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Biomedical subjects

T E McAlindon

Publications and source records attributed to T E McAlindon.

At least 19 recordsLinked to original sources
PubMed2006

Effects of oral glucosamine sulphate on serum glucose and insulin during an oral glucose tolerance test of subjects with osteoarthritis.

BACKGROUND: and objective: Glucosamine is suggested to affect glucose transport and insulin resistance. The effects of oral glucosamine on serum glucose and insulin levels at the initiation and throughout the duration of a 3-h oral glucose tolerance test were examined. METHODS: Sera from 16 patients with osteoarthritis, but with no other diagnosed medical condition who had fasted overnight, were obtained every 15-30 min during the 3 h of continued fasting and during the 3 h after ingestion of 75 g of glucose with or without ingestion of 1500 mg of glucosamine sulphate. Glucose was analysed by high-performance liquid chromatography using a Metrohm-Peak 817 Bioscan, and the area under the curve (AUC) for glucose was calculated. Insulin was measured by radioimmunoassay every 30 min for 2 h. RESULTS: Three participants who were found to have previously undiagnosed abnormalities of glucose tolerance demonstrated significant (p = 0.04) incremental elevations in glucose levels after ingestion of glucosamine sulphate. The other 13 participants also had mean incremental elevations that were not significant (p = 0.20). Glucosamine sulphate ingestion had no effect on insulin levels. CONCLUSION: The results suggest that glucosamine ingestion may affect glucose levels and consequent glucose uptake in patients who have untreated diabetes or glucose intolerance.

Adult↗
PubMed2006

Sulphate and osteoarthritis: decrease of serum sulphate levels by an additional 3-h fast and a 3-h glucose tolerance test after an overnight fast.

BACKGROUND: Low sulphate levels in blood may contribute to osteoarthritis by decreasing cartilage chondroitin sulphation. OBJECTIVE: To measure serum levels of sulphate during 3 h of fasting or glucose ingestion after overnight fasts to determine how much sulphate lowering may occur during this period. METHODS: Sera from 14 patients with osteoarthritis who fasted overnight were obtained every 15-30 min during 3 h of continued fasting and during 3 h after ingestion of 75 g of glucose. Sulphate was assayed by high-performance liquid chromatography with a Metrohm-Peak 761 Compact IC and simultaneously assayed for glucose by high-performance liquid chromatography with a Metrohm-Peak 817 Bioscan. RESULTS: Continuation of overnight fasting for 3 h resulted in a near-linear 3-h decrease in levels for all 14 patients ranging from 3% to 20% with a mean drop of 9.3%, whereas the 3-h decrease after glucose ingestion ranged from 10% to 33% with a mean drop of 18.9%. CONCLUSION: A 3-h continuation of fasting caused a marked reduction in serum sulphate levels, whereas ingestion of 75 g of glucose in the absence of protein resulted in doubling the reduction. This suggests that fasting and ingestion of protein-free calories may produce periods of chondroitin undersulphation that could affect osteoarthritis.

Adult↗
PubMed2005

Low levels of human serum glucosamine after ingestion of glucosamine sulphate relative to capability for peripheral effectiveness.

