calcium, vitamin d supplementation, and physical function in the women's health initiative

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alcium, Vitamin D Supplementation, andhysical Function in the Women’s Healthnitiative

OBERT L. BRUNNER, PhD; BARBARA COCHRANE, PhD, RN; REBECCA D. JACKSON, MD; JOSEPH LARSON, MS;ORA LEWIS, MD, MSPH; MARIAN LIMACHER, MD; MILAGROS ROSAL, PhD; SALLY SHUMAKER, PhD; ROBERT WALLACE, MD; FOR THE
OMEN’S HEALTH INITIATIVE INVESTIGATORS
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BSTRACTbjectives The Women’s Health Initiative (WHI) random-zed trial of calcium/vitamin D supplementation foundeduced bone loss with active treatment compared tolacebo. Now we examine whether the treatment affectedelf-reported physical functioning and objective measuresf physical functioning.esign A randomized, double-blind, placebo-controlledrial of 1,000 mg calcium carbonate plus 400 IU vitamin3 per day or matching placebo pills.

. L. Brunner is an associate professor, University ofevada School of Medicine, Reno. B. Cochrane is anssociate professor, University of Washington School ofursing, Seattle. J. Larson is a statistical research asso-

iate, Fred Hutchinson Cancer Research Center, Seattle,A. R. D. Jackson is a professor, The Ohio State Uni-

ersity Medical Center, Columbus. C. Lewis is a profes-or, Division of Preventive Medicine, The University oflabama at Birmingham. M. Limacher is a professor,epartment of Cardiology, University of Florida Collegef Medicine, Gainesville. M. Rosal is an associate profes-or, Preventive and Behavioral Medicine, University ofassachusetts Medical School, Worcester. S. Shumaker

s a professor, Department of Public Health Sciences,ake Forest University School of Medicine, Winston-alem, NC. R. Wallace is a professor, Department of Ep-

demiology, University of Iowa, Iowa City.Address correspondence to: Robert Brunner, PhD,niversity of Nevada School of Medicine, PMB 251, MS45, Reno, NV 89557. E-mail: [email protected] accepted: March 25, 2008.Copyright © 2008 by the American Dietetic

ssociation.0002-8223/08/10809-0006$34.00/0

fdoi: 10.1016/j.jada.2008.06.432

472 Journal of the AMERICAN DIETETIC ASSOCIATION

ubjects/setting The study included 33,067 women (50 to 79ears old) at 40 US study centers.ain outcome measures Physical functioning was assessedy questionnaire at enrollment in WHI, 1 year prior toalcium/vitamin D trial randomization and at studylose-out (average follow-up 7.1 years). Objective physicalerformance and self-reported exercise measures wereollected at WHI baseline (1 year prior to calcium/vitamin enrollment) and 2 years and 4 years after calcium/itamin D trial enrollment in a subsample (n�3,137).tatistical analyses performed Calcium/vitamin D effectsere tested in unadjusted and interaction linear models

or each of the physical function measures. Covariatesere baseline total calcium intake, fracture risk score,

reatment arm in the hormone therapy and dietary mod-fication trials (ie, active drug or placebo, low-fat dietntervention or usual diet, respectively) and age.esults Neither intention to treat nor high adherencenalyses produced substantial effects of calcium/vitamin compared to placebo on physical functioning or perfor-ance. The interaction analyses also did not result in

ifferences because of calcium/vitamin D.onclusions As the first long-term randomized trial to ex-mine the effectiveness of calcium and vitamin D in pro-ecting against decline of physical functioning in olderomen, the results did not support benefit. Am Diet Assoc. 2008;108:1472-1479.

he importance of preserving physical functioningand independence continues to grow in public healthbecause the average lifespan of the US population

as increased and the percentage of the population inlder age categories is growing rapidly (1). Aging is asso-iated with a number of physiological and functionalhanges that can contribute to increased disability,railty, falls, and fractures, thus lowering quality of life2,3). One of the factors that has a strong influence on
unctional capacity is dietary status (4). The Women’s
© 2008 by the American Dietetic Association

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ealth Initiative (WHI) showed that calcium and vitaminsupplementation in a randomized trial design resulted

n considerably less bone loss at the hip in postmeno-ausal women given the supplement compared with pla-ebo (5), but whether general physical functioning alsomproved is not known. The importance of this question isupported by studies showing that in women with lowerone mineral density, there is also poorer physical per-ormance, an important component of physical function-ng (6).

