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BACKGROUND AND AIMS: Crohn's disease (CD) symptoms are a main driver for impaired quality of life and fast relief is important for patient care. Stool frequency (SF) and abdominal pain score (APS) are patient reported outcomes (PROs) measuring symptom severity, which are supported as treatment targets by the STRIDE-II consensus. This post hoc analysis examined the efficacy of risankizumab (RZB), a humanised monoclonal antibody with high specificity for interleukin-23 p19, for providing early symptom relief, along with the prognostic value of early symptom relief for achieving future clinical and endoscopic endpoints. METHODS: Individual and combined measures of SF and AP at weeks 1, 2, and 3 were assessed in patients with moderate to severe CD who received 600 mg intravenous RZB or placebo (PBO) in the ADVANCE or MOTIVATE induction studies. Multivariate logistic regression was used to examine the predictiveness of early symptom improvement for clinical and endoscopic outcomes following RZB induction and maintenance. RESULTS: Higher rates of SF/APS clinical remission and enhanced clinical response were observed as early as week 1 with RZB versus PBO. A larger proportion of patients achieved clinical endpoints with RZB versus PBO, irrespective of prior bio-failure status. Early PRO improvement was associated with a greater likelihood of achieving clinical and endoscopic improvement following 12-weeks induction and 52-weeks maintenance RZB dosing. CONCLUSIONS: After the first intravenous RZB induction dose, significantly greater rates of symptom improvement versus PBO were achieved. Improvements could be observed as early as week 1 and were predictive of week 12 and 52 clinical and endoscopic improvement.

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OBJECTIVES: To determine the association between weight trajectory, health status, and mortality in older women. DESIGN: Cohort study. SETTING: Study of Osteoporotic Fractures. PARTICIPANTS: Older community-dwelling women (age: baseline (1986-88), mean 68, range 65-81; Year 20 (2006-08), mean 88, range 83-102 (N = 1,323)). MEASUREMENTS: Body weight measured repeatedly over 20 years (mean 8 times). Logistic and Cox proportional hazard models were used to evaluate whether 20-year weight trajectory measures were associated with hip fracture, falls, physical performance, and mortality. RESULTS: In models adjusted for age, clinic, calcium use, Year 20 weight, walking speed, comorbidity score, smoking, self-reported health, and walking for exercise, women with moderate weight loss (>9.0 kg) over 20 years had a 74% greater risk of death (hazard ratio (HR) = 1.74, 95% confidence interval (CI) = 1.37-2.20) in the 5 years after the Year 20 visit than those with no weight loss and more than twice the risk of hip fracture (HR = 2.56, 95% CI = 1.39-4.70). They were 3.6 times (odds ratio (OR) = 3.60, 95% CI = 1.86-6.95) as likely to have poor physical function at the Year 20 visit as women with no weight loss but no greater risk of 2 or more falls in the 1.5 years after the Year 20 visit. Weight variability and abrupt weight decline were not associated with adverse health oucomes (falls, fractures, mortality), but those in the highest quartile of variability were 2.3 times (OR = 2.26, 95% CI = 1.34-3.80) as likely to have poor physical function scores. CONCLUSION: In women surviving past 80 years of age, moderate weight loss over 20 years was associated with greater risk of hip fracture, poor physical function, and mortality but not of falls. Future work should separate voluntary from involuntary weight loss.

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OBJECTIVES: The association between weight change and cognition is controversial. We examined the association between 20-year weight change and cognitive function in late life. DESIGN: Cohort study. SETTING: Study of Osteoporotic Fractures (SOF). PARTICIPANTS: One thousand two hundred eighty-nine older, community-dwelling women (mean baseline age 68 (65-81) and 88 (82-102) at cognitive testing). MEASUREMENTS: Study of Osteoporotic Fractures participants had body weight measured repeatedly over 20 years (mean 8 weights). Adjudicated cognitive status was classified as normal (n = 775) or mild cognitive impairment (MCI)/dementia (n = 514) at Year 20. Logistic models were used to evaluate whether absolute weight change, rate of weight loss per year, presence of abrupt, unrecovered weight loss, and weight variability were associated with MCI or dementia. RESULTS: Women with greater rate of weight loss over 20 years had increased chance of developing MCI or dementia. In age/education/clinic-adjusted "base" models, each 0.5 kg/yr decrease resulted in 30% increased odds of MCI/dementia (OR = 1.30 [95% CI: 1.14, 1.49]). After adjustment for age, education, clinic, depression, and walking speed, there was 17% (OR = 1.17 [95% CI: 1.02, 1.35]) increased odds of MCI/dementia for each 0.5 kg/yr decrease in weight. In base models, variability in weight was significant. Each 1% average deviation from each woman's predicted weight curve was associated with 11% increased odds of MCI/dementia (OR = 1.11 [95% CI: 1.04, 1.18]). The estimate was attenuated after full adjustment (OR = 1.06 [95% CI: 0.99, 1.14]). The presence of an abrupt weight decline was not associated with MCI/dementia. CONCLUSIONS: Rate of weight loss over 20 years was associated with development of MCI or dementia in women surviving past 80 years, suggesting that nutritional status, social-environmental factors, and/or adipose tissue function and structure may affect cognitive function with aging.

