COMMENTARY

Rickets vs. abuse: a national and international epidemic

Kathy A. Keller & Patrick D. Barnes

Received: 4 November 2007 /Revised: 28 July 2008 /Accepted: 18 August 2008# Springer-Verlag 2008

Keywords Rickets . Child abuse .Metabolic bone disease .

Nonaccidental injury

In the May 2007 issue of Pediatric Radiology, the article“Can classic metaphyseal lesions follow uncomplicatedcaesarean section?” [1] suggested that enough trauma couldoccur under these circumstances to produce fractures previ-ously described as “highly specific for child abuse” [2].However, the question of whether themetaphyses were normalto begin with was not raised. Why should this be an issue?

Vitamin D deficiency (DD), initially believed to primarilyaffect the elderly and dark-skinned populations in the US, isnow being demonstrated in otherwise healthy young adults,children, and infants of all races. In a review article onvitamin D published in the New England Journal ofMedicine last year [3], Holick reviewed some of the recentliterature, showing deficiency and insufficiency rates of52% among Hispanic and African-American adolescents inBoston, 48% among white preadolescent females in Maine,42% among African American females between 15 and49 years of age, and 32% among healthy white men and

women 18 to 29 years of age in Boston. A recent study ofhealthy infants and toddlers aged 8 to 24 months in Bostonfound an insufficiency rate of 40% and a deficiency rate of12.1% [4].

In September 2007, a number of articles about congen-ital rickets were published in the Archives of Diseases inChildhood including an international perspective of motherand newborn DD reported from around the world [5].Concentrations of 25-hydroxyvitamin D [25(OH)D] lessthan 25 nmol/l (10 ng/ml) were found in 18%, 25%, 80%,42% and 61% of pregnant women in the UK, UAE, Iran,northern India and New Zealand, respectively, and in 60 to84% of non-western women in the Netherlands. Currently,most experts in the US define DD as a 25(OH)D level lessthan 50 nmol/l (20 ng/ml). Levels between 20 and 30 ng/mlare considered to indicate insufficiency, reflecting increas-ing parathyroid hormone (PTH) levels and decreasingcalcium absorption [3]. With such high prevalence of DDin our healthy young women, congenital deficiency isinevitable, since neonatal 25(OH)D concentrations areapproximately two-thirds the maternal level [6].

Bodnar et al. [7] at the University of Pittsburgh, in thelargest US study of mother and newborn infant vitamin Dlevels, found deficient or insufficient levels in 83% of blackwomen and 92% of their newborns, as well as in 47% ofwhite women and 66% of their newborns. The deficiencieswere worse in the winter than in the summer. Over 90% ofthese women were on prenatal vitamins. Research iscurrently underway to formulate more appropriate recom-mendations for vitamin D supplementation during pregnan-cy (http://clinicaltrials.gov, ID: R01 HD043921).

The obvious question is, “Why has DD once againbecome so common?” Multiple events have led to the highrates of DD. In the past, many foods were fortified with

Pediatr RadiolDOI 10.1007/s00247-008-1001-z

Editor’s note: See related articles in this issue: Slovis TL, Chapman Sdoi:10.1007/s00247-008-0997-4; Chesney RW doi:10.1007/s00247-008-0993-8; Jenny C doi:10.1007/s00247-008-0995-6; Slovis TL,Chapman S doi:10.1007/s00247-008-0994-7

K. A. KellerPediatric Radiology of America,Stanford, CA 94305, USA

P. D. Barnes (*)Department of Radiology, Lucile Packard Children’s Hospital,725 Welch Road,Palo Alto, CA 94304, USAe-mail: pbarnes@stanford.edu

