Osteoporosis in Pediatrics Review

DOI: 10.1542/pir.22-2-56 2001;22;56 Pediatr. Rev.

Joel Steelman and Philip Zeitler Osteoporosis in Pediatrics

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Osteoporosis in PediatricsJoel Steelman, MD,* and

Philip Zeitler, MD, PhD†Objectives After completing this article, readers should be able to:

1. Identify determinants of bone mass.2. Delineate pediatric populations at risk for osteoporosis.3. Describe test procedures to measure parameters such as bone mineral density, bone

formation, and bone resorption.4. Describe methods to interpret pediatric DEXA scan results.5. Identify measures to maximize peak bone mass in children and adolescents.6. Identify osteoporosis treatments available for children and adolescents.

DefinitionBone consists of a collagen matrix into which calcium, in the form of hydroxyapatite, isdeposited. The accumulation and maintenance of the substance of bone is the result of acontinuous process of formation, predominately mediated by osteoblasts, and resorption,facilitated by osteoclasts. During childhood and adolescence, the process of formationpredominates, leading to a net increase in bone mass and size. Infancy and adolescence areperiods of particularly rapid formation. Peak bone mass is achieved shortly after completionof puberty and normally remains stable until the third decade of life, when age-related(involutional) bone loss begins.

Osteoporosis is defined as a systemic skeletal disease characterized by low bone mass andmicroarchitectural deterioration of bone tissue, with a consequent increase in bonefragility and susceptibility to fractures. It is the most common metabolic bone disorder inadults. Approximately 13.8 billion dollars were spent in 1995 in the United States fortreatment of osteoporotic fractures. Osteoporosis incidence increases with age; an esti-mated 30% to 40% of adults older than age 60 years have osteoporosis. Genetics, age, andmenopause are important, relatively unchangeable determinants of osteoporosis risk inadulthood. However, other factors, such as chronic illness, nutrition, medications, andlifestyle, clearly modify the rapidity and severity of bone loss in aging adults.

EpidemiologyOsteoporosis generally has been considered an adult disease, but there is increasingevidence that its roots lie in childhood. The loss in bone mass begins in the third decade oflife and involves a steady decline (about 1% annually) from the peak bone mass attained inearly adulthood. Therefore, failure to achieve optimal peak bone mass represents asignificant and preventable risk factor for osteoporosis in later years. Furthermore, osteo-porosis that is symptomatic during childhood is emerging as a newly recognized problemamong specific at-risk populations. Thus, it is becoming increasingly clear that childhoodfactors, such as diet, lifestyle, chronic illness, and medications, can have both an importantshort-term impact on bone health and a sustained effect on the achievement of peak bonemass, with the potential for long-term morbidity in adulthood.

Both intrinsic and extrinsic factors (Table 1) play roles in determining peak bone massin an individual. Unmodifiable intrinsic factors, including genetic background, race, andgender, have a dominant role (75% to 80%). However, potentially modifiable extrinsicfactors comprise a significant component of the variability in ultimate bone mass.

*Pediatric Endocrine Fellow.†Assistant Professor of Pediatric Endocrinology, The Children’s Hospital, Denver, CO.Dr Zeitler has received a supply of drugs from Novartis Pharmaceuticals for a research protocol.

Article musculoskeletal

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Intrinsic FactorsGENDER AND RACE. Important gender and racial dif-

ferences exist in bone mineral density accretion. Forexample, males have higher bone mass at nearly all agesand at the time of peak bone mass achievement. Thehigher peak bone mass, in combination with larger bonesize and slower decline in sex steroid levels, results in alower incidence of osteoporotic fractures among agingmen than women. Risk of osteoporosis and fracture alsois lower among African-Americans, both male and fe-male, because of higher peak bone mass relative to peersin other ethnic groups. Less is known about bone min-eral density in other ethnic groups, but these data areemerging rapidly.

FAMILY HISTORY. There is also a familial componentto bone mineral density in adults. For example, elderlywomen and men have an increased risk for osteoporosiswhen there is a history of other family members affectedby osteoporosis. Similarly, premenopausal daughters ofpostmenopausal women who have osteoporosis havelower bone mineral densities than do daughters of post-menopausal women who do not have osteoporosis.However, attempts at identifying a specific geneticmarker responsible for the familial determinant of peakbone mass have been unsuccessful. Suspect genetic can-didates that have been evaluated include vitamin D re-ceptor alleles, estrogen receptor alleles, insulin-likegrowth factor (IGF)-1 receptor alleles, and alleles in-volved in collagen synthesis.

