Unsuspected
Nutritional
Rickets
Mary Rudolf, MBBS, Karunyan Arulanantham, MBBS, and
Robert M. Greenstein, MD
From the Departments of Pediatrics of the Waterbur,’ Regional Pediatric Services, Newington Children ‘s Hospital, and the University of Connecticut Health Center, Newington
ABSTRACT. Based on the presentation and clinical fea-tures of four cases of nutritional rickets, it is suggested that particular groups of children, namely vegetarians, children breast-fed for an unusually long time, and black
children, are at risk to develop the nutritional deficiencies ofvitamin D and calcium that lead to clinical rickets. The diagnoses in these cases were made by fortuitous radio-logic examination, even though the children had been
receiving regular pediatric supervision, indicating a lack of awareness of the condition. This report is intended to
emphasize the reemergence of nutritional rickets and to illustrate the different modes of its clinical presentation. Pediatrics 66:72-76 1980; rickets, vitamin D deficiency,
calcium deficiency, vegetarians, breast-feeding.
It is generally taught that nutritional rickets is a rare entity,’ and it has been referred to as a medical curiosity in the major children’s clinics.2 Over a one-year period four children in the Hartford area of Connecticut were found to have rickets. This
strongly suggested that rickets was reemerging as a significant hazard to children, and review of the cases was undertaken to assess whether they indi-cated that particular groups of children were at risk to develop the nutritional deficiencies that lead to clinical rickets.
CASE REPORTS
Case I
D.G., a black male child, presented at 17 months of age
to the orthopedic clinic with inability to walk. He was the ninth child born after a normal pregnancy and had a birth weight of 2.7 kg. He had had pediatric supervision in his
first year of life and his immunizations were up-to-date. At 8 months of age he was unsuccessfully treated with orthopedic shoes and a bar for bilateral metatarsus ad-ductus. At 17 months he had severe retardation of motor
function, being unable to crawl or walk. He could only pull himself to a standing position and was functioning at a 7- to 8-month level.
At the orthopedic clinic roentgenograms of the feet
showed typical rachitic changes with wide cupping of the metaphyses of the long bones and an increase in growth plate thickness. Further roentgenograms showed rachitic
changes in the bones of the wrist and thoracic cage,
generalized demineralization of the bones, and bilateral coxa vara. He was then referred to the pediatric clinic
where he was found to have the classic clinical signs of
rickets: growth failure (height and weight below the third
percentile), generalized hypotoma, widening of the distal radius, bowing ofthe legs, and rachitic “rosary” deformity of the anterior thorax.
Dietary history revealed that he had been nursed from birth and was still being breast-fed five times a day. From age 4 months his breast milk intake was reportedly
sup-plemented with 240 ml of vitamin D-fortified cows’ milk per day but his diet contained no other dairy foods. His
exposure to the sun was judged to be normal for a
nonambulatory child. The mother’s diet, which included three glasses of milk daily, was judged to be balanced and adequate. Due to a laboratory accident, biochemical
pa-rameters were not measured before treatment was started (Table). At a later date vitamin D absorption was found to be normal based on serum 25-hydroxycholecalciferol
concentration pre- and post-oral vitamin D loading. On 1,500 IU ofvitamin D and a diet including dairy products, the patient had an accelerated growth rate (4 cm in 2#{189}
months) with radiologic healing of the rickets and
diinu-nition in serum alkaline phosphatase. He has remained well during follow-up for 9 months on a maintenance dose of 400 IU of vitamin D daily.
Received for publication March 21, 1979; accepted Oct 1, 1979.
Reprint requests to (K.A.) do Research Office, Newington
Chil-dren’s Hospital, Newington, CT 06111.
PEDIATRICS (ISSN 0031 4005). Copyright © 1980 by the American Academy of Pediatrics.