Bone health in general and osteoporotic changes inarticular are complex and multifactorial with nutri-ional, genetic, and lifestyle determinants and interac-ions that remain to be comprehensively elucidated (7). Aecent review by Heany (8) indicated that among vita-ins and minerals, calcium and vitamin D are the most

losely related to bone health. Therefore, because av-rage calcium and vitamin D levels in the Unitedtates are below optimal, supplementation has an im-ortant role in bone health, to reduce calcium loss andone remodeling, which are responsible for osteoporotichanges (9).Very low energy and nutrient intakes are primary nu-

ritional predictors of poorer functional autonomy (10),ith low calcium intake, in particular, implicated in itsecline (11). Recent reports have shown that calcium anditamin D status predicts functional mobility in bothommunity dwelling (12) and home-bound elderly sub-ects (13). Calcium and vitamin D metabolic processes areuite complex, and investigators have proposed both di-ect and indirect effects of calcium and vitamin D onhysical functioning. For example, there are vitamin Deceptors contained in both muscle cells and bone (14),uch that deficiency may directly affect strength (15)nd indirectly affect measures of physical performance16,17).

Several studies have demonstrated that lower serum5(OH)D is related to poorer physical performance (18)nd to decreased physical activity (19). Physical activityn turn supports bone maintenance, muscle strength, andalance (20,21), which are important components of phys-cal performance. After menopause, the effectiveness ofxercise to increase bone mineral density depends ondequate availability of calcium from diet and supple-ents (22). Older individuals previously deficient in vi-

amin D and then supplemented show significant im-rovements in muscle strength and physical performanceith most improvement in subjects assigned physical

raining (23). There is also evidence, in women, of aodest association between several measures of boneineral density and self-reported general physical func-

ioning (24).Given the relationships among physical activity, phys-

cal performance, functional status, and quality of life,he additional evidence that calcium and vitamin D sup-lementation increases bone and muscle strength andctivity levels offers compelling rationale to support theurrent study. Its purpose was to examine the effects ofalcium and vitamin D supplementation on various as-ects of physical functioning and physical activity. TheHI calcium and vitamin D trial provided an unique

pportunity to prospectively study the effects of calcium/
itamin D supplementation on both subjective and objec- s
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ive measures of physical functioning, as well as subjec-ively reported physical activity, physical limitations,itality, bodily pain, and activities of daily living. In ordero fully understand study findings, we also investigatedhe interaction of calcium/vitamin D treatment and base-ine calcium intake (ie, before calcium/vitamin D trialandomization) and treatment and fracture risk levels potential modifiers of calcium/vitamin D effects onoth subjective and objective measures of physicalunctioning.

ETHODSubjectshe eligibility criteria, recruitment procedures and pri-ary findings for the WHI calcium/vitamin D trial have

een published (25,26). Briefly, postmenopausal women50 to 79 years old) were randomized to one or both of the

HI hormone therapy and dietary modification trials at0 US centers between 1993 and 1998. These participantsere invited at their first or second annual follow-up visit

o join the calcium/vitamin D trial, with 36,282 (53.3%)ligible and interested participants being subsequentlynrolled. To ensure consistency in time intervals betweenalcium/vitamin D trial enrollment and follow-up mea-ures, only the 33,067 women who joined at the firstnnual visit (91% of the calcium/vitamin D trial sample)ere included in the current analysis (Figure). Among

Sub-total for current analysisWomen Randomized to CaD One Year after WHI Baseline

CaD: n=16,573 Placebo: n=16,494

Total Women in Calcium/Vitamin D Trial

(CaD)

CaD: n=18,176 Placebo: n=18,106

Physical Function (Self-report)

Physical Function (Objective)

Exercise(Self-report)

CaD BaselineCaD: n=16,569

Placebo: n=16,492

CaD CloseoutCaD: n=14,320

Placebo: n=14,185

CaD Year 2CaD: n=1,352

Placebo: n=1,278


Placebo: n=1,170


Placebo: n=15,326


Placebo: n=15,227


Placebo: n=1,417


Placebo: n=15,502

igure. Profile of the calcium with vitamin D trial of the Women’sealth Initiative (WHI). The number of participants tested or completinguestionnaires at each time point are shown.

ubjects in the calcium/vitamin D trial, 31.1% (n�10,275)

eptember 2008 ● Journal of the AMERICAN DIETETIC ASSOCIATION 1473

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ere also in hormone therapy only, 54.9% (n�18,150) inietary modification only and 14% (n�4,642) were in bothhe hormone therapy and dietary modification trials. In-ormed consent was obtained separately for each of therials, using forms approved by local institutional reviewoards.

