than 30 kg/m2 will not enrich the sample of subjects who will have more rapid JSN than those with a BMI of only 30 kg/m2.
We examined whether plasma concentrations of biomarkers of the collagenase cleavage of type II collagen (C2C), types I and II collagens (C1,2C), type II collagen synthesis (CPII), proteoglycan ...aggrecan turnover (CS846), and the ratio C2C:CPII would distinguish subjects with progressive radiographic osteoarthritis (OA) from those with stable disease.
Subjects were 120 obese middle-aged women with unilateral knee OA who participated in a 30-month clinical trial of structure modification with doxycycline, in which a standardized semiflexed anteroposterior view of the knee was obtained at baseline, 16 months, and 30 months. Subjects were selected from a larger sample to permit a priori comparisons between 60 OA progressors and 60 nonprogressors, as defined by joint space narrowing (JSN) in the medial tibiofemoral compartment. Each group contained 30 subjects who exhibited clinically significant increases in knee pain over 30 months and 30 who did not. Plasma samples were obtained every 6 months for determination of C2C, CPII, CS846, and C1,2C.
None of the biomarkers was a significant predictor of progression of JSN. Over the interval from baseline to 16 months, the mean and the maximum of the intercurrent CS846 values were significantly associated with JSN (i.e., 0.12-0.14 mm of JSN per SD decrease in mean or maximum CS846; p < 0.01). The mean of serial CS846 levels was related to JSN also during the interval between months 16 and 30.
Markers of type II collagen synthesis/degradation and of proteoglycan aggrecan turnover were not predictive of JSN in knee OA in this pilot study. However, serial concentrations of proteoglycan aggrecan epitope CS846 were associated with JSN during both the intervals studied.
Objective: To evaluate the risk factors for early radiographic changes of knee osteoarthritis. Methods: Subjects (n = 114) with unilateral or bilateral grade 0–1 knee osteoarthritis underwent x ray ...examination of the knees (semiflexed anteroposterior view) and assessment with the Western Ontario and McMaster Universities (WOMAC) Osteoarthritis Index at baseline and 30 months later. Severity of joint space narrowing (JSN) and osteophytosis were graded in randomly ordered serial radiographs by two readers, blinded to the sequence of the films, using standard pictorial atlases. Results: The odds of an initial appearance of radiographic features of knee osteoarthritis at month 30 were more than threefold greater in African Americans than in whites (osteophytosis: odds ratio (OR) 3.30, 95% confidence interval (CI) 1.04 to 10.54; JSN: OR 3.49, 95% CI 1.16 to 10.68). In addition, the appearance of osteophytosis was positively related to baseline stiffness (OR 1.91/2.1 points on the 2–10 WOMAC scale, 95% CI 1.29 to 2.82). Conclusions: The distinction between incident and established, but early, radiographic knee osteoarthritis is difficult because of the limits to which all possible evidence of the disease can be ruled out in a conventional baseline knee radiograph. Nonetheless, our finding that African Americans were at greater risk of early osteophytosis and JSN than other subjects differs from the results of our previous analysis of risk factors for progressive knee osteoarthritis in the same subjects. The development of osteophytes also was associated with joint stiffness. Future investigations should focus on the systemic and local influences that these ostensible risk factors represent.
To examine whether urine concentrations of type II collagen neoepitope (uTIINE) distinguish subjects with progressive radiographic and/or symptomatic knee osteoarthritis (OA) from those with stable ...disease.
Subjects were 120 obese middle-aged women with unilateral knee OA who participated in a 30-month randomized-controlled trial of structure modification with doxycycline, in which a standardized semiflexed anteroposterior view of the knee was obtained at baseline, 16 months and 30 months. Subjects were selected from a larger sample to permit
a priori comparisons between 60 OA progressors and 60 nonprogressors, as defined by joint space narrowing (JSN) in the medial tibiofemoral compartment. Each group contained 30 subjects who exhibited clinically significant increases in knee pain over 30 months and 30 who did not. Urine samples were obtained every 6 months for determination of the creatinine (Cr)-adjusted uTIINE concentration.
