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Biomedical subjects

David J Hunter

Publications and source records attributed to David J Hunter.

At least 19 recordsLinked to original sources
PubMed2026

Effect of an oral complementary medicine combination for symptomatic knee osteoarthritis: A double-blind, randomized, placebo-controlled trial.

OBJECTIVE: Many individuals use complementary medicine therapies for osteoarthritis, despite limited scientific supporting evidence. These therapies have demonstrated anti-inflammatory, antioxidative, and chondroprotective effects via different molecular pathways, suggesting potential therapeutic benefits. This trial aimed to evaluate the efficacy and safety of a novel oral complementary medicine combination in adults with symptomatic knee osteoarthritis at 12 weeks. DESIGN: The 12-week, double-blind, randomized, placebo-controlled ATLAS trial was conducted in Australia from July 2024 to April 2025 (ACTRN12623000380695). Eligible participants were aged ≥40 years with symptomatic knee osteoarthritis and radiographic Kellgren-Lawrence grade ≥2. Participants were randomized 1:1 to receive the complementary medicine combination, comprising a total daily dose of Boswellia serrata extract 250 mg, pine bark extract 100 mg, methylsulfonylmethane 1500 mg, curcumin 500 mg, and piperine 5 mg, or placebo. The primary outcome was the 12-week change in knee pain (0-100 mm visual analogue scale (VAS)). A 95% confidence interval excluding differences >18 mm between groups was interpreted as the absence of a clinically meaningful difference. Harms were monitored weekly. RESULTS: Eighty-four participants were recruited (mean [SD], age 63.7 [8.0] years, BMI 29.0 [5.5] kg/m2), and 57% were female. At 12-weeks, both groups (intention-to-treat population: complementary medicine, n=42; placebo, n=41) showed a decrease in VAS pain (least squares means: complementary medicine 20.1 mm vs placebo 20.3 mm), however with no difference between groups: 0.16 mm (95% CI -6.81 to 7.12). The safety profile of experiencing any AE was similar between groups (risk difference, -3.4% [95% CI -24.8-17.9%]); and most adverse events were mild or moderate. Four participants experienced serious adverse events, unrelated to the treatment. CONCLUSIONS: The complementary medicine combination was not superior to placebo for improving pain over 12 weeks, and the evidence does not support the use of this combination to treat people with symptomatic knee osteoarthritis.

Humans↗
PubMed2006

Androgen receptor polymorphisms and endometrial cancer risk.

The androgen receptor (AR) gene is a transcription factor responsible for mediating the physiological effects of androgens. Evidence suggests that androgens and the androgen receptor are involved in uterine cell proliferation. A polymorphic CAG repeat in exon 1 of the AR gene encodes a polyglutamine tract that is inversely correlated with the transcriptional activity of this gene. We assessed the association between the functional CAG repeat polymorphism and AR haplotypes and the risk of endometrial cancer in two nested case-control studies within the Nurses' Health Study (n = 222 cases, 666 controls) and the Women's Health Study (n = 137 cases, 411 controls) using conditional and unconditional logistic regression. Associations between AR CAG repeat polymorphism and endometrial cancer risk were similar in the 2 case-control studies. In the pooled analysis, women with an average repeat allele > or =22 repeats compared to <22 repeats were at a statistically significant decreased risk of endometrial cancer (odds ratio (OR) = 0.76; 95% confidence interval (CI), 0.59-0.98). Women with one or two long alleles (> or =27 repeats) compared to both alleles <22 repeats were also at a statistically significant decreased risk (OR = 0.60; 95% CI, 0.36-0.99). We observed a modest yet statistically significant association for each one unit increase in the average repeat length and endometrial cancer risk (OR = 0.94; 95% CI, 0.88-1.00). Associations for the AR CAG average repeat length and endometrial cancer risk differed by menopausal status (p = 0.02). No significant associations between the AR haplotypes and endometrial cancer risk were observed. Our findings suggest that an increasing number of functional CAG repeats may be associated with endometrial carcinogenesis because of AR's reduced ability to recruit coregulators and other transcriptional components. (supplementary material for this article can be found on the International Journal of Cancer website at http://www.interscience.wiley.com/jpages/0020-7136/suppmat/index.html).

