Knee osteoarthritis patients with severe nocturnal pain have altered proximal tibial subchondral bone mineral density.

OBJECTIVE: Our objective was to investigate relationships between proximal tibial subchondral bone mineral density (BMD) and nocturnal pain in patients with knee osteoarthritis (OA). METHODS: The preoperative knee of 42 patients booked for knee arthroplasty was scanned using quantitative computed tomography (QCT). Pain was measured using the Western Ontario and McMaster Universities Arthritis Index (WOMAC) and participants were categorized into three groups: 'no pain', 'moderate pain', and 'severe pain' while lying down at night. We used depth-specific image processing to assess tibial subchondral BMD at normalized depths of 0-2.5 mm, 2.5-5.0 mm and 5-10 mm relative to the subchondral surface. Regional analyses of each medial and lateral plateau included total BMD and maximum BMD within a 10 mm diameter core or 'focal spot'. The association between WOMAC pain scores and BMD measurements was assessed using Spearman's rank correlation. Regional BMD was compared pairwise between pain and no pain groups using multivariate analysis of covariance using age, sex, and BMI as covariates and Bonferroni adjustment for multiple comparisons. RESULTS: Lateral focal BMD at the 2.5-5 mm depth was related to nocturnal pain (ρ = 0.388, P = 0.011). The lateral focal BMD was 33% higher in participants with 'severe pain' than participants with 'no pain' at 2.5-5 mm depth (P = 0.028) and 32% higher at 5-10 mm depth (P = 0.049). There were no BMD differences at 0-2.5 mm from the subchondral surface. CONCLUSION: This study suggests that local subchondral bone density may have a role in elucidating OA-related pain pathogenesis.

Regional depth-specific subchondral bone density measures in osteoarthritic and normal patellae: in vivo precision and preliminary comparisons.

SUMMARY: Computed tomography-based depth-specific image processing is able to precisely identify regional differences between healthy patellae and patellae with osteoarthritis. INTRODUCTION: This study aims to assess the precision errors and potential differences in regional, depth-specific subchondral bone mineral density (BMD) in normal and osteoarthritic (OA) human patellae in vivo using CT-based density analyses. METHODS: Fourteen participants (2 men and 12 women; mean age, 51.4; SD, 11.8 years) were scanned using clinical quantitative CT (QCT) three times over 2 days. Participants were categorized as either normal (n = 7) or exhibiting radiographic OA (n = 7). Average subchondral BMD was assessed at three depths relative to the subchondral surface. Regional BMD analysis included: total lateral facet BMD, total medial facet BMD, and superior/middle/inferior BMD of lateral and medial facets at normalized depths of 0-2.5, 2.5-5, and 5-7.5 mm from the subchondral surface. We assessed precision using root mean square coefficients of variation (CV%). We evaluated differences between OA and normal BMD by (1) calculating percentage differences between the groups (in relation to normal BMD) (2) relating percentage differences to respective CV% errors and (3) determining effect sizes using Cohen's d. RESULTS: Root mean square CV% precision errors ranged from 1.1 to 5.9 %. Percentage differences between OA and normal BMD varied from -1.6 to -30.1 % (BMD lower in OA patellae). In relation to precision errors, percentage differences were, on average, 5.5× greater than CV% errors. Cohen's d effect sizes ranged from -1.7 to -0.1. Largest differences were noted at depths of 2.5-5 and 5-7.5 mm from the subchondral surface. CONCLUSIONS: Patellar subchondral BMD measures were precise (average CV%, ≤3 %). This region- and depth-specific CT-based imaging tool characterized regional standardized BMD differences between normal and OA patellae in vivo.

Does cartilage volume or thickness distinguish knees with and without mild radiographic osteoarthritis? The Framingham Study.

