Steven R. Cummings, M.D., Michael C. Nevitt, Ph.D., Warren S. Browner, M.D., M.P.H., Katie Stone, M.A., Kathleen M. Fox, Ph.D., Kristine E. Ensrud, M.D., M.P.H., Jane Cauley, Dr.P.H., Dennis Black, Ph.D., Thomas M. Vogt, M.D., M.P.H., for The Study of Osteoporotic Fractures Research Group
Background Many risk factors for hip fractures have been suggestedbut have not been evaluated in a comprehensive prospective study.
Methods We assessed potential risk factors, including bone mass,in 9516 white women 65 years of age or older who had had noprevious hip fracture. We then followed these women at 4-monthintervals for an average of 4.1 years to determine the frequencyof hip fracture. All reports of hip fractures were validatedby review of x-ray films.
Results During the follow-up period, 192 women had first hipfractures not due to motor vehicle accidents. In multivariableage-adjusted analyses, a maternal history of hip fracture doubledthe risk of hip fracture (relative risk, 2.0; 95 percent confidenceinterval, 1.4 to 2.9), and the increase in risk remained significantafter adjustment for bone density. Women who had gained weightsince the age of 25 had a lower risk. The risk was higher amongwomen who had previous fractures of any type after the age of50, were tall at the age of 25, rated their own health as fairor poor, had previous hyperthyroidism, had been treated withlong-acting benzodiazepines or anticonvulsant drugs, ingestedgreater amounts of caffeine, or spent four hours a day or lesson their feet. Examination findings associated with an increasedrisk included the inability to rise from a chair without usingone's arms, poor depth perception, poor contrast sensitivity,and tachycardia at rest. Low calcaneal bone density was alsoan independent risk factor. The incidence of hip fracture rangedfrom 1.1 (95 percent confidence interval, 0.5 to 1.6) per 1000woman-years among women with no more than two risk factors andnormal calcaneal bone density for their age to 27 (95 percentconfidence interval, 20 to 34) per 1000 woman-years among thosewith five or more risk factors and bone density in the lowestthird for their age.
Conclusions Women with multiple risk factors and low bone densityhave an especially high risk of hip fracture. Maintaining bodyweight, walking for exercise, avoiding long-acting benzodiazepines,minimizing caffeine intake, and treating impaired visual functionare among the steps that may decrease the risk.
One of every six white women will have a hip fracture duringher lifetime.1 Many potential risk factors for hip fracture,such as lower body weight, cigarette smoking, caffeine intake,use of long-acting sedatives, and inactivity, have been identifiedin casecontrol2,3,4 and prospective5,6,7,8 studies. However,the findings of casecontrol studies might be affectedby selection and recall biases, and most previous prospectivestudies have examined only a small number of the many risk factorsfor hip fracture. To identify important risk factors, we assembleda cohort of older women, identified many potential risk factors,measured bone mass, and followed the women for hip fractures.
Methods
Subjects
From 1986 to 1988, we recruited women who were able to walkand who were at least 65 years of age in Portland, Oregon; Minneapolis;Baltimore; and the Monongahela Valley, Pennsylvania, throughmailings to women on lists such as voter-registration lists.9The study group consisted of 9516 white women; black women (becauseof their low incidence of hip fractures) and white women whohad undergone bilateral hip replacement or had an earlier hipfracture were excluded. The study was approved by the appropriatecommittees on human research, and all the women provided writteninformed consent.
