CLINICAL REPORT Optimizing Bone Health in...

CLINICAL REPORT

Optimizing Bone Health in Children and Adolescents

abstractThe pediatrician plays a major role in helping optimize bone health inchildren and adolescents. This clinical report reviews normal bone ac-quisition in infants, children, and adolescents and discusses factorsaffecting bone health in this age group. Previous recommended dailyallowances for calcium and vitamin D are updated, and clinical guid-ance is provided regarding weight-bearing activities and recommen-dations for calcium and vitamin D intake and supplementation.Routine calcium supplementation is not recommended for healthychildren and adolescents, but increased dietary intake to meet dailyrequirements is encouraged. The American Academy of Pediatricsendorses the higher recommended dietary allowances for vitamin Dadvised by the Institute of Medicine and supports testing for vitaminD deficiency in children and adolescents with conditions associatedwith increased bone fragility. Universal screening for vitamin D defi-ciency is not routinely recommended in healthy children or in childrenwith dark skin or obesity because there is insufficient evidence of thecost–benefit of such a practice in reducing fracture risk. The pre-ferred test to assess bone health is dual-energy x-ray absorptiometry,but caution is advised when interpreting results in children andadolescents who may not yet have achieved peak bone mass. Foranalyses, z scores should be used instead of T scores, and correctionsshould be made for size. Office-based strategies for the pediatricianto optimize bone health are provided. This clinical report has beenendorsed by American Bone Health. Pediatrics 2014;134:e1229–e1243

The antecedents of osteoporosis are established in childhood andadolescence, and the pediatrician plays a major role in helping op-timize bone health in the pediatric age group. Osteoporosis, a diseaseof increased bone fragility, is a major cause of morbidity and economicburden worldwide. It is estimated that by the year 2020, one-half ofAmericans older than 50 years will be at risk for osteoporotic frac-tures.1 Once thought to be an inevitable part of aging, osteoporosis isnow considered to have its roots in childhood, when preliminarypreventative efforts can be initiated. In fact, bone mass attained inearly life is thought to be the most important modifiable determinantof lifelong skeletal health.2 Osteoporosis is not restricted to adults; itcan occur in children and adolescents. The aim of the present clinicalreport was to review bone acquisition during infancy, childhood, andadolescence; discuss assessment of bone health, particularly as itapplies to children and adolescents; and update pediatricians onstrategies to improve bone health in the pediatric age group. Bone

Neville H. Golden, MD, Steven A. Abrams, MD, andCOMMITTEE ON NUTRITION

KEY WORDScalcium, dual-energy x-ray absorptiometry, DXA, osteoporosis,pediatrics, vitamin D

ABBREVIATIONS1,25-OH2-D—1,25 dihydroxyvitamin D25-OH-D—25-hydroxyvitamin DAAP—Academy of PediatricsBMC—bone mineral contentBMD—bone mineral densityDMPA—depot medroxyprogesterone acetateDXA—dual-energy x-ray absorptiometryIGF-1—insulin-like growth factor 1IOM—Institute of MedicinePTH—parathyroid hormoneRDA—recommended dietary allowance

This document is copyrighted and is property of the AmericanAcademy of Pediatrics and its Board of Directors. All authors havefiled conflict of interest statements with the American Academy ofPediatrics. Any conflicts have been resolved through a processapproved by the Board of Directors. The American Academy ofPediatrics has neither solicited nor accepted any commercialinvolvement in the development of the content of this publication.

The guidance in this report does not indicate an exclusive courseof treatment or serve as a standard of medical care. Variations,taking into account individual circumstances, may be appropriate.

This clinical report has been endorsed by American Bone Health,a national, community-based organization that provideseducation programs, tools, and resources to help the publicunderstand bone disease and bone health.

www.pediatrics.org/cgi/doi/10.1542/peds.2014-2173

doi:10.1542/peds.2014-2173

All clinical reports from the American Academy of Pediatricsautomatically expire 5 years after publication unless reaffirmed,revised, or retired at or before that time.

PEDIATRICS (ISSN Numbers: Print, 0031-4005; Online, 1098-4275).

Copyright © 2014 by the American Academy of Pediatrics

PEDIATRICS Volume 134, Number 4, October 2014 e1229

FROM THE AMERICAN ACADEMY OF PEDIATRICS

Guidance for the Clinician inRendering Pediatric Care

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health needs of pregnant women, lac-tating mothers, and preterm infantsare discussed elsewhere.3,4 This clinicalreport has been endorsed by AmericanBone Health, a national, community-based organization that provides edu-cation programs, tools, and resourcesto help the public understand bonedisease and bone health.

BONE ACQUISITION DURINGCHILDHOOD AND ADOLESCENCE

Bone is a living structure comprisinga matrix of collagen, hydroxyapatitecrystals, and noncollagenous proteins.The matrix becomes mineralized withdeposits of calcium and phosphate,which confers strength to the struc-ture. Bone mineral deposition beginsduring pregnancy, with two-thirds of inutero accrual occurring during thethird trimester.5 Bone mineral content(BMC) increases 40-fold from birthuntil adulthood, and peak bone massis achieved toward the end of thesecond decade of life, although theremay still be some net bone depositioninto the third decade.6–11 Approxi-mately 40% to 60% of adult bonemass is accrued during the adoles-cent years, with 25% of peak bonemass acquired during the 2-year pe-riod around peak height velocity. Afterinfancy, peak bone mineral accretionrates occur, on average, at 12.5 yearsfor girls and 14.0 years for boys.12 Atage 18 years, approximately 90% ofpeak bone mass has been accrued.13

Childhood and adolescence, therefore,are critical periods for skeletal min-eralization. Age of peak bone massaccrual lags behind age of peak heightvelocity by approximately 6 to 12months in both boys and girls.12 Thisdissociation between linear growth andbone mineral accrual may confer in-creased vulnerability to bone fragilityand may explain, to some degree, theincreased rate of forearm fractures inboys 10 through 14 years of age and

in girls 8 through 12 years of age.14,15

After peak bone mass is achieved, thereis a slow but progressive decline inbone mass until a theoretical fracturethreshold is reached. Any condition in-terfering with optimal peak bone massaccrual can, therefore, increase frac-ture risk later in life.