OBJECTIVES: To examine whether the quantity of cartilage or semiquantitative scores actually differ in knees with mild radiographic osteoarthritis compared with knees without osteoarthritis. METHODS: Framingham Osteoarthritis Study participants had knee tibiofemoral magnetic resonance imaging-based measurements of cartilage. Using three-dimensional FLASH-water excitation sequences, cartilage volume, thickness and subregional cartilage thickness were measured and cartilage scored semiquantitatively (using the whole-organ magnetic resonance imaging score; WORMS). Using weight-bearing radiographs, mild osteoarthritis was defined as Kellgren/Lawrence (K/L) grade 2 and non-osteoarthritis as K/L grade 0. Differences between osteoarthritis and non-osteoarthritis knees in median cartilage measurements were tested using the Wilcoxon rank sum test. RESULTS: Among 948 participants (one knee each), neither cartilage volume nor regional thickness were different in mild versus non-osteoarthritis knees. In mild osteoarthritis, cartilage erosions in focal areas were missed when cartilage was quantified over large regions such as the medial tibia. For some but not all subregions of cartilage, especially among men, cartilage thickness was lower (p<0.05) in mild osteoarthritis than non-osteoarthritis knees. Because semiquantitative scores captured focal erosions, median WORMS scores were higher in mild osteoarthritis than non-osteoarthritis (all p<0.05). In moderate/severe osteoarthritis (K/L grades 3 or 4), osteoarthritis knees had much lower cartilage thickness and higher WORMS scores than knees without osteoarthritis. CONCLUSIONS: In mild osteoarthritis, the focal loss of cartilage is missed by quantitative measures of cartilage volume or thickness over broad areas. Regional cartilage volume and thickness (eg, medial tibia) are not different in mild osteoarthritis versus non-osteoarthritis. Subregional thickness may be decreased in mild osteoarthritis. Semiquantitative scoring that assesses focal cartilage damage differentiates mild osteoarthritis from non-osteoarthritis.

Prevalence of bone attrition on knee radiographs and MRI in a community-based cohort.

OBJECTIVES: Bone attrition probably constitutes remodeling of the bone, resulting in flattening or depression of the articular surfaces. Defining bone attrition is challenging because it is an accentuation of the normal curvature of the tibial plateaus. We aimed to define bone attrition on magnetic resonance imaging (MRI) of the knee using information from both radiographs and MRIs, and to assess whether bone attrition is common prior to end stage disease osteoarthritis (OA) in the tibio-femoral joint. METHODS: All knees of participants in the community-based sample of the Framingham OA Study were evaluated for bone attrition in radiographs and MRIs. Radiographs were scored based on templates designed to outline the normal contours of the tibio-femoral joint. MRIs were analyzed using the semi-quantitative Whole-Organ Magnetic Resonance Imaging Scoring (WORMS) method. The prevalence of bone attrition was calculated using two different thresholds for MRI scores. RESULTS: Inter-observer agreement for identification of bone attrition was substantial for the radiographs (kappa=0.71, 95% CI 0.67-0.81) and moderate for MRI (kappa=0.56, 95% CI 0.40-0.72). Of 964 knees, 5.7% of the radiographs showed bone attrition. Of these, 91% of MRIs were also read as showing bone attrition. We selected a conservative threshold for bone attrition on MRI scoring (> or = 2 on a 0-3 scale) based on agreement with attrition on the radiograph or when bone attrition on MRI co-occurred with cartilage loss on OA. Using this threshold for bone attrition on MRI, bone attrition was common in knees with OA. For example, in knees with mild OA but no joint space narrowing, 13 of 88 MRIs (14.8%) showed bone attrition. CONCLUSIONS: Using MRI we found that many knees with mild OA without joint narrowing on radiographs had bone attrition, even using conservative definitions. The validity of our definition of bone attrition should be evaluated in further studies. Bone attrition may occur in milder OA and at earlier stages of disease than previously thought.

Premorbid knee osteoarthritis is not characterised by diffuse thinness: the Framingham Osteoarthritis Study.