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OBJECTIVE: To assess direct and indirect healthcare resource utilization and costs of privately insured US employees with ulcerative colitis (UC) from a societal perspective. RESEARCH DESIGN AND METHODS: Employees aged 18-64 with ≥ 2 UC diagnoses and no more than one diagnosis of Crohn's disease (CD) were identified from a large, de-identified, private insurance US claims database from January 1, 2005 through March 31, 2013. Patients with UC were matched 1:1 to non-IBD controls based on demographics and index date (a randomly selected UC diagnosis). All patients were required to have continuous eligibility for ≥ 1 year before (baseline period) and after (study period) the index date. Descriptive analyses compared baseline characteristics and study period outcomes. Multivariate cost analysis adjusted for baseline comorbidities. Sub-group analyses compared patients with moderate-to-severe UC with matched controls. MAIN OUTCOME MEASURES: Costs (2013 US dollars) were measured from a societal perspective, which included direct (patient and payer costs) and indirect (lost wages because of time away from work) costs. RESULTS: Patients with UC (n = 4314; mean age = 45.1 years, 63.6% male) had significantly higher baseline comorbidity rates compared with controls. In the study period, significantly more patients with UC (p < 0.0001) had higher hospitalization rates (16.9% vs 6.2%), emergency department visits (31.1% vs 22.0%), prescription drug use (95.3% vs 72.0%), and work loss (100% vs 81.4%). Patients with UC also had significantly higher adjusted total direct ($15,548 vs $4812) and indirect costs ($4125 vs $1961). Patients with moderate-to-severe UC (n = 1728) had significantly (p < 0.0001) higher hospitalization rates (26.5% vs 6.2%) and adjusted total direct ($23,085 vs $4932) and indirect costs ($5666 vs $1960). CONCLUSIONS: Patients with UC had higher resource utilization and direct and indirect costs compared with matched controls. The excess burden was greatest in patients with moderate-to-severe UC.

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The objective of the study was to assess if small- and large-for gestational age term infants have greater health care utilization during the first year of life. The sample included 28,215 singleton term infants (37-42 weeks) without major birth defects delivered from 1998 through 2007 and continuously enrolled at Kaiser Permanente Northwest for 12 months after delivery. Birth weight for gestational age was categorized into 3 levels: <10th percentile (SGA), 10-90th percentile (AGA), >90th percentile (LGA). Length of delivery hospitalization, re-hospitalizations and sick/emergency room visits were obtained from electronic records. Logistic regression models estimated associations between birth weight category and re-hospitalization. Generalized linear models estimated adjusted mean number of sick/emergency visits. Among term infants, 6.2 % were SGA and 13.9 % were LGA. Of infants born by cesarean section, SGA infants had 2.7 higher odds [95 % 1.9, 3.8] than AGA infants of staying ≥5 nights during the delivery hospitalization; of those born vaginally, SGA infants had 1.5 higher adjusted odds [95 % 1.1, 2.1] of staying ≥4 nights. LGA compared to AGA infants had higher odds of re-hospitalization within 2 weeks of delivery [OR 1.25, 95 % CI 0.99, 1.58] and of a length of stay ≥4 days during that hospitalization [OR 2.6, 95 % CI 1.3, 5.0]. The adjusted mean number of sick/emergency room visits was slightly higher in SGA (7.8) than AGA (7.5) infants (P < .05). Term infants born SGA or LGA had greater health care utilization than their counterparts, although the increase in utilization beyond the initial delivery hospitalization was small.