The skeleton is an active organ, con-stantly undergoing remodeling, evenafter linear growth has been com-pleted. During remodeling, bone for-mation, mediated via osteoblasts, andbone resorption, mediated by osteo-clasts, occur concurrently. Remodelingis regulated by local cytokines aswell as by circulating hormones, in-cluding parathyroid hormone (PTH),1,25-dihydroxyvitamin D (1,25-OH2-D),insulin-like growth factor 1 (IGF-1),and calcitonin. In young children, therate of cortical bone remodeling is ashigh as 50% per year. Net bone massdepends on the balance between boneresorption and bone formation. Ifformation exceeds resorption, as itshould during childhood and adoles-cence, net bone mass increases. If re-sorption exceeds formation, net bonemass is reduced.

PRIMARY PREVENTION:OPTIMIZING BONE HEALTH INHEALTHY CHILDREN

Factors affecting bone health areshown in Table 1. Genetic factors ac-count for approximately 70% of thevariance in bone mass,16 although nospecific responsible genes have beenidentified. Male subjects have higherbone mass than female subjects, andblack women have higher bone massthan white non-Hispanic women or Asianwomen. Mexican-American women havebone densities between those of whitenon-Hispanic and black women. Modifi-able determinants of bone mass includenutritional intake of calcium, vitamin D,protein, sodium, and carbonated bev-erages (ie, soda); exercise and lifestyle;

maintenance of a healthy body weight;and hormonal status. Nutrition andphysical activity are each necessaryand function synergistically to improvebone acquisition and maintenance.

CALCIUM

Calcium is necessary for bone accre-tion, and dietary calcium intake duringinfancy, childhood, and adolescenceaffects bone mass acquisition. Ap-proximately 99% of total body calciumis found in the skeleton, and calcium isabsorbed by both passive and activetransport, the latter mediated by vi-tamin D. Milk intake during childhoodand adolescence is associated withhigher BMC and reduced fracture riskin adulthood.17 The Institute of Medi-cine (IOM) has published updated di-etary reference intakes for calcium andvitamin D, and the American Academyof Pediatrics (AAP) endorses theserecommendations for infants, children,and adolescents (Table 2).18 The rec-ommended dietary allowance (RDA) isthe dietary intake that meets the re-quirements of almost all (97.5%) of thepopulation. Adequate intake is a singlevalue likely to meet the needs of mostchildren and is used for infants youn-ger than 12 months, for whom RDAshave not been established. The upperlimit represents the highest averagetotal daily intake likely to pose no risk

TABLE 1 Factors Affecting Bone Mass

NonmodifiableGeneticsGenderEthnicity

ModifiableNutritionCalciumVitamin DSodiumProteinSoda

Exercise and lifestyleBody weight and compositionHormonal status

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of adverse health effects for most peo-ple in that age group.

Sources of Calcium

Term Infants and Children

The primary source of nutrition forhealthy term infants in the first yearof life is human milk or, alternatively,infant formula if human milk is notavailable. Although the BMC may behigher in formula-fed infants than inbreastfed infants in the first year oflife, the breastfed infant does notdemonstrate any evidence of clinicalmineral deficiency, and there is noevidence that the breastfed infantshould not be the standard for bonemineral accretion. No data supporthigh mineral intake or supplementa-tion with calcium for healthy breastfedinfants.19 After the first year of life, themajor source of dietary calcium ismilk and other dairy products, whichtogether account for 70% to 80% ofdietary calcium intake. Each 8-oz (240-mL)serving of milk provides approximately300 mg of calcium, and the calciumcontent of low-fat or flavored milk issimilar to that of whole milk (Table 3).20

However, low-fat chocolate milk con-tains added sugar and more caloriesthan does low-fat plain milk. One cupof yogurt or 1.5 oz of natural cheeseeach provides approximately 300 mg ofcalcium. Other dietary sources of calciuminclude green leafy vegetables, legumes,nuts, and calcium-fortified breakfast

cereals and fruit juices. Vegetables con-tributed approximately 7% of the cal-cium in the food supply between 2000and 2006.21 Bioavailability of calciumfrom vegetables is generally high but isreduced by binding with oxalates inspinach, collard greens, rhubarb, andbeans. Although vegetables are a goodsource of bioavailable calcium, thequantity of vegetables required tomeet daily requirements is substantial,making it difficult to attain dietarycalcium requirements with vegeta-bles alone. Certain cereals (eg, wholebran cereals) contain phytates, whichalso reduce bioavailability.

Preadolescents and Adolescents

The calcium RDA for preadolescents andadolescents aged 9 through 18 yearsis 1300 mg/d. In the United States, theaverage dietary calcium intake of ado-lescent girls is 876 mg/d (67% of theRDA), and less than 15% meet the RDA.22

In 2011, only 14.9% of high school stu-dents drank three or more 8-oz serv-ings of milk per day, with only 9.3% ofgirls doing so.23 Milk consumption byadolescents has declined at the sametime that soda consumption has in-creased.24 Some adolescent girls avoidmilk products because they considerthem to be “fattening.” Such mythsshould be dispelled. For example, one8-oz serving of skim milk contains nofat and only approximately 80 kcal, ap-proximately the same caloric content

as an apple. In contrast, a can of sodacontains 140 kcal. Furthermore, milkprovides protein and a number of im-portant nutrients other than calcium,including vitamin D, phosphorus, andmagnesium, which are important inbone health. Milk alternatives, such assoy- or almond-based beverages, mayhave a reduced amount of bioavailablecalcium per glass, even when fortifiedwith calcium.25 Further research isneeded regarding the mineral levelsand bioavailability of these beverages.

