Clinical utility of comprehensive circulating tumor DNA genotyping compared with standard of care tissue testing in patients with newly diagnosed metastatic colorectal cancer.

BACKGROUND: Comprehensive biomarker testing is essential in selecting optimal treatment for patients with metastatic colorectal cancer (mCRC); however, incomplete genotyping is widespread, with most patients not receiving testing for all guideline-recommended biomarkers, in part due to reliance on burdensome sequential tissue-based single-biomarker tests with long waiting times or availability of only archival tissue samples. We aimed to demonstrate that liquid biopsy, associated with rapid turnaround time (TAT) and lower patient burden, effectively identifies guideline-recommended biomarkers in mCRC relative to standard of care (SOC) tissue testing. PATIENTS AND METHODS: Prospectively enrolled patients with previously untreated mCRC undergoing physician discretion SOC tissue genotyping submitted pretreatment blood samples for comprehensive circulating tumor DNA (ctDNA) analysis with Guardant360 and targeted RAS and BRAF analysis with OncoBEAM. RESULTS: Among 155 patients, physician discretion SOC tissue genotyping identified a guideline-recommended biomarker in 82 patients, versus 88 identified with comprehensive ctDNA (52.9% versus 56.8%, noninferiority demonstrated down to α = 0.005) and 69 identified with targeted PCR ctDNA analysis (52.9% versus 44.5%, noninferiority rejected at α = 0.05). Utilizing ctDNA in addition to tissue increased patient identification for a guideline-recommended biomarker by 19.5% by rescuing those without tissue results either due to tissue insufficiency, test failure, or false negatives. ctDNA median TAT was significantly faster than tissue testing when the complete process from sample acquisition to results was considered (median 10 versus 27 days, P < 0.0001), resulting in accelerated biomarker discovery, with 52.0% biomarker-positive patients identified by ctDNA versus 10.2% by SOC tissue 10 days after sample collection (P < 0.0001). CONCLUSIONS: Comprehensive ctDNA genotyping accurately identifies guideline-recommended biomarkers in patients with mCRC at a rate at least as high as SOC tissue genotyping, in a much shorter time. Based on these findings, the addition of ctDNA genotyping to clinical practice has significant potential to improve the care of patients with mCRC.

The efficacy of different vitamin D supplementation delivery methods on serum 25(OH)D: A randomised double-blind placebo trial.

BACKGROUND: The use of vitamin D supplementation has increased due to greater recognition of widespread deficiency. AIMS: There has been little research on the effectiveness of different delivery methods and therefore the aim of was to test the efficacy of different delivery methods on serum 25(OH)D. METHODS: Using a randomised repeated measures double-blind placebo design (registered under ClinicalTrials.gov Identifier no. NCT03463642), changes in serum 25(OH)D over a 4-week period using a capillary spot method were monitored. 62 female participants blindly chose a number related to a supplementation delivery method: pill placebo, pill, oral liquid, oral liquid placebo, Skin oil application (SOA) placebo, SOA plus vitamin D3 suspension, or SOA plus vitamin D3 suspension with essential oil enhancer; active vitamin D supplements contained 100,000IU. Participants took their allocated supplements over a 24-hr period with serum 25(OH)D retested 4 weeks later. Liquid chromatography-tandem mass spectrometry method was applied to dried blood spot samples by an independent laboratory. RESULTS: ANCOVA reported a significant difference between the groups (F1,6 = 146.68; p < 0.001, eta2 = 0.51). Separate analysis within the delivery methods (pill, SOA, oral liquid) indicated significant differences between the active and placebo supplementation groups (p < 0.01). Post hoc analysis of absolute changes indicated vit D pill and SOA + vit D + essential oil had significant increases (p < 0.05) in serum 25(OH)D compared to all other interventions with no significant difference between them. CONCLUSIONS: In human participants vitamin D oral pill has the greatest effect on serum 25(OH)D levels. Skin oil application delivery of vitamin D using a penetrator enhancer has also been shown to be an effective method of delivery.