Adult↗
PubMed2006

Intakes of vitamins A, C and E and folate and multivitamins and lung cancer: a pooled analysis of 8 prospective studies.

Intakes of vitamins A, C and E and folate have been hypothesized to reduce lung cancer risk. We examined these associations in a pooled analysis of the primary data from 8 prospective studies from North America and Europe. Baseline vitamin intake was assessed using a validated food-frequency questionnaire, in each study. We calculated study-specific associations and pooled them using a random-effects model. During follow-up of 430,281 persons over a maximum of 6-16 years in the studies, 3,206 incident lung cancer cases were documented. Vitamin intakes were inversely associated with lung cancer risk in age-adjusted analyses; the associations were greatly attenuated after adjusting for smoking and other risk factors for lung cancer. The pooled multivariate relative risks, comparing the highest vs. lowest quintile of intake from food-only, were 0.96 (95% confidence interval (CI) 0.83-1.11) for vitamin A, 0.80 (95% CI 0.71-0.91) for vitamin C, 0.86 (95% CI 0.76-0.99) for vitamin E and 0.88 (95% CI 0.74-1.04) for folate. The association with vitamin C was not independent of our previously reported inverse association with beta-cryptoxanthin. Further, vitamin intakes from foods plus supplements were not associated with a reduced risk of lung cancer in multivariate analyses, and use of multivitamins and specific vitamin supplements was not significantly associated with lung cancer risk. The results generally did not differ across studies or by sex, smoking habits and lung cancer cell type. In conclusion, these data do not support the hypothesis that intakes of vitamins A, C and E and folate reduce lung cancer risk.

Antioxidants↗
PubMed2005

Anemia is an independent predictor of mortality and immunologic progression of disease among women with HIV in Tanzania.

OBJECTIVES: To examine the association of anemia with mortality and disease progression among a cohort of women with HIV in Dar es Salaam, Tanzania. METHODS: Time to all-cause death, AIDS-related death, and a 50% decrease in CD4 cell count among 1078 HIV-positive pregnant women enrolled in a clinical trial of vitamin supplementation from 1995-2003. RESULTS: Adjusted models showed that anemia was associated with an increased risk of all-cause mortality (relative hazard [RH]: 2.06, 95% CI: 1.52 to 2.79 for moderate anemia and RH: 3.19, 95% CI: 2.23 to 4.56 for severe anemia) and AIDS-related mortality (RH: 2.21, 95% CI: 1.53 to 3.19 for moderate anemia and RH: 3.47, 95% CI: 2.25 to 5.33 for severe anemia), independent of CD4 cell count, World Health Organization clinical stage, age, pregnancy, vitamin supplementation, and body mass index. Anemia was also associated with a more rapid decline in CD4 counts, measured as time to a 50% drop in CD4 cell count from baseline. Erythrocyte characteristics suggestive of iron deficiency were also associated with all-cause and AIDS-related death and a 50% decline in CD4 cell count. CONCLUSIONS: Anemia is an independent predictor of mortality and disease progression in this cohort. Screening for anemia, coupled with prevention and treatment efforts, should be included in HIV care initiatives, particularly those that target women.

Anemia↗
PubMed2005

Moving upstream or muddying the waters? Incentives for managing for health.

OBJECTIVES: The objective of this study was to identify factors influencing the capacity of NHS managers to 'manage for health'. STUDY DESIGN: Semi-structured interviews (32) were carried out over the telephone or face to face with national stakeholders (15) and NHS senior managers (17) from four Strategic Health Authorities (SHAs) and five Primary Care Trusts (PCTs) in England. Interviews were transcribed and a qualitative analysis carried out. RESULTS: The current system of targets and incentives prioritised access to acute services, public health skills were too thinly spread, baseline data were inadequate, decision-making for public health investment was fragmented and evidence for effective interventions was scanty. Health improvement targets should be plausible, longer term and locally owned, but key factors in creating a proactive public health organisation were a strong public health ethos, and effective management and leadership skills. Strengthening the NHS's role in managing for health was welcomed, but enthusiasm was tempered by concurrent NHS policy initiatives and incentives pulling in opposing directions. CONCLUSIONS: Key NHS policy initiatives have been developed in isolation from each other. While their combined effect remains unpredictable, they may serve to threaten the welcome shift towards managing for health improvement.