Case 2
L.C., an 18-month-old Jamaican girl, was referred by a
TABLE. Clinical and Biochemical Data Case Age (mo) Ht (cm) Wt (kg) Calcium (mg/100 ml) [9.4-11]t Phosphorus (mg/100 ml) [3.5-6.5] Alkaline Phosphatase (lU/liter) Presentation [80-96]
1 17 51 9.3 10.4* 4#{216}* >#{216} Inability to walk; orthopedic
clinic
2 18 72 7.4 8.9 2.0 >2,500 Hypotonia; neurology clinic
3 18 74 1 1.2 6.2 3.8 708 Bowlegs, abnormal gait;
or-thopedic clinic
4 36 84 10.1 6.2 3.4 361 Failure to thrive; genetics
clinic
* Values were obtained following initiation of treatment.
t Normal range is shown in brackets.
months and sat at 5 months of age but stood with support only at 1 year. At 18 months she could not walk. Growth
records revealed plateauing of linear growth from 9 to 12 months of age. On examination her height and weight were below the third percentile (height age 9 months, weight age 7 months). She had generalized hypotonia and weakness of the proximal girdle muscles. No focal
neu-rologic defects were noted. Denver Developmental testing demonstrated delay in the gross motor area with func-tioning at a 9-month level, although other areas were normal. The initial impression was that she had aprimary
neurologic or muscular disorder.
The following day the mother consulted another
phy-sician for the same complaint. Here the following dietary
history was obtained. She had been breast-fed until 3
months of age, after which formula feeding was begun. She had not taken the formula well and reported inter-mittent episodes of vomiting. She had been seen several times at a pediatric clinic where an antiemetic and In-cremin with iron (a multivitamin and iron preparation which contains no vitamin D) were prescribed. By 9
months of age the vomiting had become less frequent and at this time her diet included meat, peas, fruits, juices,
and the vitamin preparation but did not contain dairy
products.
Because of this history and the clinical observation of bowlegs, radiologic examination was obtained, which showed typical changes of rickets. Biochemical testing was consistent with the diagnosis of nutritional rickets (Table). Malabsorption and renal disease were ruled out. On 10,000 units of vitamin D daily, increased milk
con-sumption, and supplemental calcium (commercial
cal-cium carbonate (Turns), 3 tablets daily) she showed a
marked improvement in muscle tone and five months later was walking. She also had an accelerated growth rate with an increase of 8.5 cm in the first seven months after therapy had been started. The biochemical
param-eters returned to normal and there was radiologic
im-provement of the rickets. Twelve months ago the dose of
vitamin D was reduced to 400 IU daily and she has
remained well with no recurrence of the disease.
Case 3
D.B., a black male child, presented at age 18 months
to the orthopedic clinic because of extrern bowing of his legs. Roentgenograms were taken which revealed changes
characteristic of rickets. Biochemical testing revealed hy-pocalcemia, increased levels of alkaline phosphatase, and
a low-normal serum phosphate level (Table).
His height was at the fiftieth percentile at 9 months of age but had plateaued thereafter and at presentation was at the third percentile with a height age of 10 months. He sat up at 7 months but began walking only at 14 months
of age. At the time of presentation he had a squat duck-like gait. Neurologic examination did not reveal signifi-cant hypotonia.
Dietary history revealed that he had been breast-fed for 6 months. After weaning he had refused milk and milk
products and was maintained on a diet of meats, vegeta-bIos, and juices. Vitamins were discontinued at age 9
months because the mother attributed staining of teeth to the vitamins. An analysis of the current diet of the child based on a 24-hour recall of intakes revealed insuf-ficient calcium (approximately 100 mg) and vitamin D
(less than 100 IU).
on 10,000 units of vitamin D, increased milk intake, and calcium supplements (Neo-Calglucon, 5 cc three
times daily), radiologic and biochemical improvements
were seen within ten weeks. Ten months after treatment, height had increased to the fiftieth percentile and there
was good remodeling of the lower extremities. For a period of 12 months he has continued to progress and
remain healthy on 400 IU of vitamin D daily.
Case 4
M.G., a black male child, was referred to the genetics
clinic at 3 years of age by his pediatrician for failure to thrive and dysmorphic facial features. The diagnosis of rickets was made when a roentgenogram of the left wrist,
taken to assess bone maturity, showed changes typical of rickets.