Extrinsic FactorsCALCIUM AND VITAMIN D. Calcium and vitamin D

play important roles in bone formation. Optimal calciumintake is necessary to maximize and maintain peak bonemass and to minimize bone loss during aging. Calciumrequirements increase during periods of rapid growth,such as in infancy and adolescence. Furthermore, supple-mental calcium intake has been shown to improve bonemineral density in both children and adults. In retrospec-tive studies, adequate calcium intake during childhood

and adolescence was associated with a lower incidence ofosteoporosis in postmenopausal women. Similarly, in a3-year, prospective, pediatric study of twins, twins given1,000 mg of calcium daily had significantly greater bonemineral density in the spine and radius compared withcontrol twins.

Vitamin D is critical for normal calcium absorptionfrom the diet. Although vitamin D in its inactive formcan be synthesized endogenously from cholesterol me-tabolites in the presence of sunlight, dietary vitamin Dserves as an important precursor for activation in mostnontropical latitudes. A diet poor in vitamin D, the use ofanticonvulsants that accelerate vitamin D catabolism,and low sunlight exposure all can lead to low levels ofvitamin D and subsequent impairment of calcium ab-sorption. The recommended daily allowance (RDA) forvitamin D is 400 IU/d. Treatment with larger amountsmay be necessary in deficiency states.

The importance of adequate intake of calcium andvitamin D in maintaining bone health cannot be overem-phasized. Numerous epidemiologic studies have indi-cated that the average dietary calcium intake is about 50%of the RDA in most adolescents (particularly in girls).Dietary sources should be the primary means for obtain-ing daily calcium, but calcium supplements or a combi-nation of diet and supplements may be required toachieve adequate daily intake. Table 2 outlines the mostrecent guidelines from an American Academy of Pediat-rics (AAP) policy statement about calcium intake, whichare based on guidelines from the National Academy ofScience. The major source of dietary calcium in mostdiets is milk or other dairy products. It should be empha-sized that skim and reduced-fat milk or dairy productscontain the same amount of calcium as milk and dairyproducts that have higher fat contents. Table 3 lists thecalcium content in a few common foods.

BODY WEIGHT AND WEIGHT BEARING. A positive cor-relation between body weight, as reflected by body mass

Table 1. Determinants of BoneMassIntrinisic Factors Extrinsic Factors

● Gender ● Diet● Family background ● Hormonal mileu● Ethnicity ● Illness

Table 2. National Academy ofScience Adequate Calcium IntakeGuidelines

Age Group Adequate Daily Calcium Intake

Birth to 6 mo 210 mg6 to 12 mo 270 mg1 to 3 y 500 mg4 to 8 y 800 mg9 to 18 y 1,300 mg

musculoskeletal osteoporosis

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index (BMI), and bone mineral density has been noted inadults and adolescents. For example, low body weight inmenopausal women is an independent risk factor forfracture. Impact exercises that place weight-bearingforces on the skeleton, such as soccer or tennis, also havepositive effects on bone size and mineralization. Forexample, in a study of twins, longer duration of weight-bearing activity was related to increases in femoral neckbone mineral density, indicating that moderate increasesin physical activity are associated with moderate increasesin skeletal mass.

OTHER RISK FACTORS. Smoking, in addition to itsother attendant risks, has been associated with decreasedbone mineral density in a prospectively studied adoles-cent population. Alcohol abuse, a factor not yet studiedin adolescent populations, also has been cited as anosteoporosis risk factor in the elderly.

All the major hormones of the body, includinggrowth hormone, thyroid hormone, parathyroid hor-mone, and sex steroids, have various effects on bone.Excesses or deficiencies in any of these hormones canlead to decreased bone mineral density.

Lastly, the overall health of an individual representsthe most important modifiable osteoporosis risk factor.A number of chronic pediatric illnesses can result inimpaired bone formation or increased bone resorption,leading to symptomatic osteoporosis. The negative ef-fects of chronic illness on the bones may be magnifiedfurther by the impact of poor nutrition, decreased phys-ical activity, and medications.

PathogenesisOsteoporosis in an otherwise healthy child or adolescentis extremely rare, although cases of idiopathic juvenileosteoporosis have been reported. Rather, pediatric os-teoporosis is much more likely to be seen in the setting ofchronic illness. This impact of illness and treatment is

being recognized increasingly as a significant contributorto the morbidity associated with survival of severe pedi-atric disease. Tables 4 and 5 and the next sections reviewsome of the illnesses and treatments that place childrenand adolescents at risk for osteoporosis.