OBJECTIVE: It is hypothesised that, like low bone density and fracture, thin cartilage predisposes to osteoarthritis (OA). Inferences about the effects of cartilage thickness on the development of OA can be made by evaluating the status of an unaffected non-diseased contralateral knee, in persons with unilateral OA, which we shall label the "premorbid knee". The primary objective of this analysis was to compare cartilage thickness in premorbid knees with non-OA knees drawn from persons without any knee OA to determine if cartilage in the premorbid knee was thinner than in the knee drawn from someone without OA in either knee. METHODS: From 2002 to 2005, The Framingham Osteoarthritis Study recruited subjects without respect to OA from the community. We obtained posteroanterior, semiflexed and lateral films of both knees and knee magnetic resonance imaging to quantify cartilage volume in one knee. The cartilage plates of the patella, medial and lateral femur, medial and lateral tibia were quantified, using a 3D FLASH-water excitation sequence (in plane resolution 0.3x0.3 mm, 512 matrix, slice thickness 1.5 mm) and digital post-processing, involving three-dimensional reconstruction. Radiographs were used to define the OA status of knees with disease defined as Kellgren and Lawrence grade > or = 2 and or patellofemoral OA on the lateral film. Of 1020 participants included in this analysis, 720 had no OA in either knee (no-knee OA sample), and 55 subjects had no OA in the knee that was examined using magnetic resonance imaging and OA in the contralateral knee (premorbid knee OA sample). We compared cartilage thickness and percentage of cartilage coverage (total bone interface covered with cartilage) between these groups. After initial plate-specific univariate comparisons we performed a multiple regression to assess the association between OA status (premorbid versus no OA knee) and cartilage thickness adjusting for age, sex and body mass index. We used the Generalised Estimating Equation to account for correlation between plates. To further determine if the cartilage was diffusely thinned or had only increased areas of denuded cartilage, we removed plates with denuded areas (less than 95% cartilage coverage) from the analysis. RESULTS: 55% of subjects were women. There was no difference in cartilage thickness between the premorbid knees and the no-knee OA sample. After adjusting for age, sex and body mass index and removing plates with less than 95% coverage from the analysis, we found the same or even thicker cartilage in premorbid knees compared with the knee OA sample. CONCLUSIONS: Premorbid knees do not have diffuse cartilage thinness. Rather the cartilage is normal or thicker with denuded areas suggesting that this may be the initial pathology rather than diffuse thinning.

The association of bone attrition with knee pain and other MRI features of osteoarthritis.

OBJECTIVE: To determine whether bone attrition (flattening or depression of the subchondral bone) was associated with the presence and severity of knee pain and to evaluate the coexistence of attrition and other MRI features likely associated with pain. METHODS: Participants in the Framingham Osteoarthritis Study, a community cohort unselected for OA, answered questions about knee pain and underwent knee x rays and MRI. Attrition, bone marrow lesions (BMLs) and effusions were scored on MRI using the WORMS scale. We assessed attrition in knees with and without pain, and using logistic regression examined its association with pain adjusting for age, gender, Kellgren-Lawrence (K-L)grade, BMI, BML and effusion. We also explored the relation between attrition, pain severity and nocturnal pain. RESULTS: Attrition (Grade >2) was present in 28% (167/592) of painful knees and in 10% (106/1035) of nonpainful knees (adjusted OR 1.6 (95% CI 1.1 to 2.2)). Of knees with OA (n=368), 74% had pain if attrition was present and 58% if it was absent (adjusted OR 1.2 (95%CI 0.7 to 2.0)). Of knees without OA (n=1222), pain was reported in 39% of knees with attrition and in 27%without it (adjusted OR 2.1 (95% CI 1.1 to 4.0)). We found no association between either attrition/pain severity or attrition/nocturnal pain. Attrition often co-occurred with other OA features associated with pain such as BMLs and effusions. CONCLUSIONS: Attrition was associated independently with knee pain. Unlike knees without OA, the association was lost in OA knees where other pathological features that may cause pain also coexisted.

Meniscal damage associated with increased local subchondral bone mineral density: a Framingham study.