Lactose intolerance occurs in childrenand adolescents and is more commonin black, Hispanic, and Asian subjects.Some of these children and adoles-cents will be able to tolerate smallamounts of dairy products other thanmilk. Others may benefit from lactose-reduced or lactose-freemilks and cheesesand/or lactase enzymes.26

Calcium Supplementation

Although a number of studies havedemonstrated a positive effect of cal-cium supplementation on BMC in healthychildren and adolescents,27,28 a recentmeta-analysis of randomized controlledtrials examining the effectiveness ofcalcium supplementation in increasingBMD in healthy children found thatthere was no effect of calcium supple-mentation on BMD of the lumbar spineor femoral neck; a small effect wasnoted on upper-limb BMD and totalbody BMC equivalent to approximately

TABLE 2 Calcium and Vitamin D Dietary Reference Intakes

Age Calcium Vitamin D

RDA (mg/d) (Intake That Meets Needsof ≥97.5% of Population)

UL (mg/d)a RDA (IU/d) (Intake That Meets Needsof ≥97.5% of Population)

UL (IU/d)a

Infants0–6 mo 200b 1000 400b 10006–12 mo 260b 1500 400b 1500

1–3 y 700 2500 600 25004–8 y 1000 2500 600 30009–13 y 1300 3000 600 400014–18 y 1300 3000 600 4000a Upper limit (UL) indicates level above which there is risk of adverse events. The UL is not intended as a target intake (no consistent evidence of greater benefit at intake levels above theRDA).b Reflects adequate intake reference value rather than RDA. RDAs have not been established for infants.




a 1.7% increase in bone mass.29 Theinvestigators concluded that, from apublic health perspective, calcium sup-plementation of healthy children is un-likely to result in a clinically significantreduction in fracture risk. For mostchildren and adolescents, the emphasisshould be on establishing healthy di-etary behaviors with a well-balanceddiet that includes calcium intake at ornear the recommended levels through-out childhood and adolescence. Dietarysources of calcium should be recom-mended in preference to calcium sup-plements, not only because of theimproved bioavailability of dietarysources of calcium, but also primarilyto encourage lifelong healthy dietaryhabits.

VITAMIN D

Vitamin D (calciferol) is a fat-solublehormone necessary for calcium ab-sorption and utilization. Without vitaminD, only 10% to 15% of dietary calcium isabsorbed.30 Vitamin D includes endoge-nous conversion of vitamin D2, ingestedanimal-derived cholecalciferol (vitaminD3), and plant-derived ergocalciferol (vi-tamin D2). Although there is increasingevidence that vitamin D may also havepotential benefits on cardiometabolicrisk factors, immunity, and cancer pre-vention, the focus of the present reportis on bone health.

In 2011, the IOM revised the RDAs forvitamin D intake to be higher than pre-vious recommendations (Table 2), and

the AAP endorsed these recommen-dations.31 Vitamin D deficiency results inrickets in young children (peak in-cidence: 3–18 months of age) and in-creased fracture risk in older children,adolescents, and adults. Deficiency isparticularly common in those living innorthern climates, those with darkskin, and those with inadequate expo-sure to sunlight, but deficiency alsooccurs in sunny climates.32,33 NationalUS data reveal higher rates of vitaminD deficiency in adolescents comparedwith younger children34 and increasingprevalence from the 1988–1994 to2001–2004 data collections.35 Cross-sectional studies of vitamin D statusin adolescents have found deficiency in17% to 47% of adolescents,32,33,36,37 withincreased risk in black and Hispanicteenagers33,37,38 and lower vitamin Dconcentrations in the winter.36–38 Chil-dren and adolescents who are obeseare at increased risk,33,39,40 possiblybecause of sequestration of vitamin Din body fat. Certain medications, suchas anticonvulsant, glucocorticoid, anti-fungal, and antiretroviral medications,increase requirements and predisposesubjects to deficiency. Severe vitamin Ddeficiency is associated with reducedbone mass in adolescents.41,42 On thebasis of results of a longitudinal pro-spective study of 6712 physically activegirls aged 9 through 15 years, vitamin Dintake—not calcium or dairy intake—during childhood is associated withreduced risk of stress fractures.43

Vitamin D3 is synthesized in the skinfrom 7-dehydrocholesterol on exposureto sunlight, binds to vitamin D–bindingprotein, and is transported to the liverwhere it undergoes hydroxylation toform 25-hydroxyvitamin D (25-OH-D). Thehalf-life of 25-OH-D is 2 to 3 weeks, andserum 25-OH-D is a good indicator ofvitamin D stores. Circulating 25-OH-Dundergoes a second round of hydrox-ylation in the kidney to form 1,25-OH2-D,the active form of the hormone. In

TABLE 3 Dietary Sources of Calcium

Food Serving Size Calories per Portion Calcium Content (mg)

Dairy foodsMilkWhole milk 8 oz 149 276Reduced fat milk (2%) 8 oz 122 293Low-fat milk (1%) 8 oz 102 305Skim milk (nonfat) 8 oz 83 299Reduced-fat chocolate milk (2%) 8 oz 190 275Low-fat chocolate milk (1%) 8 oz 158 290

YogurtPlain yogurt, low-fat 8 oz 143 415Fruit yogurt, low-fat 8 oz 232 345Plain yogurt, nonfat 8 oz 127 452

CheeseRomano cheese 1.5 oz 165 452Swiss cheese 1.5 oz 162 336Pasteurized processed American cheese 2 oz 187 323Mozzarella cheese, part skim 1.5 oz 128 311Cheddar cheese 1.5 oz 171 307Muenster cheese 1.5 oz 156 305

Nondairy foodsSalmon 3 oz 76 32Sardines, canned 3 oz 177 325White beans, cooked 1 cup 307 191Broccoli, cooked 1 cup 44 72Broccoli, raw 1 cup 25 42Collards, cooked 1 cup 49 226Spinach, cooked 1 cup 41 249Spinach, raw 1 cup 7 30Baked beans, canned 1 cup 680 120Tomatoes, canned 1 cup 71 84

Calcium-fortified foodOrange juice 8 oz 117 500Breakfast cereals 1 cup 100–210 250–1000Tofu, made with calcium 0.5 cup 94 434Soy milk, calcium fortifieda 8 oz 104 299

Data source: Dietary Guidelines for Americans, 2010. Available at: www.ndb.usda.gov.a Not all soy beverages are fortified to this level.


www.ndb.usda.gov

contrast to 25-OH-D, 1,25-OH2-D has a half-life of 4 hours.44 Under control of PTH,1,25-OH2-D promotes intestinal absorptionof calcium and phosphorus, increasesrenal reabsorption of filtered calcium, andmobilizes calcium from skeletal stores.