BACKGROUND: Oral glucosamine preparations are widely used as a treatment for osteoarthritis, purportedly functioning by a variety of mechanisms suggested by results of in vitro experiments, and generally using glucosamine concentrations well in excess of 100 micromol/l. OBJECTIVE: To use high performance liquid chromatography with a high sensitivity Metrohm-Peak instrument for pulsed amperometric measurement of human serum glucosamine; a detection limit of 0.5 micromol/l at 1:10 serum dilution allowed measurement of low levels of glucosamine in human serum, which previously has not been possible. METHODS: Eighteen subjects with osteoarthritis were given 1,500 mg of commercial glucosamine sulphate after an overnight fast, and serum was then obtained at baseline and every 15-30 minutes over 3 hours, and additionally, from two subjects at 5 and 8 hours. Urine samples were collected at baseline and 3 hours after ingestion from three subjects. RESULTS: Baseline glucosamine was below the detection limit of 0.5 mumol/l for all subjects, but after ingestion, glucosamine was detected in 17/18 subjects, beginning to rise at 30-45 minutes to a maximum at 90-180 minutes, with a range of 1.9-11.5 micromol/l (0.34-2 microg/ml). CONCLUSION: This maximum concentration of 11.5 micromol/l has previously been shown to contribute less than 2% of the galactosamine incorporated into chondroitin sulphate in incubations of glucosamine with cultured human chondrocytes, and is a much lower concentration than the glucosamine concentrations claimed by other investigators to have various significant in vitro effects. This raises questions about current biological rationales for glucosamine use that were based on in vitro effects of glucosamine at much higher concentrations.

Administration, Oral↗
PubMed2005

High sensitivity, specificity and predictive value of the Connective Tissue Disease Screening Questionnaire among urban African-American women.

The Connective Tissue Disease Screening Questionnaire (CSQ), developed to screen populations for SLE and other CTDs, has been validated in a predominantly Caucasian population with hospital-based controls. We aimed to test the performance characteristics of the CSQ in an urban, predominantly African-American population. The CSQ was administered by interview to women recruited for a study of environmental risk factors and SLE, including 99 cases with SLE validated by medical record review and 202 healthy controls recruited from the community. Overall, 88% of subjects had African heritage, 6% were Hispanic and 4% were non-Hispanic Caucasian. Controls were more likely to report African heritage than cases (91% versus 82%, P = 0.001). Sensitivity for detecting SLE was 88% and specificity was 91%. In this study, where the prevalence of SLE was 33%, predictive value of a positive CSQ was 82% and predictive value of a negative CSQ was 94%. The CSQ has slightly lower sensitivity but greater specificity for SLE in an urban, predominantly African-American population with community-based controls compared with a Caucasian population with hospital-based controls. These results suggest that the CSQ has adequate sensitivity and specificity and could be used in population studies to screen African-American women for SLE.

Adult↗
PubMed2003

Assessment of strategies for identifying diagnosed cases of systemic lupus erythematosus through self-report.

The objective of this work was to assess the optimal way to identify potential systemic lupus erythematosus (SLE) cases in large epidemiologic studies through self-reported information about diagnosis of SLE, symptoms and medications, and to investigate the utility of a criteria checklist sent directly to participants' physicians. We used data collected in 1997 from 53322 participants in a study of African-American women, the Black Women's Health Study, including a lupus screening questionnaire (LSQ) and questions about SLE diagnosis and medications. We confirmed self-reported SLE through medical records and criteria checklists sent to participants' physicians. Among those for whom we received medical records and/or criteria checklists, we compared the predictive value and proportion of missed cases of several algorithms using combinations of self-reported SLE diagnosis, LSQ score and medication use to self-reported SLE diagnosis alone. We obtained a physician checklist or medical chart for 251 individuals who reported SLE, of whom 212 (84%) fulfilled ACR criteria for definite or probable SLE, or had clinical lupus (SLE diagnosis recorded in medical charts plus appropriate medication use). The use of LSQ score or medication use in addition to self-report of SLE tended to decrease the false positive rate but also to reduce the proportion of true cases identified. Checklists of ACR criteria completed by subjects' physicians documented more criteria than medical records. In conclusion, among participants who consented to medical record review, SLE prediction algorithms using questions about lupus symptoms and medications offered slightly higher predictive value for detecting cases than self-reported diagnosis alone, but at the cost of case detection. SLE case confirmation strategies can be complemented by the use of criteria checklists sent directly to participants' physicians.

Adult↗
PubMed2001

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.

Age Factors↗
PubMed2001

Microchimerism in a female patient with systemic lupus erythematosus.