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BACKGROUND: Limited information is available on associations between maternal depression and anxiety and infant health care utilisation. METHODS: We analysed data from 24 263 infants born between 1998 and 2007 who themselves and their mothers were continuously enrolled for the infant's first year in Kaiser Permanente Northwest. We used maternal depression and anxiety diagnoses during pregnancy and postpartum to categorise infants into two depression and anxiety groups and examined effect modification by timing of diagnosis (pregnancy only, postpartum only, pregnancy and postpartum). Using generalised estimating equations in multivariable log-linear regression, we estimated adjusted risk ratios (RR) between maternal depression and anxiety and well baby visits (<5 and ≥ 5), up to date immunisations (yes/no), sick/emergency visits (<6 and ≥ 6) and infant hospitalisation (any/none). RESULTS: Infants of mothers with perinatal depression or anxiety were as likely to attend well baby visits and receive immunisations as their counterparts (RR = 1.0 for all). Compared with no depression or anxiety, infants of mothers with prenatal and postpartum depression or anxiety, or postpartum depression or anxiety only were 1.1 to 1.2 times more likely to have ≥ 6 sick/emergency visits. Infants of mothers with postpartum depression only had marginally increased risk of hospitalisation (RR = 1.2 [95% confidence interval 1.0, 1.4]); 70% of diagnoses occurred after the infant's hospitalisation. CONCLUSIONS: An understanding of the temporality of the associations between maternal depression and anxiety and infant acute care is needed and will guide strategies to decrease maternal mental illness and improve infant care for this population.

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BACKGROUND: 25-Hydroxyvitamin D [25(OH)D] levels are lower in obese individuals. Determining whether low vitamin D status can predispose weight gain requires a longitudinal study. METHODS: From a community-based multicenter U.S. prospective cohort of 9704 (Study of Osteoporotic Fractures [SOF]), 4659 women aged ≥65 with baseline 25(OH)D measurement were followed for 4.5 years. They were weighed at baseline and follow-up visits, and a subset (n=1054) had 25(OH)D levels remeasured at follow-up. RESULTS: Women with 25(OH)D levels ≥30 ng/mL had lower baseline weight (141.6 pounds) compared to women with 25(OH)D levels <30 ng/mL (148.6 pounds) (p<0.001). Overall, 25(OH)D status was not associated with weight change over 4.5 years, although there was a significant interaction between 25(OH)D status and weight change category (loss, gain, stable) (p<0.0001). In women who gained ≥5% weight, those with baseline 25(OH)D levels ≥30 ng/mL gained 16.4 pounds (12.2% of baseline weight) over 4.5 years compared to 18.5 pounds (13.9% of baseline weight) in women with levels <30 ng/mL (p=0.04). In women who lost ≥5% weight or remained stable (<5% weight change), there was no association between 25(OH)D status at baseline and weight change. Among women who gained weight and had 25(OH)D measured at both visits, having sustained or developing 25(OH)D levels ≥30 ng/mL was associated with less weight gain between visits (14.81 vs. 16.34 pounds, p=0.04). CONCLUSIONS: Higher 25(OH)D levels are associated with lower weight gains, suggesting low vitamin D status may predispose to fat accumulation.

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OBJECTIVE: The aim of this study was to determine whether older postmenopausal women with a history of bilateral oophorectomy before natural menopause (surgical menopause) have a higher risk of nonvertebral postmenopausal fracture than women with natural menopause. METHODS: We used 21 years of prospectively collected incident fracture data from the ongoing Study of Osteoporotic Fractures, a cohort study of community-dwelling women without previous bilateral hip fracture who were 65 years or older at enrollment, to determine the risk of hip, wrist, and any nonvertebral fracture. χ(2) and t tests were used to compare the two groups on important characteristics. Multivariable Cox proportional hazards regression models stratified by baseline oral estrogen use status were used to estimate the risk of fracture. RESULTS: Baseline characteristics differed significantly among the 6,616 women within the Study of Osteoporotic Fractures who underwent either surgical (1,157) or natural (5,459) menopause, including mean age at menopause (44.3 ± 7.4 vs 48.9 ± 4.9 y, P < 0.001) and current use of oral estrogen (30.2% vs 6.5%, P < 0.001). Fracture rates were not significantly increased for surgical versus natural menopause, even among women who had never used oral estrogen (hip fracture: hazard ratio [HR], 0.87; 95% CI, 0.63-1.21; wrist fracture: HR, 1.10; 95% CI, 0.78-1.57; any nonvertebral fracture: HR, 1.11; 95% CI, 0.93-1.32). CONCLUSIONS: These data provide some reassurance that the long-term risk of nonvertebral fracture is not substantially increased for postmenopausal women who experienced premenopausal bilateral oophorectomy, compared with postmenopausal women with intact ovaries, even in the absence of postmenopausal estrogen therapy.