Sources of Vitamin D

Sunlight

Exposure to UV B radiation in the rangeof 290 to 315 nm from sunlight is themajor source of vitamin D. Synthesisof vitamin D depends on latitude, skinpigmentation, sunscreen use, and timeof day of exposure. Synthesis of vita-min D is minimal during winter monthsnorth of 33° latitude in the northernhemisphere and south of 33° latitudein the southern hemisphere. Exposure ofarms and legs to 0.5 minimal erythemaldose of sunlight for 5 to 15 minutes, 2 to3 times a week, produces approximately3000 IU of vitamin D.31 Subjects with darkskin require exposure 3 to 5 times lon-ger. Sunscreen with a sun protectionfactor 8 or higher effectively preventstransmission of UV B radiation throughthe skin and blocks the synthesis ofvitamin D3. Maximal synthesis occursbetween the hours of 10:00 AM and 3:00 PM

in the spring, summer, and fall.45 Childrenand adolescents are spending more timeindoors and, because of concerns re-garding skin cancer later in life, whenthey do go outside, they often wear sunprotection, which limits the skin’s abilityto synthesize vitamin D. With decreasedsynthesis of vitamin D from reduced sunexposure, dietary sources of vitamin Dbecome more important.

Dietary Sources

Natural dietary sources of vitamin Dare limited but include cod liver oil,fatty fish (eg, salmon, sardines, tuna),and fortified foods. Farm-raised salmonhas lower concentrations of vitamin Dthan does fresh, wild-caught salmon.31

Human milk does not provide adequateamounts of vitamin D (approximately

20 IU/L). In the United States and Canada,all infant formula is fortified with vitaminD. Cow milk, infant formula, and fortifiedfruit juices each contain approximately100 IU of vitamin D per 8 oz (Table 4).

Recommended Daily Intake andVitamin D Supplementation

Adequate vitamin D intake for infantsyounger than 1 year is 400 IU/d. TheRDA is 600 IU for children 1 year andolder. Because human milk containsinadequate amounts of vitamin D (un-less the lactating mother is takingsupplements of approximately 6000 IU/d),breastfed and partially breastfed infantsshould be supplemented with 400 IU ofvitamin D per day beginning in the firstfew days of life and continued until theinfant has been weaned and is drinkingat least 1 L/d of vitamin D–fortified infantformula or cow milk. Daily supplemen-tation of breastfed infants with 400 IUof vitamin D during the first months oflife increases 25-OH-D amounts to nor-mal concentrations.46,47 Although the RDA

for children older than 1 year and foradolescents is 600 IU, children who areobese and children on anticonvulsant,glucocorticoid, antifungal, and anti-retroviral medications may require 2to 4 times the recommended dose ofvitamin D to achieve serum 25-OH-Dvalues the same as children withoutthese conditions; at this time, however,definitive recommendations for thesechildren remain unavailable.

Although approximately 98% of cowmilk in the United States is fortifiedwith vitamin D, some yogurts, cheeses,juices, and breakfast cereals are alsofortified with similar amounts of vitaminD (Table 4) and can generally be rec-ommended in preference to nonfortifiedfoods. For those who are unable toachieve adequate amounts of vitamin Din their diet or who have vitamin Ddeficiency, vitamin D supplements areavailable in 2 forms: vitamin D2 (ergo-calciferol), derived from plants, andvitamin D3 (cholecalciferol), synthesizedby mammals. Drisdol (Sanofi-Aventis US,

TABLE 4 Sources of Vitamin D

Food Serving Size Vitamin D Contenta (IU)

Natural sourcesSalmonFresh wild 3.5 oz 600–1000Fresh farmed 3.5 oz 100–250

Sardines, canned 3.5 oz 300Mackerel, canned 3.5 oz 250Tuna, canned 3.5 oz 236Shitake mushroomFresh 3.5 oz 100Canned 3.5 oz 1600

Egg, hard-boiled 3.5 oz 20Vitamin D–fortified foodsInfant formula 1 cup (8 oz) 100Milk 1 cup (8 oz) 100Orange juiceb 1 cup (8 oz) 100Yogurtsb 1 cup (8 oz) 100Cheesesb 3 oz 100Breakfast cerealsb 1 serving 40–100

Pharmaceutical sources inthe United StatesVitamin D2 (ergocalciferol) 1 capsule 50 000Drisdol (vitamin D2) liquid 1 cc 8000

Supplemental sourcesMultivitamin 400, 500, 1000Vitamin D3 400, 800, 1000, 2000, 5000, 10 000, 50 000

a The activity of 40 IU of vitamin D is equivalent to 1 μg.b Not all brands of orange juice, yogurt, and cheese are fortified with vitamin D.




Bridgewater, NJ) is a vitamin D2 prepa-ration that contains 8000 IU/mL, andmost multivitamins contain 400 IU pertablet. Some calcium preparations alsocontain vitamin D. In adolescent girls,supplementation of 200 to 400 IU ofvitamin D3 was effective in increasingBMD in a dose-response manner.48 Thedaily upper limits are as follows: in-fants up to 6 months of age: 1000 IU;infants 6 to 12 months of age: 1500 IU;children 1 through 3 years of age: 2500IU; children 4 through 8 years of age:3000 IU; and children and adolescents9 through 18 years of age: 4000 IU(Table 2).

Assessment of Vitamin D Status

Measurement of serum 25-OH-D con-centration reflects both endogenoussynthesis and dietary intake of vitaminD and is the optimal method of as-sessment of vitamin D status.45 The2011 RDAs were selected to ensurethat nearly all those who receive theRDA will have a serum 25-OH-D con-centration greater than 20 ng/mL. Thisvalue was derived on the basis of anassumption of minimal exposure tosunlight and minimal solar vitamin Dconversion. The 25-OH-D concentrationof 20 ng/mL was also set as a targetby the Pediatric Endocrine Society andthe European Society for PaediatricGastroenterology, Hepatology and Nu-trition.44,49 In contrast, the EndocrineSociety has defined vitamin D de-ficiency as a 25-OH-D concentration<20 ng/mL (50 nmol/L) and insufficiencyas a 25-OH-D concentration between 21and 29 ng/mL (52.3–72.5 nmol/L).45 Con-troversy remains as to whether thereare specific health benefits to a highertarget, such as 30 ng/mL or higher, forhealthy children. In a population of healthywhite Danish and Finnish girls, a dailyintake of approximately 750 IU of vitaminD was necessary to enable 97.5% of thesubjects to achieve a 25-OH-D concentra-tion above 20 ng/mL, in support of theIOM recommendations.50