Osteogenesis ImperfectaOsteogenesis imperfecta is an inherited disorder of col-lagen formation that leads to abnormal bone formationand rapid turnover. There are four different types, withseverity ranging from lethal to relatively mild. The age atwhich low bone density and fractures appear varies, de-pending on the type. The “classic” physical finding ofblue sclera is not seen consistently; therefore, a relativelyhigh index of suspicion is needed to diagnose this con-dition in children sustaining frequent fractures with min-imal trauma. Currently, the disorder usually is diagnosedby collagen analysis from a skin biopsy, although moreexact genetic diagnosis is available.

Gastrointestinal (GI) DiseaseGI diseases associated with low bone mineral densityinclude inflammatory bowel disease, celiac disease, andcholestatic liver disease. The causes of osteoporosis inthese diseases are probably multifactorial and includepoor nutrition, calcium malabsorption, vitamin D defi-ciency, delayed puberty, glucocorticoid usage, and pos-sibly direct inflammatory effects. Glucocorticoid usage isa particularly strong predictor of reduced bone mineraldensity in patients who have inflammatory bowel disease.In celiac disease and inflamatory bowel disease, osteopo-rosis appears to be related primarily to calcium andvitamin D malabsorption. Optimal management of thesedisorders improves bone mineral density, and adequateprovision of nutrients is extremely important. In celiacdisease, treatment with a strict gluten-free diet has re-sulted in normalization of bone mineral density. Malab-sorption of calcium and vitamin D as well as impairmentof vitamin D hydroxylation are factors related to the riskfor osteoporosis in cholestatic liver disease.

Endocrine DisordersGrowth hormone plays an important role in the devel-opment and maintenance of bone mineral densitythrough the action of locally produced IGF-1 on osteo-blast function. Therefore, it is not surprising that growthhormone deficiency can affect bone metabolism nega-tively, and decreased bone mineral density is a feature ofgrowth hormone deficiency in both children and adults.A recent study in growth hormone-deficient adultsshowed an 8% decrease in femoral neck bone mineral

Table 3. Calcium Content in SomeCommonly Eaten Foods

FoodServingPortion

CalciumContent

Milk 1 c 300 mgCheddar cheese 1.5 oz 300 mgLow-fat yogurt 8 oz 300 to 415 mgCalcium-fortified

orange juice1 c 300 mg

Cooked brocolli 1/2 c 35 mg




density relative to healthy matched controls. Similarly,bone mineral density at the spine and hip were signifi-cantly reduced in young adults who experiencedchildhood-onset growth hormone deficiency an average

of 7 years after discontinuation ofprevious growth hormone therapycompared with healthy controls,further demonstrating the positiveeffects of growth hormone on bonemass.

Long-standing hyperthyroid-ism, either from Grave disease orsupraphysiologic dosages of thy-roid hormone, can lead to osteo-porosis by stimulating increasedbone turnover. Hyperparathyroid-ism leads to increased osteo-clast-mediated bone resorption.Although primary hyperparathy-roidism is rare in children, second-ary hyperparathyroidism is a well-recognized complication of renaldisease and severe vitamin D defi-ciency. The osteoporosis associatedwith glucocorticoid excess is the re-sult of increased bone resorptionand impaired bone formation. Glu-cocorticoid excess due to therapyfor an underlying disease is encoun-tered much more commonly thanCushing syndrome or disease.

Estrogen has been shown to beimportant in increasing and main-taining bone mass in both womenand men. Menarche and regularmenses in females are strong pre-dictors of increasing bone mass. Ina 2-year study of late adolescentgirls that quantified multiple factorsinto an estrogen exposure score,girls whose exposure scores werelower had significantly lower spinalbone mineral densities relative totheir peers in the study. Estrogendeficiency leading to bone lossor lower bone mass is seen morecommonly in females, but malehypogonadism should not be over-looked. Lower testosterone levelsin men are associated with lowerbone mineral density and an in-

creased incidence of hip and spine fractures. Treatmentof hypogonadal men has been shown to normalize bonemineral density rapidly and to maintain long-term nor-mal bone mineral density.