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OBJECTIVE: To assess health care utilization during the first year of life among early term-born infants. STUDY DESIGN: We assessed health care utilization of 22420 singleton term infants (37-42 weeks gestational age [GA]) without major birth defects, fetal growth restriction, or exposure to diabetes or hypertension in utero, delivered between 1998 and 2007 and continuously enrolled at Kaiser Permanente Northwest for 12 months after delivery. GA, duration of delivery hospitalization, and postdelivery rehospitalizations and sick/emergency room visits in the first year of life were obtained from electronic medical records. Logistic regression models were used to estimate associations between GA and number of hospitalizations and length of stay. Generalized linear models were used to estimate the adjusted mean number of sick/emergency visits. RESULTS: Overall, 20.9% of term infants were born early. Infants delivered vaginally at 37 weeks GA had a 2.2 greater odds (95% CI, 1.6-3.1) of staying 4 or more days compared with those born at 39-40 weeks GA. Similar association was found among infants delivered by cesarean delivery at 37 or 38 weeks GA. Infants born at 37 weeks GA had increased odds of being rehospitalized within 2 weeks of delivery (OR, 2.6; 95% CI, 1.9-3.6). The adjusted mean number of sick/emergency room visits was higher for infants born at 37 and 38 weeks GA than for those born at 39-40 weeks GA (8.1, 7.7, and 7.3, respectively; P < .0001). CONCLUSIONS: Early term-born infants had greater health care utilization during their entire first year of life than infants born at 39-40 weeks GA.

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BACKGROUND: Fractures have been associated with subsequent increases in mortality, but it is unknown how long that increase persists. METHODS: A total of 5580 women from a large community-based, multicenter US prospective cohort of 9704 (Study of Osteoporotic Fractures) were observed prospectively for almost 20 years. We age-matched 1116 hip fracture cases with 4 control participants (n = 4464). To examine the effect of health status, we examined a healthy older subset (n = 960) 80 years or older who attended the 10-year follow-up examination and reported good or excellent health. Incident hip fractures were adjudicated from radiology reports by study physicians. Death was confirmed by death certificates. RESULTS: Hip fracture cases had 2-fold increased mortality in the year after fracture compared with controls (16.9% vs 8.4%; multivariable adjusted odds ratio [OR], 2.4; 95% CI, 1.9-3.1]. When examined by age and health status, short-term mortality was increased in those aged 65 to 69 years (16.3% vs 3.7%; OR, 5.0; 95% CI, 2.6-9.5), 70 to 79 years (16.5% vs 8.9%; OR, 2.4; 95% CI, 1.8-3.3), and only in those 80 years or older with good or excellent health (15.1% vs 7.2%; multivariable adjusted OR, 2.8; 95% CI, 1.5-5.2). After the first year, survival of hip fracture cases and controls was similar except in those aged 65 to 69 years, who continued to have increased mortality. CONCLUSIONS: Short-term mortality is increased after hip fracture in women aged 65 to 79 years and in exceptionally healthy women 80 years or older. Women 70 years or older return to previous risk levels after a year. Interventions are needed to decrease mortality in the year after hip fracture, when mortality risk is highest.

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OBJECTIVE: To estimate risk of delivering macrosomic, large-for-gestational-age and small-for-gestational-age neonates in obese women with gestational weight gain outside the 2009 Institute of Medicine recommendation (11-20 pounds). METHODS: In a retrospective cohort study, we evaluated 2,080 obese women (body mass index 30 or higher) with singleton pregnancies that resulted in term live births within one health maintenance organization between 2000 and 2005; women with diabetes or hypertensive disorders were excluded. Gestational weight gain was categorized as less than 0, 0 to less than 11, 11-20 (referent), greater than 20-30, greater than 30-40, and greater than 40 pounds and as above, below, or within Institute of Medicine recommendations. We conducted multivariable logistic regression to estimate the odds of large for gestational age and small for gestational age (birth weights greater than the 90th percentile and less than the 10th percentile for gestational age, respectively) and macrosomia (greater than 4,500 g) adjusting for potential confounders. RESULTS: Eighteen percent gained below, 25% within, and 57% above Institute of Medicine recommendations. Prevalence of macrosomia, large for gestational age, and small for gestational age were 4.3%, 19.8%, and 4.3%, respectively. Compared with weight gain of 11-20 pounds, weight gain above recommendations did not significantly decrease small-for-gestational-age risk but was associated with increased odds of macrosomia (adjusted odds ratio [OR] 3.36; 95% confidence interval [CI] 1.74-6.51; 6.0% compared with 2.1%) and large for gestational age (adjusted OR 1.80; 95% CI 1.36-2.38; 23.8% compared with 16.6%). Weight gain below recommendations was associated with increased odds of small for gestational age (adjusted OR 3.94; 95% CI 2.04-7.61; 8.8% compared with 2.7%) and decreased odds of large for gestational age (adjusted OR 0.56; 95% CI 0.37-0.84; 11.2% compared with 16.6%). CONCLUSION: Regarding small for gestational age and large for gestational age, there is no benefit of weight gain above Institute of Medicine recommendations. Weight gain below recommendations decreases large for gestational age but increases small-for-gestational-age risk. LEVEL OF EVIDENCE: II.