Screening for Vitamin D Deficiency

Evidence is insufficient to recommenduniversal screening for vitamin D de-ficiency. The Endocrine Society rec-ommends that “at-risk individuals”should be screened; these includechildren with obesity, black and His-panic children, children with malab-sorption syndromes, and children onglucocorticoid, anticonvulsant, antifungal,and antiretroviral medications.45 Thereis concern, however, with these rec-ommendations, because they wouldinvolve screening, treating, and retestinglarge numbers of children without goodevidence of the cost–benefit in reducingfracture risk (as opposed to improvingserum 25-OH-D concentrations) in ahealthy population.51 For example, blackyouth have lower 25-OH-D concen-trations than do white youth, but blacksubjects also have higher bone massand reduced fracture risk. The IOM andexisting AAP reports do not make rec-ommendations specific to screening. Inthe absence of evidence supporting therole of screening healthy individualsat risk for vitamin D deficiency in re-ducing fracture risk and the potentialcosts involved, the present AAP reportadvises screening for vitamin D de-ficiency only in children and adoles-cents with conditions associated withreduced bone mass and/or recurrentlow-impact fractures. More evidence isneeded before recommendations canbe made regarding screening of healthyblack and Hispanic children or childrenwith obesity. The recommended screen-ing is measuring serum 25-OH-D con-centration, and it is important to besure this test is chosen instead ofmeasurement of the 1,25-OH2-D con-centration, which has little, if any,predictive value related to bone health.

Treatment of Vitamin D Deficiency

Both vitamin D2 and vitamin D3 in-crease serum 25-OH-D concentrations.In adults, some52,53 but not all54 studies

have suggested that vitamin D3 is moreeffective in increasing serum 25-OH-Dconcentrations than is vitamin D2. Ininfants and toddlers, 2000 IU of vitaminD2 daily, 2000 IU of vitamin D3 daily, and50 000 IU of vitamin D2 weekly wereequivalent in increasing serum 25-OH-Dconcentrations.55 Infants and toddlerswith vitamin D deficiency can be given50 000 IU of vitamin D2 or vitamin D3weekly for 6 weeks or 2000 IU of vitaminD2 or vitamin D3 daily for 6 weeks, fol-lowed by a maintenance dose of 400 to1000 IU/d. Children and adolescents canbe treated with vitamin D2 or vitamin D3(50 000 IU, 1 capsule weekly) for 6 to 8weeks or 2000 IU of vitamin D2 or vi-tamin D3 daily for 6 to 8 weeks toachieve a serum 25-OH-D concentrationgreater than 20 ng/mL, followed by amaintenance dose of 600 to 1000 IU/d(Table 5).18,45 After completion of treat-ment, repeat serum 25-OH-D concen-trations should be obtained. It is notunusual for a second course of treat-ment to be necessary to achieve ade-quate concentrations of serum 25-OH-D.There is no strong evidence aboutwhether to treat healthy children whohave serum 25-OH-D concentrations be-tween 21 and 29 ng/mL.

SODA CONSUMPTION, PROTEIN,AND OTHER MINERALS

In 2010, 24.3% of US high school stu-dents drank at least 1 serving of sodadaily.56 A recent meta-analysis of 88studies reported that soda consump-tion is associated with lower intake ofmilk and calcium, and larger effectsizes were found with longitudinal andexperimental studies compared withcross-sectional studies. The replacementof milk in the diet by soda can preventadolescents from achieving adequatecalcium and vitamin D intake, and be-cause soda consumption has no healthbenefit, it should be avoided.57

Diets low in protein or high in sodiumwill predispose subjects to reduced


calcium retention.58,59 Sodium and cal-cium share the same transport systemin the proximal tubule, and a high-sodiumdiet promotes increased urinary calciumexcretion and should be avoided.

EXERCISE AND LIFESTYLE

Mechanical forces applied to the skeleton(mechanical loading) increase boneformation, and weight-bearing exerciseimproves bone mineral accrual inchildren and adolescents.60 In healthychildren, an exercise program in-corporating high-impact, low-frequencyexercises such as jumping, skipping,and hopping for 10 minutes 3 times aweek increased BMD of the femoralneck in the intervention group com-pared with control subjects.61–63 Thegreatest effect was observed in chil-dren in early puberty. A population-based prospective controlled trial inSweden demonstrated that a school-based, moderately active, 4-year exer-cise program increased bone massand size in children aged 7 through9 years without increasing fracturerisk.64 Adolescent female athletes havehigher BMD than nonathletes, providedthey are menstruating regularly. Whenfemale athletes become amenorrheic,the protective effect of exercise on BMDis lost.65 Children who are immobilizedhave rapid declines in bone mass.

Increases in BMD are site specific,depending on the loading patterns ofthe specific sport. For example, BMD isgreater in gymnasts at the hip andspine, in runners at the femoral neck,and in rowers at the lumbar spine; tennisplayers have higher radial BMD in the

dominant arm than in the nondominantarm. High-impact sports (eg, gymnastics,volleyball, karate) or odd-impact sports(eg, soccer, basketball, racquet sports)are associated with higher BMD andenhanced bone geometry.66

For most children and adolescents,walking, jogging, jumping, and dancingactivities are better for bone healththan are swimming or bicycle riding.Excessive high-impact exercise can,however, increase fracture risk. A pro-spective longitudinal study of 6831 highschool girls found that those who par-ticipated in more than 8 hours per weekof running, basketball, cheerleading, orgymnastics were twice as likely tosustain a fracture compared with lessactive girls. The authors suggested thatgirls who participate in these sportsshould also include cross-training inlower impact activities.67

Lifestyle choices may also confer ad-ditional risk for BMD deficits. In adults,smoking, caffeine, and alcohol intake areall associated with reduced BMD,68–70

and these behaviors should be avoidedin children and adolescents.

BODY WEIGHT

Body weight and composition are im-portant modifiable determinants ofbone mass. Mechanical loading duringweight-bearing activities stimulates boneformation, andmultiple studies in healthyadolescents8,71–73 and in those with an-orexia nervosa74–77 have demonstratedthat BMD is directly correlated withBMI. Lean body mass is most stronglyassociated with BMD,78 but increasedadiposity can also be associated with

increased fracture risk.79 Maintenanceof a healthy body weight during child-hood and adolescence is thereforerecommended to optimize bone health.