Systemic lupus erythematosus (SLE) is a serious multisystem disease that has a striking propensity to affect women. The cause of SLE remains elusive. Fetomaternal cell trafficking, or the passage of fetal cells into the maternal circulation, is now a well-established phenomenon. In addition, fetal cells have been implicated in the development of preeclampsia and in the pathogenesis of scleroderma. We undertook this study to determine whether fetomaternal cell trafficking might also be involved in pathogenic processes in SLE. Fluorescence in situ hybridization analysis was performed using X and Y chromosome-specific probes on affected and unaffected tissue obtained at autopsy from a woman who had previously given birth to 2 males and who had died of complications of SLE. The goal of the analysis was to detect the presence of male cells of putative fetal origin. Male cells were found in every histologically abnormal tissue type that was examined, but were not found in histologically normal tissue. These data suggest that fetal cells may be associated with SLE. It is unclear whether their presence may be related to disease causation, an effect of disease progression, or unrelated to disease pathology. However, this case study is an important step toward understanding the potential relationship between fetomaternal cell trafficking and SLE pathology.

Adult↗
PubMed2001

The validity of different definitions of radiographic worsening for longitudinal studies of knee osteoarthritis.

Several definitions have been used to characterize radiographic worsening of knee osteoarthritis in longitudinal studies, yet a valid definition with maximal power to detect differences between groups is not known. We used serial radiographs from the Framingham Osteoarthritis Study to compare five dichotomous definitions according to construct validity (strength of association) and discriminant power (power to reject null hypotheses of no difference) for 1) known risk factors for knee osteoarthritis, and 2) development of new knee pain. For risk factors: definitions that included scores for osteophytes (bone spurs) showed good construct validity and discriminant power; a definition using the Kellgren and Lawrence grade of overall knee osteoarthritis was conservative with good construct validity but low discriminant power; a definition based solely on ordinal assessment of joint space narrowing had weak construct validity and low discriminant power. All definitions had comparably strong associations with the development of new knee pain. Similar associations with new knee pain were found when the analysis was confined to either knees with no osteoarthritis at baseline or knees with prevalent osteoarthritis, with increased standard errors for prevalent osteoarthritis. Use of any of these definitions, other than joint space narrowing alone, would permit detection of associations with most known risk factors. Definitions incorporating both osteophytes and joint space narrowing offer the most precise estimation of the association of risk factors with disease worsening.

Aged↗
PubMed2001

Indole-3-carbinol in women with SLE: effect on estrogen metabolism and disease activity.

Estrogen metabolism in women with SLE is weighted towards 16alpha-hydroxyestrone, an estrogenic compound that might fuel disease activity. Indole-3-carbinol (I3C) is a nutritional compound that can shift estrogen metabolism towards less estrogenic metabolites. However, the effects of I3C in women with SLE have not been studied. Open-label 1-week metabolic study of 375 mg/day I3C was carried out in women with SLE, followed by a 3-month observational period for disease activity. The primary outcome measure was the change in ratio of urinary 2:16alpha hydroxyestrone levels. Secondary measures included the SLE Disease Activity Index. Seventeen clinically premenopausal women fulfilling ACR criteria for probable/definite SLE (mean age 37.9 y, range 20-49 y, mean disease duration 4.3 y, range 0.5-15) completed the 1-week metabolic study; 12 took I3C for 3 months. The mean 2:16alpha hydroxyestrone ratio increased by 1.84 to 3.15 (P = 0.0001). Mean SLEDAI scores were 10.0 (baseline); 6.25 (3 months); and 8.8 (3 months after withdrawal; P = NS). Women with SLE can manifest a metabolic response to I3C and might benefit from its antiestrogenic effects. We did not observe any striking effects on SLE disease activity during the 3-month observational period.

Adult↗
PubMed2000

Glucosamine and chondroitin for treatment of osteoarthritis: a systematic quality assessment and meta-analysis.