rocedureshe calcium/vitamin D trial was a randomized, double-lind and placebo-controlled (5) clinical trial of 1,000 mgalcium carbonate plus 400 IU vitamin D-3 or matchinglacebo in a regimen of two pills per day (study pillsrovided by Glaxo SmithKline, Bensalem, PA). After Oc-ober 1997, a “swallowable” pill was added to the chew-ble pill, and both options were offered to all subjectshroughout the remainder of the trial. A total of 43.3% ofhe participants switched study pill types (chewable vswallowable) at some point during the study, with 46%witching at least once in the active calcium/vitamin Droup and 40.5% switching at least once in the placeboroup).Adherence was assessed at least annually from theeight of remaining pills along with a structured inter-iew. Adherence �80% triggered efforts to optimize ad-erence with monthly reevaluations as needed to helpith side effects or other issues.uestionnaires. Physical functioning was assessed in ques-ionnaires that were collected for all subjects at initialnrollment in WHI (1 year prior to calcium/vitamin Drial randomization) and again at the study end (close-ut), an average of 7.1 years later. These self-report itemsad specific relevance to physical functioning, ie, theange of activities the individual can or cannot carry out.hese examined domains are consistent with those sug-ested by the World Health Organization in their Inter-ational Classification of Functioning, Disability andealth (27). Several relevant (28,29) subscales from thehort Form-36, a well-established standardized question-aire, were analyzed, all being scored 0 to 100 with aigher score indicating a more favorable state of health.he Short Form-36 domains included: General Health

five items), a subscale assessing quality of life with re-ard to one’s general health; Physical Functioning (ninetems), a subscale assessing quality of life with regard tobility to function physically; Role Limitations Physicalfour items), which assessed quality of life with regard toimitations due to physical health problems; Vitality, En-rgy, Fatigue (four items), which assessed quality of lifeith regard to energy/fatigue; Bodily Pain and Stiffness

two items), assessing quality of life with regard to painnd stiffness.The reported level of functional independence (no, not

imited at all; yes, limited a little; yes, limited a lot) oractivities of daily living” derived from four items describ-ng bathing, dressing, eating, and getting in/out of bed.hese were totaled as a single variable.Recreational physical activity was quantified as a con-

inuous variable in METS (ratio of metabolic rate duringhe activity to the resting metabolic rate) per week usingvalidated questionnaire (30) and published database of

hysical activities and MET intensities (31). The con-
truction of composite physical activity variables from t
474 September 2008 Volume 108 Number 9

tems providing examples of activities representing vari-us intensity levels has been described in detail (32). Theomputed variables were: MET hours per week (kcal/eek per kg) energy expenditure from walking (�10 min-tes without stopping); expenditure of energy (kcal/eek�kg) from mild (low intensity) exercise (eg, slowancing, bowling); expenditure of energy (kcal/week�kg)rom moderate exercise (eg, biking outdoors, using anxercise machine); expenditure of energy (kcal/week�kg)rom hard exercise (eg, aerobics, swimming laps); totalecreational physical activity per week (MET level for thectivity multiplied by the number of hours exercised pereek and summing values for all the types of activities).he assigned MET values for strenuous-, moderate-, and

ow-intensity activities were 7, 4, and 3 METS, respec-ively. For mean speed of walking (average, 2-3 mph; fast,-4 mph; and very fast, �4 mph), the assigned METalues were 3, 4, and 4.5, respectively. In addition, min-tes per week of moderate or strenuous recreational ac-ivity were calculated to include walking fairly fast orery fast and participating in activities such as jogging,erobics, swimming.hysical Clinical Data. A random subsample (n�3,137) ofubjects had three objective physical function measuresade at WHI baseline and again 3 and 6 years later (2

ears and 5 years after calcium/vitamin D trial enroll-ent). For grip strength (Jamar hand dynamometer;afayette Instruments, Lafayette, IN), two measure-ents were made in the dominant hand with staff coach-

ng for maximal performance. Measures were recorded tohe nearest kilogram, rounded up. The chair-stand testas conducted if the subject was able to stand at least

nce without using hands/arms from a straight-backed,onpadded, flat-seated, armless chair. Two 15-second tri-ls of repeated chair stands were performed with armsolded across the chest with a 1- to 2-minute rest inetween trials. Chair stands were counted as the partic-pant arose, and counts for both trials recorded. Theimed walk utilized a course marked on the floor with endines 6 m apart and “X” marked just beyond each end line.articipants used ambulatory aids as needed, walking atsual speed to one X with a second trial performed to thether X. The result was recorded as number of seconds (toearest one-tenth second) from start to when a foot com-letely crossed the end line.