Health Status↗
PubMed2005

CYP19 (aromatase) haplotypes and endometrial cancer risk.

Endogenous estrogen exposure is an important determinant of endometrial cancer risk. Aromatase, encoded by CYP19, catalyzes the aromatization of androstenedione and testosterone to estrone and estradiol, respectively. Several common genetic polymorphisms in CYP19 have been identified, including a TCT insertion/deletion and a (TTTA)(n) repeat polymorphism in intron IV as well as a 3'UTR C/T polymorphism. We evaluated these 3 polymorphisms plus an additional 9 noncoding polymorphisms as individual genotypes and predicted haplotypes as risk factors for endometrial cancer using a nested case-control study design. Invasive endometrial cancer cases (n = 222) and matched controls (n = 666) were identified among participants in the Nurses' Health Study who had provided a blood sample in 1989-1990 (n = 32,826). We estimated haplotypes from unphased genotype data spanning > 123 kb of CYP19. Six haplotypes constructed from 10 SNPs were estimated with a frequency > or = 5%. The highest prevalence haplotype (33% among cases, 28% among controls) was significantly associated with endometrial cancer risk (p = 0.03). Loci with variant alleles that comprise the risk haplotype were independently associated with endometrial cancer, with relative risk estimates ranging from 1.68 (95% CI 1.13-2.48) to 2.07 (95% CI 1.33-3.23), comparing variant allele carriers to wild-type homozygotes. We observed significant interactions between menopausal status and 2 of the high-risk loci (p = 0.03 and p < 0.01), with > 2-fold increased risk for variant allele carriers who were postmenopausal but no association between genotype and endometrial cancer among premenopausal women. We evaluated associations between CYP19 haplotypes and plasma steroid hormone levels. The haplotype associated with endometrial cancer risk is also significantly associated with the ratios of estrone to androstenedione and estradiol to testosterone, the products and substrates of the enzyme aromatase, encoded by CYP19. Our data suggest that there is a high-frequency CYP19 haplotype related to higher estrogen to androgen ratios and increased risk of endometrial cancer and that this association may primarily pertain to postmenopausal women.

Adult↗
PubMed2005

Dietary patterns and the risk of postmenopausal breast cancer.

The association between individual foods and breast cancer has been inconsistent. Therefore, we examined the association between diet and risk of postmenopausal breast cancer by the alternative approach of dietary patterns. Dietary patterns were identified with factor analysis from food consumption data collected from a food frequency questionnaire in 1984. Relative risks were computed using proportional hazard models and adjusted for known risk factors for breast cancer. Between 1984 and 2000, we ascertained 3,026 incident cases of postmenopausal breast cancer. We identified 2 major dietary patterns. The prudent pattern is characterized by higher intake of fruits, vegetables, whole grains, low-fat dairy products, fish and poultry, while the Western pattern is characterized by higher intake of red and processed meats, refined grains, sweets and desserts and high-fat dairy products. Neither of the patterns was associated with overall risk of postmenopausal breast cancer. However, a positive association between the Western pattern score was observed among smokers at baseline (relative risk = 1.44, comparing top to bottom quintiles; 95% CI = 1.02-2.03; p for trend = 0.03). An inverse association was observed between the prudent pattern and estrogen receptor-negative cancer (relative risk = 0.62; 95% CI = 0.45-0.88; p for trend = 0.006). Among the major food groups, higher consumptions of fruits (relative risk for 1 serving/day increase = 0.88; 95% CI = 0.80-0.97; p = 0.009) and vegetables (relative risk = 0.94; 95% CI = 0.88-0.99; p = 0.03) were significantly associated with decreased risk for ER(-) breast cancer. In conclusion, we did not observe an overall association between the prudent or Western pattern and overall breast cancer risk. However, a Western-type diet may elevate risk of breast cancer among smokers, and a prudent diet may protect against estrogen receptive-negative tumors.

Breast Neoplasms↗
PubMed2005

Prospective study of N-acetyltransferase-2 genotypes, meat intake, smoking and risk of colorectal cancer.