The patient was born at term with a birth weight of 2.1 kg following a pregnancy complicated by heavy
ma-ternal alcoholism and was discharged postnatally to foster care. He had the dysmorphic facial features of the fetal alcohol syndrome, in addition to microcephaly (head
circumference appropriate for 8 months of age), and
retardation of growth (height and weight age 14 months).
Neurologic testing showed delay in all parameters of development but hypotonia was not noted. Biochemical
studies related to rickets revealed a very low serum
and an elevated alkaline phosphatase level (Table). Se-rum 25 hydroxycholecalciferol was 20.5 ng/ml (normal 10 to 55 ng/ml).
Dietary history revealed that the patient had fed
poorly from early infancy with no milk or dairy foods in
the diet, as his foster mother felt he could not tolerate milk. During the child’s infancy the mother had become a vegetarian and placed the child on a diet of sesame seeds, soybean powder, honey, and water as substitutes for milk. At age 3 his diet was varied but contained no dairy products. Vitamin C and multivitamins were given to the child at irregular intervals. Evaluation of diet by a
24-hour recall of intake revealed a deficiency of vitamin
D (<50 IU per day) and calcium (200 mg daily).
In the hospital he ate a varied diet including milk and
milk products without any intolerance. In addition he received 1,600 IU of vitamin D daily and calcium supple-ments. In 10 weeks there was radiologic healing of his
rickets and biochemical parameters returned to normal. The vitamin D intake was reduced to 400 IU daily and he has remained well on this dose.
DISCUSSION
Nutritional rickets is a systemic disorder charac-terized by growth failure, bony deformity, hypo-tonia, listlessness, and delayed motor development. The skeletal manifestations of rickets are due to inadequate mineralization of osteoid, which gives rise to bones that are less rigid and liable to be deformed by the normal physical forces acting on them. Failure of mineralization is seen radiolog-ically as an increase in the width of the growth plate and distortion of the growing ends of long bones.
Nutritional rickets is primarily attributed to in-adequate supplies or availability of vitamin D. A major source of vitamin D under normal circum-stances is the conversion of 7-dehydrocholesterol in the skin to cholecalciferol by ultraviolet light. Cho-lecalciferol thus produced and that absorbed from food sources is further metabolized in the liver and kidney to la,25-dihydroxycholecalciferol which is currently thought to be the major substance me-diating the biological actions of vitamin D.
Recently there have been reports suggesting that pure calcium deficiency in the presence of adequate vitamin D levels could cause the clinical picture of rickets.3’4 The proof of this hypothesis was based on clinical and radiologic healing of rickets with a diet
free of vitamin D but with adequate calcium con-tent. Dairy foods, which are the major food source of vitamin D, are also the major sources of calcium. Therefore, deficiencies in calcium and vitamin D often accompany each other. Furthermore, a major action of vitamin D is to enhance calcium absorp-tion from the gut, and in vitamin D deficiency calcium absorption would be impaired, leading to secondary calcium deficiency. A case of rickets in a
premature infant attributed to primary phosphate deficiency has also been reported.5
The dietary sources of vitamin D in nature are few and currently milk fortified with vitamin D is
an important source in the United States.6 The
recommended daily allowance of vitamin D for all
ages is 400 IU (10 tg)7 even though 100 IU (2.5 jig) may be adequate for prevention of ricket.cand for calcium absorption.8 The recommended daily allow-ances for calcium and phosphorus are 800 mg each for children 1 to 4 years of age, but the estimated minimum requirements are approximately 100 mg.7
Prophylactic measures have decreased the mci-dence of nutritional rickets, which was a common condition even as late as the 1940s. Available
sta-tistics indicate a very low incidence of clinical
rick-eta in recent years. Of 100,000 pediatric admissions in the 266 teaching hospitals in the United States between 1956 and 1960, only 0.4% of cases was reported as due to rickets.9 Only 0.2% of 2,118 children examined in the Preschool Nutrition Study of 1968 to 1970 showed epiphyseal swelling of the wrists,’0 and in 1969 the Ten State Survey of 6,119 children of low-income families revealed that only 0.10% had bowing of the legs.” In the last year, however, reports of rickets among children on ye-getarian diets have been published, which suggest that there is perhaps a reemergence of the