OBJECTIVE: Because menisci and the medial vs lateral tibial plateau bone mineral density ratio (M:L BMD) are associated with loading within the knee, we postulated there to be an association between compartment-specific meniscal damage and M:L BMD. We hypothesized that knees with higher M:L BMD, consistent with increased medial subchondral BMD, would be associated with medial meniscal damage, and lower ratios with lateral meniscal damage. METHODS: We conducted a cross-sectional study evaluating participants in the Framingham Osteoarthritis Cohort having magnetic resonance images (MRIs), BMDs, and x-rays of the knee. Medial and lateral meniscal damage were defined on MRI. We performed a logistic regression with medial meniscal damage as the outcome testing M:L BMD groups as predictor variables. We adjusted for age and sex; we used generalized estimating equations (GEE) to adjust for correlation between knees. Identical analyses were performed evaluating lateral meniscal damage. RESULTS: When evaluating the relation of M:L BMD to medial meniscal damage, the odds ratios (ORs) of prevalent medial meniscal damage from lowest to highest quartile of M:L BMD were 1.0 (referent), 1.9, 2.4 and 8.9, P for trend <0.0001. When evaluating the relation of M:L BMD to lateral meniscal damage, the ORs of prevalent lateral meniscal damage from lowest to highest quartile of M:L BMD were 1.0 (referent), 0.3, 0.2, and 0.2, P for trend = 0.001. CONCLUSIONS: Meniscal damage is associated with higher regional tibial BMD in the same compartment. Our findings highlight the close relationship between meniscal integrity and regional tibial subchondral BMD.

Exploring the relation of alcohol consumption to risk of breast cancer.

There are lingering questions regarding the relation between alcohol consumption and breast cancer risk in women. The authors performed a meta-analysis of epidemiologic studies carried out through 1999 to examine the dose-response relation and to assess whether effect estimates differed according to various study characteristics. Overall, there was a monotonic increase in the relative risk of breast cancer with alcohol consumption, but the magnitude of the effect was small; in comparison with nondrinkers, women averaging 12 g/day of alcohol consumption (approximately one typical drink) had a relative risk of 1.10 (95% confidence interval (CI): 1.06, 1.14). Estimates of relative risk were 7% greater in hospital-based case-control studies than in cohort studies or community-based case-control studies, 3% greater in studies published before 1990 than in studies published later, and 5% greater in studies conducted outside of the United States than in US studies. The findings of five US cohort studies published since 1990 yielded a relative risk of 1.06 (95% CI: 1.00, 1.11) for consumers of 12 g/day, as compared with nondrinkers. Cohort studies with less than 10 years of follow-up gave estimates 11% higher than cohort studies with longer follow-up periods. No meaningful difference was seen by menopausal status or type of beverage consumed.

Lipidemic effects of an interesterified mixture of butter, medium-chain triacylglycerol and safflower oils.

The objective of this study was to determine if the positional structure of dietary triacylglycerol affected lipidemic responses. Thirty healthy adults (16 men and 14 postmenopausal women) with low-density lipoprotein cholesterol (LDL-C) concentrations >3.37 mM (130 mg/dL) enrolled in a prospective, single-blind, cross-over outpatient clinical trial that consisted of two 5-wk dietary phases. After baseline screening, subjects were instructed to follow individualized meal plans (weight maintenance diets with 36% of total energy from fat, half of which was from a test oil) and randomized to receive either butter (B) or an interesterified mixture (IM) of butter, medium-chain triacylglycerol (MCT), and safflower oils. Blood drawn during weeks 5 and 10 of feeding was analyzed for total cholesterol (TC), high density lipoprotein cholesterol (HDL-C),LDL-C, and triacylglycerols (TAG). Mean plasma levels of TC (B, 6.98+/-1.06 mM; IM, 7.09+/-1.20 mM), HDL-C (B,1.30+/-0.35 mM; IM, 1.29+/-0.34 mM), and LDL-C (B, 4.91+/-0.95 mM; IM, 4.92+/-1.10 mM) were not significantly different between the two dietary treatments. Mean TAG levels were higher for the interesterified B-MCT mixture (B, 1.75+/-0.72 mM; IM, 1.96+/-0.86 mM, P < 0.05). We conclude that an IM of B, MCT, and safflower oils as compared to native B has no appreciable effect on plasma cholesterol concentrations but is associated with a modest rise in plasma TAG.

Acute effects of a high-fat meal with and without red wine on endothelial function in healthy subjects.

