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ORIGINAL ARTICLE

Changes in femur neck bone density in US adults

between 19881994 and 20052008: demographic

patterns and possible determinants

A. C. Looker &L. J. Melton III &L. G. Borrud &

J. A. Shepherd

Received: 24 November 2010 /Accepted: 24 February 2011 /Published online: 6 April 2011# International Osteoporosis Foundation and National Osteoporosis Foundation 2011

Abstract

Summary This analysis compares femur neck bone mineral

density (FNBMD) and bone determinants in adults between

National Health and Nutrit ion Examination Surve y

(NHANES) III (19881994) and NHANES 20052008.

FNBMD was higher in NHANES 20052008 than in

NHANES III, but between-survey differences varied by

age, sex, and race/ethnicity. The likelihood that FNBMD

has improved appears strongest for older white women.

Introduction Recent data on hip fracture incidence and

femur neck osteoporosis suggest that the skeletal status of

older US adults has improved since the 1990s, but the

explanation for these changes remains uncertain.

Methods The present study compares mean FNBMD of

adults ages 20 years and older between the third (NHANES

III, 19881994) and NHANES 20052008. Dual-energy X-

ray absorptiometry systems (pencil beam in NHANES III,

fan beam in NHANES 20052008) were used to measure

hip BMD, and several bone determinants are compared

between surveys to assess their potential role in explaining

observed FNBMD differences.

Results FNBMD was higher overall in NHANES 2005

2008 than in NHANES III, but between-survey differences

varied by age, sex, and race/ethnicity. Although FNBMD

differences in several groups were small enough (3%) to

be attributable to use of different dual-energy X-ray

absorptiometry (DXA) systems in the two surveys, vari-

ability in size and direction of the differences does not

support artifactual differences in DXA methodology as the

sole explanation. Several FNBMD determinants (body size,

smoking, selected bone-active medications, self-reported

health status, calcium intake, and caffeine consumption)

changed in a bone-improving direction in older adults, but

FNBMD in older non-Hispanic white women remained

significantly higher in 20052008 even after adjusting for

DXA methodology or for the selected bone determinants.

Conclusion The likelihood that FNBMD has improved

appears strongest for older white women, but the reason

for the improvement in this group remains unclear.

Keywords Bone density . Femoral neck. Gender. Race/

ethnicity . Secular trends

Introduction

We recently reported a significant decline in the prevalence of

femur neck osteoporosis in older US adults between 1988

1994 and 20052006 [1]. This improvement in femoral neck

The findings and conclusions in this report are those of the authorsand do not necessarily represent the views of the Centers for Disease

Control and Prevention or the Department of Health and Human

Services.

A. C. Looker (*)

National Center for Health Statistics,

Centers for Disease Control and Prevention,

Room 4310, 3311 Toledo Road,

Hyattsville, MD 20782, USA

e-mail: ALooker@cdc.gov

L. J. Melton III

Division of Epidemiology, College of Medicine, Mayo Clinic,

Rochester, MN, USA

e-mail: melton.j@mayo.edu

L. G. Borrud

National Center for Health Statistics,

Centers for Disease Control and Prevention,

Room 4327, 3311 Toledo Road,

Hyattsville, MD 20782, USA

e-mail: LBorrud@cdc.gov

J. A. Shepherd

Department of Radiology, University of California San Francisco,

San Francisco, CA, USA

e-mail: john.shepherd@radiology.ucsf.edu

Osteoporos Int (2012) 23:771780

DOI 10.1007/s00198-011-1623-0

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bone mineral density (FNBMD) is consistent with the

decline in hip fracture incidence observed in both national

and community-based studies during the same time period

[25]. Although our previous study provided valuable public

health information by documenting a decline in osteoporosis

prevalence in older US adults, it suffered from some important

constraints. First, the focus on osteoporosis prevalence, as

defined by the World Health Organization approach [6],limited the examination of FNBMD changes to older adults

only. Second, the availability of FNBMD data for only

2 years (e.g., 20052006) at the time of the previous report

limited our statistical power and the number of possible

explanatory factors that could be examined. Specifically, the

previous study examined the impact of changes in body

mass index (BMI) and use of osteoporosis medications on

the observed difference in osteoporosis prevalence. Both

were positively associated with higher FNBMD, and both

increased during the relevant time period [711], but neither

factor appeared to explain the observed FNBMD difference

observed between 19881994 and 20052006.We undertook the present study to address these important

data gaps. In this report, we examine FNBMD changes across

the entire adult age range, not just ages 50 years and over, in

order to provide a more complete picture of changes in

FNBMD in the US population. We also evaluated changes by

race/ethnicity, and we greatly increased the number of potential

explanatory factors that were examined for their potential

impact on the observed FNBMD differences in the population.