Eccentric exercises; why do they work, what are the problems and how can we improve them?

Eccentric exercises (EE) have proved successful in the management of chronic tendinopathy, particularly of the Achilles and patellar tendons, where they have been shown to be effective in controlled trials. However, numerous questions regarding EE remain. The standard protocols are time-consuming and require very motivated patients. EE are effective in some tendinopathies but not others. Furthermore, the location of the lesion can have a profound effect on efficacy; for example, standard EE in insertional lesions of the Achilles are ineffective. Until recently little was known of the effect of EE on tendinopathic tendons, although a greater understanding of this process is emerging. Additionally, recent in vivo evidence directly comparing eccentric and concentric exercises provides a possible explanation for the therapeutic benefit of EE. The challenge now is to make EE more effective. Suggestions on areas of future research are made.

The mechanism for efficacy of eccentric loading in Achilles tendon injury; an in vivo study in humans.

OBJECTIVE: Degenerative disorders of tendons present an enormous clinical challenge. They are extremely common, prone to recur and existing medical and surgical treatments are generally unsatisfactory. Recently eccentric, but not concentric, exercises have been shown to be highly effective in managing tendinopathy of the Achilles (and other) tendons. The mechanism for the efficacy of these exercises is unknown although it has been speculated that forces generated during eccentric loading are of a greater magnitude. Our objective was to determine the mechanism for the beneficial effect of eccentric exercise in Achilles tendinopathy. METHODS: Seven healthy volunteers performed eccentric and concentric loading exercises for the Achilles tendon. Tendon force and length changes were determined using a combination of motion analysis, force plate data and real-time ultrasound. RESULTS: There was no significant difference in peak tendon force or tendon length change when comparing eccentric with concentric exercises. However, high-frequency oscillations in tendon force occurred in all subjects during eccentric exercises but were rare in concentric exercises (P < 0.0001). CONCLUSION: These oscillations provide a mechanism to explain the therapeutic benefit of eccentric loading in Achilles tendinopathy and parallels recent evidence from bone remodelling, where the frequency of the loading cycles is of more significance than the absolute magnitude of the force.

Dietary determinants of post-menopausal bone loss at the lumbar spine: a possible beneficial effect of iron.

INTRODUCTION: Previous studies suggesting different effects of diet on post-menopausal bone loss may have given conflicting results because they sometimes failed to exclude confounding conditions or used imprecise methodology. DESIGN: To identify dietary determinants of bone loss from the lumbar spine after menopause in women not taking hormone replacement who developed no evidence of spondylotic or sclerotic degenerative disease, forty-three women were followed with repeated (mean = 12) measurements of bone mineral density (BMD) at L2-4 for 11-14 years. Eleven developed evidence suggestive of degenerative disease and were excluded. Diet was assessed at the beginning of the study and 2.5 years later using 3-day and 7-day periods of weighed intakes. Nutrients estimated were: carbohydrate, fat, protein, fibre, calcium, magnesium, iron, phosphorus, copper, zinc and six vitamins. We tested the ability of diet to predict post-menopausal bone loss using stepwise regression. RESULTS: Each woman's BMD change was described by a single coefficient after log transformation of the BMD data. The best model for BMD loss including dietary factors alone had two significant determinants: daily energy or protein (p=0.0003) intake was adverse, while dietary iron (p=0.002) was predictive of bone maintenance, an effect that persisted if iron was expressed as a ratio to energy intake. Adding body mass index to the model increased the goodness of fit (R (2)adj rose from 0.33 to 0.42) without affecting the statistical significance of the dietary determinants. CONCLUSIONS: Diet may influence bone loss after menopause, with dietary iron (or an associated factor) possibly having a protective effect on bone at the spine.

Current concepts in the management of tendon disorders.