Assessment of Risk Factors
Questionnaire and Interview
The women were questioned and examined in outpatient clinics.We ascertained their numbers of years of education, naturalhair color as young adults, height and nonpregnant weight atthe age of 25, ethnic origin, numbers of pregnancies and ofchildren who were breast-fed, ages at the last menstrual period,parental history of fractures, falls during the previous year,smoking habits and alcohol intake, and self-rated health. Weasked about physician-diagnosed fractures since the age of 50,osteoporosis, spine fracture, hyperthyroidism, osteoarthritis,gastric surgery, hysterectomy, oophorectomy, cataracts, andstroke. The women were also asked about current therapy andtherapy during the previous year with estrogen, diuretics, corticosteroids,thyroid hormones, anticonvulsant agents, antacids, sleepingaids, and anxiolytic drugs. Long-acting benzodiazepines weredefined as those with half-lives of at least 24 hours.10
The amount of dietary calcium was assessed by a food-frequencyquestionnaire,11 and caffeine intake was estimated.12 We alsoasked about walking; exercise13; the number of hours spent sittingand lying down per day; and the amount of difficulty experiencedin walking, climbing and descending stairs, preparing meals,shopping, and doing housework.14
Examinations
We measured weight, height (by stadiometer), waist and hip circumferences,and knee height.15 Body-mass index (the weight in kilogramsdivided by the square of the height in meters) was calculatedwith knee height substituted for total height. Tests of neuromuscularfunction included whether the subject could rise up from a chair(without using her arms) five times; the number of step-upsshe completed in 10 seconds; the strength of her grip, triceps,knee extensions, and hip abduction (measured with a hand-heldisometric dynamometer)16; her walking speed (over a 6-m course);and her ability to walk and stand in a tandem position withher eyes open and closed. We assessed cognitive function witha modified version of the MiniMental State Examination.17,18We measured corrected visual acuity19 and contrast sensitivity20(separately averaging the scores for low and high spatial frequencies).We assessed depth perception using the HowardDohlmandevice21 and scored it as the standard deviation of four trials.Blood pressure and pulse were measured with the subject supineand after she had been standing for one minute22; orthostatichypotension was defined as a drop in systolic blood pressureof 20 mm Hg or more on standing.
We measured calcaneal bone mineral density, a measurement mainlyof weight-bearing trabecular bone and a strong predictor ofhip fractures,23 using single-photon absorptiometry (OsteoAnalyzer,SiemensOsteon, Wahiawa, Hawaii). During a second examination,conducted between 1988 and 1990, we measured the bone densityof the proximal femur, using dual x-ray absorptiometry (QDR1000, Hologic, Waltham, Mass.) in 7786 women (82 percent ofthe survivors at that time).24 To determine the mean coefficientof variation for these measurements, a few staff members weremeasured at the four clinical centers, and the mean coefficientof variation was found to be 1.2 percent for both the calcaneusand femoral neck.24
Ascertainment of Hip Fractures
We contacted the women about fractures by postcard or telephoneevery four months and were able to complete 99 percent of thesecontacts. We confirmed all hip fractures by reviewing radiographs.25
Statistical Analysis
We used proportional-hazards analysis to identify potentialpredictors of hip fracture and best subset analysis26 and backwardstepwise analysis to identify independent risk factors. We foundno interactions between risk factors and clinical centers. Unlessspecified, correlations between variables in multivariable modelswere less than 0.5. We report age-adjusted relative hazardsas relative risks with 95 percent confidence intervals. Analyseswere performed with the use of Statistical Analysis Software(SAS, Cary, N.C.).
We also explored whether the effects of certain risk factorscould be explained by their effect on bone density at the hip,limiting the analyses to those variables maternal historyof hip fracture, height at age 25, and history of hyperthyroidism that were unlikely to change from base line to the measurementof hip bone density.
Results
Characteristics of the 9516 subjects are shown in Table 1. Duringan average 4.1 years of follow-up, 192 women had first hip fracturesnot due to motor vehicle accidents, 565 died, and 92 were lostto follow-up. In multivariable analyses, we identified 16 independentrisk factors for hip fracture (Table 2) besides bone density.A woman whose mother had had a hip fracture had twice the riskof hip fracture of women without such a maternal history, especiallyif her mother fractured her hip before the age of 80 (relativerisk, 2.7; 95 percent confidence interval, 1.7 to 4.4) ratherthan at 80 or later (relative risk, 1.6; 95 percent confidenceinterval, 1.0 to 2.7).
Table 2. Multivariable Models of Risk Factors for Hip Fracture with and without Adjustment for Fractures and Calcaneal Bone Density among 9516 White Women.
The more weight a woman had gained since the age of 25, thelower her risk of hip fracture (Figure 1). The women who weighedless than they had at 25 had a doubled risk of hip fracture(relative risk, 2.2; 95 percent confidence interval, 1.6 to3.0). Women who were tall at the age of 25 also had a greaterrisk.
Figure 1. Association between the Change in Body Weight after the Age of 25 and the Risk of Hip Fracture.
The rate of hip fracture is adjusted for age. The T bars denote the upper 95 percent confidence limits.