Consumption of red meat has been associated with elevated risk of colorectal cancer; however, mechanisms underlying this relationship are not well established. N-acetyltransferase 2 (NAT2) appears to activate carcinogenic heterocyclic amines found in meat as well as cigarette smoke. Genetic variation in this enzyme, associated with rapid acetylation, may modulate the influence of meat intake on cancer risk. We examined the risk of incident colorectal cancer according to NAT2 genotypes, meat intake and smoking in a prospective, nested case-control study among 32,826 women enrolled in the Nurses' Health Study who provided prediagnostic blood specimens. We matched 183 women with colorectal cancer to 443 controls. Although acetylator genotype alone was not associated with the risk of colorectal cancer, women with rapid acetylator genotypes experienced a greater risk associated with intake of > or = 0.5 serving of beef, pork or lamb as a main dish per day compared to intake of less meat (multivariate OR = 3.01; 95% CI = 1.10-8.18). In contrast, among slow acetylators, intake of beef, pork or lamb was not associated with risk of colorectal cancer (multivariate OR = 0.87; 95% CI = 0.35-2.17). The interaction between acetylator genotype and meat intake approached statistical significance (P interaction = 0.07). Moreover, compared to slow acetylators who smoked < or = 35 pack-years and ate < 0.5 serving/day of red meat, the OR for rapid acetylators who smoked > 35 pack-years and ate > or = 0.5 serving/day was 17.6 (95% CI 2.0-158.3). These prospective data suggest that red meat may increase the risk of colorectal cancer, particularly among genetically susceptible individuals. The influence of NAT2 genotype on this association supports a role for heterocyclic amines in mediating the effect of red meat on colorectal carcinogenesis.

Adult↗
PubMed2005

Hemochromatosis gene mutations, body iron stores, dietary iron, and risk of colorectal adenoma in women.

BACKGROUND: Some experimental evidence suggests that iron may play a role in colorectal carcinogenesis, but human data for this role have been conflicting, possibly because of problems related to study design or measurement of iron exposure. We assessed dietary iron intake and genetic and biochemical markers of iron status in a prospective, nested case-control study of women enrolled in the Nurses' Health Study. METHODS: Among 32 826 women who provided a blood specimen, we identified 527 women with colorectal adenoma and 527 matched control subjects who underwent endoscopy but were not diagnosed with adenoma after blood collection. We assessed iron intake, mutations in the HFE gene that are associated with hereditary hemochromatosis (i.e., H63D and C282Y), and plasma biochemical measures of total body iron, including transferrin saturation and the ratio of the concentrations of transferrin receptors to ferritin. Logistic regression models were used to estimate relative risks (RR) and 95% confidence intervals (CI). All statistical tests were two-sided. RESULTS: Women with any HFE gene mutation had higher total body iron stores, as reflected by higher transferrin saturations (P < .001) and lower levels of the ratio of transferrin receptors to ferritin (P = .02), than women with no HFE gene mutation. However, HFE gene mutations were not associated with risk of adenoma (multivariable RR = 1.08, 95% CI = 0.83 to 1.39; P = .58). Moreover, comparison of extreme categories showed no associations between adenoma and the extent of transferrin saturation (multivariable RR = 0.96, 95% CI = 0.63 to 1.47; Ptrend = .66), the ratio of transferrin receptors to ferritin (multivariable RR = 0.98, 95% CI, 0.60 to 1.60; Ptrend = .99), or dietary iron intake (multivariable RR = 1.04, 95% CI = 0.68 to 1.57; Ptrend = .94). CONCLUSIONS: Although our study used several distinct measures of iron status (i.e., genetic mutations, biochemical markers, and dietary intake) and a nested case-control design, we did not observe a role for iron in the pathogenesis of colorectal neoplasia in women.

Adenoma↗
PubMed2005

Smoking and the risk of endometrial cancer: results from the Nurses' Health Study.