Primary disorders of tendons are common and constitute a high proportion of referrals to rheumatologists. Certain tendons are particularly vulnerable to degenerative pathology; these include the Achilles, patella, elements of the rotator cuff, forearm extensors, biceps brachi and tibialis posterior tendons. Disorders of these tendons are often chronic and can be difficult to manage successfully in the long term. Significant advances have been made in understanding the pathophysiology of these conditions. Histopathological evidence, together with advances in imaging techniques, has made us more appreciative of the degenerative (rather that inflammatory) nature of these conditions. Additionally the presence of neovascularization is now well-recognized in long-standing tendinopathy. We review the mechanical, vascular and developing neural theories that attempt to explain the aetiology of degenerative tendinopathy. We also explore theories of why specific tendons (such as the Achilles and supraspinatus tendons) are particularly prone to degenerative pathology. Traditionally, treatments have placed a heavy emphasis on anti-inflammatory strategies, which are often inappropriate. Recently, however, significant advances in the practical management of tendon disorders have been made. In particular the advent of 'eccentric loading' training programmes has revolutionized the treatment of Achilles tendinopathy in some patients. This concept is currently being extended to include other commonly injured tendons. Other current treatments are reviewed, as are potential future treatments.

Are synchronised swimmers at risk of amenorrhoea?

OBJECTIVE: Synchronised swimming is a sport that shares certain characteristics with other aesthetically pleasing sports such as gymnastics and dance. The purpose of this investigation was to ascertain whether the highest ranked synchronised swimmers in the United Kingdom experience menstrual abnormalities, a common medical problem seen in these related activities. METHODS: Twenty three members of the Great Britain synchronised swimming squad completed a questionnaire on menstrual history. Body composition and VO(2)MAX were measured in the laboratory during regular physiological screening. RESULTS: Three of the 23 subjects were oligomenorrhoeic and none were amenorrhoeic. All were postmenarchal. Mean estimated body fat percentage was 23%, and mean VO(2)MAX was 47.2 ml/kg/min. CONCLUSIONS: It appears that synchronised swimmers in the United Kingdom are relatively protected from menstrual disturbances for reasons that cannot be explained in isolation.

Cerebral injury after cardiac surgery: identification of a group at extraordinary risk. Multicenter Study of Perioperative Ischemia Research Group (McSPI) and the Ischemia Research Education Foundation (IREF) Investigators.

BACKGROUND AND PURPOSE: Cerebral injury after cardiac surgery is now recognized as a serious and costly healthcare problem mandating immediate attention. To effect solution, those subgroups of patients at greatest risk must be identified, thereby allowing efficient implementation of new clinical strategies. No such subgroup has been identified; however, patients undergoing intracardiac surgery are thought to be at high risk, but comprehensive data regarding specific risk, impact on cost, and discharge disposition are not available. METHODS: We prospectively studied 273 patients enrolled from 24 diverse US medical centers, who were undergoing intracardiac and coronary artery surgery. Patient data were collected using standardized methods and included clinical, historical, specialized testing, neurological outcome and autopsy data, and measures of resource utilization. Adverse outcomes were defined a priori and determined after database closure by a blinded independent panel. Stepwise logistic regression models were developed to estimate the relative risks associated with clinical history and intraoperative and postoperative events. RESULTS: Adverse cerebral outcomes occurred in 16% of patients (43/273), being nearly equally divided between type I outcomes (8.4%; 5 cerebral deaths, 16 nonfatal strokes, and 2 new TIAs) and type II outcomes (7.3%; 17 new intellectual deterioration persisting at hospital discharge and 3 newly diagnosed seizures). Associated resource utilization was significantly increased--prolonging median intensive care unit stay from 3 days (no adverse cerebral outcome) to 8 days (type I; P<0.001) and from 3 to 6 days (type II; P<0.001), and increasing hospitalization by 50% (type II, P=0.04) to 100% (type I, P<0.001). Furthermore, specialized care after hospital discharge was frequently necessary in those with type I outcomes, in that only 31% returned home compared with 85% of patients without cerebral complications (P<0.001). Significant risk factors for type I outcomes related primarily to embolic phenomena, including proximal aortic atherosclerosis, intracardiac thrombus, and intermittent clamping of the aorta during surgery. For type II outcomes, risk factors again included proximal aortic atherosclerosis, as well as a preoperative history of endocarditis, alcohol abuse, perioperative dysrhythmia or poorly controlled hypertension, and the development of a low-output state after cardiopulmonary bypass. CONCLUSIONS: These prospective multicenter findings demonstrate that patients undergoing intracardiac surgery combined with coronary revascularization are at formidable risk, in that 1 in 6 will develop cerebral complications that are frequently costly and devastating. Thus, new strategies for perioperative management--including technical and pharmacological interventions--are now mandated for this subgroup of cardiac surgery patients.