tatistical Methodsaseline measures and change from baseline were calcu-

ated as means and standard deviations for the both thective calcium/vitamin D and placebo groups and meansnd standard errors for differences between the tworeatment arms. The effects of calcium/vitamin D on the6 physical function measures were tested in linear mod-ls, with the variable of interest as a function of calcium/itamin D treatment assignment. In addition to the mainodels, interaction models evaluated the relationship be-

ween calcium/vitamin D and baseline total calcium in-ake as well as the relationship between calcium/vitamin

and fracture risk score on physical function. A linearodel was developed for each of the 16 outcome measuresith both calcium/vitamin D treatment assignment and

he baseline covariate of interest, as well as the interac-

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ion between the two. All models were adjusted for WHIrial treatment assignment in the hormone therapy andietary modification trials (ie, active drug or placebo,ow-fat diet intervention or usual diet, respectively) andge as a continuous variable. To look at the effects ofalcium/vitamin D over time, a series of longitudinalodels were also run for the physical function and phys-

cal activity variables (those with more than one mea-urement after baseline), again modeling the effect ofnterest as a function of calcium/vitamin D treatmentssignment.All subjects were also enrolled in at least one of the

ther WHI clinical trials (hormone therapy, dietary mod-fication). Therefore, all statistical models were adjustedor the other WHI trial treatment assignments and age ascontinuous variable. A fracture risk score (scale 0 to 9;ean�2.3, standard deviation�1.1) was computed. Theine risk factors making up the scale included: age 70ears or older; Asian or white ethnicity; current smoker;istory of any fracture; never used hormones; total cal-ium intake �600 mg; history of two or more falls in pastear; weight �127 lb; relative who broke bone before age0. The first four of these were collected at initial WHIcreening and the last five were based on all data avail-ble up until calcium/vitamin D trial randomization. Par-icipants with nonmissing values for at least six of nine

Table 1. Baseline self-reported and objective measures of physical fuD (CaD) or to placebo

Variable

CaD

n Mean SDb

Physical function (self-report)General health 16,549 75.98 16.9Physical functioning 16,529 81.57 20.0Role limitation physical 16,550 76.16 34.5Vitality (energy/fatigue) 16,545 64.71 19.4Bodily pain/stiffness 16,564 74.83 23.0Activities of daily living 16,462 4.03 0.2Incontinence 13,088 8.81 2.4

Physical function (objective)Grip strength, kg 1,511 22.81 5.7Chair stands 1,476 6.52 1.8Timed walk, seconds 1,507 6.50 5.5

Physical activityd (self-report)Walking 15,545 4.16 5.6Mild exercise 15,545 1.39 3.2Moderate exercise 15,545 2.70 4.9Hard exercise 15,545 2.97 7.4Minutes of recreational exercise 15,545 166.94 176.8Total energy expenditure from

recreational activity 15,545 11.22 13.2

aDifference statistics displayed include the differences between the two means (CaD�Pmodeling the physical function or physical activity measure of interest as a function of Cinterventions.bSD�standard deviation.cSE�standard error.dAll METS (ratio of metabolic rate during the activity to the resting metabolic rate) exce

riteria were included in the analysis. Those with fewer a

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han six nonmissing factors had their value for fractureisk set to missing.To address the issue of multiple comparisons, criteria

or statistical significance were adjusted using a Bonfer-oni method correction for both the main effects (��0.0030.05/16�0.003]) and interaction models (��0.0016 [0.05/16�2)]). This correction was reflected in all P valuesesignated as statistically significant. All analysesere completed with SAS version 9.1 (SAS Institute

nc, Cary, NC).

ESULTShe primary findings are shown in Tables 1 and 2. Base-

ine (1 year prior to calcium/vitamin D trial randomiza-ion) and close-out (end of study) scores for each measurere given for the active calcium/vitamin D and placeboroups. The three far-right columns show calcium/vita-in D vs placebo differences and probability levels. In all

ases improvement in function (or mitigation of antici-ated decline with aging) is indicated as a positive differ-nce between calcium/vitamin D and placebo (ie, a calci-m/vitamin D benefit). P values refer to tests of differencesetween calcium/vitamin D and placebo from baseline toollow-up. At follow-up, the women had generally de-lined on most physical function and physical activityeasures with self-reported exercise tending to be higher

n and physical activity in women randomized to calcium and vitamin

Placebo Differencea (CaD–Placebo)

n Mean SD Mean SEc P value

16,475 75.83 17.02 0.15 0.19 0.39416,452 81.36 20.33 0.21 0.22 0.39816,480 75.96 34.68 0.20 0.38 0.63516,470 64.59 19.57 0.12 0.21 0.56316,489 74.98 23.20 �0.15 0.25 0.57716,397 4.03 0.29 �0.003 0.003 0.30813,047 8.83 2.51 �0.02 0.03 0.609

1,417 22.96 5.75 �0.15 0.21 0.6301,391 6.63 1.82 �0.11 0.07 0.1851,414 6.19 4.64 0.30 0.19 0.114

15,493 4.16 5.67 �0.001 0.06 0.94015,493 1.31 3.09 0.08 0.04 0.02815,493 2.68 4.88 0.02 0.06 0.70315,493 2.93 7.20 0.05 0.08 0.61215,493 163.99 171.16 2.95 1.98 0.150

15,493 11.07 12.81 0.15 0.15 0.351

) and their corresponding standard errors. P values are from linear regression analysestment assignment, adjusted for age and other Women’s Health Initiative trial treatment

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eached a “traditional” (uncorrected) level of probabilityP�0.05) with two favoring calcium/vitamin D (year 5imed walk and minutes of hard exercise) and one favor-ng placebo (number of activities of daily living adverselyffected). The more conservative P value criterionP�0.003), adjusting for multiple comparisons, was nottatistically significant. To be more certain that signifi-ant findings were not overlooked, a repeated measuresnalysis of variance was also done with essentially iden-ical results.