vitamin D. At present, milk is the only product required tobe fortified in the US, although studies have shown that upto 70% of sampled milk does not contain the requiredamount of vitamin D. There are few other natural foodsources of vitamin D. While exposure to the sun’s UVBrays remains the best natural source of vitamin D, duringthe winter months, above the 35° latitude (at the level ofAtlanta, Georgia) there is a loss of UVB rays that arenecessary for skin synthesis of vitamin D. In addition,along with the concern for skin cancer and skin aging, therehas been a significant increase in the use of sunscreen andprotective clothing. A sun protection factor of 8 blocksabout 95% of the UVB rays, and with regard to vitamin D,sunscreen use produces the same effect as a burka worn bycertain Islamic women, who, even in the sunny climate ofthe Middle East, continue to have high rates of DD. Theincrease in obesity is another important factor since fatstorage of this vitamin decreases its availability to the restof the body. In a recently published study, the vitamin Dstatus of neonates born to obese mothers was found to bepoorer than the vitamin D status of neonates born to leanmothers [8].

Over the past few decades, there has been a significantincrease in the frequency and the duration of breast-feeding,both of which are risk factors for infant nutritional DD. In2003, the American Academy of Pediatrics publishedguidelines recommending that all breast-fed infants receive100% of their daily vitamin D requirement from supple-mentation. Research has demonstrated breast milk to be sodeficient in vitamin D that the average lactating womanmust feed her infant 8 l (about 89 three-ounce bottles) ofbreast milk per day to provide the recommended dailyvitamin D intake of 200 IU [9]. Even infants born tomothers who are replete with vitamin D demonstratedecreasing levels within 8 weeks if not supplemented[10]. Ziegler et al. [11] at the University of Iowa, during astudy of iron levels in breast-fed infants, incidentally foundthat the majority of their unsupplemented infants had DD,with severe DD common in the winter. Recent literaturesuggests that supplementing lactating women with 2,000 to4,000 IU per day (rather than the current recommendationof 400 IU per day) is required to provide both the motherand her breast-fed infant with adequate vitamin D [12].

What are the radiographic findings of congenital andnutritional rickets in infants younger than 6 months old, theage at which we typically first see the fraying and cuppingassociated with rickets? The appearance of DD in earlyinfancy will vary with many factors, including age atpresentation, prenatal maternal DD, nutritional history,geographic location, sun exposure, skin color, and season.Past case reports of congenital rickets range from normal-appearing bones to diffuse bone rarefaction, fractures atbirth, and metaphyseal fraying and cupping [13–18]. The

best location to search for radiographic evidence of congenitalrickets and nutritional rickets in infants less than 3 monthsof age is in the cranium [19]. The skull, as a reflection ofrapid brain growth in early life, is the most affected bone atthis age. Softening of the skull (craniotabes), especially inthe occipital region with palpable enlargement of the suturesand fontanelles, was a common clinical finding withcongenital rickets in the past, and is once again beingdescribed in association with newborn DD [20]. Demineral-ized sutures create a diastatic appearance with poorly definedmargins on radiographs (pseudodiastasis). The skull is betterevaluated on the head CT scan, which should be done toexclude sutural diastasis from increased intracranial pressure.Indistinctness of the facial bones and the orbital roof makethe teeth and petrous bones appear relatively dense onradiographs [21].

Metaphyseal changes of the long bones appear first atthe most recently formed metaphyseal margin, the Laval-Jeantet ring. These metaphyseal changes are usuallysymmetric, and will occur first in the fastest-growing longbones (the femurs, tibiae and fibulae). The metaphysealchanges in the distal femurs and proximal tibiae occur firstalong the medial aspects [22], and the early metaphysealchanges in the distal ulnar can be found even when thedistal radial metaphyses appear normal [23]. While thephyseal and metaphyseal changes can be subtle in earlyinfancy, with treatment, the metaphyses may becomeincreasingly sclerotic and deformed [23]. While these earlymetaphyseal changes may mimic Salter-Harris II fractures,they are asymptomatic and, with treatment, usually resolvewithout the interval stages of fracture healing (subperiostealnew bone formation, callous, and remodeling) within a fewweeks. When subperiosteal changes are present, particularlyin the tibiae, a lateral view may reveal early bowingdeformity. Bowing deformities of the long bones prior toweight bearing are not common, but when present, theyreflect positional stresses or musculotendinous forces,such as the “saber shin deformity” where the pull of theAchilles tendon on the calcaneus causes the tibiae to bowanteriorly [19].

