Bone Health and Assessment in Children

Virginia Stallings, MDThe Children’s Hospital of Philadelphia

University of Pennsylvania School of Medicine

Overview

Assessing bone health in children:

Quantitative Ultrasound (QUS)

Dual Energy Xray Absorptometry (DXA)

Peripheral Quantitative Computed Tomography (pQCT)

DXA – Distal Femur site

Body Composition

Development of a Calcium Food Frequency Questionnaire

Vitamin D status

Bone Health Assessment

http://www.bowhouse.com.au

Children are not

little adults!

From Baroncelli 2008, Pediatric Research 62(3): 220-228.

Ultrasound Sites and TechniquesPhalanges – IGEA Tibia – Sunlight Omnisense

Calcaneus – Sahara, Cuba

Principles of QUS

Properties of the ultrasound wave (shape, amplitude) are altered by the material through which it passes in a way that is characteristic of the structural properties of the material

Material density and biomechanical properties (elastic modulus, compressive strength) of bone influence QUS waves

Principles of QUS

Trabecular bone scatters energy of ultrasound waves

Cortical bone absorbs energy of ultrasound waves

Principles of QUS

QUS applied to peripheral sites (calcaneus, phalanges, patella, radius, tibia)

Most ultrasound devices use a transmitter and detector to measure attenuation of the ultrasound wave

Critical angle reflectometry uses a single probe to measure the reflected wave as it travels along cortical bone and determine the speed of sound

Speed of Sound

From Baroncelli 2008, Pediatric Research 62(3): 220-228.

SoS – speed of sound; AD-SoS – amplitude dependent SoS; BTT – Bone transmission time (independent of soft tissue)

Sunlight Omnisense

Portable Versatile – can

measure radius or tibia Probe sizes for different

ages/sizes Pediatric reference data

from Israel

QUS Pediatric Reference Data

From Zadik et al. Osteoporosis International (10):857-62, 2003

Tibia Radius

Quantitative Ultrasound (QUS)

Advantages: Rapid assessment Radiation-free Inexpensive and portable Easily accessible measurement sites Can be used in subjects without sleep/sedation

Limitations: What are the bone properties (cortical vs

trabecular) being measured? Is it stable within an individual, and predictive of

fracture?

Dual energy x-ray absorptiometry - DXA

• Bone Mass, gm• Bone area, cm2

• Bone Density, gm/cm2

Advantages of DXA

Non-invasive test for measurement of BMD

Rapid, safe, easily tolerated, very low radiation exposure

Can assess bone density at different skeletal sites, both axial and peripheral

Widely available (100,000 in operation)

Excellent precision in children and adults

Pediatric Applications for DXA

Hologic infant software - Whole Body Scan Requires no movement (sleep or sedation) Clothing / swaddling material can affect body

composition results No reference data for current generation of

DXA scanners

Pediatric Applications for DXA

Infant Spine scans Not traditionally used for infants Rapid scan time Doesn’t require sedation No body composition data, but clothing less of an issue

AgeAll Study Subjects

Last 100 Subjects

6-12 mo 46/62 = 74% 25/31 = 81%

12-18 mo 26/35 = 74% 13/14 = 93%

18-24 mo 34/39 = 87% 25/26 = 96%

24-30 mo 34/36 = 94% 20/21 = 95%30-36 mo 32/33 = 97% 15/16 = 94%

Success Rate for Infant DXA Measurements Cincinnati Children's Medical Center

Why do both DXA and QUS

Tibia QUS is a measure of cortical bone DXA spine scan is an integrated measure of

cortical and trabecular bone Studies of cortical and trabecular bone

density changes during puberty stage suggest different effects in the 2 bone compartments

Why do both DXA and QUS

DXA can also be used for non-traditional measurement sites like the tibia to validate tibia QUS measurements

DXA is widely available and used clinically for children and adults, so study results may have greater clinical utility