HORMONAL STATUS

Several hormones affect bone mass.Estrogen plays an important part inmaintaining BMD in women, and es-trogen deficiency is associated with in-creased bone resorption and increasedfracture risk. Testosterone, growthhormone, and IGF-1 all promote boneformation, whereas glucocorticoid ex-cess both increases bone resorptionand impairs bone formation.

SECONDARY PREVENTION:ASSESSMENT OF POPULATIONS ATRISK FOR INCREASED BONEFRAGILITY

Conditions Associated WithReduced Bone Mass in Childrenand Adolescents

Conditions associated with reduced bonemass and increased fracture risk inchildren and adolescents are listed inTable 6. Osteogenesis imperfecta, idio-pathic juvenile osteoporosis, and Turnersyndrome are rare conditions with in-creased bone fragility, best managedby pediatric endocrinologists, geneticists,and specialists in pediatric bone health.Children with chronic illnesses are, how-ever, frequently managed by generalpediatricians. Cystic fibrosis, systemiclupus erythematosus, juvenile idiopathicarthritis, inflammatory bowel disease,celiac disease, chronic renal failure,childhood cancers, and cerebral palsy

TABLE 5 Treatment of Vitamin D Deficiency

Age Preparation and Dosea

Infants, 0–12 mo Vitamin D2 or D3 50 000 IU weekly for 6 wk or Vitamin D2 or D3 2000 IU daily for 6 wkFollowed by a maintenance dose of 400–1000 IU daily

Children and adolescents, 1–18 y Vitamin D2 or D3 50 000 IU weekly for 6-8 wk or Vitamin D2 or D3 2000 IU daily for 6–8 wkFollowed by a maintenance dose of 600–1000 IU daily

Vitamin D2, ergocalciferol; vitamin D3, cholecalciferol.a Vitamin D3 may be more potent than vitamin D2.




can all be associated with reduced bonemass.78,80–84 Risk factors include malnu-trition, increased metabolic requirements,intestinal malabsorption, low body weight,chronic inflammation with increasedcytokine production, hypogonadism,immobilization, and the effects of pro-longed glucocorticoid therapy. Childrenwith cerebral palsy are at particularrisk. One study found that 77% of chil-dren with cerebral palsy had a femoralneck BMD z score less than –2.0, and26% of children older than 10 yearshad sustained a fracture.84

Eating disorders are prevalent in ad-olescents.85 Anorexia nervosa is asso-ciated with reduced BMD and increasedfracture risk,74–76,86–89 and the reductionin bone mass occurs after a relativelyshort duration of illness.74,90 Etiologic

factors include poor nutrition, lowbody weight, estrogen deficiency, andhypercortisolism. The degree of re-duction of BMD is directly related to thedegree of malnutrition, and in girls, isrelated to the duration of amenorrhea.Low BMD is also found in boys withanorexia nervosa and is associated withlow testosterone concentrations.91 Pa-tients with partial eating disorders orthose with bulimia nervosa may alsohave reduced bone mass, especially ifthey are or have been of low weight.89,92,93

The “female athlete triad” refers to 3interrelated conditions seen in femaleathletes: low energy availability, men-strual dysfunction, and reduced BMD.94

Low energy availability refers to in-adequate energy intake for the levelof physical activity. The energy deficitmay be unintentional secondary toa lack of knowledge regarding theincreased energy requirements ofathletes or it may be intentional andassociated with an underlying eatingdisorder. There is suppression ofthe hypothalamic-pituitary-ovarian axis,resulting in amenorrhea, a low estro-gen state, reduced bone mass, andincreased fracture risk.

Endocrine conditions associated with glu-cocorticoid or PTH excess, hypogonadism,hyperthyroidism, or deficiency of growthhormone or IGF-1 are all associated withlow bone mass (Table 6). Certain medi-cations, including anticonvulsants andchemotherapeutic agents, prolonged useof proton pump inhibitors, and selectiveserotonin reuptake inhibitors, can alsohave a negative effect on bone mass.Depot medroxyprogesterone acetate(DMPA) is a very effective long-actingcontraceptive that has been credited,to some degree, for the reduction inadolescent pregnancy rates in theUnited States over the past decade.Prolonged use of DMPA in adolescentgirls is associated with hypothalamicsuppression and reduced bone mass,however.95 In 2004, the US Food and

Drug Administration issued a blackbox warning to inform practitionersabout the negative effects of DMPAon bone mass. Discontinuation of DMPAis associated with rapid improvementsin bone mass, although it is not knownhow much of potential maximum peakbone mass is recovered.96 For mostadolescents, the risk of fracture whiletaking DMPA is low, and the benefit oftaking the medication outweighs therisks. The Society for Adolescent Healthand Medicine recommends continuingto prescribe DMPA to adolescent girlsneeding contraception but recommendsexplanation of the risks and benefits.97

The American College of Obstetrics andGynecology further states that concernsabout the effect of DMPA on BMD shouldneither prevent practitioners from pre-scribing it nor limit its use to 2 con-secutive years.98 In adolescent girls,low-dose oral contraceptives containingless than 30 μg of ethinyl estradiol mayinterfere with peak bone mass acquisitioncompared with oral contraceptives con-taining ≥30 μg of ethinyl estradiol.99,100

Despite a possible reduction in BMDin oral contraceptive users, a recentCochrane review of observational stud-ies found no association between oralcontraceptive use and increased frac-ture risk.101

Assessment of Bone Health

The ideal method of assessment ofclinically relevant bone health is de-termination of fracture risk on thebasis of longitudinal data. However, thereis a paucity of longitudinal studies ex-amining factors affecting bone health inchildren on the basis of incidence offractures. Fracture risk depends not onlyon skeletal fragility but also on age, bodyweight, history of fractures, and theforce of an injury. Skeletal fragility, inturn, is dependent on a number of factorsin addition to bone mass, including bonesize, geometry, microarchitecture, andbending strength. For example, bendingstrength depends on the radius of a bone,