Table 4. Illnesses Associated With IncreasedOsteoporosis RiskIllnesses Comments

● Celiac disease ● Malabsorption of calcium and vitamin D

● Inflammatory bowel disease ● Glucocorticoids in IBD

● Cholestatic liver disease

● Solid organ and bonemarrow transplants

● Glucocorticoid use● Immunosuppressive use

● Collagen-Vascular disease ● Glucocorticoid use

● Hypogonadism/Amenorrhea ● Secondary ammenorrhea in elite female athletes

● Chronic renal disease ● Secondary hyperparathyroidism● Impaired vitamin D hydroxylation

● Growth hormone deficiency

● Cushing syndrome

● Spina bifida ● Lack of weight bearing

● Neuromuscular disorders ● Hypotonia

● Severe cerebral palsy ● Effect of anticonvulsants on vitamin D

● Cystic fibrosis ● Malabsorption of calcium and vitamin D● Glucocorticoid use

● “Steroid-dependent” asthma ● Chronic oral glucocorticoids● High doses of inhaled glucocorticoids

● Anorexia nervosa ● Malnutrition● Secondary amenorrhea

● Osteogenesis imperfecta

● Hyperthyroidism

● Hyperparathyroidism




Respiratory IllnessesChildren who have cystic fibrosis now are living well intoadulthood due to improvements in management. Unfor-tunately, the recognition of osteoporosis as a complica-tion of cystic fibrosis is becoming more common as thesepatients reach adulthood. A number of factors are be-lieved to be causal, including growth retardation, malab-sorption with compromised nutrition, delayed puberty,and the effects of glucocorticoids used in treatment.

Systemic glucocorticoid therapy can be very beneficialin severe asthma, but systemic therapy also is associatedwith significant adverse effects, including osteoporosis.Inhaled glucocorticoid therapy can provide effectivetherapy of asthma with fewer adverse effects and hasbecome a mainstay in the treatment of chronic asthma.However, recent data suggest that inhaled glucocorti-coid therapy may have more negative effects than previ-ously appreciated, such as adrenal suppression or reduc-tion in bone mineral density. A study of children usinginhaled glucocorticoids for at least 3 years recently dem-onstrated a negative association between the duration ofinhaled steroid use and total body bone mineral density.

Malignancy and Organ TransplantOsteoporosis, including the occurrence of pathologicfractures, is seen with increasing frequency in pediatricmalignancies as survival rates improve. Factors such asaggressive chemotherapy, high-dose chronic glucocorti-coid treatment, irradiation, poor nutrition, and de-creased physical activity are postulated to affect bonemineral density adversely. In addition, the underlyingillness may promote poor bone development; severalstudies have shown impaired bone formation with nor-mal or increased bone resorption at the time of initial

diagnosis. The potential effect of childhood illness onlong-term bone health is underscored by the finding ofwidespread osteoporosis in a study of long-term survi-vors of acute lymphocytic leukemia treatment who weremostly in their late 20s and had been diagnosed andtreated during childhood. Finally, exposure to cranialirradiation has been shown to be a particularly importantpredictor of persistent low bone mass density.

Recipients of organ transplants are also at increasedrisk for osteoporosis, which has been reported in cases ofrenal, hepatic, cardiac, and bone marrow transplantation.Transplant patients share many of the same osteoporosisrisk factors as patients who have malignancies, includingpoor nutrition, chemotherapy treatment (including glu-cocorticoids), and irradiation effects. Treatment withimmunosuppressive agents represents an additional riskfactor for this population.

Anorexia NervosaA variety of factors can lead to osteoporosis in anorexianervosa. Malnutrition with a low BMI has been shown toimpair bone formation directly and increase bone resorp-tion. Amenorrhea resulting from undernutrition and ex-cessive exercise leads to chronically low estrogen produc-tion, which further increases the osteoporosis risk. Mostworrisome is the finding of persistently low bone mineraldensity in young adult women who have a history oflong-term anorexia, despite establishment of regularmenses and attainment of a normal BMI. This observa-tion supports the concern that impairment of bone min-eral accretion during the critical period of adolescencemay have long-term consequences for bone health. Theathletic triad is a condition in young women associatedwith osteoporosis. It is within the spectrum of anorexianervosa and is comprised of amenorrhea, eating disor-ders, and osteoporosis.

Collagen-Vascular DiseasesThe direct inflamatory effects of illness, as well as the useof glucocorticoids in treatment, play a role in osteoporo-sis associated with collagen-vascular disease. A study in62 children who had juvenile rheumatoid arthritisshowed decreased bone mineral density in 50% to 60% ofthe population, with a strong correlation between theloss of bone mineral density and disease duration.