In addition to BMI and osteoporosis drugs, changes in 12 other

bone determinants (i.e., smoking, health status, dietary

calcium, sodium, caffeine, alcohol intake, milk intake, personal

and maternal fracture history, weight history, height, and use of

drugs that may decrease FNBMD) are explored to assess their

potential role in explaining the observed FNBMD differences.

This more detailed look at potential explanatory factors was

made possible by the release of an additional two years of

FNBMD data from the National Health and Nutrition

Examination Survey (NHANES) for 20072008. Thus, the

specific objectives of the present study are: (a) to describe the

differences in FNBMD between NHANES III (19881994)

and NHANES 20052008 by age, sex, and race/ethnicity for

adults ages 20 years and older; and (b) to identify additional

bone determinants that may have changed in a manner

consistent with improved FNBMD and assess their potential

impact on the observed FNBMD differences between surveys.

Methods

Sample

The NHANES are conducted by the National Center for

Health Statistics (NCHS), Centers for Disease Control and

Prevention, to assess the health and nutritional status of

large representative cross-sectional samples of the non-

institutionalized, US civilian population. In NHANES III, a

nationally representative sample was obtained in two 3-year

cycles between 1988 and1994. Starting in 1999, data from a

nationally representative sample have been collected each

year, but data are released for 2-year periods to protect

confidentiality and increase statistical reliability. Thepresent study was based on data collected in NHANES III

as well as NHANES 20052008. In each NHANES, data

were collected via household interviews and standardized

physical examinations conducted in specially equipped

mobile examination centers [12, 13]. All procedures in

both surveys were approved by the NCHS Research Ethics

Review Board, and written informed consent was obtained

from all subjects.

NHANES III and NHANES 20052008 were designed

to provide reliable estimates for three race/ethnic groups

(self-reported by the participants): non-Hispanic whites

(NHW), non-Hispanic blacks (NHB), and MexicanAmericans (MA). The analytic sample from NHANES

III in the present study consists of 14,646 adults ages

20 years and older with valid FNBMD data, which

represents 63% of the sample in this age range who were

originally selected for the survey, 78% of the participants

in this age range who were interviewed, and 88% of

those who received physical examinations. The analytic

sample from NHANES 20052008 consists of 8,220

adults ages 20 years and older with valid FNBMD data,

which represents 56% of the subjects in this age range

who were eligible to participate in the survey, 75% of the

interviewed participants and 78% of those who were

examined.

Variables

In the present study, BMD data at the femur neck were

analyzed because it has been proposed as the reference

skeletal site for defining osteoporosis in epidemiological

studies [6]. FNBMD was measured in NHANES 2005

2008 with Hologic QDR 4500A fan-beam densitometers

(Hologic, Inc., Bedford, MA, USA) using Discovery

version 12.4 software. Scanning was done in the fast mode

[14]. In NHANES III, FNBMD was measured with Hologic

QDR 1000 pencil beam densitometers [15]. Rigorous

quality control (QC) programs were employed in both

surveys, which included use of anthropomorphic phantoms

and review of each QC and respondent scan at a central site

(Department of Radiology of the University of California,

San Francisco in NHANES 20052008, and Department of

Diagnostic Radiology of the Mayo Clinic in NHANES III)

[14, 15]. In both surveys, the left hip was scanned unless

there was a history of previous fracture or surgery.