CONTEXT: Glucosamine and chondroitin preparations are widely touted in the lay press as remedies for osteoarthritis (OA), but uncertainty about their efficacy exists among the medical community. OBJECTIVE: To evaluate benefit of glucosamine and chondroitin preparations for OA symptoms using meta-analysis combined with systematic quality assessment of clinical trials of these preparations in knee and/or hip OA. DATA SOURCES: We searched for human clinical trials in MEDLINE (1966 to June 1999) and the Cochrane Controlled Trials Register using the terms osteoarthritis, osteoarthrosis, degenerative arthritis, glucosamine, chondroitin, and glycosaminoglycans. We also manually searched review articles, manuscripts, and supplements from rheumatology and OA journals and sought unpublished data by contacting content experts, study authors, and manufacturers of glucosamine or chondroitin. STUDY SELECTION: Studies were included if they were published or unpublished double-blind, randomized, placebo-controlled trials of 4 or more weeks' duration that tested glucosamine or chondroitin for knee or hip OA and reported extractable data on the effect of treatment on symptoms. Fifteen of 37 studies were included in the analysis. DATA EXTRACTION: Reviewers performed data extraction and scored each trial using a quality assessment instrument. We computed an effect size from the intergroup difference in mean outcome values at trial end, divided by the SD of the outcome value in the placebo group (0.2, small effect; 0.5, moderate; 0.8, large), and applied a correction factor to reduce bias. We tested for trial heterogeneity and publication bias and stratified for trial quality and size. We pooled effect sizes using a random effects model. DATA SYNTHESIS: Quality scores ranged from 12.3% to 55.4% of the maximum, with a mean (SD) of 35.5% (12%). Only 1 study described adequate allocation concealment and 2 reported an intent-to-treat analysis. Most were supported or performed by a manufacturer. Funnel plots showed significant asymmetry (P< or =.01) compatible with publication bias. Tests for heterogeneity were nonsignificant after removing 1 outlier trial. The aggregated effect sizes were 0.44 (95% confidence interval [CI], 0.24-0.64) for glucosamine and 0.78 (95% CI, 0.60-0.95) for chondroitin, but they were diminished when only high-quality or large trials were considered. The effect sizes were relatively consistent for pain and functional outcomes. CONCLUSIONS: Trials of glucosamine and chondroitin preparations for OA symptoms demonstrate moderate to large effects, but quality issues and likely publication bias suggest that these effects are exaggerated. Nevertheless, some degree of efficacy appears probable for these preparations.

Chondroitin↗
PubMed2000

Risk factors for the incidence and progression of radiographic knee osteoarthritis.

OBJECTIVE: Preventive strategies against knee osteoarthritis (OA) require a knowledge of risk factors that influence the initiation of the disorder and its subsequent progression. This population-based longitudinal study was performed to address this issue. METHODS: Ninety-nine men and 255 women aged > or =55 years had baseline interviews and weight-bearing knee radiographs in 1990-1991. Repeat radiographs were obtained in 1995-1996 (mean followup duration 5.1 years, median age at followup 75.8 years). Risk factors assessed at baseline were tested for their association with incident and progressive radiographic knee OA by logistic regression. RESULTS: Rates of incidence and progression were 2.5% and 3.6% per year, respectively. After adjusting for age and sex, the risk of incident radiographic knee OA was significantly increased among subjects with higher baseline body mass index (odds ratio [OR] 18.3, 95% confidence interval [95% CI] 5.1-65.1, highest versus lowest third), previous knee injury (OR 4.8, 95% CI 1.0-24.1), and a history of regular sports participation (OR 3.2, 95% CI 1.1-9.1). Knee pain at baseline (OR 2.4, 95% CI 0.7-8.0) and Heberden's nodes (OR 2.0, 95% CI 0.7-5.7) were weakly associated with progression. Analyses based on individual radiographic features (osteophyte formation and joint space narrowing) supported differences in risk factors for either feature. CONCLUSION: Most currently recognized risk factors for prevalent knee OA (obesity, knee injury, and physical activity) influence incidence more than radiographic progression. Furthermore, these factors might selectively influence osteophyte formation more than joint space narrowing. These findings are consistent with knee OA being initiated by joint injury, but with progression being a consequence of impaired intrinsic repair capacity.