Determinants of the first decade of bone loss after menopause at spine, hip and radius.

This study documented bone loss at three different sites in the early postmenopausal period, and examined potential predictors. Forty-three women underwent repeated measurements of bone density at the lumbar spine, proximal femur and distal radius for up to 14 years. Individual rates of bone loss were calculated for the spine and hip; for radial trabecular bone, rates were calculated separately for two time periods, earlier and later after menopause. In the spine and radius, initially high rates of loss diminished with time after menopause. No positive correlations for bone loss were found between the three sites, suggesting that faster than average bone loss was specific to individual bones. High body mass index (BMI) was significantly protective against fast bone loss at the spine and radius; in the spine, each unit increase in BMI was associated with a approximately 5% reduction in the rate of bone loss. Of the other variables measured (maximum oxygen consumption, lean body mass, fat mass, mean psoas muscle area at the L3 level, hand grip strength as well as anthropometry) only bone densitometry was sufficiently predictive to help guidance on hormone replacement or other prophylactic therapy. The data suggest that the known relationship between excessive leanness and risk of osteoporosis and vertebral fracture after menopause might in part be due to fast post-menopausal bone loss. Because bulk of psoas muscle was associated with low spine loss rates, the data also support a role for applied muscular loading in local maintenance of bone density.

The radiological investigation of lumbar spondylolysis.

Lumbar spondylolysis represents a stress fracture of the pars interarticularis and occurs most commonly at the L5 level. Pars defects can be imaged with plain radiography, bone scintigraphy, computed tomography (CT) and magnetic resonance imaging (MRI). Plain radiographic projections of particular value include the coned lateral view of the lumbosacral junction, which displays the majority of defects, and the anteroposterior view with 30 degrees cranial angulation. The value of oblique radiography is unproven. Planar bone scintigraphy (PBS) is more sensitive than radiography and single photon emission computed tomography (SPECT) more sensitive and specific than PBS. Both these techniques, however, are less specific than radiography and CT. CT, when performed with a reverse gantry angle and thin sections, is the investigation of choice for identifying radiographically occult lyses. Conventional lumbar spine MRI techniques are valuable for demonstrating normality of the pars, but may be associated with a high false positive rate for the diagnosis of pars defects.

The acute effects of exercise on bone turnover.