TABLE 6 Conditions Associated WithReduced Bone Mass in Childrenand Adolescents

Genetic conditionsOsteogenesis imperfectaIdiopathic juvenile osteoporosisTurner syndrome

Chronic illnessCystic fibrosisConnective tissue disorders (lupus, juvenile

idiopathic arthritis, juveniledermatomyositis)

Inflammatory bowel disease, celiac diseaseChronic renal failureChildhood cancerCerebral palsyChronic immobilization

Eating disorders, including anorexia nervosa,bulimia nervosa, eating disorders nototherwise specified, and the female athletetriad

Endocrine conditionsCushing syndromeHypogonadismHyperthyroidismHyperparathyroidismGrowth hormone deficiencyDiabetes mellitus

MedicationsGlucocorticoidsAnticonvulsantsChemotherapyLeuprolide acetateProton pump inhibitorsSelective serotonin reuptake inhibitorsDMPA


and a large bonewill bemore resistant tofracture than a smaller bone, even whenboth bones have the same BMC or BMD.Bone mass, which accounts for approx-imately 70% of bone strength, can beused as a surrogate measure of bonehealth, recognizing that a low bone massin children does not necessarily translateto increased fracture risk.

Dual-energy x-ray absorptiometry (DXA)is the preferred method of assessmentof bone mass because of its availability,speed, precision, and low dose of ra-diation (5–6 mSv for the lumbar spine,hip, and whole body, which is less thanthe radiation exposure of a transcon-tinental flight and one-tenth that of astandard chest radiograph).102 DXA mea-sures BMC and calculates areal BMDby dividing BMC by the area of the re-gion scanned. DXA machines are widelyavailable, and robust pediatric referencedatabases for children older than 5years are included with the software ofthe major DXA manufacturers.103–106 Inpediatric patients, the preferred sitesof measurement are the lumbar spineand whole body.107 In children, the hipis less reliable because of variability inpositioning and difficulties identifyingbony landmarks. Scanning time of thehip or spine is less than 1 minute; forthe whole body, it is approximately 5minutes. In adults, each SD reductionin BMD below the young adult meandoubles the fracture risk. Osteoporosisis operationally defined as a BMD 2.5or more SDs below the young adultmean (a T score less than –2.5), andosteopenia is defined as a BMD ≥1 SDbelow the young adult mean (a T scoreof less than –1.0). However, cautionshould be used in interpreting DXA re-sults in children. First, because childrenhave not yet achieved peak bone mass,z scores (the number of SDs below theage-matched mean) should be used in-stead of T scores. Second, DXA measures2-dimensional areal BMD (expressedas grams per square centimeter), as

opposed to 3-dimensional volumetricBMD (expressed in grams per cubiccentimeter), and areal BMD underes-timates true volumetric BMD in subjectswith smaller bones. Third, many childrenwith chronic illness have growth retar-dation and delayed puberty. Therefore,a correction should be made for heightor height age, and a number of math-ematical corrections have been pro-posed.108–110

The International Society for ClinicalDensitometry recommends that theterm “osteopenia” no longer be usedin pediatric DXA reports and that thediagnosis of osteoporosis not be madeon the basis of DXA results alone.107 Inthe pediatric age group, the diagnosisof osteoporosis requires both a lowBMD or BMC (defined as a z score lessthan –2) and a clinically significantfracture (defined as a long-bone frac-ture of the lower extremity, a vertebralcompression fracture, or 2 or morelong-bone fractures of the upper ex-tremity).107,111 Longitudinal studies inchildren and adolescents have demon-strated a high degree of tracking overa period of 3 years.112 In other words,children with low bone density continueto have low bone density over time. Incontrast to adults, in pediatrics, there isno specific BMD z score below whichfractures are more likely to occur, butthere is a growing body of literaturedemonstrating an association betweenlow bone mass measured by using DXAand fracture risk in children.113–115

Limited evidence is available to guidepediatricians regarding when to or-der a DXA. In general, a DXA should beperformed to identify children andadolescents at risk for skeletal fra-gility fractures and to guide treatmentdecisions. The AAP’s “Clinical Report—Bone Densitometry in Children andAdolescents” recommends ordering aDXA for children and adolescents withclinically significant fractures (definedearlier) sustained after minimal trauma

(defined as falling from standing heightor less) and in those with medicalconditions associated with increasedfracture risk.116 Evidence is insufficientto support obtaining a DXA in childrenand adolescents taking medicationsthat can adversely affect bone or inhealthy children with recurrent trau-matic fractures of the fingers or toes.DXA scans are usually repeated after1 year and should not be repeated at aninterval of less than 6 months.

Quantitative computed tomographymeasures true volumetric BMD, butthe radiation exposure dose is high(30–7000 mSv). Newer modalities, suchas peripheral quantitative computedtomography, can measure volumetricBMD of the appendicular skeleton withmuch lower radiation doses but are notwidely available for clinical use. Quanti-tative ultrasonography is a noninvasivemethod of assessing bone health bymeasuring speed of an ultrasound waveas it is propagated along the surface ofbone. This method is difficult to in-terpret because of a lack of pediatricreference data, however, and poor pre-cision in the pediatric population.

TERTIARY PREVENTION: SPECIFICTREATMENTS TO INCREASE BONEMASS IN POPULATIONS ATINCREASED RISK OF FRACTURE

In most chronic diseases associatedwith low BMD, treatment of the un-derlying condition helps improve bonemass, and specific interventions willdepend on the underlying condition.

Calcium Supplementation

Depending on the medical condition,for those children and adolescents whoare unable to consume enough calciumfrom dietary sources, including fortifiedfoods, calcium supplementation can beprescribed. The most common forms ofsupplemental calcium are calcium car-bonate (40% elemental calcium) andcalcium citrate (21% elemental calcium).




Calcium carbonate should be taken withmeals to promote absorption, but cal-cium citrate does not require gastricacid for absorption and can be taken onan empty stomach.117 Calcium supple-ments are available in liquid, tablet, andchewable preparations.