Aged↗
PubMed2000

Bone mineral density and risk of incident and progressive radiographic knee osteoarthritis in women: the Framingham Study.

OBJECTIVE: To examine the relations of bone mineral density (BMD) and change in BMD to risk of incident and progressive radiographic knee osteoarthritis (OA) in a longitudinal cohort study. METHODS: Female participants aged 63 to 91 years (mean age 71) in the Framingham Study received anteroposterior weight bearing knee radiographs at biennial examinations 18 (1983-85) and 22 (1992-93). Knee radiographs were given scores for global severity of OA (Kellgren-Lawrence scale: range 0 to 4) and for the presence of osteophytes and joint space narrowing (range 0 to 3). Femoral neck BMD was assessed using dual photon absorptiometry at examination 20 and dual x-ray absorptiometry at examination 22. We examined the relations of BMD at examination 20 and its change between examination 20 and examination 22 to incident and progressive knee OA, as well as to worsening of individual radiographic features adjusting for age, body mass index, and other potential confounding factors. RESULTS: In total, 473 women (ages 63 to 91 yrs) had complete assessments. Over 8 years of followup, risk of incident radiographic knee OA increased from 5.6% among women in the lowest age-specific quartile of BMD to 14.2, 10.3, and 11.8% among women in the 2nd, 3rd, and highest quartiles, respectively. Multivariate adjusted OR of incident OA for each increase quartile of BMD were 1.0, 2.5, 2.0, and 2.3, respectively (p for trend = 0.222). This was mainly reflected in an increased risk of osteophyte development. However, risk of progressive OA decreased from 34.4 to 22.0, 20.3, and 18.9% as BMD increased. Compared to those in the lowest quartile of BMD, adjusted OR for progressive disease were 0.3, 0.2, and 0.1 among women in the 2nd, 3rd, and highest quartiles (p for trend <0.001), respectively, mainly due to its effect on lowering the risk of joint space loss. Compared to those who lost BMD >0.04 g/cm2 over the followup period, women who gained BMD were at increased risk of incident but at a significantly decreased risk of progressive knee OA. BMD change was not associated with osteophyte development, but gain in BMD lowered the risk of joint space loss. CONCLUSION: High BMD and BMD gain decreased the risk of progression of radiographic knee OA, but may be associated with an increased risk of incident knee OA. The protective effect was mainly through its influence on reducing the risk of joint space loss. Our results offer insights into how bone may affect the course of the most common joint disease, and thus may have potential therapeutic implications.

Absorptiometry, Photon↗
PubMed1999

Level of physical activity and the risk of radiographic and symptomatic knee osteoarthritis in the elderly: the Framingham study.

PURPOSE: Because osteoarthritis may be caused by "wear and tear," we examined the association between level of physical activity and risk of knee osteoarthritis in the elderly. SUBJECTS AND METHODS: Eligible subjects were participants in the Framingham Heart Study cohort who had radiographically normal knees at biennial exam 18 (1983-1985) and who also completed a physical activity questionnaire at exam 20 (1988-1989). Follow-up knee radiographs were obtained at biennial exam 22 (1992-1993). The study outcomes were the development of incident radiographic or symptomatic knee osteoarthritis between the baseline and follow-up exams. RESULTS: The number of hours per day of heavy physical activity was associated with the risk of incident radiographic knee osteoarthritis (odds ratio = 1.3 per hour, 95% confidence limits 1.1-1.6, P for trend = 0.006). Adjustment for age, sex, body mass index, weight loss, knee injury, health status, total calorie intake, and smoking strengthened this association (eg, odds ratio for > or = 4 hours heavy physical activity/day compared with no heavy physical activity = 7.0, 95% confidence limits 2.4-20, P for trend = 0.0002). Risk was greatest among individuals in the upper tertile of body mass index (odds ratio for > or = 3 hours/day of heavy physical activity = 13.0, 95% confidence limits 3.3-51). For incident symptomatic knee osteoarthritis, the results were similar, although the number of cases was small. No effects on these outcomes were observed from moderate and light physical activity, number of blocks walked, or number of flights of stairs climbed daily. CONCLUSIONS: Heavy physical activity is an important risk factor for the development of knee osteoarthritis in the elderly, especially among obese individuals. Light and moderate activities do not appear to increase risk.