An inverse association between smoking and endometrial cancer has generally been observed, primarily among current smokers. To assess this association, we analyzed data from the prospective Nurses' Health Study. From 1976 to 2000, 702 cases of invasive endometrial cancer were identified during 1.8 million person-years of follow-up. Smoking status was assessed in 1976 and updated every 2 years. Cox proportional hazards models were used to calculate multivariate relative risks (RRs), controlling for endometrial cancer risk factors. Compared to never smokers, the multivariate RR of endometrial cancer was significantly lower among both current smokers (RR = 0.63; 95% CI = 0.50-0.79) and past smokers (RR = 0.73; 95% CI = 0.62-0.87). When additionally adjusting for body mass index (BMI), the RR for current smokers was attenuated (RR = 0.72; 95% CI = 0.57-0.90), but the RR for past smokers did not change. Risk was lower among women who smoked 35 or more cigarettes a day (RR = 0.60; 95% CI = 0.39-0.91) and among those who smoked for 40 or more years (RR = 0.63; 95% CI = 0.45-0.87). Tests for trend, which excluded never smokers, were not statistically significant for any of the smoking variables analyzed. These data indicate that both current and past smoking are associated with a lower risk of endometrial cancer. The findings provide insight into disease etiology and suggest that the influence of smoking on endometrial cancer risk occurs even in early adulthood, is long-lasting, and may not be attributed solely to short-term hormonal modulation.

Adult↗
PubMed2005

Genetic variants in the UGT1A6 enzyme, aspirin use, and the risk of colorectal adenoma.

Genetic variation in the uridine diphosphate glucuronosyltransferase 1A6 (UGT1A6) enzyme is associated with impaired metabolism of aspirin. To determine whether polymorphisms in the UGT1A6 enzyme modulate the protective benefit of regular aspirin use on colorectal adenoma, we conducted a prospective, nested case-control study of 1062 women who provided blood specimens and detailed data on aspirin use before undergoing lower endoscopy. All statistical tests were two sided. Although UGT1A6 genotype was not associated with overall adenoma risk (multivariable odds ratio [OR] = 1.10, 95% confidence interval [CI] = 0.85 to 1.41), functional variant genotypes statistically significantly modified the effect of aspirin on adenoma (P(interaction) = .02). Among the 616 women with variant genotypes, regular use of aspirin (two or more standard tablets per week) was associated with a decreased risk of adenoma (multivariable OR for adenoma = 0.66 [95% CI = 0.45 to 0.95], OR = 0.63 [95% CI = 0.43 to 0.91] for 0.5-7 standard tablets per week and OR = 0.41 [95% CI = 0.24 to 0.71] for more than 7 tablets per week; P(trend) = .001). In contrast, among women with wild-type genotypes, regular aspirin use was not associated with a reduced risk nor did they obtain any additional benefit with higher doses (P(trend) = .50). These results were consistent among women with advanced adenomas (P(interaction) = .003). Thus, functional polymorphisms in the UGT1A6 enzyme statistically significantly modify the effect of aspirin on colorectal neoplasia, and certain subsets of the population, defined by genotype, may obtain differential benefit from aspirin chemoprevention.

Adenoma↗
PubMed2005

Alcohol consumption and high-density lipoprotein levels: the effect of ADH1C genotype, gender and menopausal status.

We previously demonstrated that a functional polymorphism in alcohol dehydrogenase type 1C (ADH1C, also known as ADH3) modifies the association between moderate alcohol consumption and high-density lipoprotein (HDL) levels and risk of myocardial infarction among older men. In this study, we investigated the effect of the ADH1C gamma(1) and gamma(2) alleles on the relationship between alcohol consumption and HDL levels among four populations with varied exposure to endogenous and exogenous estrogens: premenopausal women, middle-to-older aged men, postmenopausal women currently using postmenopausal hormones (PMH) and postmenopausal women not currently using PMH. We observed an interaction between moderate alcohol consumption and ADH1C genotype on HDL level that was similar among middle-to-older aged men and postmenopausal women not using PMH. Among the moderate drinkers (approximately a half a drink per day for women and a full drink per day for men), there was a significant 5.3mg/dL (P=0.02) higher level of multivariate adjusted HDL level comparing the gamma(2) homozygotes (slow oxidizers) to the gamma(1) homozygotes (fast oxidizers). This interaction was not present among premenopausal women or postmenopausal women using PMH, who had higher overall HDL levels irrespective of alcohol consumption. Our results confirm that ADH1C genotype modifies the association between alcohol consumption and HDL levels among men and postmenopausal women not using PMH who drink moderately. However, this was not observed among individuals with estrogen-elevated HDL levels, specifically premenopausal women and postmenopausal women taking PMH, suggesting that these populations may benefit less from alcohol consumption with respect to coronary heart disease.

Adult↗
PubMed2005

Body fatness during childhood and adolescence and incidence of breast cancer in premenopausal women: a prospective cohort study.