Poorer self-rated health, a history of hyperthyroidism, andtherapy with long-acting benzodiazepines or anticonvulsant drugsindependently increased the risk of hip fracture. None of theseven hip fractures among women taking anticonvulsant drugsresulted from seizures or loss of consciousness. As caffeineintake increased, so did the risk of hip fracture. Women whospent four hours per day or less on their feet had twice therisk of women who spent more than four hours per day on theirfeet, whereas women who regularly walked for exercise had a30 percent lower risk of hip fracture than women who did notwalk regularly. Risk tended to decrease as the distance walkedper day increased (relative risk, 0.9 per five blocks walkedper day; 95 percent confidence interval, 0.8 to 1.0).
Four characteristics observed in the physical examination indicatedan increased risk of hip fracture: the inability to rise froma chair without using one's arms, a faster resting pulse rate,poorer depth perception, and poorer low-frequency contrast sensitivity.
Bone Density and History of Fracture
Lower calcaneal bone density and a history of any type of fracturesince the age of 50 independently increased the risk of hipfracture (Table 2). Wrist fractures (relative risk, 1.9; 95percent confidence interval, 1.4 to 2.7), self-reported spinefractures (relative risk, 1.9; 95 percent confidence interval,1.2 to 2.9), and all other types of fractures (relative risk,1.5; 95 percent confidence interval, 1.0 to 2.1) were all associatedwith an increased risk of hip fracture.
All risk factors remained significantly associated with therisk of hip fracture after bone density was added to the multivariablemodel. Therapy with anticonvulsant drugs was no longer a significantfactor after a history of fractures was also added (Table 2).
Adjustment for Femoral-Neck Bone Density
In analyses limited to the 7786 women in whom the bone densityof the hip had been measured, 83 of whom later had hip fractures,a history of maternal hip fracture was significantly associatedwith an increased risk of hip fracture before (relative risk,2.0; 95 percent confidence interval, 1.2 to 3.6) and after (relativerisk, 1.9; 95 percent confidence interval, 1.1 to 3.2) adjustmentfor femoral-neck bone density. Similarly, adjustment for femoral-neckbone density did not affect the significant associations betweenheight at the age of 25 or previous hyperthyroidism and therisk of hip fracture.
Number of Risk Factors, Bone Density, and Prediction of Hip Fracture
Fifteen percent of the women had five or more of the risk factorslisted in Table 2 (including older age and previous fracture,but not low bone density); their incidence of hip fracture was19 (95 percent confidence interval, 15 to 22) per 1000 woman-years(Figure 2). By comparison, the 47 percent of women who had twoor fewer risk factors had an incidence of only 1.1 (95 percentconfidence interval, 0.5 to 1.6) per 1000 woman-years. The 6percent of women who had five or more risk factors and calcanealbone density in the lowest third for their age had an incidenceof hip fracture of 27 (95 percent confidence interval, 20 to34) per 1000 woman-years and had 62 (32 percent) of the hipfractures reported.
Figure 2. Annual Risk of Hip Fracture According to the Number of Risk Factors and the Age-Specific Calcaneal Bone Density.
The risk factors (from Table 2) are as follows: age 80; maternal history of hip fracture; any fracture (except hip fracture) since the age of 50; fair, poor, or very poor health; previous hyperthyroidism; anticonvulsant therapy; current long-acting benzodiazepine therapy; current weight less than at the age of 25; height at the age of 25 168 cm; caffeine intake more than the equivalent of two cups of coffee per day; on feet 4 hours a day; no walking for exercise; inability to rise from chair without using arms; lowest quartile (standard deviation >2.44) of depth perception; lowest quartile (0.70 unit) of contrast sensitivity; and pulse rate>80 per minute.
Factors Not Significant after Multivariate Adjustment
For a number of factors that were initially associated withthe risk of hip fracture in age-adjusted models, these associationswere diminished and no longer statistically significant afteradjustment for other variables (Table 3). For example, currentsmokers had about twice as high a risk of hip fracture as nonsmokersor former smokers. The smokers had gained less (or lost more)weight, had poorer health, had more difficulty rising from achair, spent fewer hours on their feet, were less likely towalk for exercise, and had faster heart rates. Adjusting forthese effects explained most of the association between smokingand hip fracture.
Table 3. Predictors Significantly Associated with Hip Fractures in Age-Adjusted Models but Not in Multivariable Models.