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Bone mineral density (BMD) is a strong predictor of fracture, yet most fractures occur in women without osteoporosis by BMD criteria. To improve fracture risk prediction, the World Health Organization recently developed a country-specific fracture risk index of clinical risk factors (FRAX) that estimates 10-year probabilities of hip and major osteoporotic fracture. Within differing baseline BMD categories, we evaluated 6252 women aged 65 or older in the Study of Osteoporotic Fractures using FRAX 10-year probabilities of hip and major osteoporotic fracture (ie, hip, clinical spine, wrist, and humerus) compared with incidence of fractures over 10 years of follow-up. Overall ability of FRAX to predict fracture risk based on initial BMD T-score categories (normal, low bone mass, and osteoporosis) was evaluated with receiver-operating-characteristic (ROC) analyses using area under the curve (AUC). Over 10 years of follow-up, 368 women incurred a hip fracture, and 1011 a major osteoporotic fracture. Women with low bone mass represented the majority (n = 3791, 61%); they developed many hip (n = 176, 48%) and major osteoporotic fractures (n = 569, 56%). Among women with normal and low bone mass, FRAX (including BMD) was an overall better predictor of hip fracture risk (AUC = 0.78 and 0.70, respectively) than major osteoporotic fractures (AUC = 0.64 and 0.62). Simpler models (eg, age + prior fracture) had similar AUCs to FRAX, including among women for whom primary prevention is sought (no prior fracture or osteoporosis by BMD). The FRAX and simpler models predict 10-year risk of incident hip and major osteoporotic fractures in older US women with normal or low bone mass.

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OBJECTIVE: To evaluate the incremental effect of weight gain above that recommended for term pregnancy (15 pounds) on postpartum weight retention at 1 year among obese women. METHODS: In a retrospective cohort study, we identified 1,656 singleton gestations resulting in live births among obese women (body mass index at or above 30 kg/m) between January 2000 and December 2005 in Kaiser Permanente Northwest. Pregnancy weight change (last available predelivery weight minus weight at pregnancy onset) was categorized as less than 0, 0-15, greater than 15 to 25, greater than 25 to 35, and greater than 35 pounds. Postpartum weight change (weight at 1 year postpartum minus weight at pregnancy onset) was defined as less than 0, 0-10, and greater than 10 pounds. RESULTS: Total gestational weight gain was -33.2 (weight loss) to +98.0 pounds (weight gain). Nearly three fourths gained greater than 15 pounds, and they were younger and weighed less at baseline than women who gained 15 pounds or less. Pregnancy-related weight change showed a significant relationship with postpartum weight change. For each pound gained during pregnancy, there was a 0.4-pound increase above baseline weight at 1 year postpartum. In adjusted logistic regression models, the risk of a postpartum weight greater than 10 pounds over baseline was twofold higher for women gaining greater than 15 to 25 pounds compared with women gaining 0-15 pounds (odds ratio [OR] 2.18, 95% confidence interval [CI] 1.54-3.10), fourfold higher for women gaining greater than 25 to 35 pounds (OR 3.91, 95% CI 2.75-5.56), and almost eightfold higher for women gaining greater than 35 pounds (OR 7.66, 95% CI 5.36-10.97). CONCLUSION: Incremental increases in gestational weight gain beyond the current recommendation for obese women substantially increase the risk of weight retention at 1 year postpartum. LEVEL OF EVIDENCE: II.