Rachitic flaring of the anterior rib ends will also besubtle on radiographs in the acute stage at this age, but maybecome more pronounced with healing. Loss of corticaldistinction, subperiosteal new bone formation in the longbone diaphyses, insufficiency fractures and Looser zones(i.e. pseudofractures) of the ribs and forearms have all beendescribed in infants [19, 23, 24]. It may be particularlydifficult to distinguish rib fractures from Looser zones ininfants on radiographs alone. Timing of fractures in childrenwith rickets is not possible since published parametersassume normal underlying bone. The only assumption thatcan be made of fractures in an infant with DD is that thehealing will be delayed.

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It is also important to remember when searching forradiographic evidence of vitamin deficiencies that multipledeficiencies are the rule and may modify the radiographicappearance of the skeletal response. In addition, theappearance of rickets will be altered by factors such asseasonal and dietary changes that cause waxing and waningof the deficiency [23].

Radiographs alone may not give us enough informationabout the bone health in these infants. Prior studies on theaccuracy of radiographs in determining bone mineralization

have shown that adults with osteoporosis have 30–40%bone mineral loss before it becomes evident on radio-graphs. Unfortunately, the value of DXA bone densitystudies at this age may be limited. Bishop and Plotkin [25]studied the bone mineral density of the lumbar spine byDXA in infants with fractures due to osteogenesis imper-fecta and in infants with fractures thought to be non-accidental, and found both groups within the referencerange and not significantly different until after 6 months ofage. However, differences in bone mineral density have

ba

Right Left

c d

Fig. 1 Case 1, a 2-month-old Caucasian girl. a Axial CT images(bone algorithm) demonstrate diastatic-appearing coronal and sagittalsutures with poorly defined margins (arrows). Brain CT scan showedno intracranial abnormality, and there were no clinical findings forincreased intracranial pressure, confirming the pseudodiastatic appear-ance of craniotabes. b Chest radiographs. The lateral view shows aflared appearance of the anterior rib ends (white outlined arrows) witha compression fracture of T8 that is confirmed on the AP and obliqueviews (black outlined arrows). Also, notice the healing right posterior

fracture of the tenth rib vs. pseudofracture (Looser zone, small blackarrows). c AP views of the forearms demonstrate transverse lucencywith sclerotic borders of the right distal radial metadiaphysis andtransverse sclerotic changes in the same location of the left distalradius (i.e. Looser zones-arrows). d AP views of the lower extremitiesshow mild irregular sclerotic changes of the tibial and fibularmetaphyses, distal more than proximal (arrows). The oblique fractureof the right tibia was asymptomatic on presentation and was nevernoted on multiple prior visits to the pediatrician

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been documented in young infants with osteogenesisimperfecta using quantitative CT [26], which may be amore accurate modality in early infancy. Quantitative USfor bone strength may be a useful adjunct to CT to give us abetter understanding of bone health [27].

While MRI is unnecessary in detecting physeal wideningin older infants and children, in younger infants, when theepiphyses are minimally, if at all, ossified, it is the bestmodality for evaluating physeal abnormalities. MRI hasalready been used to describe rickets in older children [28],with the failure of ossification in the hypertrophic zone andpersistence of cartilage into the metaphysis. The physealwidth of the distal femur showed little variability (0.9 to1.9 mm) in a study of MRI in normal children, whichcorrelates with a prior histologic study [29].

Case reports

Case 1 A 2-month-old Caucasian girl (Fig. 1) was broughtto the pediatrician for an asymptomatic leg bump. Ahealing oblique right tibial fracture was found on theradiograph. The skeletal survey was interpreted as 16fractures suspicious for inflicted injury. The mother’svitamin D level was 8.7 ng/ml (insufficiency 20–30 ng/ml,deficiency <20 ng/ml). The infant was not checked for DD.