Chronic Renal DiseaseImpaired vitamin D hydroxylation and secondary hyper-parathyroidism are well-recognized complications ofchronic renal disease. Osteoporosis results from bothimpairment of bone formation due to a relative defi-

Table 5. Treatments Predisposing toOsteoporosis

Treatments Comments

Irradiation ● Direct effects on bone● Pituitary hormone deficiencies

from cranial irradiationChronic glucocorticoid

use● Definitely with oral use and

possibly with high-doseinhaled steroids

Chemotherapy ● Methotrexate● Cyclosporin A● FK-506

Long-termanticonvulsanttherapy

● Vitamin D deficiency




ciency of vitamin D and from increased bone resorptionfrom secondary hyperparathyroidism.

Central Nervous System (CNS) andNeuromuscular Disease

A variety of factors place children in this heterogeneousgroup at risk for osteoporosis. As mentioned previously,mechanical stress forces (weight-bearing and impact ex-ercises) increase bone size and mineralization. Impairedmobility, hypotonia, and decreased weight bearing aremore likely to be encountered in CNS or neuromusculardiseases. These factors can diminish the important influ-ence of mechanical stress forces on bone growth andmineralization. In addition, chronic anticonvulsant ther-apy used to treat a seizure disorder increases the risk ofvitamin D deficiency.

EvaluationA National Institutes of Health-sponsored panel of ex-perts met in March 2000 to discuss issues of prevention,diagnosis, and therapy of osteoporosis. Some of the moreimportant conclusions reached included:

1. Optimization of bone health is a process that mustoccur throughout life.

2. Certain risk factors exist in adults (many of the samerisks cited in children) that increase the probability ofosteoporosis.

3. Osteoporosis screening should be consideredstrongly in individuals who have one or more osteopo-rosis risk factors.

Radiographic StudiesAdult osteoporosis has been diagnosed on the basis ofeither radiologic or laboratory studies. Radiologic stud-ies, in particular dual-energy x-ray absorptiometry(DEXA), appear to be superior to laboratory studies andhave become the established diagnostic modalities. Mul-

tiple adult studies using DEXA to measure bone mineraldensity have shown correlation between decreased bonemineral density at specific bone regions (such as the hipor spine) and increased fracture risk in those boneregions.

DEXA technology measures the transmission ofx-rays of two different photon energies through thebody. The attenuation of these transmitted energies de-pends on the composition of the tissues through whichthe beam passes. A detector measures the energies pass-ing out of the body, and computer-calculated values ofbone mineral content and bone mineral density are re-ported. Table 6 summarizes some terms commonly seenon DEXA reports.

Although the availability of bone mineral densitymeasurement by DEXA and pediatric software packagesfor various DEXA scanners has expanded rapidly in thepediatric population, results must be interpreted care-fully. Interpretation of pediatric DEXA results has beenhampered by several factors (Table 7). The lack of diag-nostic criteria for osteoporosis in the pediatric popula-tion represents the greatest barrier to the clinical appli-cation of DEXA scans in pediatrics. Misdiagnosis ofosteoporosis or the degree of osteoporosis may lead toincreased anxiety and unnecessary treatments or unnec-essary alterations in current treatments. Pediatriciansshould strongly consider contacting a pediatric specialistwho has expertise in bone metabolism before ordering aDEXA scan and for assistance in interpretation.

Interpretation of DEXA data in pediatrics always mustbe relative to age-specific and gender-specific normalvalues (Z scores). T score values relate the reported bonemineral density to the peak bone mineral density attainedfor a person’s gender and are not useful in pediatricpatients. Furthermore, if old and new DEXA data arebeing compared, it is critical to verify that the same brandof DEXA machine was used in both readings. Bone

Table 6. Common Terms Seen in a DEXA ReportTerm Units Comments

Bone mineral content Grams of hydroxyapatite A calculated calcium content of a specific bone regionthat is based on the attenuation of photon energypassing through that bone region

Bone mineral density Grams of hydroxyapatite per cm2

of bone regionBone mineral content per area for a specific bone region

T Score — A standard deviation score for a subject’s bone mineraldensity relative to the peak bone mineral densityattained for his or her gender. Not useful in pediatrics

Z Score — A standard deviation score for a subject’s bone mineraldensity relative to age- and gender-matched controls




mineral density values obtained by different machinebrands cannot be compared directly. Lastly, short stat-ure, delayed skeletal maturity, and delayed puberty caninfluence interpretation of DEXA scan results.