INTRODUCTION: Body mass index (BMI) during adulthood is inversely related to the incidence of premenopausal breast cancer, but the role of body fatness earlier in life is less clear. We examined prospectively the relation between body fatness during childhood and adolescence and the incidence of breast cancer in premenopausal women. METHODS: Participants were 109,267 premenopausal women in the Nurses' Health Study II who recalled their body fatness at ages 5, 10 and 20 years using a validated 9-level figure drawing. Over 12 years of follow up, 1318 incident cases of breast cancer were identified. Cox proportional hazards regression was used to compute relative risks (RRs) and 95% confidence intervals (CIs) for body fatness at each age and for average childhood (ages 5-10 years) and adolescent (ages 10-20 years) fatness. RESULTS: Body fatness at each age was inversely associated with premenopausal breast cancer incidence; the multivariate RRs were 0.48 (95% CI 0.35-0.55) and 0.57 (95% CI 0.39-0.83) for the most overweight compared with the most lean in childhood and adolescence, respectively (P for trend < 0.0001). The association for childhood body fatness was only slightly attenuated after adjustment for later BMI, with a multivariate RR of 0.52 (95% CI 0.38-0.71) for the most overweight compared with the most lean (P for trend = 0.001). Adjustment for menstrual cycle characteristics had little impact on the association. CONCLUSION: Greater body fatness during childhood and adolescence is associated with reduced incidence of premenopausal breast cancer, independent of adult BMI and menstrual cycle characteristics.

Adiposity↗
PubMed2005

Plasma carotenoids, retinol, and tocopherols and risk of breast cancer.

The roles of carotenoids, retinol, and tocopherols in breast cancer etiology have been inconclusive. The authors prospectively assessed the relations between plasma alpha-carotene, beta-carotene, beta-cryptoxanthin, lycopene, lutein/zeaxanthin, retinol, alpha-tocopherol, and gamma-tocopherol and breast cancer risk by conducting a nested case-control study using plasma collected from women enrolled in the Nurses' Health Study. A total of 969 cases of breast cancer diagnosed after blood draw and prior to June 1, 1998, were individually matched to controls. The multivariate risk of breast cancer was 25-35% less for women with the highest quintile compared with that for women with the lowest quintile of alpha-carotene (odds ratio (OR) = 0.64, 95% confidence interval (CI): 0.47, 0.88; p(trend) = 0.01), beta-carotene (OR = 0.73, 95% CI: 0.53, 1.02; p(trend) = 0.01), lutein/zeaxanthin (OR = 0.74, 95% CI: 0.55, 1.01; p(trend) = 0.04), and total carotenoids (OR = 0.76, 95% CI: 0.55, 1.05; p(trend) = 0.05). The inverse association observed with alpha-carotene and breast cancer was greater for invasive cancers with nodal metastasis. The authors conclude that some carotenoids are inversely associated with breast cancer. Although the association was strongest for alpha-carotene, the high degree of collinearity among plasma carotenoids limits our ability to conclude that this association is specific to any individual carotenoid.

Adult↗
PubMed2005

Adult recall of adolescent diet: reproducibility and comparison with maternal reporting.

Many cancers have long latency periods, and dietary factors in adolescence may plausibly affect cancer occurrence in adulthood. Because of a lack of prospective data, retrospective collection of data on adolescent diet is essential. The authors evaluated a 124-item high school food frequency questionnaire (HS-FFQ) assessing diet during high school (15-35 years in the past) that was completed in 1998 by 45,947 US women in the Nurses' Health Study II (NHSII) cohort. To assess reproducibility, the authors readministered the HS-FFQ approximately 4 years later to 333 of these women. The mean Pearson correlation for 38 nutrient intakes was 0.65 (range, 0.50-0.77), and the mean Spearman rank correlation for food intakes was 0.60 (range, 0.37-0.77). Current adult diet was only weakly correlated with recalled adolescent diet (for nutrient intakes, mean r = 0.20). For assessment of validity, 272 mothers of the NHSII participants were asked to report information on their daughters' adolescent diets using the HS-FFQ. In this comparison, the mean Pearson correlation was 0.40 (range, 0.13-0.59) for nutrients, and the mean Spearman rank correlation for foods was 0.30 (range, 0.10-0.61). While further studies are warranted, these findings imply that this food frequency questionnaire provides a reasonable record of adolescent diet.