Exercise is known to have long-term benefits on bone mass, but little is known about the short-term effects of exercise on bone turnover. The purpose of this study was to investigate whether acute effects of exercise on bone remodelling could be detected by measuring blood and urinary markers of bone turnover. We measured biochemical markers of bone turnover in ten healthy, young men before and up to 32 hours after 30 minutes of brisk treadmill walking. Blood samples were taken before, immediately after and at 0.5, 1, 8, 24 and 32 hours after the exercise. These were assayed for osteocalcin and bone specific alkaline phosphatase. Twenty-four hour urine samples were taken over three days (day before, day of and day after exercise) and measured for pyridinoline and deoxypyridinoline crosslinks. Crosslink excretion was standardised for total body bone mineral content (TBBMC) and urinary creatinine. Total body bone mineral density (and content) and body composition were measured by dual energy X-ray absorptiometry. No changes in the levels of either osteocalcin or alkaline phosphatase were seen at any time point following the exercise. Both urinary crosslinks exhibited an increase in levels on the day of the exercise and a further significant increase the day after (pyridinoline 38.7%, p = 0.05; deoxypyridinoline 42.3%, p = 0.025; median, corrected for TBBMC). There were significant negative correlations between the crosslinks, osteocalcin and body fat percentage. In conclusion, the exercise appears to have stimulated bone resorption within 32 hours of moderate exercise, but there was no measurable effect on bone formation after 32 hours. A longer study period may be necessary to detect changes in bone formation.

Adverse cerebral outcomes after coronary bypass surgery. Multicenter Study of Perioperative Ischemia Research Group and the Ischemia Research and Education Foundation Investigators.

BACKGROUND: Acute changes in cerebral function after elective coronary bypass surgery is a difficult clinical problem. We carried out a multicenter study to determine the incidence and predictors of -- and the use of resources associated with -- perioperative adverse neurologic events, including cerebral injury. METHODS: In a prospective study, we evaluated 2108 patients from 24 U.S. institutions for two general categories of neurologic outcome: type I (focal injury, or stupor or coma at discharge) and type II (deterioration in intellectual function, memory deficit, or seizures). RESULTS: Adverse cerebral outcomes occurred in 129 patients (6.1 percent). A total of 3.1 percent had type I neurologic outcomes (8 died of cerebral injury, 55 had nonfatal strokes, 2 had transient ischemic attacks, and 1 had stupor), and 3.0 percent had type II outcomes (55 had deterioration of intellectual function and 8 had seizures). Patients with adverse cerebral outcomes had higher in-hospital mortality (21 percent of patients with type I outcomes died, vs. 10 percent of those with type II and 2 percent of those with no adverse cerebral outcome; P<0.001 for all comparisons), longer hospitalization (25 days with type I outcomes, 21 days with type II, and 10 days with no adverse outcome; P<0.001), and a higher rate of discharge to facilities for intermediate- or long-term care (69 percent, 39 percent, and 10 percent ; P<0.001). Predictors of type I outcomes were proximal aortic atherosclerosis, a history of neurologic disease, and older age; predictors of type II outcomes were older age, systolic hypertension on admission, pulmonary disease, and excessive consumption of alcohol. CONCLUSIONS: Adverse cerebral outcomes after coronary bypass surgery are relatively common and serious; they are associated with substantial increases in mortality, length of hospitalization, and use of intermediate- or long-term care facilities. New diagnostic and therapeutic strategies must be developed to lessen such injury.

Multicenter preoperative stroke risk index for patients undergoing coronary artery bypass graft surgery. Multicenter Study of Perioperative Ischemia (McSPI) Research Group.

BACKGROUND: The paradox of present cardiac surgery is that the more elderly and debilitated patients benefit most from cardiac surgery compared with medical therapy, yet they sustain greater overall risk for morbidity and mortality after cardiac surgery. The goal of the present study was to develop a preoperative index predicting major perioperative neurological events in patients undergoing coronary artery bypass graft surgery. METHODS AND RESULTS: As part of a prospective, multicenter, observational study (McSPI Research Group), we enrolled 2417 patients at 24 academic medical centers in the United States. Patients who died intraoperatively or had concomitant open-heart procedures were excluded from analysis, resulting in a total of 2107 for analysis. Sixty-eight patients (3.2%) developed adverse neurological events, defined as cerebrovascular accident, transient ischemic attack (TIA), or persistent coma. Bivariate analysis was applied to determine associations between preoperative variables and neurological events. Significant bivariate predictors were identified then logically grouped, and for each cluster, a score was calculated based on principal components. Key predictor variables were age, history of previous neurological disease, diabetes, history of vascular disease, previous coronary artery surgery, unstable angina, and history of pulmonary disease, the coefficients for which were used to develop a preoperative stroke risk index that was validated by bootstrap (c-index = 0.778). Stroke risk could then be determined for each patient, calculating a patient's risk for stroke within 95% confidence intervals. CONCLUSIONS: With the McSPI stroke risk index developed in this study, neurological risk can be estimated, and the most appropriate group for perioperative therapy can be identified. Further refinement and validation of this index, however, are necessary and are under way in current studies.