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BACKGROUND: Whether repeat bone mineral density (BMD) measurement adds benefit beyond the initial BMD measurement in predicting fractures in older women is unknown. METHODS: We prospectively measured total hip BMD in 4124 older women (mean +/- SD age, 72 +/- 4 years) from 1989 to 1990 and again 8 years later. Incident nontraumatic hip and nonspine fractures were validated by radiology reports (>95% follow-up). In addition, spine fractures were defined morphometrically in 2129 of these women by lateral spine x-ray films from 1991 to 1992 and then again 11.4 years later. Prediction of fracture risk was assessed with proportional hazards models and receiver operating characteristic curves for BMD measures. RESULTS: Over a mean of 5 years after the repeat BMD measure, 877 women experienced an incident nontraumatic nonspine fracture (275 hip fractures). In addition, 340 women developed a spine fracture. After adjustment for age and weight change, initial and repeat BMD measurements were similarly associated with fracture risk (per unit standard deviation lower in BMD) for nonspine (hazard ratio, 1.6), spine (odds ratio, 1.8-1.9), and hip (hazard ratio, 2.0-2.2) fractures (P<.001 for all models). Areas under the receiver operating characteristic curves (AUC) revealed no significant differences to discriminate nonspine (AUC, 0.65), spine (AUC, 0.67-0.68), or hip (AUC, 0.73-0.74) fractures between models with initial BMD, repeat BMD, or initial BMD plus change in BMD. Stratification by initial BMD t scores (normal, osteopenic, or osteoporotic), high bone loss, or hormone therapy did not alter results. CONCLUSION: In healthy, older, postmenopausal women, repeating a measurement of BMD up to 8 years later provides little additional value besides the initial BMD measurement for predicting incident fractures.

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Whether nulliparity increases fracture risk is unclear from prior studies, which are limited by small samples or lack of measured bone mineral density. No study has evaluated whether the effect of parity differs by skeletal site. We prospectively analyzed the relationship of parity to the risk of incident nontraumatic hip, spine, and wrist fractures in 9704 women aged 65 years or older participating in the Study of Osteoporotic Fractures to determine if parity reduces postmenopausal fracture risk, and if so, if this risk reduction is (1) greater at weight-bearing skeletal sites and (2) independent of bone mineral density. Parity was ascertained by self-report. Incident hip and wrist fractures were determined by physician adjudication of radiology reports (mean follow-up, 9.8 years) and spine fractures by morphometric criteria on serial radiographs. The relationship of parity to hip and wrist fracture was assessed by proportional hazards models. Spine fracture risk was evaluated by logistic regression. Compared with parous women, nulliparous women (n = 1835, 19%) had an increased risk of hip and spine, but not wrist, fractures. In multivariate models, parity remained a significant predictor only for hip fracture. Nulliparous women had a 44% increased risk of hip fractures independent of hip bone mineral density (hazards ratio, 1.44; 95% CI, 1.17-1.78). Among parous women, each additional birth reduced hip fracture risk by 9% (p = 0.03). Additionally, there were no differences in mean total hip, spine, or radial bone mineral density values between nulliparous and parous women after multivariate adjustment. In conclusion, childbearing reduces hip fracture risk by means that may be independent of hip bone mineral density.

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BACKGROUND: Previous studies demonstrate that postmenopausal women who use estrogen are somewhat protected from bone loss and fractures compared with nonusers, but the extent to which estrogen users remain at risk for osteoporosis and fractures is uncertain. OBJECTIVE: To determine long-term probabilities for incident fractures among postmenopausal estrogen users. METHODS: We examined data from the Study of Osteoporotic Fractures, a prospective cohort study with 10 years of follow-up (1986-1999). This cohort includes 8816 women 65 years and older from community settings in 4 areas of the United States. MAIN OUTCOME MEASURES: Hip, wrist, vertebral, and nonvertebral fractures. RESULTS: At baseline, using criteria developed by the World Health Organization, 40% of continuous estrogen users were osteopenic and 13% were osteoporotic at the hip or spine. Although women currently using estrogen lost less bone density than past users or those who never used estrogen, all user groups on average lost bone from the hip and calcaneus. During 10 years of observation, the adjusted probability of nonvertebral fractures was 19.6% for continuous estrogen users, similar to current partial users and lower than past users and those who never used estrogen (P<.05). These comparisons were similar for hip, wrist, and vertebral fractures. CONCLUSIONS: Although estrogen use is associated with reduced prevalence of low bone density, less bone loss, and lower probabilities for fractures, osteoporosis and fractures are common in older women who used estrogen continuously since menopause. Estrogen users should be considered in strategies designed to detect, prevent, and treat osteoporosis.

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