Alcohol ingestion was associated with a lower risk of hip fracture(Table 3). The risk was somewhat lower among those who drankseven or fewer drinks per week (relative risk as compared withnondrinkers, 0.7; 95 percent confidence interval, 0.5 to 0.9)than among those who drank more (relative risk, 0.9; 95 percentconfidence interval, 0.5 to 1.4). However, alcohol intake wasno longer significantly associated with a lower risk of hipfracture after adjustment for the better self-reported healthand ability to stand up from a chair among those who drank alcohol.27
Current thyroid-hormone therapy was no longer significantlyassociated with the risk of hip fracture after adjustment fora history of hyperthyroidism, which was reported by 36 percentof those taking thyroid hormone.
Greater weight, body-mass index, and modified body-mass indexwere all associated with a decreased risk of hip fracture, butnot quite as strongly as was the percentage of weight changesince the age of 25. Neither current weight nor modified body-massindex remained significantly associated with the risk of hipfracture after adjustment for weight gain. However, the percentageof weight change was correlated with current weight (r = 0.75)and body-mass index (r = 0.76).
A history of falling indicated an increased risk of hip fracture(Table 3); the risk increased 30 percent with each additionalfall (relative risk, 1.30 per fall from 0 to > 5; 95 percentconfidence interval, 1.1 to 1.5). After adjustment for the inabilityto rise from a chair, spending four hours or less on one's feet,and poor health, however, a history of falling and the numberof falls were no longer significantly associated with hip fracture.
Poor performance on almost every test of neuromuscular function,such as gait speed, was associated with an increased risk ofhip fracture. When the models included the inability to risefrom a chair without using one's arms, no other measurementof neuromuscular function remained significantly associatedwith the risk of hip fracture.
The risk decreased with increasing numbers of births (relativerisk, 0.9 per birth; 95 percent confidence interval, 0.8 to1.0). This association was not quite statistically significantafter adjustment for weight change since the age of 25.
Factors Not Significantly Associated with the Risk of Hip Fracture
Factors that were not significantly associated with the riskof hip fracture included hair color, ethnic ancestry, whetherthere was a maternal history of fractures other than hip fracture,the number of children breast-fed, the timing of menopause,past smoking status, whether the subject had cataracts, andwhether she had used short-acting benzodiazepines (Table 4).
Table 4. Factors Not Significantly Associated with Hip Fracture in Age-Adjusted Models.
Dietary calcium intake was not related to the risk of hip fracture.There was no increased risk among the 11 percent of women whoingested 400 mg of calcium or less per day (relative risk, 1.1;95 percent confidence interval, 0.5 to 2.3), even when womentaking calcium supplements or estrogen were excluded.
Estrogen is often prescribed for osteoporosis, a fact that couldlead to an underestimation in observational studies of the effectivenessof estrogen to prevent hip fracture. To minimize this bias,we analyzed the effect of estrogen in women with no previousdiagnosis of osteoporosis or fracture. In this group, estrogentherapy appeared to have a strong protective effect (Table 4),but the confidence limits were wide.
Diabetes mellitus was not associated with a significantly increasedrisk (relative risk, 1.3; 95 percent confidence interval, 0.8to 2.1). After adjustment for obesity, there was a trend towardan increased risk of hip fracture in diabetic women not takinginsulin (relative risk, 1.6; 95 percent confidence interval,0.9 to 2.7). There was also a trend toward an increased riskof hip fracture among those with a history of gastric surgery(relative risk, 2.0), Parkinson's disease (relative risk, 1.6),and previous stroke (relative risk, 1.6), but these conditionswere uncommon and the lower 95 percent confidence limit wasless than 1.0 in each instance.
Discussion
We found that many factors influence the risk of hip fracturein older women and that the assessment of risk factors and themeasurement of bone density have complementary value for theprediction of hip fracture. A small number of women with multiplerisk factors and low bone density have an especially high risk.They account for a large proportion of hip fractures and shouldbe the focus of intensive efforts to prevent them.
A woman whose mother had a hip fracture, especially before theage of 80, is at least twice as likely to have a hip fractureherself as a woman without such a maternal history. Other typesof maternal fractures did not increase hip-fracture risk, andthe risk was independent of bone mass, height, and weight. Inheritedcharacteristics of the proximal femur besides density, or perhapsa propensity to fall on the hip, may account for this familialpredisposition.