It has been suggested that a high-fat meal may acutely impair endothelium-dependent vasodilation and that this impairment may be prevented by concomitant intake of antioxidants. Because red wine contains antioxidant polyphenols and may reduce cardiovascular disease, we examined the effect of red wine on postprandial endothelial function. Using a crossover design, 13 healthy volunteers consumed a high-fat meal (0.8 g fat/kg body weight) with red wine (3 ml/kg) or an isocaloric control beverage on 2 separate days, 1 week apart. Flow-mediated dilation of the brachial artery was examined by vascular ultrasound at baseline and at 2, 4, and 6 hours after the meal. At these times, flow-mediated dilation with the high-fat meal and control beverage was 9.5 +/- 5.0%, 7.9 +/- 5.1%, 6.8 +/- 3.6%, and 7.3 +/- 4.6%, respectively (nonsignificant trend). There was also a nonsignificant trend for flow-mediated dilation after the high-fat meal with wine: 8.0 +/- 4.1%, 5.7 +/- 4.7%, 6.4 +/- 3.1%, and 6.9 +/- 3.8%, respectively. There was no difference in the effects between wine and the control beverage (p = 0.77). Triglycerides increased 2- to 2.7-fold over baseline (p = 0.0001) with a peak occurring 5 hours after the high-fat meals. In contrast to previous studies, the present study did not demonstrate a significant effect of a high-fat meal on endothelial vasomotor function in healthy subjects. Under these conditions, we did not demonstrate a beneficial acute effect of red wine on endothelial function.

Contribution of tap water to mineral intakes of Canadian preschool children.

Tap water consumption was estimated from 3 day weighed dietary records in 102 Canadian preschool children (4-5 yr of age; 58 males, 44 females). Cold tap water samples were also collected from each child's household (64 hard water households, 38 soft water households) and analyzed for calcium, magnesium, sodium, zinc, copper, and sodium by atomic absorption spectrophotometry. Median consumption of tap water consumed alone and tapwater alone plus that used in beverages (ml per day) was 36.5 (range 0-791) and 171.5 (range 0-1036), respectively. Average intakes of macrominerals for males (M) and females (F) from all sources of hard tap water were (mg/day): calcium (M) 16.5, (F) 13.2; magnesium (M) 6.6, (F) 4.5; and sodium (M) 2.3, (F) 2.3. Average intakes of macrominerals from soft water are as follows: calcium (M) 0.1, (F) 0.1; magnesium (M) 0, (F) 0; and sodium (M) 31.0, (F) 24.4. Trace element intakes from tap water were negligible. Hard tap water provided less than 8% of the Canadian Recommended Nutrient Intake (RNI) for magnesium, less than 3% for calcium, and less than 1% for zinc. Mineral contributions of soft tap water to the RNIs were less than 2%.

Hormonal patterns in vaginal smears from puerperal women.

Maturation indices were determined for 1,000 vaginal smears from women three weeks to nine months postpartum. Atrophic smears predominated three to six weeks after delivery in women who were lactating, but only one-third of the non-lactators had an atrophic pattern during those weeks. There was a progressive increase in the incidence of estrogenic patterns observed beyond the sixth postpartum week, irrespective of the persistence of lactation. The incidence of mixed patterns (equal numbers of parabasal, intermediate and superficial cells) was remarkedly constant (about 5 per cent) regardless of lactation or time beyond delivery. This study confirms the traditional view of hormonally related puerperal vaginal cytologic patterns, and is at variance with recent claims that vaginal atrophy is unusual in the puerperium.

Significance of cervicovaginal cytology after radiation therapy for cervical carcinoma.

During follow-up examinations; 1,338 cervicovaginal cytologic smears were obtained from 254 women who had irradiation therapy for cervical cancer. These specimens were meticulously searched for the various cellular phenomena that may characterize such preparations, and some of the findings were subjectively quantitated. Correlations were made with histopathologic diagnoses, clinical findings, and results of treatment. Patients with malignant postradiation cells who were promptly treated for latent new or recurrent tumors generally responded well to treatment of the secondary tumor. The presence of malignant cells at any time after completion of therapy is an ominous sign, irrespective of the clinical status, and should lead to intensive effort to identify the site of a new or persisting lesion. The significance of dysplasia in postradiation smears is not entirely clear, and in certain instances it is difficult to distinguish severely dysplastic cells from either repair cells or malignant cells.