The calcium/vitamin D and placebo groups were com-ared in linear regression models with interaction termsf total baseline calcium intake (from diet, supplements,

Table 2. Change from baseline to follow-upa in self-reported andsupplemented with calcium and vitamin D (CaD) compared to place

Variable

CaD

n Mean SDc

Physical function (self-report)e

General health 14,019 �6.00 15.9Physical functioning 13,732 �10.11 19.9Role limitation physical 14,080 �14.20 41.1Vitality (energy/fatigue) 14,013 �4.28 17.7Bodily pain/stiffness 14,244 �7.04 25.0Activities of daily living 14,134 0.04 0.4Incontinence 9,494 0.52 2.2

Physical function (objective)Grip strength, kg (year 2) 1,334 �1.20 5.6Grip strength, kg (year 5) 1,185 �2.49 5.8Chair stands (year 2) 1,250 �0.09 1.5Chair stands (year 5) 1,065 �0.38 1.8Timed walk, seconds (year 2) 1,298 0.11 7.0Timed walk, seconds (year 5) 1,160 0.26 6.2

Physical Activity (self-report)f

Walking (year 2) 14,626 �0.10 5.2Walking (year 5) 14,343 �0.35 5.5Mild exercise (year 2) 14,626 0.11 3.6Mild exercise (year 5) 14,343 0.13 3.9Moderate exercise (year 2) 14,626 0.08 5.6Moderate exercise (year 5) 14,343 0.23 6.2Hard exercise (year 2) 14,626 0.28 7.4Hard exercise (year 5) 14,343 0.36 8.3Minutes of recreational

exercise (year 2) 14,626 4.81 162.2Minutes of recreational

exercise (year 5) 14,343 4.73 177.8Total energy expenditure from

recreational activity (year 2) 14,626 0.38 11.8Total energy expenditure from

recreational activity (year 5) 14,343 0.38 13.1

aChange was calculated as the difference between the given follow-up year and baselibDifference statistics displayed include the differences between the two means (CaD�Pmodeling the physical function or physical activity measure of interest as a function of Cinterventions.cSD�standard deviation.dSE�standard error.eFollow-up self-reported psychosocial measures were completed at study end (close-oufAll METS (ratio of metabolic rate during the activity to the resting metabolic rate) exce

nd medications) first and then fracture risk score, with n


ach specific physical function variable as a response.hese models also had the main effects of calcium/vita-in D treatment assignment and variable of interest

djusted for hormone therapy treatment assignment, di-tary modification treatment assignment, and age. Nei-her of the interactions with calcium intake or fractureisk score had a substantial impact on the results, indi-ating that the effect of calcium/vitamin D supplementa-ion did not significantly change for different levels ofaseline calcium intake or fracture risk (P�0.02 for allnteractions).

Only those women who were at least 80% adherent totudy pills were examined in a subgroup analysis (data

ctive physical function and physical activity measures in women

Placebo Differenceb (CaD–Placebo)

n Mean SD Mean SEd P value

13,895 �6.00 15.85 �0.01 0.19 0.82813,566 �9.97 19.83 �0.13 0.24 0.39013,964 �14.58 41.85 0.38 0.50 0.57313,898 �4.37 18.03 0.08 0.21 0.89014,114 �7.30 24.77 0.27 0.30 0.46313,999 0.03 0.47 0.01 0.01 0.0179,417 0.53 2.27 �0.01 0.03 0.921

1,265 �1.27 5.30 0.06 0.21 0.7901,162 �2.64 5.69 0.15 0.24 0.5241,188 �0.12 1.60 0.03 0.06 0.6231,053 �0.43 1.81 0.04 0.08 0.6031,238 0.23 6.38 �0.12 0.27 0.5801,141 0.81 6.43 �0.54 0.26 0.030

14,559 �0.12 5.07 0.03 0.06 0.65614,303 �0.32 5.70 �0.03 0.07 0.63414,559 0.18 3.64 �0.07 0.04 0.09514,303 0.10 3.75 0.03 0.05 0.46614,559 0.08 5.59 0.01 0.07 0.94114,303 0.25 6.15 �0.02 0.07 0.79014,559 0.20 7.37 0.09 0.09 0.31114,303 0.17 8.22 0.19 0.10 0.049