Adolescent↗
PubMed2005

Knee height, knee pain, and knee osteoarthritis: the Beijing Osteoarthritis Study.

OBJECTIVE: Few risk factors for knee osteoarthritis (OA) are appreciated, and the discordance between symptoms and the severity of structural disease has not been explained. Knee height contributes to moments around the knee. The longer the leg, the more torque is present. Although this would suggest that having long legs would be related to the occurrence of knee OA and pain, this issue has not been studied. Our aim was to explore the association between knee height, knee pain, and knee OA. METHODS: We recruited a random sample of Beijing residents ages 60 years and older. Subjects answered questions about joint symptoms, and radiographs of their knees were obtained. A knee joint with a Kellgren/Lawrence grade of >/=2 was defined as having radiographic OA. Patellofemoral OA was defined as being present when grade >/=1 osteophytes or grade >/=1 joint space narrowing was observed on skyline views of the patella or anterior femur. Subjects were considered to have symptomatic OA when both radiographic OA and self-reported pain were present in the same joint. Knee height was measured on the right leg using a sliding broad-blade caliper; the subject was seated, and the subject's feet were bare. We used logistic regression analyses to assess whether knee height was associated with prevalent radiographic and symptomatic OA. We then assessed whether knee height was associated with knee symptoms independently of structural change. RESULTS: A total of 1,006 men (mean +/- SD age 68.4 +/- 6.4 years) and 1,500 women (mean +/- SD age 67.5 +/- 6.1 years) participated in this study. Higher knee height was associated with an increasing prevalence of both radiographic and symptomatic OA, especially among women. For radiographic OA, the magnitude of association was similar for the patellofemoral and tibiofemoral compartments. Among women with knee pain, higher knee height was associated with more severe knee pain (P = 0.0004 for the highest quartile versus the lowest quartile of knee height) independently of the severity of radiographic OA. CONCLUSION: Knee height is associated with prevalent radiographic and symptomatic knee OA. It may also play an important role in knee symptoms. This study highlights the importance of mechanical forces in the determination of OA and knee symptoms.

Anthropometry↗
PubMed2005

Bone marrow lesions in the knee are associated with increased local bone density.

OBJECTIVE: Bone marrow lesions are associated with pain and compartment-specific progression of joint space narrowing in patients with knee osteoarthritis (OA). Bone marrow lesions occur in regions under increased loading, and excess loading produces increased bone mineral density (BMD). The ratio of BMD in the medial tibial plateau compared with that in the lateral tibial plateau (M:L BMD ratio) reflects loading in the knee. Therefore, we hypothesized that a higher M:L BMD ratio would be associated with medial bone marrow lesions, and that lower ratios would be associated with lateral bone marrow lesions. METHODS: Participants in the Framingham Osteoarthritis Study underwent magnetic resonance imaging (MRI), measurement of bone mineral density (BMD), and knee radiography between 2002 and 2004. MRI was used to define medial and lateral bone marrow lesions in the medial and lateral tibiofemoral compartments, respectively. We performed a logistic regression analysis with medial bone marrow lesions as the outcome, testing M:L BMD ratio groups as predictor variables. We adjusted for age, sex, body mass index, and systemic BMD, using generalized estimating equations to adjust for correlations between knees. An identical analysis evaluating lateral bone marrow lesions was performed. RESULTS: Medial bone marrow lesions were strongly associated with a high M:L BMD ratio. The odds ratios (ORs) for prevalent medial bone marrow lesions, for the lowest to the highest quartile of M:L BMD ratios, were 1.0 (referent), 1.3, 5.0, and infinity (P for trend < 0.0001). Lateral bone marrow lesions were strongly associated with low M:L BMD ratios (the ORs for prevalent lateral bone marrow lesions, for the highest to the lowest quartile, were 1.0 [referent], 3.0, 26.8, and 54.0 [P for trend < 0.0001]). CONCLUSION: Medial bone marrow lesions occur in knees with relatively higher local medial tibial bone density, and lateral bone marrow lesions occur in knees with relatively higher lateral tibial bone density, supporting the hypothesis that local BMD reflects loading within the knee. Our findings emphasize the importance of loading in the pathophysiology of OA.

Aged↗