Calcium content (bone mineral content) for a specificbone region is calculated based on attenuation of x-rayspassing through that bone region. Bone mineral densityreadings are reported in two-dimensional units of gramsof hydroxyapatite per cm2 area of a particular boneregion. These readings are affected strongly by a person’sheight, with greater bone heights giving relatively largerbone area values. Therefore, a child who has short statureand smaller bone heights will have a downward skew inbone mineral density reading relative to a peer of averageheight. Similarly, a child who has significantly delayedskeletal maturation or puberty (as reflected by a delayedbone age) likely will have a bone mineral density readingmore appropriate for his or her skeletal maturation thanfor chronologic age.

Several studies have proposed approaches to addressthe biasing influences of short stature, delayed skeletalmaturity, and delayed puberty on DEXA readings. Forexample, analysis of bone mineral density relative to“height age” (the age at which the child’s height wouldbe at the 50th percentile) has been proposed to mitigatethe effects of short stature on bone mineral densityreadings. Alternatively, calculation of a three-dimen-sional volumetric bone mineral density value (grams ofhydroxyapatite per cm3 of a particular bone region) byusing a mathematical model has been proposed to cor-rect for short stature bias. Mathematically calculatedvolumetric bone mineral density readings correlate wellwith actual three-dimensional bone mineral density read-ings obtained by quantitative computed tomography.Lastly, analysis of bone mineral density readings relativeto the gender-specific normals for the patient’s bone age

rather than chronologic age may correct for the biases ofdelayed skeletal maturation or delayed puberty.

Laboratory StudiesLaboratory measures of bone metabolism markers inserum or urine, believed to reflect the activity of eitherosteoblasts or osteoclasts, have been studied in adults asa means of screening for osteoporosis and monitoringosteoporosis treatment. Adult studies have shown thatthe accuracy of these markers for osteoporosis diagnosisand monitoring is inferior to bone mineral density mea-surements. Bone metabolism markers also can be mea-sured in the pediatric population, but the accuracy con-cerns noted in adult studies as well as other problemshamper their widespread use. Many of the markers havediurnal variation, and all are influenced strongly by pu-berty. Furthermore, there are no pediatric referenceranges for many of the newer markers. Measurement ofthese markers in conjunction with clinical evaluation andradiologic findings may aid in the initial investigation ofpediatric osteoporosis and possibly assist in monitoringtherapy. Due to their multiple limitations in pediatrics,bone metabolism markers should not be relied on exclu-sively to make important clinical decisions. Measurementof several indices at once, as well as serial measurements,may help to overcome some of these limitations. Table 8summarizes several laboratory assays for bone metabo-lism markers.

ManagementPrevention

One of the goals of routine health supervision visits isanticipatory guidance regarding healthy lifestyle habits.Components of healthy lifestyle habits include regularphysical activity, a healthy diet, and in the adolescentyears, avoidance of smoking and other tobacco products.The AAP has created specific policy statements outliningrecommendations to achieve each of these goals. Promo-tion of these healthy lifestyle habits during a healthsupervision visit also may decrease the risk of futureosteoporosis.

The general pediatrician may be relegated to a minorrole in the care of a chronically ill child. However,complications arising from a disease or its treatment maybe overlooked, especially when the child is receiving carefrom multiple subspecialists. By maintaining regular con-tact with the family and remaining informed of currenttreatment, the general pediatrician may be in the bestposition to perceive the “big picture” of potential risks ofchronic illness and therapy, including the risk of osteo-porosis. The promotion of a healthy lifestyle within

Table 7. Common Pitfalls in DEXAInterpretation● Comparatively small numbers of reference range

studies● Predominance of Caucasian subjects used to generate

normal reference ranges● Differences between readings from the different

brands of DEXA machines● Lack of a definition of pediatric osteoporosis● Effects of gender, race, height, and puberty on bone

mineral density readings




limitations imposed by the chronic illness may be par-ticularly important in preventing avoidable long-termproblems in at-risk populations. The prevention of os-teoporosis is an excellent example of this principle.