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Potential explanatory bone determinants

Bone determinants which might potentially underlie observed

trends in FNBMD between surveys were selected from risk

factors that are identified in the National Osteoporosis

Foundation (NOF) Guide to Prevention and Treatment of

Osteoporosis [16] or used in the World Health Organization

fracture risk assessment (FRAX) model [17]. Only bonedeterminants that were measured in a comparable manner in

both surveys were used in the present study. They included

the following:

Body mass index and weight at age 25 years

BMI was calculated as body weight (kilograms) divided by

height (meters squared). Body weight was measured to the

nearest 0.01 kg using an electronic load cell scale, and

standing height was measured with a fixed stadiometer.

Respondents self-reported their body weight in pounds at

age 25 years.

Personal hip, wrist, or spine fracture history and maternal

hip fracture history

History of hip, spine, or wrist fracture was based on a self-

reported fracture at these sites that occurred after age

20 years. Maternal hip fracture history was based on self-

report that the respondentsbiological mother had fractured

her hip.

Cigarette smoking, high alcohol intake, and positive health

status

Cigarette smokers were defined as respondents who self-

reported that they currently or formerly smoked, while high

alcohol users were defined as respondents who self-

reported that they usually consumed three or more drinks

per day when they drank alcohol. Respondents who self-

reported that their health in general was excellent, very

good, or good were considered to have positive health

status.

Milk, calcium, sodium, and caffeine intake

Milk users were defined as respondents who reported

drinking milk alone or on cereal one or more times per

week during the past 30 days. Calcium, sodium, and

caffeine intakes from foods and beverages were based on

a single 24-h dietary recall. Respondents were also asked to

report how often vitaminmineral supplements and antacids

were taken in the past month and how much was taken on

each occasion. Nutrient composition of the supplements

was based on the supplements label information. The

average daily intake of calcium from supplements was

calculated in the present study using the number of days the

supplement was used, the amount taken per day and the

serving size unit from the product label. The average daily

calcium intake from supplements for each respondent was

summed with their reported calcium intake from food to

estimate total calcium intake.

Medication use

Medication users were defined as those who were currently

taking the prescription medications described below. In

both surveys, respondents showed the containers for all

current prescription medications to the interviewer, who

recorded the name of the product. The December 2007

Multum Lexicon Drug Database (Cerner Multum Inc,

Denver, CO, USA; http://www.multum.com/Lexicon.htm)

was used to assign generic drug names and codes in both

surveys. Medications that increase BMD were based on

those included in a recent systematic review of thecomparative effectiveness of treatments to prevent osteo-

porotic fractures [7]. These medications were categorized

into two groups: sex hormones (estrogen and testosterone)

and other drugs such as bisphosphonates, selective estrogen

receptor modifiers (SERMs), and other non-estrogen drugs.

Medications that decrease BMD were defined as those

identified in the NOF guide [16] and included glucocorti-

coids, antineoplastic drugs, anticonvulsants, barbiturates,

anticoagulants, IV nutrition products, lithium, cyclosporine,

and tacrolimus. The specific drugs in the subgroups of

medications that increase or decrease BMD are shown in

Appendix 1. Respondents who reported taking drugs that

increase BMD concurrently with drugs that decrease BMD

(n =168) were defined as users of drugs that increase BMD.

Statistical analysis

Analyses were conducted with PC-SAS (Version 10.0, SAS

Institute, Cary, NC, USA) and SUDAAN (Version 9.03,

Research Triangle Institute, NC, USA). All analyses used

sample weights and took into account the complex design

of the surveys [18].

Unadjusted mean FNBMD by age, sex, race/ethnicity

and survey were plotted. Differences in the FNBMD

change between surveys by age, sex, and race/ethnicity

were tested for statistical significance using first-order

interaction terms (e.g., surveysex, surveyage, survey

race/ethnicity) in linear regression models. All interactions

terms were statistically significant (p

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methodology between surveys. These analyses were based

on results from a small number of studies which have

compared BMD values measured on the same DXA

systems used in NHANES III and NHANES 20052008

[1923]. These studies produced varying results, so

consensus on the best method to adjust BMD for potential

DXA differences is lacking. As a result, two different

approaches to explore the possible effect of the DXAmethod change were used in the present study. In the first

analysis, the FNBMD value of each respondent from

NHANES III was increased by 3%, since the largest

discrepancy between the two scanner systems reported in

published studies [1923] was a difference of 3% at either

the femur neck or total hip. Estimates of mean DXA

method-adjusted FNBMD values from NHANES III were

then calculated and compared with mean FNBMD from

NHANES 20052008 within race/ethnic and sex groups

after also adjusting age. In the second analysis, we applied

a linear regression equation developed previously by

Cummings et al. [23] to compare BMD measurementscollected with Hologic QDR 1000 and 4500 instruments

in the Study of Osteoporotic Fracture and Osteoporotic

Fractures in Men studies. This equation was used to adjust

FNBMD values from NHANES III which were then

compared with mean FNBMD from NHANES 2005

2008 within sex and race/ethnic group after also adjusting

for age.