The effect of weight-bearing exercise on bone mineral density: a study of female ex-elite athletes and the general population.

The aim of this retrospective cohort study was to estimate the changes in bone mineral density (BMD) as a consequence of exercise in female ex-athletes and age-matched controls. Eighty-three ex-elite female athletes (67 middle and long distance runners, 16 tennis players, currently aged 40-65) were recruited from the original records of their sporting associations. Controls were 585 age-matched females. The main outcome measures were BMD of lumbar spine (LS), femoral neck (FN), and forearm, estimated by dual-energy X-ray absorptiometry (DXA) scan. Levels of physical activity were assessed using a modified Allied Dunbar Fitness Survey scale and classified as (a) ex-athletes, (b) active controls (> or = 1 h of vigorous physical activity currently and in the past), (c) low activity controls with inconsistent or intermediate levels of activity, and (d) inactive controls (< 15 minutes of exercise per week). After adjustment for differences in age, weight, height, and smoking, athletes had greater BMDs than controls: 8.7% at the LS (95% confidence interval [CI] 5.4-12.0; p < 0.001) and 12.1% at FN (CI 9.0-15.3; p < 0.001). The benefits of exercise appeared to persist after cessation of sporting activity. Active controls (n = 22) had greater BMDs than the inactive group (n = 347): 7.9% LS (CI 2.0-13.8; p = 0.009) and 8.3% FN (CI 2.7-13.8; p = 0.004). The low activity controls (n = 216) had an intermediate BMD. Tennis players had greater BMDs compared with runners: 12.0% LS (CI 5.7-18.2; p = 0.0004) and 6.5% FN (CI -0.2-13.2; p = 0.066). The BMD of tennis players' dominant forearms were greater than their nondominant forearms. In conclusion, regular vigorous weight-bearing exercise of 1 h or more per week is associated with an increase in BMD within a normal population. This study confirms long-term weight-bearing exercise as an important factor in the regulation of bone mass and fracture prevention.

Multicenter study of target-controlled infusion of propofol-sufentanil or sufentanil-midazolam for coronary artery bypass graft surgery. Multicenter Study of Perioperative Ischemia (McSPI) Research Group.