14,559 5.55 158.46 �0.74 1.88 0.690

14,303 3.54 174.33 1.19 2.08 0.568

14,559 0.33 11.55 0.05 0.14 0.724

14,303 0.20 12.95 0.18 0.15 0.255

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ISCUSSION

nalyses of the WHI randomized controlled trial of cal-ium and vitamin D supplementation showed no evidencef treatment effects on measures of physical functioningr physical activity. Neither self-reported nor objectiveeasures suggested that calcium/vitamin D treatment

roduced an improvement or mitigated the decline inhysical functioning over time. This conclusion was un-hanged after controlling for age and treatment arm inhe parallel trials (hormone therapy and dietary modifi-ation). Also, analyses of subjects who were highly�80%) adherent to the treatment did not alter the mainesults. These latter analyses were important becauseomen adherent to the active calcium/vitamin D regimenere shown to have reduced hip fractures (5). This latternding counters possible criticisms of the dose being too

ow by demonstrating that the treatment was biologicallyctive and effective.Regardless of treatment assignment, there was a de-

line in physical functioning (not unexpected in this olderohort) between baseline and follow-up time points (3, 6,nd 7 years later) for most measures, whether self-re-orted or objective. Thus the measures were sufficientlyensitive to demonstrate a change in physical functioningith age, despite being unaffected by supplemental cal-

ium/vitamin D.There were some reasons to expect from past work and

rom known physiologic mechanisms that calcium/vita-in D treatment, especially in adherent women, wouldave a positive effect. The active calcium/vitamin D doseas shown to be effective in reducing bone loss and frac-

ures, even though women were not selected because ofestrictions of activity level, poor nutritional adequacy, orther background risk issues, such as genetics or inade-uate sun exposure (33). It is important to recognize thatalcium/vitamin D supplementation reduced falls inomen in very high-risk categories (34), but improved

unctioning has not been demonstrated in healthier post-enopausal women (35). Some published data argue

gainst the idea that improving bone health alone shouldead to fewer physical limitations in healthy women. Forxample, neither hormone therapy nor alendronate, po-ent inhibitors of bone loss, have been shown to affectge-related declines in physical functioning (36,37). Also,nly low serum vitamin D levels (�20 ng/mL) were asso-iated with current and declining physical performanceevels (38). The physical performance of subjects in theresent study did decline over time. However, in thisample, which was not selected for low vitamin D levels,here may still have been insufficient power to detectitigation of physical function deficits. Arguing against

ossible insufficient power was our analysis of women atigher risk of fracture (ie, with low baseline intake ofalcium and vitamin D, family history), which showed noreatment benefit for physical functioning. Strengths ofhis study were its range of measures, both subjective andbjective, none of which suggested improvement with ac-ive treatment. Potential limitations included the length
f treatment, age at which treatment was started, b
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ealthy status of the cohort (including relatively fewomen clearly deficient in calcium or vitamin D), andosages used.

ONCLUSIONShis is the first long-term randomized trial to examinehether supplementing calcium and vitamin D protectsgainst decline of physical functioning in communitywelling older women; the results did not support benefit.ecause the level of vitamin D supplementation, whichas considered adequate at the time this trial began, isow considered low, caution is warranted in statementsbout potential efficacy of vitamin D in maintaining ormproving physical function. This study included rela-ively healthy women, and the conclusion of lack of ben-fit should not be extended to higher risk groups. Never-heless, consideration of the level of calcium and vitamin

intake at baseline did not change the conclusion thatupplementation did not improve physical functioningeasures. In future studies, additional sensitive and

omprehensive measures of physical function should beonsidered. Also, it will be important to further examinehe relationship between baseline vitamin D blood levelsnd the effectiveness of calcium/vitamin D supplementa-ion for improving physical function.

Helping individuals to develop clear expectations of theffects of calcium and vitamin D, when they are consid-ring dietary or supplemental intake, is consistent withhe role of registered dietitians in any practice setting.his study, in the context of the rapidly growing numberf published reports in the scientific and lay literature onurported health effects of calcium and vitamin D high-ights the importance for the dietitian to be knowledge-ble of the complex relationships among dietary intake,upplementation, and physiological effects of calcium anditamin D, as well as the evidence base for their effect onealth and physical functioning.

arbara Cochran received research support from the Na-ional Institutes of Health. Joseph Larson received re-earch support from the National Institutes of Health.obert L. Brunner received research support from theational Institutes of Health and the National Cancer

nstitute of Canada. Marian Limacher received researchupport from the Boeringer-Ingelheim, National Insti-utes of Health. Cora Lewis received research supportrom the National Institutes of Health. Robert Wallaceeceived research support from the National Institutes ofealth and Pfizer, is on the Data and Safety Monitoringoard of Novartis, and is a consultant for Merck. Rebecca. Jackson received research support from Proctor andamble and is on the Speaker’s Bureau of Sanofi-Aventis/lliance for Better Bone Health. Sally Shumaker re-eived research support from the National Institutes ofealth. Milagros Rosal received research support from

he National Institutes of Health.The WHI program is funded by the National Heart,

ung and Blood Institute, US Department of Health anduman Services. The National Heart, Lung and Blood

nstitute (sponsor) was involved in the design and meth-ds of the clinical trial on which the present analysis was
ased.