To identify possible determinants of observed differ-

ences in FNBMD between surveys, linear and logistic

regression were used to find bone determinants that had

changed significantly between surveys in a direction

consistent with the positive difference in FNBMD observed

between surveys in adults age 50 years and older. These

analyses were limited to older adults because between-

survey FNBMD differences were larger and more consis-

tent in direction in this age range. Linear regression was

used to compare FNBMD differences in older adults

between surveys before and after adjusting for the risk

factors identified in the previous step. A reduction in

between-survey FNBMD differences after adjusting for

these bone determinants would suggest that these factors

may have played a role in the FNBMD differences. Co-

linearity between inter-related risk factors, such as height,

BMI, and weight at age 25, was addressed by ensuring that

bivariate correlations were

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of adjusting for the selected bone determinants depended on

sex and race/ethnicity. Among NHW and NHB men,

adjusting for bone determinants resulted in mean FNBMD

values that were essentially the same in both surveys.

However, adjusting for the bone determinants only slightly

reduced the mean FNBMD difference in NHW women, and

the difference remained statistically significant. In NHB

women, mean FNBMD did not differ significantly between

surveys either before or after adjusting for the selected bone

determinants. In both MA men and women, adjusting

increased the FNBMD difference between surveys, but the

direction of the differences varied by sex. In MA women,

age-adjusted FNBMD in NHANES 20052008 was signif-

icantly higher than in NHANES III, and remained signif-

icant after adjusting for all selected bone determinants. In

MA men, mean FNBMD became significantly lower in

NHANES 20052008 compared to NHANES III after

adjusting for all bone determinants.

Two approaches were used to adjust for the potentialimpact of DXA methodology differences in older adults,

but because conclusions were similar in all subgroups, only

results for the approach in which FNBMD values from

NHANES III were increased by +3% are shown in Table2.

Although reduced in size (from 6% to 4%), the FNBMD

difference in NHW women remained statistically significant

after applying this adjustment. However in NHW men and

MA women, FNBMD differences were no longer significant

after adjusting for DXA methodology differences. Among

MA men, the adjustment increased the size of the FNBMD

difference between surveys (from 2% to 6%), so that

mean FNBMD became significantly lower in NHANES20052008 compared to NHANES III. FNBMD differences

in NHB men and women did not differ significantly either

before or after adjusting for DXA method differences.

Results of the analyses to explore reasons for the

disparate effect of adjusting for the selected bone determi-

nants on FNBMD differences in older NHW men versus

women are summarized in Fig. 2. There were significant

surveysex interactions for BMI, weight at age 25,

smoking, and calcium intake, which indicates that the

changes in these factors between surveys differed between

NHW men and women. Changes for three of the variables

were larger in NHW men than in women. Specifically, the

increases in BMI and weight at age 25 years between

surveys were greater in men (~45%) than in women

(~1%). Differences in smoking by sex differed between

surveys in direction as well as in magnitude: smoking

declined by roughly 15% in the men between NHANES III

and NHANES 20052008, but increased slightly (~2%) in

women during the same time period. In contrast, the

increase in calcium intake between surveys among NHW

women (53%) was more than twice as great as the increase

in calcium intake among NHW men (24%). The other

factors tested did not show significant surveysex inter-

actions (data not shown). The interaction for use of non-

estrogen medications (bisphosphonates, SERMS, etc.) was

not tested because the point estimates for NHANES III

were not statistically reliable for men or women.