BACKGROUND: The use of target-controlled infusions of anesthetics for coronary artery bypass graft surgery has not been studied in detail. The effects of target-controlled infusions of propofol or sufentanil, supplemented by infusions of sufentanil or midazolam, respectively, were evaluated and compared. METHODS: At 14 clinical sites, 329 patients were given a target-controlled infusion of propofol (n = 165) to produce effect-site concentration (Ce) of > or = 3-micrograms/ml or a target-controlled infusion of sufentanil (n = 164). Sufentanil or midazolam, respectively, also were infused. Systolic hypertension, hypotension, tachycardia, and bradycardia were assessed by measuring heart rate and blood pressure every minute during operation. Myocardial ischemia was assessed perioperatively by monitoring ST segment deviation via continuous three-lead Holter electrocardiography, and it was evaluated during operation by monitoring left ventricular wall motion abnormality via transesophageal echocardiography. RESULTS: The measured cardiovascular parameters were satisfactory and usually similar for the patients receiving propofol-sufentanil or sufentanil-midazolam. The primary endpoint of the percentage of patients with intraoperative ST segment deviation (23 +/- 6% vs. 24 +/- 6%, P = 0.86) did not differ significantly between the two groups. The incidence of left ventricular wall motion abnormality shown on transesophageal echocardiography before (19 +/- 4% vs. 26 +/- 4%, P = 0.25) and after (23 +/- 4% vs. 31 +/- 5%, P = 0.32) cardiopulmonary bypass also did not differ significantly for the two groups. Changes in intraoperative target concentration were more frequent with propofol-sufentanil anesthetic than with sufentanil-midazolam (11.7 +/- 7.1 vs. 7.3 +/- 3.6, P < 0.001). The incidence of intraoperative hypotension (77% vs. 55%, P < 0.001), the use of inotropic/vasopressor medications (93% vs. 84%, P = 0.01), and the administration of crystalloids (2.8 +/- 1.4 L vs. 2.4 +/- 1.2 L, P < 0.001) were significantly greater in the propofol-sufentanil group. Conversely, the incidence of intraoperative hypertension (43% vs. 54%, P = 0.05) and the use of antihypertensive/vasodilator medications (70% vs. 90%, P < 0.001) were significantly less in the propofol-sufentanil group. CONCLUSIONS: Target-controlled infusions of propofol or sufentanil, supplemented by infusions of sufentanil or midazolam, respectively, were suitable to provide anesthesia for coronary artery bypass graft surgery. Continuous monitoring revealed a high prevalence of hemodynamic abnormalities. Despite greater hypotension in the propofol-sufentanil group and greater hypertension in the sufentanil-midazolam group, episodes of myocardial ischemia were similar for both groups and were not temporally related to episodes of hemodynamic abnormalities.

Risk of osteoarthritis associated with long-term weight-bearing sports: a radiologic survey of the hips and knees in female ex-athletes and population controls.

OBJECTIVE: To estimate the risk of osteoarthritis (OA) of the hip and knee due to long-term weight-bearing sports activity in ex-elite athletes and the general population. METHODS: A retrospective cohort study was conducted of 81 female ex-elite athletes (67 middle- and long-distance runners, and 14 tennis players), currently ages 40-65, recruited from original playing records, and 977 age-matched female controls, taken from the age-sex register of the offices of a group general practice in Chingford, Northeast London, England. The definition of OA included radiologic changes (joint space narrowing and osteophytosis) in the hip joints, patellofemoral (PF) joints, and tibiofemoral (TF) joints. RESULTS: Compared with controls of similar age, the ex-athletes had greater rates of radiologic OA at all sites. This association increased further after adjustment for height and weight differences, and was strongest for the presence of osteophytes at the TF joints (odds ratio [OR] 3.57, 95% confidence interval [95% CI] 1.89-6.71), at the PF joints (OR 3.50, 95% CI 1.80-6.81), narrowing at the PF joints (OR 2.97, 95% CI 1.15-7.67), femoral osteophytes (OR 2.52, 95% CI 1.01-6.26), and hip joint narrowing (OR 1.60, 95% CI 0.73-3.48), and was weakest for narrowing at the TF joints (OR 1.17, 95% CI 0.71-1.94). No clear risk factors were seen within the ex-athlete groups, although the tennis players tended to have more osteophytes at the TF joints and hip, but the runners had more PF joint disease. Within the control group, a small subgroup of 22 women who reported long-term vigorous weight-bearing exercise had risks of OA similar to those of the ex-athletes. Ex-athletes had similar rates of symptom reporting but higher pain thresholds than controls, as measured by calibrated dolorimeter. CONCLUSION: Weight-bearing sports activity in women is associated with a 2-3-fold increased risk of radiologic OA (particularly the presence of osteophytes) of the knees and hips. The risk was similar in ex-elite athletes and in a subgroup from the general population who reported long-term sports activity, suggesting that duration rather than frequency of training is important.