DiagnosisSubsequent to the experience in adults, DEXA rapidly isbecoming an established modality for the measurementof bone mineral density in children and adolescents. Aswith adults, screening of children or adolescents whohave one or more osteoporosis risk factors should beconsidered strongly, particularly in the setting of frac-tures associated with minimal trauma. In addition, areport of osteopenia on plain film radiographs in anindividual who has one or more osteoporosis risk factorsshould be followed up with a quantitative measurementof bone mineral density by DEXA.

TreatmentAfter critical examination of data in an individual at riskfor osteoporosis, including physical examination, DEXAscan readings corrected for statural or pubertal variation,and any additional studies, the clinician must decidewhether and how to treat low bone mineral density.

Three major limitations affect such decisions. First, thereis no standard definition for osteoporosis in the pediatricage group. Second, there is no consensus on the degreeof bone mineral deficit that places children or adolescentsat risk for fractures. Third, there are no large, well-controlled studies to assess the efficacy and safety ofpotential osteoporosis treatments in children andadolescents.

Review of the relatively small amount of literature(prospective studies and case reports) published on thetreatment of pediatric osteoporosis provides some per-spective about the criteria considered diagnostic for os-teoporosis, as well as a sense of the severity of bonemineral deficit present in at-risk populations. The major-ity of patients reported in these articles had bone mineraldensity Z scores below 22 (range, 22 to 25.5) and hada history of one or more fractures. Based on these data,treatment should be strongly considered in children andadolescents who have severely low bone mineral density(Z scores below 22), especially in the setting of fractureswith minimal trauma.

There is little debate over the likely benefits andminimal risks associated with some treatments. In lesssevere cases, interventions such as ensuring adequate

Table 8. Bone Metabolism MarkersMarker Location Notes

Bone FormationAlkaline phosphatase Serum Most widely used test; 80% of activity is derived from

boneBone-specific alkaline phosphatase Serum Assay not widely availableOsteocalcin Serum Product of osteoblast function; specificity of test reportedly

is goodProcollagen type I carboxyterminal propeptide Serum Cleavage product from formation of type I collagen; other

sources of type I collagen besides bone hamper testspecificity

Procollagen type I amino terminal propeptide Serum Cleavage product from formation of type I collagen; othersources of type I collagen besides bone hamper testspecificity

Bone ResorptionTartrate-resistant acid phosphatase Serum Produced by osteoclasts; assay not widely available; data on

normal values are scarceHydroxyproline Urine Amino acid component of collagen; wide variation in day-

to-day values as well as effects from dietary sourceshamper specificity

Pyridinoline/Deoxypyridinoline Urine Cross-linking peptides within collagen; specificity reportedto be good

Collagen type I cross-linked C-telopeptide Serum A fragment from cross-linking peptides within collagen;assay not widely available, and data on normal valuesscarce.

Collagen type I cross-linked N-telopeptide Urine A fragment from cross-linking peptides within collagen;values strongly affected by puberty; specificity reportedto be good.




calcium and vitamin D intake, optimizing general nutri-tion, and promoting weight-bearing physical activitywithin the limits of the patient’s illness will providebenefit with minimal risk. Similarly, replacement of es-trogen, testosterone, or growth hormone in proven de-ficiency is appropriate and widely supported. Serum cal-cium and urinary calcium excretion normalized tocreatinine should be monitored regularly in individualsreceiving supplemental calcium and vitamin D to helpavoid the pitfall of nephrocalcinosis from overtreatment.

Antiresorptive agents slow bone resorption while al-lowing bone formation to continue, theoretically leadingto a net gain in bone mass. Although the efficacy andsafety of the two most common types of antiresorptiveagents, the bisphosphonates and calcitonin, have beenestablished in large, well-controlled adult treatmentstudies, these agents have not been used in large numbersof children or adolescents. Consequently, there are nolarge, well-controlled studies to assess their efficacy andsafety. However, cautious and thoughtful use of theseagents should be considered in children or adolescentswhose bone mineral density is severely low or who havefailed to improve after receiving more conventional treat-ment or who have suffered multiple fractures.

Bisphosphonates are taken up rapidly by the bone,where they prevent bone mineral hydrolysis and exertdirect inhibitory effects on osteoclast activity. They areavailable in oral and intravenous forms and have beenused in a variety of adult conditions, including Pagetdisease, postmenopausal osteoporosis, fibrous dysplasia,glucocortiocoid-induced osteoporosis, and hypercalce-mia of malignancy. Gastrointestinal upset and the conse-quent need for relatively complicated oral dosing regi-mens are the biggest obstacles to oral bisphosphonatetherapy.