Many of the other risk factors are also believed to act by reducingbone mass. However, adjustment for calcaneal bone density didnot substantially affect the risk of hip fracture associatedwith caffeine intake, a change in weight, walking for exercise,anticonvulsant drug therapy, or a history of fracture. Thesefactors may affect the risk of hip fracture in other ways, perhapsby influencing characteristics of bone other than density orby affecting the risk of falling.
Gaining weight reduces a woman's risk of hip fracture, and losingweight increases it. Previous studies have found that heavierwomen have a lower risk of hip fracture.4,5,7 Weight loss mayalso be a marker for an underlying illness that increases risk.The high degree of correlation between weight change, currentweight, and obesity limits our ability to determine whetherthe risk of hip fracture is affected more by previous changeor by current weight.
We confirmed that women who were tall when they were young havea greater risk of hip fracture,8 perhaps because they fall farther.28,29Taller women also have a longer hip-axis length (the distancefrom the greater trochanter to the inner pelvic brim), whichhas been associated with a greater risk of hip fracture.30
Hyperthyroidism may or may not reduce bone mass.12,31,32,33,34In our study, reduced bone mass did not account for the strongassociation between previous hyperthyroidism and the risk ofhip fracture. Hyperthyroidism may cause long-lasting impairmentsof bone strength not detected by densitometry, or impairmentsof neuromuscular function not detected by our examinations.It can also reduce muscle strength. The association betweenresting tachycardia and hip fracture may be due to undiagnosedhyperthyroidism, although a faster pulse may also indicate decreasedphysical fitness or impaired cardiac function.
Our finding that caffeine consumption increases the risk ofhip fracture agrees with the findings of two previous studies.6,35Although a high caffeine intake has also been associated withreduced bone mass,12,36,37 our results suggest that caffeinemay influence the risk of hip fracture in other ways.
Women who spent four hours or less per day on their feet hada substantially increased risk of hip fracture, whereas walkingfor exercise reduced the risk. Exercise may be a marker forhealth and functional status, but the association between activityand hip-fracture risk remained significant after adjustmentfor self-rated health and findings on tests of neuromuscularfunction.
We confirmed that therapy with long-acting benzodiazepines increasesthe risk of hip fracture4,10; older women should avoid thesedrugs. We also confirmed that women taking anticonvulsant drugshave a very high risk of hip fracture,38 although none of thesewomen had a hip fracture during a seizure. We previously foundno association between the use of anticonvulsant drugs and lowerappendicular bone mass in this cohort,12 suggesting that theincreased risk might be due to impairments of neuromuscularfunction we did not measure.
The inability to rise from a chair without using one's armsis associated with an increased risk of falls39 and a twofoldincrease in the risk of hip fracture. None of the other assessmentsof neuromuscular function added significantly to the predictionof subsequent hip fracture.
Poor depth perception and a reduced ability to perceive contrast(but not poor visual acuity) increased the risk of hip fractureindependently. This suggests that treatment or prevention ofophthalmologic conditions that impair depth perception and contrastsensitivity, such as cataracts, diabetic retinopathy, and glaucoma,may help prevent hip fracture.
Women who have had wrist fractures have a greater risk of hipfractures than those who have not had wrist fractures.40,41Our results indicate that any type of postmenopausal fracturesignals an increased risk of hip fracture. This increased riskis independent of bone mass, implying that a history of fracturesmay indicate an increased risk of falling or defects in bonestrength not detected by densitometry.
Our analysis suggests that smoking increases the risk of hipfracture by limiting normal weight gain and by its adverse effectson the health, neuromuscular fitness, and exercise patternsof older women.27 The lower risk for former smokers impliesthat quitting smoking diminishes the risk of hip fracture.
Although consistent with the view that current estrogen therapyprotects against hip fracture,42 these results are limited bythe small number of women in our study who were taking estrogen.Another analysis of estrogen therapy and fractures in this cohorthas confirmed that estrogen therapy protects against osteoporoticfractures.43 Our analysis illustrates the point that observationalstudies will underestimate the effectiveness of estrogen ifthey do not account for the fact that many women take estrogenfor osteoporosis. Our study may underestimate the benefit inthose with osteoporosis to the degree that estrogen is takenby women with more severe osteoporosis.