Treatment of Vitamin D Deficiency

Screening for vitamin D deficiency byobtaining a serum 25-OH-D concen-tration is recommended in patients atincreased risk of bone fragility and inthose with recurrent low-impact frac-tures. Although a serum 25-OH-D con-centration of 20 ng/mL is considerednormal for healthy children and adoles-cents, some experts aim for achievementof a serum 25-OH-D concentration above30 ng/mL in populations at increased riskof fracture, given the potential benefitsand unlikely risk of toxicity of doses re-quired to achieve this concentration (theupper limit for a child older than 9years is 4000 IU/d).118 Pediatric treat-ment regimens for vitamin D deficiencyare outlined in Table 5.

Bisphosphonates

Bisphosphonates inhibit osteoclast-mediated bone resorption and havebeen used to increase BMD and reducefracture risk in childrenwith osteogenesisimperfecta,119–121 cerebral palsy,122 andconnective tissue disorders123,124 and chil-dren treated with corticosteroids.123,125–127

Pilot studies have also been conductedin adolescents with anorexia nervosa.128

In osteogenesis imperfecta, an open-label study examining the use of cyclicadministration of intravenous pamidro-nate reported reduced pain and fracturesassociated with dramatic increases inBMD.119 A recent multicenter, randomizedcontrolled trial found increases in lum-bar spine BMD (51% vs 12% in controlsubjects) with oral alendronate but nosignificant change in fracture in-cidence.121 Use of bisphosphonates inchildren remains controversial because

of the potential adverse effects ofthese agents and their long half-lives.Bisphosphonates are incorporated intobone and may be slowly released fromthe bone even after the medication hasbeen discontinued. Because of the pau-city of studies on efficacy and long-termsafety, at this time these agents shouldnot be used to treat asymptomatic re-duction in bone mass in children, andtheir use should be restricted to osteo-genesis imperfecta and other selectconditions with recurrent fractures, se-vere pain, or vertebral collapse.129,130

Oral Contraceptives

Adolescent girls with anorexia nervosaor the female athlete triad are fre-quently prescribed oral contraceptivesto improve bone mass, even with noevidence of their efficacy.131 Prospectivecohort studies and randomized con-trolled trials have both shown that oralcontraceptives do not increase bonemass in subjects with anorexia ner-vosa or in female athletes.75,132–135 Be-cause of this lack of demonstratedefficacy, their use is not recommendedto increase bone mass. In girls withanorexia nervosa, oral contraceptiveswill induce monthly menstruation, whichmay be incorrectly interpreted as an in-dication of adequate weight restoration.

THE ROLE OF THE PEDIATRICIAN

1. Ask about dairy intake, nondairysources of calcium and vitamin D,use of calcium and/or vitamin Dsupplements, soda consumption,and type and amount of exerciseat health maintenance visits. Sug-gested ages to ask these questionsare 3 years, 9 years, and duringthe annual adolescent health main-tenance visits.

2. Encourage increased dietary intakeof calcium- and vitamin D–containingfoods and beverages. Dairy productsconstitute the major source of die-tary calcium, but calcium-fortified

drinks and cereals are available.Low-fat dairy products, includingnonfat milk and low-fat yogurts,are good sources of calcium. Chil-dren 4 through 8 years of age re-quire 2 to 3 servings of dairyproducts or equivalent per day. Ado-lescents require 4 servings per day(Table 3). Suggested targeted ques-tions include: “What kind of milk ordairy products do you consume?”“How many servings do you con-sume a day?” (One serving is an 8-oz glass of milk, an 8-oz yogurt, or1.5 oz of natural cheese.) “In additionto dairy, what calcium-fortified foodsdo you buy or have you thoughtabout buying?” Current data do notsupport routine calcium supplemen-tation for healthy children and ado-lescents. The RDA of vitamin D forchildren 1 year and older is 600 IU.Children who are obese and childrenon anticonvulsant, glucocorticoid,antifungal, or retroviral medicationsmay require higher doses, but spe-cific end points and targets remainpoorly defined.

3. Encourage weight-bearing activi-ties. Walking, jumping, skipping,running, and dancing activitiesare preferable to swimming or cy-cling to optimize bone health.

4. Routine screening of healthy childrenand adolescents for vitamin D defi-ciency is not recommended. Thosewith conditions associated with re-duced bone mass (Table 6) or recur-rent low-impact fractures shouldhave a serum 25-OH-D concentrationmeasured. Those who have vitamin Ddeficiency should be treated andhave 25-OH-D concentrations mea-sured after completion of treatment.

5. Consider a DXA in medical condi-tions associated with reduced bonemass and increased bone fragilityand in children and adolescentswith clinically significant fracturessustained after minimal trauma. In


children, z scores should be usedinstead of T scores. In those withgrowth or maturational delay, cor-rections should be made for heightor height age.

6. In adolescent female subjects, dis-courage preoccupation with extremethinness. A DXA should be consid-ered in an adolescent athlete whohas been amenorrheic for morethan 6 months. Athletes, parents,and coaches should be educatedabout the female athlete triad. Thereis no evidence to support prescrib-ing oral contraceptives to increasebone mass in those with anorexianervosa or the female athlete triad.

7. Until more studies demonstratingsafety and efficacy in other popula-

tions have been conducted, use ofbisphosphonates in children and ado-lescents should be restricted to osteo-genesis imperfecta and conditionsassociated with recurrent fractures,severe pain, or vertebral collapse.

LEAD AUTHORSNeville H. Golden, MDSteven A. Abrams, MD

COMMITTEE ON NUTRITION, 2013–2014Stephen R. Daniels, MD, PhD, ChairpersonSteven A. Abrams, MDMark R. Corkins, MDSarah D. de Ferranti, MDNeville H. Golden, MDSheela N. Magge, MDSarah Jane Schwarzenberg, MD

FORMER COMMITTEE MEMBERJatinder J. S. Bhatia,MD, Immediate Past Chairperson

LIAISONSLaurence Grummer-Strawn, PhD – Centers forDisease Control and PreventionRear Admiral Van S. Hubbard, MD, PhD – NationalInstitutes of HealthJeff Critch, MD – Canadian Pediatric SocietyBenson M. Silverman, MD† – Food and DrugAdministrationValery Soto, MS, RD, LD – US Department ofAgriculture

STAFFDebra L. Burrowes, MHA† Deceased.

FINANCIAL DISCLOSURE:The authors have indicated they do not havea financial relationship relevant to this article todisclose.

POTENTIAL CONFLICT OF INTEREST:The authors have indicated they have no po-tential conflicts of interest to disclose.

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