Most clinicians have been extremely reluctant to usebisphosphonate treatment in children because of theo-retical concerns about negative effects on growth, basedon animal studies showing inhibition of bone calcifica-tion by some of the first generation of bisphosphonates.Bisphosphonate treatment has been used successfully insmall numbers of pediatric patients for a variety of con-ditions, including fibrous dysplasia, hypercalcemia of ma-lignancy, and miscellaneous forms of severe osteoporosis.The largest and most successful use of bisphosphonatesto date has been in children who had osteogenesis im-perfecta, very low bone mineral density, and fractures,who were treated for 1 year with intravenous bisphos-phonate. Treatment resulted in significantly fewer frac-

tures, improved mobility, and improved growth. A num-ber of additional controlled trials of bisphosphonates inpediatric osteoporosis are underway.

Calcitonin is produced by C cells in the thyroid glandand acts in opposition to parathyroid hormone. It hasbeen approved for use in postmenopausal women unableto take estrogen replacement and is available in nasalspray. However, its efficacy in adult studies has been nobetter than that of bisphosphonates, and waning effec-tiveness (tachyphylaxis) may be seen with prolonged use.Successful osteoporosis treatment with calcitonin hasbeen reported in small numbers of children who hadthalassemia and renal disease.

SummaryThe morbidity and mortality from adult osteoporosiscontinues to grow as the United States population agesand lives longer. Although the condition manifests manyyears later, the roots of osteoporosis begin in childhoodand adolescence. The efforts of pediatricians to promotehealthy life choices—sensible diet, regular exercise, andavoidance of tobacco—may help to decrease the preva-lence of osteoporosis when the current generation ofchildren reaches old age. Furthermore, the recognitionof childhood osteoporosis as a consequence of chronicillness and its treatment can help pediatricians screen forthis condition, institute preventive measures, and referfor appropriate treatments when necessary.

Suggested ReadingBoot AM, De Ridder M, Pols H, Krenning E, De Muinck S. Bone

mineral density in children and adolescents: relation to puberty,calcium intake, and physical activity. J Clin Endocrinol Metab.1997;82:57–62

Cassidy J. Osteopenia and osteoporosis in children. Clin Exp Rheu-matol. 1999;17:245–250

Committee on Nutrition. Calcium requirements of infants, chil-dren, and adolescents. Pediatrics. 1999;104:1152–1157

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PIR QuizQuiz also available online at www.pedsinreview.org.

9. Which of the following statements regarding bone mass in children is true?

A. African-Americans have a higher risk of osteoporosis than Caucasians because of lower bone mass.B. Extrinsic factors, such as diet and chronic illness, are the primary determinants of a child’s bone mass.C. Increased calcium intake has not been proven to improve peak bone mass.D. Males have a higher bone mass than females.E. Peak bone mass is not achieved until early adulthood.

10. Which of the following has been shown to improve bone mass and decrease the risk of osteoporosis?

A. Limited sun exposure.B. Smoking cigarettes.C. Use of corticosteroids.D. Use of whole milk rather than low-fat milk.E. Weight-bearing exercises.

11. You are the pediatrician for a child who has cerebral palsy and epilepsy. You recognize that this child isat risk for osteoporosis, and you order a DEXA scan to make the diagnosis. Which of the followingstatements regarding DEXA scans in children is true?

A. Criteria for diagnosing osteoporosis in children have been well established.B. Data must be interpreted relative to a child’s age and gender.C. Delayed puberty has no effect on DEXA results.D. Results are easy for the pediatrician to analyze.E. The information obtained is less useful than laboratory markers such as osteocalcin and alkaline

phosphatase.

12. You are caring for an adolescent who has a history of chronic steroid use for systemic lupuserythematosus, and her radiographs show evidence of osteopenia. Findings from a DEXA scan areconsistent with osteoporosis. You want to help her prevent fractures. Which of the following statementsregarding treatment of osteoporosis in adolescents is true?

A. Bisphosphonates may help prevent bone resorption but have gastrointestinal side effects.B. Calcitonin has been proven effective in preventing fractures in children who have osteoporosis.C. Increasing intake of calcium and vitamin D has not been shown to be beneficial.D. The patient is not at increased risk for fractures if her osteoporosis is mild.E. Weight-bearing activities should be discouraged.




DOI: 10.1542/pir.22-2-56 2001;22;56 Pediatr. Rev.

Joel Steelman and Philip Zeitler Osteoporosis in Pediatrics

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