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The active study drug and placebo were supplied bylaxo SmithKline Consumer Healthcare (Pittsburgh,A).

HI Investigators

Program Office: (National Heart, Lung, and Bloodnstitute, Bethesda, Maryland)

Elizabeth Nabel, Jacques Rossouw, Linda Pottern,hari Ludlam, Joan McGowan, Nancy Geller, Leslieord.Clinical Coordinating Center: (Fred Hutchinson

ancer Research Center, Seattle, WA)Ross Prentice, Garnet Anderson, Andrea LaCroix,uth Patterson, Anne McTiernan, Barbara Cochrane,ulie Hunt, Lesley Tinker, Charles Kooperberg, MartincIntosh, C. Y. Wang, Chu Chen, Deborah Bowen, Alanristal, Janet Stanford, Nicole Urban, Noel Weiss, Emilyhite; (Wake Forest University School of Medicine, Win-

ton-Salem, NC) Sally Shumaker, Ronald Prineas, Mich-lle Naughton; (Medical Research Laboratories, High-and Heights, KY) Evan Stein, Peter Laskarzewski; (Sanrancisco Coordinating Center, San Francisco, CA)teven R. Cummings, Michael Nevitt, Lisa Palermo;

University of Minnesota, Minneapolis, MN) Lisa Har-ack; (Fisher BioServices, Rockville, MD) Frank Camma-ata, Steve Lindenfelser; (University of Washington, Se-ttle, WA) Bruce Psaty, Susan Heckbert.Clinical Centers: (Albert Einstein College of Medi-

ine, Bronx, NY) Sylvia Wassertheil-Smoller, William Fr-shman, Judith Wylie-Rosett, David Barad, Ruth Free-

an; (Baylor College of Medicine, Houston, TX) Jenniferays, Ronald Young, Jill Anderson, Sandy Lithgow, Paulray; (Brigham and Women’s Hospital, Harvard Medicalchool, Boston, MA) JoAnn Manson, J. Michael Gaziano,laudia Chae, Kathryn Rexrode, Caren Solomon (Brownniversity, Providence, RI) Annlouise R. Assaf, Carolheeler, Charles Eaton, Michelle Cyr (Emory Univer-

ity, Atlanta, GA); Lawrence Phillips, Margaret Ped-rsen, Ora Strickland, Margaret Huber, Vivian Porter;Fred Hutchinson Cancer Research Center, Seattle, WA)hirley A.A. Beresford, Vicky M. Taylor, Nancy F. Woods,aureen Henderson, Robyn Andersen; (George Washing-

on University, Washington, DC) Judith Hsia, Nancyaba, Joao Ascensao; (Harbor-UCLA Research and Edu-

ation Institute, Torrance, CA) Rowan Chlebowski, Rob-rt Detrano, Anita Nelson, Michele Geller; (Kaiser Per-anente Center for Health Research, Portland, OR)velyn Whitlock, Victor Stevens, Njeri Karanja; (Kaiserermanente Division of Research, Oakland, CA) Betteaan, Stephen Sidney, Geri Bailey Jane Hirata; (Medicalollege of Wisconsin, Milwaukee, WI) Jane Morleyotchen, Vanessa Barnabei, Theodore A. Kotchen, Marynn C. Gilligan, Joan Neuner; (MedStar Research Insti-

ute/Howard University, Washington, DC) Barbara V.oward, Lucile Adams-Campbell, Lawrence Lessin,onique Rainford, Gabriel Uwaifo; (Northwestern Uni-

ersity, Chicago/Evanston, IL) Linda Van Horn, Philipreenland, Janardan Khandekar, Kiang Liu, Carolosenberg; (Rush University Medical Center, Chicago,