Baseline uTIINE levels were unrelated to JSN in the placebo group. However, among subjects in the active treatment group, a 1-standard deviation increment in baseline uTIINE (68
ng/mM Cr) was associated with a marginally significant, two-fold increase in the odds of progression of JSN (odds ratio 2.04, 95% confidence interval 0.98–4.28). The within-subject mean of uTIINE values at baseline, 6 months and 12 months was associated with concurrent JSN measured at 16 months (0.10
mm of JSN per 69
ng/mM Cr,
P
=
0.008). Similar results were seen in the interval between months 16 and 30 and in analyses using the maximum of intercurrent uTIINE levels.
Baseline uTIINE was not a consistent predictor of JSN in subjects with knee OA. However, serial measurements of uTIINE reflect concurrent JSN.
Objective: To determine whether urinary concentrations of the cross linked C-telopeptide of type II collagen (CTx-II) distinguish subjects with progressive radiographic or symptomatic knee ...osteoarthritis from those with stable disease. Methods: Subjects were 120 obese women with unilateral knee osteoarthritis who participated in a 30 month, randomised, placebo controlled trial of structure modification by doxycycline, in which a standardised semiflexed anteroposterior view of the knee was obtained at baseline and 30 months. Subjects were selected from a larger sample to permit comparisons of urinary CTx-II levels between 60 progressors and 60 non-progressors with respect to medial joint space narrowing. Each group contained 30 subjects who, across five semi-annual assessments, reported on at least two occasions an increase of ⩾20% in 50 ft walk pain (minimum = 1 cm on a 10 cm visual analogue scale), relative to the previous visit. The remainder reported no increases in knee pain. Urine samples were obtained semi-annually for determination of the CTx-II and creatinine concentrations. Results: In an analysis of the placebo group only, the frequency of radiographic progressors in the upper and middle tertiles (48% and 60%, respectively) of the baseline CTx-II distribution was not significantly different than that in the lower tertile (64%). These results were unchanged after inclusion of data from subjects in the doxycycline group. Furthermore, serial CTx-II levels did not distinguish subjects with progressive radiographic or symptomatic knee osteoarthritis from those with stable disease. Conclusions: In this pilot study, urinary CTx-II concentration was not a useful biomarker of osteoarthritis progression.
Objective: To ascertain the extent to which the “Chingford knee” (that is, contralateral knee of the middle aged, obese, female patient with unilateral knee osteoarthritis (OA)) is a high risk ...radiographically normal joint as opposed to a knee in which radiographic changes of OA would have been apparent in a more extensive radiographic examination. Methods: Subjects were 180 obese women, aged 45–64 years, with unilateral knee OA, based on the standing anteroposterior (AP) view. Subjects underwent a series of radiographic knee examinations: semiflexed AP, supine lateral, and Hughston (patellofemoral (PF)) views. Bony changes of OA were graded by consensus of two readers. Medial tibiofemoral joint space width was measured by digital image analysis. Knee pain was assessed by the WOMAC OA Index after washout of all OA pain drugs. Results: Despite the absence of evidence of knee OA in the standing AP radiograph, only 32 knees (18%) were radiographically normal in all other views. Ninety four knees (52%) exhibited TF knee OA in the semiflexed AP and/or lateral view. PF OA was seen in 121 knees (67%). Subjects with PF OA reported more severe knee pain than those without PF OA (mean WOMAC scores 9.9 v 8.3, p<0.05). Conclusion: The Chingford knee is not a radiographically normal joint. The high rate of incidence of OA reported previously for this knee (∼50% within two years) may also reflect progression of existing OA or changes in radioanatomical positioning at follow up that showed evidence of stable disease that was present at baseline.
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