Case 2 A 2-month-old Caucasian girl (Fig. 2) was broughtto the pediatrician for her regular well-baby check and for

right knee swelling. A metaphyseal fracture of the rightdistal femur was diagnosed by radiograph and a follow-upskeletal survey was interpreted as up to 28 fractures highlyspecific for nonaccidental trauma. The mother’s vitamin Dlevel, checked in the summer, was <4 ng/ml. Two monthsafter being changed to formula feeding, the infant’s vitaminD level, in the summer, was 17.8 ng/ml.

Case 3 A 4-month-old Caucasian boy (Fig. 3) had leftlower leg swelling after an accident at day care. Radio-graphs demonstrated a fracture and follow-up skeletalsurveys were interpreted as seven or eight fractures thatwere nonspecific. The mother was found to have a vitamin Dlevel of 14 ng/ml and a PTH of 120 pg/ml (levels >72 pg/mlindicative of hyperparathyroidism). After 6 months of formulafeeding, the infant’s vitamin D level was 19.6 ng/ml, and thealkaline phosphatase level was 2,386 U/l (normal range 145–320 U/l).

Case 4 A 2-month-old girl (Fig. 4) with an African-American mother and Caucasian father presented with aviral respiratory illness. A chest radiograph demonstratedhealing rib fractures. Skeletal survey was interpreted as six,possibly eight, fractures highly specific for nonaccidentaltrauma. The baby had skull and cervical spine fractures.MRI demonstrated small old subdural hemorrhages. Shehad no clinical or imaging findings to suggest increasedintracranial pressure. While on prenatal vitamins during hersecond pregnancy, the mother’s vitamin D level was 17 ng/ml

b ca

Fig. 2 Case 2, a 2-month-old Caucasian girl. a AP skull radiographs.On presentation the sagittal suture appears widened (top image,arrow) but this has resolved after 5 months of formula feeding (bottomimage, arrow). Brain CT and MRI showed no intracranial abnormalityand there were no clinical findings for increased intracranial pressure.b AP spine view shows asymmetric T8 vertebral body height

deformity (arrow). c AP views of the lower extremities show mildfibular bowing deformities with a metaphyseal fracture of the rightdistal femoral metaphysis (white arrow) and left proximal tibia (whiteoutlined arrow). Metaphyseal irregularities of the right proximal anddistal tibia and fibula are also noted (thin black arrows). The left distaltibia and fibula are partially obscured

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at the beginning of the winter. The infant was not checked forDD. Even her second child, born several months after themother’s DD was documented, was not checked for DD.

These were all term infants, with two born in the winterand two born in the summer (the African-American motherand the Caucasian girl with a vitamin D level of 8.7 ng/mldelivered in the summer). They were born north of the 35°latitude. There was no indication of suspected abuse in anyof these infants prior to their first radiograph despite beingseen by physicians, nurses, home health visitors, lactationconsultants, day-care workers, audiologists, ultrasonogra-

phers, family and friends. At this level of inflicted injury,should there not be evidence of the battered infantsyndrome? Should infants with so many inflicted fracturesnot be in severe pain or distress?

Recently published rickets data from Canada [30] reveala similar pattern to the above cases. Of the 104 infants withconfirmed rickets, 94% under 1 year of age were breast-fedwithout vitamin D supplementation (three were on formula,but developed hypocalcemic seizures within the first3 weeks of life). No supplemented, breast-fed infantshowed DD (Canadian recommendations are 400 IU/day).

a

b

d

c

Fig. 3 Case 3, a 4-month-old Caucasian male. a Skull imaging. APplain radiograph demonstrates a diastatic-appearing sagittal suturewith poorly defined margins (small arrow). Axial CT image (bonealgorithm) demonstrates that the demineralization along the sagittalsuture (large arrow) and not diastasis is causing this radiographicappearance (i.e. pseudodiastasis). Brain CT scan showed no intracra-nial abnormality and there were no clinical signs of increased pressure.b AP views of the forearms demonstrate a transverse lucency throughthe distal radial diaphysis with surrounding sclerosis (thin blackarrow). A lack of symptoms, angulation or displacement is importantin differentiating fractures from Looser zones. There is a bucklefracture in the right distal radial metadiaphysis (white outlined arrow).Note the indistinct appearance of the distal ulnar metaphyses (long