The results of this study do not support widely held beliefsthat fair hair color, northern European ancestry, earlier naturalmenopause, and antacid therapy are associated with an increasedrisk of hip fracture. In contrast to other investigators,44,45we found that moderate alcohol intake did not increase the riskof hip fracture. Although breast-feeding temporarily decreasesbone mass,46 it did not increase the risk of hip fracture. Likemost3,5,7 but not all47 prospective observational studies, oursfound no relation between calcium intake and protection fromhip fracture, even in women with very low intakes. However,we assessed calcium intake only once with a short questionnaire;repeated assessments may be more accurate.
This study had several limitations. The participants were community-dwellingwhite women over the age of 65, so these findings are not generalizableto men, younger women, nursing home residents, or possibly womenof other races.48 The study had limited power to evaluate riskfactors that are relatively uncommon, such as Parkinson's disease.Other risk factors, such as osteoarthritis and calcium intake,were based only on the women's own reports. Measurement of hipinstead of calcaneal bone density may improve the predictionof hip fracture. In addition, some of the risk factors thatare independent of calcaneal bone density may not be independentof hip bone density. Predictive models derived in one groupmay not perform as well in other groups; ideally, our findingsshould be tested prospectively in other populations.
We conclude that many factors increase the risk of hip fracturein older white women living in the community. The effect ofmost individual factors is moderate, but together their impactis substantial. Women with multiple risk factors and low bonedensity are at especially high risk. A woman may be able tominimize her risk of hip fracture in a number of ways, notablyby walking for exercise, avoiding long-acting sedativehypnoticagents, reducing caffeine intake, quitting smoking, treatingimpaired vision, and taking measures that maintain bone density.
Supported by grants (1-RO1-AG05407, 1-RO1-AR35582, 5-RO1-AG05394,1-RO1-AM35584, and 1-RO1-AR35583) from the Public Health Service.
We are indebted to Stephen B. Hulley and Jennifer Kelsey fortheir support in the development of this study.
* The members of the Study of Osteoporotic Fractures ResearchGroup are listed in the Appendix.
Source Information
From the Division of General Internal Medicine (S.R.C., W.S.B.) and the Department of Epidemiology and Biostatistics (S.R.C., M.C.N., W.S.B., K.S., D.B.), University of California, San Francisco; the Department of Epidemiology and Preventive Medicine, University of Maryland, Baltimore (K.M.F.); the Division of Epidemiology, School of Public Health, University of Minnesota, Minneapolis (K.E.E.); the Department of Epidemiology, University of Pittsburgh, Pittsburgh (J.C.); and the Kaiser Permanente Center for Health Research, Portland, Oreg. (T.M.V.).
Address reprint requests to Dr. Cummings at the Prevention Sciences Group, 74 New Montgomery St., Suite 600, San Francisco, CA 94105.
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Appendix
The following investigators were members of the Study of OsteoporoticFractures Research group: University of California, San Francisco(Coordinating Center): S.R. Cummings (principal investigator),M.C. Nevitt (project director), D. Black (study statistician),H.K. Genant (director, central radiology laboratory), C. Arnaud,W. Browner, L. Christianson, M. Dockrell, C. Fox, C. Glüer,S. Harvey, M. Jergas, L. Palermo, A. Pressman, R. San Valentin,d. Seeley, P. Steiger, and K. Stone; University of Maryland,Baltimore: R. Sherwin (principal investigator), J. Scott (co-investigator),K. Fox (co-investigator), J. Lewis (project coordinator), G.Greenberg (clinic coordinator), M. Bahr, S. Trusty, L. Finazzo,S. Snyder, E. Oliner, B. Hohman, and T. Page; University ofMinnesota, Minneapolis: K. Ensrud (principal investigator),R. Grimm, Jr. (co-investigator), C. Bell (project director),E. Mitson (study coordinator), I. Chavier, K. Jacobson, S. Fillhouer,C. Shoberg, D. Michel, S. Estill, J. Hansen, and M. Baumhover;University of Pittsburgh, Pittsburgh: J.A. Cauley (principalinvestigator), L.H. Kuller (coprincipal investigator),L. Harper (project director), M. Nasim (clinic coordinator),C. Bashada, L. Buck, A. Githens, A. McCune, D. Medve, S. Rudovsky,and N. Watson; Kaiser Permanente Center for Health Research,Portland, Oreg.: T.M. Vogt (principal investigator), W.M. Vollmerand E. Orwoll (co-investigators), J. Blank (project director),F. Heinith (clinic coordinator), R. Bright, J. Downing, B. Packer,C. Souvanlausky, L. Puderbauth, and D. Franco.
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