disease.’2’3 Indeed, our four cases suggest that
cer-tam
population groups, namely blacks, inner city children, vegetarians, and inappropriately breast-fed infants, are at risk for developing this disease.The important factor contributing to the devel-opment of rickets in the patients described was the deficient diet, as healing occurred with dietary changes in all cases. Dairy food was lacking in the diets of all the children and in cases 3 and 4, where the dietary intake was estimated in greater detail, a deficiency of both vitamin D and calcium intake was found. The question of the relative importance of vitamin D and/or calcium deficiency in the cau-sation of rickets in these cases cannot be resolved in the absence of more complete data, but the finding of a serum 25-hydroxycholecalciferol con-centration within the normal range in the face of hypocalcemia in case 4 would suggest that this child’s problems may have been due to factors other than a pure inadequacy of vitamin D. The secretion ofparathormone is increased by hypocalcemia. Par-athormone stimulates the synthesis of la, 25-dihy-droxycholecalciferol which will act to increase
in-testinal calcium absorption provided sufficient
evolution of clinical rickets in this child. Further,
cases 3 and 4 did not have significant hypotonia as was seen in the nine cases of rickets presumed to be caused by a low calcium intake described by
Petti-for et al.4 However, the separation of pure calcium
deficiency from vitamin D deficiency cannot be
accomplished without facilities available in a re-search center and is, in normal clinical practice, not
essential. All four children were treated with both
vitamin D and calcium supplementation with good
results.
The cultural and educational character of the families in which these children were raised, rather than economic factors, were responsible for the inadequate diets given to these children. In the first
three cases, concerned mothers were unaware of
the nutritional requirements oftheir young children
and of the importance of milk and vitamin D in their diets. Case 4 illustrates the problem of food faddism. This child was said to have had
gastroin-testinal symptoms on conventional formula and
hence was given a sesame/soy/honey substitute by his vegetarian foster mother with consequent in-adequate intake of calcium and vitamin D. Often the so-called diagnosis of milk allergy may lead to avoidance of milk products and this contributes to inadequate calcium and vitamin D in the diet. This
may have been a factor in cases 2 and 4.
The question of vitamin D supplementation in
nursing infants is stifi controversial. Three of the reported children were breast-fed. Two developed rickets after having been weaned, but one was stifi
receiving breast milk at the time of diagnosis. There
have been other reports of vitamin D deficiency in
breast-fed babies.’4”5 This supports the view that
human breast milk, which provides about 10 IU of vitamin D daily in the winter and 20 IU daily in the summer,’6 is inadequate without supplementation, for infants’ requirements. However, the vast
major-ity of nursing infants do not develop deficiency
rickets, and a recent work suggests that the
esti-mates of vitamin D concentration in breast milk may be artificially low as only the lipid fraction of
breast milk had been assayed for vitamin D. When both the aqueous and lipid fractions of human milk
are assayed, the concentration at four to six weeks of lactation is 0.9 ± 4.0 g/10O ml (40 IU/100 ml)
which is about the same concentration as that found in fortified formula.’7 The vitamin D concentration after six weeks of lactation is not known and the
bioactivity of the aqueous fraction has not been
evaluated. At the present time vitamin D supple-mentation is still recommended for breast-fed
ba-bies.’8 None of these children received this
supple-mentation in spite of having access to medical care. All four children are black. Skin pigment impairs the transmission of ultraviolet light which is
re-quired for the conversion of 7-dehydrocholesterol below the stratum corneum to vitamin D.’9 Thus, in conditions of inadequate exposure to sunlight, black children are more prone to develop rickets than their white neighbors. All four children were from the inner-city where opportunity to play in sunny open areas is limited, crowded housing blocks out sunlight, and air pollution screens out ultravi-olet light.#{176}Also, winter weather necessitates extra clothing and shelter, further reducing the exposure to sunlight which is already decreased at that time of year. Thus it is not surprising that all four chil-then presented at the end of winter.