L) Henry Black, Lynda Powell, Ellen Mason; Marthaulati; (Stanford Prevention Research Center, Stanford,A) Marcia L. Stefanick, Mark A. Hlatky, Bertha Chen,
andall S. Stafford, Sally Mackey; (State University of M

ew York at Stony Brook, Stony Brook, NY) Dorothyane, Iris Granek, William Lawson, Gabriel San Roman,atherine Messina; (The Ohio State University, Colum-us, OH) Rebecca Jackson, Randall Harris, Electra Pas-ett, W. Jerry Mysiw, Michael Blumenfeld; (University oflabama at Birmingham, Birmingham, AL) Cora E.ewis, Albert Oberman, James M. Shikany, Monika Saf-

ord, Mona Fouad; (University of Arizona, Tucson/Phoe-ix, AZ) Tamsen Bassford, Cyndi Thomson, Marcia Ko,na Maria Lopez, Cheryl Ritenbaugh; (University at Buf-

alo, Buffalo, NY) Jean Wactawski-Wende, Maurizio Tre-isan, Ellen Smit, Susan Graham, June Chang; (Univer-ity of California at Davis, Sacramento, CA) Johnobbins, S. Yasmeen; (University of California at Irvine,A) F. Allan Hubbell, Gail Frank, Nathan Wong, Nancyreep, Bradley Monk; (University of California at Losngeles, Los Angeles, CA) Howard Judd, David Heber,obert Elashoff; (University of California at San Diego,aJolla/Chula Vista, CA) Robert D. Langer, Michael H.riqui, Gregory T. Talavera, Cedric F. Garland, Matthew. Allison; (University of Cincinnati, Cincinnati, OH)argery Gass, Suzanne Wernke; (University of Florida,ainesville/Jacksonville, FL) Marian Limacher, Michaelerri, Andrew Kaunitz, R. Stan Williams, Yvonne Brin-on; (University of Hawaii, Honolulu, HI) J. David Curb,elen Petrovitch, Beatriz Rodriguez, Kamal Masaki,antosh Sharma; (University of Iowa, Iowa City/Daven-ort, IA) Robert Wallace, James Torner, Susan Johnson,inda Snetselaar, Jennifer Robinson; (University of Mas-achusetts/Fallon Clinic, Worcester, MA) Judith Ockene,ilagros Rosal, Ira Ockene, Robert Yood, Patricia Aron-

on; (University of Medicine and Dentistry of New Jersey,ewark, NJ) Norman Lasser, Baljinder Singh, Veraasser, John Kostis, Peter McGovern; (University of Mi-mi, Miami, FL) Mary Jo O’Sullivan, Linda Parker, Tim-thy DeSantis, Diann Fernandez, Pat Caralis; (Univer-ity of Minnesota, Minneapolis, MN) Karen L. Margolis,ichard H. Grimm, Mary F. Perron, Cynthia Bjerk,arah Kempainen; (University of Nevada, Reno, NV)obert Brunner, William Graettinger, Vicki Oujevolk,ichael Bloch; (University of North Carolina, Chapelill, NC) Gerardo Heiss, Pamela Haines, David Ontjes,arla Sueta, Ellen Wells; (University of Pittsburgh, Pitts-urgh, PA) Lewis Kuller, Jane Cauley, N. Carole Milas;University of Tennessee Health Science Center, Mem-his, TN) Karen C. Johnson, Suzanne Satterfield, Ray-ond W. Ke, Stephanie Connelly, Fran Tylavsky; (Uni-

ersity of Texas Health Science Center, San Antonio, TX)obert Brzyski, Robert Schenken, Jose Trabal, Mercedesodriguez-Sifuentes, Charles Mouton; (University ofisconsin, Madison, WI) Gloria E. Sarto, Douglas Laube,

atrick McBride, Julie Mares-Perlman, Barbara Loev-nger; (Wake Forest University School of Medicine, Win-ton-Salem, NC) Denise Bonds, Greg Burke, Robinrouse, Mara Vitolins, Scott Washburn; (Wayne Stateniversity School of Medicine/Hutzel Hospital, Detroit,I) Susan Hendrix, Michael Simon, Gene McNeeley.Former Principal Investigators and Projectfficers:Baylor College of Medicine, John Foreyt, PhD, Emoryniversity, Dallas Hall, MD, George Washington Univer-

ity, Valery Miller, MD, Kaiser, Oakland, Robert Hiatt,
D, Kaiser, Portland, Barbara Valanis, DrPh, National

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ancer Institute, Bethesda, Maryland, Carolyn Clifforddeceased), University of California, Irvine, Frank Mey-kens, Jr., MD, University of Cincinnati, James Liu, MD,elson Watts, University of Miami, Marianna Baum,hD, University of Minnesota, Richard Grimm, MD, Uni-ersity of Nevada, Sandra Daugherty, MD (deceased)niversity of North Carolina, Chapel Hill, David Sheps,D, Barbara Hulka, MD, University of Tennessee, Mem-

his, William Applegate, MD, University of Wisconsin,atherine Allen, PhD (deceased).

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calcium, vitamin d supplementation, and physical function in the women's health initiative

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