white arrows), which also show early cupping, while the distal radialmetaphyses are still well defined. The early metaphyseal changes inthe wrist typically present in the ulna before the radius. c Lateral viewsof the lower extremities show symmetric anterior bowing andbroadening of the tibiae consistent with the saber shin deformity. Thisbowing occurs before weight bearing begins, and is due to the tractionof the Achilles tendon on the calcaneus. d A rickets survey wasperformed 8 months after the initial presentation, when it wasdocumented that the vitamin D level was 19.6 ng/ml and the alkalinephosphatase level was 2,386 U/l (normal range 145–320 U/l). Duringthese 6 months, the infant had been formula fed. The radialmetaphyses are deformed (arrows)

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The number of cases reported per month from February toMay was double the cases reported per month from June toDecember. The clinical and radiographic findings in theinfants less than 1 year of age were skeletal deformities,fractures, hypocalcemic seizures, delayed development andfailure to thrive. This is similar to the findings from the USin a review of rickets cases from 1986 to 2003, although theauthors also reported three infants with rickets who werebreast-fed with supplementation [31]. The current USrecommendation of 200 IU/day is a recent reduction fromthe previous recommendation of 400 IU/day.

Early detection and treatment of DD is important asserious long-term effects are now being reported andadequate vitamin D levels are important beyond bone anddental health. DD has been linked to increased rates of typeI diabetes (with a recent study suggesting a level relation-ship), schizophrenia, depression, autoimmune diseases,cancer, and asthma. In fact, nearly every tissue in the bodyhas been found to have vitamin D receptors [3]. It is clearwe are only beginning to understand what vitamin D does,and more importantly, what its deficiency implies.

Regarding the issue of classic metaphyseal lesionsoccurring in infants following uncomplicated cesareansection, these cases were diagnosed in the UK, where it

has been demonstrated that 18% of pregnant women havevitamin D levels less than 10 ng/ml. In the UK foodproducts are not required to be fortified, including milk.Should we assume that these deliveries were not as“uncomplicated” as reported, or should we consider thepossible effects of the normal trauma of delivery (even inuncomplicated cesarean sections) on infants born withcongenital rickets?

In summary, in infants less than 6 months of age withmultiple asymptomatic metaphyseal lesions (particularlyalong the medial aspect of the distal femurs and proximaltibiae as well as in the distal tibiae and fibulae), pseudodia-stasis of the sutures, transverse lucencies through theforearms and ribs, and compression fractures of the spineshould alert the radiologist to the possibility of osteomala-cia with early metaphyseal changes, insufficiency fracturesand Looser zones. Clinical correlation is important, as mostof these lesions are asymptomatic both at presentation andhistorically. With documentation of DD, 2 week follow-upradiographs may identify metaphyseal lesions that areresolving at an accelerated rate without interval subperios-teal new bone, callus or remodeling. While concomitantnonaccidental injury should never be excluded from thedifferential, it goes without saying that the suspicion or

b

c

a

Fig. 4 Case 4, a 2-month-old Caucasian/African-American girl. a APviews of the shoulders demonstrate symmetric irregular metaphysealmineralization along the lateral aspects that were asymptomatic (toparrows) and had resolved after a month of formula feeding withoutsubperiosteal new bone formation or callus. b AP views of the wristsdemonstrate the distal ulnar metaphyseal changes (thin arrows). Whilethe right distal radial metaphysis remains normal in appearance, the

left demonstrates early fraying (thick arrow). These were allasymptomatic on presentation and historically. c AP view of theknees demonstrate metaphyseal flaring and fragmentation that appearto represent classic metaphyseal lesions (top, arrows) although theywere asymptomatic and resolved without subperiosteal new boneformation, callus, or remodeling after 16 days of formula feeding(bottom)

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presence of abuse should not preclude the diagnosis andtreatment of DD. With subclinical DD being reported at suchhigh prevalences, the radiologists’ attention to these meta-bolic changes on radiographs will provide valuable input tohelp promote improvement in the vitamin D status ofpregnant women and their newborn infants.

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