Discussion

The present study examined FNBMD changes over time

across the entire adult age range, and thus extends our

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a

b

c

Fig. 1 Mean femur neck BMD. NHANES III (19881994),

NHANES 20052008

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Table 1 Selected bone determinants by NHANES survey period among adults age 50+years

Bone determinant Mean or percent %a

NHANES III 19881994 NHANES 20052008

Age (years) 64.5b 62.9b* 2

Body weight (kg) 76.2 79.3* 4

Height (cm) 166.6 167.6* 1BMI 27.4 28.1* 3

Weight at age 25 (lbs) 142.3 145.5* 2

Ever smoked (%) 57.9 53.4* 8

Positive health status (%) 75.8 80.2* 6

Drink 3+ units alcohol (%) 12.2 14.6 16

Use medications that decrease BMD (%)c 5.2 7.2* 28

Use medications that increase BMD (%)

Sex hormones 8.0 5.0* 60

Bisphosphonates, SERMS, other non-estrogen drugs 0.4 7.3* 95

Mother had a hip fracture (%) 8.7 8.6 1

Self-reported previous hip, wrist or spine fracture (%) 8.8 10.8* 19

Drink milk 1+ times/week (%) 77.2 71.7* 7

Calcium from food and supplements (mg/day) 872.4. 1,204.6* 28

Sodium from food (mg/day) 3,108.4 3,136.5 1

Caffeine (mg/day) 271.3 206.2* 32

All bone determinants have been adjusted for age, sex and race/ethnicity except where noteda

Percent change=((NHANES 20052008 estimateNHANES III estimate)/NHANES III estimate)100b

Adjusted for sex and race/ethnicityc

Glucocorticoids, antineoplastic drugs, anticonvulsants, barbiturates, heparin, IV nutrition products, lithium, cyclosporine, tacrolimus

*p

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previous study of osteoporosis prevalence in older adults by

providing a more complete picture of changes in the

skeletal status of all US adults. FNBMD in US adults was

higher overall in NHANES 20052008 than in NHANES

III (19881994), consistent with the decline in hip fracture

incidence reported during the same time period [25].However, the extent of the difference in FNBMD between

these two surveys varied noticeably by age, sex and race/

ethnicity. The inconsistency was more evident in those

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Reid et al. [28] reported that secular trends in hip axis

length (HAL) had occurred in British or Australian women

prior to the 1990s, but data on bone size-related parameters

like HAL are currently not available from NHANES 2005

2008, so that possibility could not be explored. The bone

area measurement from the DXA scan could not be used to

examine bone size trends because bone area measurements

from pencilbeam and fanbeam systems cannot be compareddirectly due to geometric projection effects. In addition,

bone area measurements from a DXA scan are not true

volumetric measures of bone. Thus, we used standing

height as proxy for bone size. Standing height has increased

slightly in the US population since the 1990s [25], which

was also reflected in our study sample, but standing height

may not fully capture variability in bone size. For example,

Guglielmi et al. [29] found height was unrelated to 3-D

quantitative computed tomography estimates of proximal

femur bone size, and Lochmuller et al. [30] reported that

adjusting for body height, weight, and projected femoral

area did not fully correct for bone volume of excisedfemurs. It is also possible that cohort effects in diet or other

health behaviors prior to adulthood played a role in the

observed FNBMD differences, but these could not be

evaluated in the present study. Yet other factors, such as

physical activity, were not measured comparably in the two

surveys and so could not be validly compared. However,

the proportion of US adults who engaged regularly in

moderate or vigorous leisure time physical activity did not

change significantly between 1997 and 2006 [31], which

suggests that physical activity is unlikely to play a major

role in the FNBMD differences observed over a similar

time period. Finally, measurement error in the bone

determinants that could be included in the present study

might also affect their ability to account for observed

FNBMD differences.

In addition to the lack of a robust method to account

for differences in DXA methodology, limitations of the

present study include possible nonresponse bias in the

estimates from both surveys. Use of sample weights in

the analysis addresses this bias to some extent, since a

nonresponse adjustment factor is included in their

calculation. However, 12% and 22%, respectively, of

the NHANES III and NHANES 20052008 respondents

ages 20 years and older who came to the examination

centers lacked valid hip DXA data, and this is not

addressed by the sample weight adjustments. Results of a

detailed non-response bias analysis conducted by NCHS

prior to the public release of the NHANES 20052006

femur data suggested that additional adjustments for non-

response were not necessary, however. A final limitation

is the exclusion of institutionalized people, an important

at-risk group for osteoporosis [32] from the NHANES

sampling frame by design.