Aged↗
PubMed1999

Regional musculoskeletal pain. The knee.

Chronic knee pain is common at all ages, particularly in the elderly, among whom it has its greatest impact. Chronic knee pain is often ascribed to osteoarthritis in adults and to chondromalacia patellae in children and adolescents. Pathological findings in both these conditions correlate poorly, however, with the severity of knee pain and disability. Psychometric variables correlate better with the impact of knee osteoarthritis, suggesting that this disorder has characteristics of a regional pain syndrome. This perception may reflect our lack of understanding of the biological mechanisms in these disorders. This possibility has been highlighted by the advent of magnetic resonance imaging, and by recent studies of muscle function, reflex quadriceps inhibition and proprioception in people with knee osteoarthritis. Established risk factors for knee osteoarthritis include increased body weight, knee injury and aspects of occupational activity. Recent studies have also suggested a possible role for oestrogens and vitamins C and D in the secondary prevention of this disorder. The emergence of 'nutraceuticals' such as glucosamine as treatments for osteoarthritis has captured the public imagination and merits further study.

Anti-Inflammatory Agents, Non-Steroidal↗
PubMed1998

Evidence for a Mendelian gene in a segregation analysis of generalized radiographic osteoarthritis: the Framingham Study.

OBJECTIVE: To investigate the inheritance of generalized osteoarthritis (OA). METHODS: OA was identified on hand and knee radiographs obtained from members of the Framingham Study cohort (the parents) in 1967-1970 and 1992-1993, and from their adult children in the Framingham Offspring Study in 1993-1994. All hand and knee radiographs evaluated for OA were graded using the Kellgren and Lawrence (K/L) scale. A measure of generalized OA was defined as the count of the number of hand and knee joints affected, as determined by the proportion of joints with a K/L grade > or =2. The OA count, treated as a continuous variable, was adjusted for age, body mass index, and a measure of physical activity for each joint area (hand or knee). Calculations were made separately for each generation and each sex, and correlations were analyzed against the standardized residual of OA. Segregation analysis was used to test whether OA aggregated in families, and if its transmission fit a Mendelian pattern. RESULTS: A total of 337 nuclear families with 2 parents and at least 1 biologic offspring were studied. In parents, the mean age was 61.2 years at the time of hand radiographs and 72.8 years at the time of knee radiographs, which were mostly obtained at a later examination. The mean age at the time of radiographs in offspring was 53.9 years. Using standardized residuals, parent-offspring and sibling-sibling correlations ranged from 0.115 to 0.306. In segregation analyses, models testing the hypotheses of no familial aggregation, no familial transmission, or a Mendelian gene alone were all rejected (P < 0.001 for each of these models). The best-fitting models were mixed models with a Mendelian mode of inheritance and a residual multifactorial component. The Mendelian recessive model provided the best fit. CONCLUSION: These analyses support a significant genetic contribution to OA, with evidence for a major recessive gene and a multifactorial component, representing either polygenic or environmental factors.

Adult↗
PubMed1998

Estrogen replacement therapy and worsening of radiographic knee osteoarthritis: the Framingham Study.