Puberty Effects on Tibia Trabecular and Cortical Bone Density in Girls and Boys

150

200

250

300

350

Tra

becu

lar

Den

sity, gm

/cm

3

1 2 3 4 5

F M F M F M F M F M

Breast / Genital Stage

900

1,0

00

1,1

00

1,2

00

1,3

00

Co

rtic

al D

en

sity, gm

/cm

3

1 2 3 4 5

F M F M F M F M F M

Breast / Genital Stage

Other Measurement Sites

Distal FemurRadius Distal Femur

Peripheral Quantitative Computed Tomography

Peripheral Quantitative CT

Cortical DensityCortical Area

Total DensityTotal Area

Trabecular DensityTrabecular Area

Cortical DensityCortical AreaBone Strength

Bone Strength Index =

(Moment of Inertia x Density)

Peripheral Quantitative CT

Muscle Cross Muscle Cross Sectional AreaSectional Area

Cortical vBMD, Cortical vBMD, dimensions and dimensions and strengthstrength

Trabecular & Trabecular & Total vBMDTotal vBMD

66%

38%

3%

Distal Femur DXA Scan

Indicated for: Children with contractures Indwelling hardware that

would interfere with a spine or total body scan

Anomalies that would interfere with scan analysis or interpretation at standard sites

Might be especially useful for immobilized children who may be at increased risk of femur fractures

Henderson et al AJR Am J Roentgenol ;178:439

Zemel et al J Clin Dens 2009 (in press)

Development of the Calcium Counts Questionnaire

Conducted by interview with the assistance of food models and probing by interviewer

Recall over the previous 4 weeks because of the high intra-individual variability in calcium intake

Quantitative FFQ based on serving size and frequency of intake

First generation questionnaire: Modified an existing calcium food-frequency

questionnaire to capture foods that children usually eat based on recommendations of experienced pediatric research dietitians

Zemel et al (in review)

Development of the Calcium Counts Questionnaire Second generation questionnaire

Reviewed results of several hundred first generation questionnaires

Dropped items that were never selected Reviewed the CSFII data for African

Americans and Caucasians children – identified the top 50 sources of dietary calcium and added them to the questionnaire

Panel of pediatric research dietitians reviewed several nutrient content sources and assigned calcium values to items by consensus

Zemel et al (in review)

Validation of the Calcium Counts Questionnaire

Compared results of the CCFFQ to 7-d weighed food diaries in 139 children 7 to 10 years of age

Conducted a test-retest over a 1 month interval to determine reproducibility

Concurrent validity was moderate (r=0.61) and test-rest reliability was high (r=0.74)

CCFFQ, like most FFQs, overestimated calcium intake compared to weighed food record

Zemel et al (in review)

Radiation Exposure

Source Effective Dose Equivalent (Sv)

Natural Radiation Sources

Natural background radiation at sea level 3,000 per year

Roundtrip transcontinental airplane flight 60 QCT

Peripheral QCT (Stratec 2000) < 0.01

Spine QCT 30 – 100 DXA (Hologic QDR-4500)

Lumbar spine 3.8

Lateral spine 1.4

Whole body 2.6 Hand-wrist x-ray 1 Ultrasound 0

Gender differences in body composition

From Butte et al. 2000 Ped Research 47(5):578-85

Pea Pod (Air Displacement Plethysmograph)

Pea Pod Infant Body Composition

Uses air displacement to determine body volume

With an accurate weight and volume measurement →body density

If assume that fat tissue has a constant density, → body composition derived from body density → fat-free mass, fat mass and percent body fat

Pea Pod Infant Body Composition

Rapid assessment Safe, reliable, accurate, provides immediate

results Used up to measure infants up to ~4 to 6

months of age (1 to 8kg 1kg) Length is the usual limtation

SUMMARY

Major advances in technology support bone health assessment in all ages

Optimal reference data are limited Interpretation of results are complex in

children with illness Stature, FFM, velocity Not just age and gender