In summary, FNBMD was higher overall in NHANES

20052008 than in NHANES III (19881994), which

suggests that hip BMD has improved in US adults. This

improvement is consistent in direction with the decrease

in hip fracture incidence reported among older adults in

the US [25]. However, FNBMD differences between

surveys were generally greater in older than in younger

adults, and they also varied considerably by sex and race/ethnicity. The variability in the size of the BMD differ-

ences in the different population groups suggests the

causes may be multifactorial. The FNBMD differences in

several groups were within the magnitude that could be

attributed to use of different DXA systems in the two

surveys. However, the lack of uniformity in the size and

direction of the FNBMD differences across the various

age, sex, and race/ethnic groups, and the identification of

several BMD determinants that changed in a manner

consistent with improved BMD over the same time period,

support the possibility that a real change in FNBMD may

have occurred. This likelihood appears strongest for olderNHW women, since the FNBMD difference remained

statistically significant after adjusting for DXA methodol-

ogy. More work is needed to identify the underlying basis

for the increase in FNBMD in these older NHW women,

since adjusting for selected bone determinants that had

improved between surveys had little impact on the

magnitude of the FNBMD difference observed in this

group.

Conflicts of interest None.

Appendix 1

Specific drugs composing medication groups

I. Medications that increase BMD

(A) Sex hormones (NHANES III and NHANES

20052008)

1. Estrogens: estradiol, estradiol valerate, estrogenic

substances, conjugated estrogens, esterified estro-

gens (alone and with methyltestosterone), estro-

pipate, ethinyl estradiol (alone or with ethynodiol

diacetate, levonorgestrel, norethindrone, norethin-

drone acetate, or desogestrel), diethylstilbesterol

(alone or with disphosphate), fluoxymesterone, or

quinestrol.

2. Testosterones: testosterone, testosterone cypio-

nate, stanozolol and nandrolone decanoate.

(B) Non-estrogen drugs

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1. NHANES III: calcitonin, calcitriol, ergocalci-

ferol, etidronate, sodium fluoride, tamoxifen,

and calcium acetate.

2. NHANES 20052008: bisphosphonates (alendro-

nate, risedronate, etidronate, pamidronate, tiludro-

nate, ibandronate, zolendronate), calcitonin,

calcitriol, fluoride, raloxifene, tamoxifen, tibolone,

strontium ranelate, parathyroid hormone, andteriparatide.

II. Medications that decrease BMD (NHANES III and

NHANES 20052008)

1. Glucocorticoids: betamethasone, budesonide, corti-

sone, dexamethasone, hydrocortisone, methlpredni-

solone, prednisolone, prednisone, and triamcinolone.

2. Antineoplastic drugs: anastrozole, bicalutamide,

capecitabine, chlorambucil, cyclophosphamide, erlo-

tinib, estramustine, exemestane, fluorouracil, fluox-

ymesterone, flutamide, goserelin, hydroxyurea,

interferon alfa 2A and 2B, irinotecan, isotretinoin,letrozole, leuprolide, levamisole, lomustine, medrox-

yprogesterone, megestrol, mercaptopurine, metho-

trexate, nilutamide, tegafur or uracil, tretinoin, and

unspecified antineoplastics.

3. Anticonvulsants: carbamazepine, clonazepam, di-

azepam, divalproex sodium, ethosuximide, gaba-

pen tin , lamotrigine, lev eti rac eta m, lorazepam,

mephobarbital, methsuximide, oxcarbazepine, phe-

nobarbital, phenytoin, pregabalin, primidone, tiaga-

bine, topiramate, valproic acid, zonisamide.

4. Barbiturates: butabarbital, butalbital

5. Anticoagulants: heparin and enoxaparin.6. IV nutrition products: LVP solution with potassium

References

1. Looker AC, Melton LJ 3rd, Borrud Harris TB, Borrud LG,

Shepherd JA (2010) Prevalence and trends in low femur bone

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