OBJECTIVE: To examine whether estrogen replacement therapy (ERT) prevents worsening of radiographic knee osteoarthritis (OA) in elderly women. METHODS: A total of 551 women ages 63-91 years (mean age 71) in the Framingham Study were followed up from biennial examination 18 (1983-1985) to examination 22 (1992-1993). Data on postmenopausal ERT were obtained every 2 years. Subjects were classified into 3 groups according to their estrogen use at biennial examination 18: never users (n = 349), past users (n = 162), and current users (n = 40). Women received anteroposterior weight-bearing knee radiographs at examinations 18 and 22. Using the Kellgren and Lawrence criteria, global radiographic knee OA was assessed, (grade range 0-4) and individual radiographic features, such as osteophytes and joint space narrowing, were scored from 0 to 3. Worsening was defined as either development of radiographic OA that was not present at baseline (incident OA) or progression of baseline radiographic OA by > or =1 Kellgren and Lawrence grade (progressive OA). Potential confounding factors included age, body mass index, weight change, smoking, knee injury, physical activity level, and bone mineral density at the femoral neck. RESULTS: During 8 years of followup, 17.4% of knee radiographic scores worsened by 1 grade and 5.8% by 2 or 3 grades among never users of ERT. Among current estrogen users, only 11.7% of knee radiographic scores worsened by 1 grade and none worsened by more than 1 grade. After adjusting for age and other potential confounding factors, the relative risk of incident radiographic knee OA in comparison with never users of estrogen was 0.8 (95% confidence interval [95% CI] 0.5-1.4) in past users and 0.4 (95% CI 0.1-3.0) in current users. Current use of estrogen also showed a trend toward decreased risk of progressive knee OA compared with never use (odds ratio [OR] 0.5, 95% CI 0.1-2.9). When both incident and progressive radiographic knee OA cases were combined, current ERT use had a 60% decreased risk compared with never use (OR 0.4, 95% CI 0.1-1.5). CONCLUSION: This is the first prospective cohort study to examine the effects of ERT on radiographic knee OA. The results indicate that current use of ERT had a moderate, but not statistically significant, protective effect against worsening of radiographic knee OA among elderly white women. These findings corroborate those of cross-sectional studies and point further to a potential benefit of female hormones in OA.

Aged↗
PubMed1998

Longitudinal analysis of the relationship between serum insulin-like growth factor-I and radiographic knee osteoarthritis.

OBJECTIVE: To examine the relation between serum insulin-like growth factor I (IGF-I) levels and both incident and progressive radiographic knee osteoarthritis (OA) in the Framingham Osteoarthritis Study. DESIGN: Subjects had bilateral weight-bearing, anterior-posterior knee radiographs performed in 1983-1985 and again in 1992-1993. IGF-I levels were measured from blood specimens obtained in 1988-1989 by a competitive binding radio-immunoassay (RIA) after separation with octadecasilyl-silica cartridges of serum IGF-I from binding proteins. Participants without baseline radiographic OA [Kellgren and Lawrence grades (K&L) = 0-1] were classified as having incident disease if they had K&L > or = 2 grades at follow-up. Progressive OA was defined as an increase in K&L score of > or = 1 in knees with baseline OA (K&L > or = 2). All analyses were knee-based and sex-specific. We examined IGF-I tertiles in relation to the risk of incident and progressive radiographic OA separately, adjusting for age, body mass index (BMI), and baseline K&L score, and used generalized estimating equations to adjust for the correlation between fellow knees. RESULTS: Four hundred and forty-one participants had knee radiographs and serum IGF-I levels measured. No associations were found for serum IGF-I levels and incident [women: OR = 0.9 (0.6-1.7), men OR = 1.2 (0.6-2.6)] or progressive [women OR = 0.9 (0.6-1.6), men OR = 0.9 (0.3-3.0)] radiographic knee OA in either sex. Neither did we observe any association between IGF-I and worsening of individual radiographic features of OA (i.e., osteophyte growth and joint space loss). CONCLUSION: In summary, this longitudinal study did not demonstrate any association of serum IGF-I and incident or progressive radiographic knee OA. Further studies are needed to clarify the role of IGF-I in OA.

Case-Control Studies↗