The striking fact that the diagnoses were made fortuitously in all these children who were receiving regular pediatric supervision illustrates a lack of awareness in the medical profession of this condi-tion. All of the patients presented with the classic features of rickets: growth retardation, hypotonia, abnormal gait, or delayed motor development, and
yet the diagnosis was not considered. They were
inappropriately referred to speciality clinics and
even there the diagnosis was not suspected on din-ical grounds. Furthermore, at least two of these children had been documented as having deficient dietary intakes of vitamin D and milk months prior to diagnosis, and yet inadequate steps had been taken to correct these deficiencies and educate the families. In only one case was the diagnosis sus-pected on clinical grounds, by a third physician dealing with the child prior to obtaining radiologic examination.
The extent of the problem of rickets, both clinical and subclinical, is difficult to assess. The State Department of Health in Connecticut has no statis-tics of the incidence or prevalence of rickets, as it is not a notifiable disease. Fortification of milk and milk products following World War II has certainly decreased the incidence of rickets, but clinicians
may have been lulled into a false sense of security.
These four cases suggest that nutritional rickets
may still be a significant problem in certain
popu-lation groups.
REFERENCES
1. Gardner LI: Endocrine and Genetic Diseases of Childhood
andAdolescence, ed 2. Philadelphia, WB Saunders Co, 1975,
p 854
2. Harrison HE: The disappearance of rickets. Am J Public Health 56:734, 1966
3. Kooh SW, Fraser D, Reilly BJ, et al: Rickets due to calcium
deficiency. N Engi JMed 297:1264, 1977
4. Pettifor JM, Ross P, Wang J, et al: Rickets in children of
rural origin in South Africa: Is low dietary calcium a factor?
J Pediatr 92: 320, 1978
5. Rowe JC, Wood DH, Rowe DW, et al: Nutritional hype-phosphatemic rickets in a premature infant fed breast milk.
N Engi J Med 300:293, 1979
fortified and natural foods and in vitamin preparations. J Pediatr 70:952, 1967
7. American Academy of Pediatrics Committee on Nutrition:
The prophylactic requirement and the toxicity of vitamin D.
Pediatrics 31:512, 1963
8. Recommended Dietary Allowances, ed 8. Food and Nutri-tion Board, National Research Council, National Academy
of Sciences, 1974
9. American Academy of Pediatrics Committee on Nutrition:
Infantile scurvy and nutritional rickets in the United States.
Pediatrics 29:646, 1962
10. Owen GM, Kram KM. Garry P, et al: A Study of nutritional status of preschool children in the United States 1968-1970.
Pediatrics 53 (suppl):597, 1974
11. Ten State Nutrition Survey, 1968-1970. Publication HSM
No 72-8134. Health Services and Mental Health Administra-tion, Committee for Disease Control, US Department of
Health, Education, and Welfare, 1972, vol 3
12. Dwyer JT, Dietz WH, Ham G, et al: Risk of nutritional
rickets among vegetarian children. Am J Dis Child 133:134,
1979
13. Erhard D: The new Vegetarians. I. Vegetarianism and its medical consequences. Nutr Today 8:4, 1973
14. O’Connor P: Vitamin D-deficiency rickets in two breast-fed
infants who were not receiving vitamin D supplementation.
Clin Pediatr 16:361, 1977
15. Castile RG, Marks U, Stickler GB: Vitamin D deficiency
rickets. Two cases with faulty infant feeding practices. Am
J Dis Child 129:964, 1975
16. Founman P, Royer P: Calcium Metabolism and the Bone,
ed 2. Philadelphia, FA Davis Co. 1968, p 113
17. Lakdawala DR. Widdowson EM: Vitamin-D in human milk.
Lancet 1:167, 1977
18. Fomon SJ: Infant Nutrition, ed 2. Philadelphia, WB Saun-ders Co, 1974, p 216
19. Loomis WF: Skin-pigment regulation of vitamin-D
biosyn-thesis in man. Science 157:501, 1967
20. Loomis WF: Rickets. Sci Am 223:76, 1970
MAYBE FEVER IS BENEFICIAL?
“ . . .fever is the result not of an out-of-order thermostat but rather of response to a regulator still in control but whose desired set point hits been increased . ..by [an] infection. All vertebrate classes tested (no sharks or lampreys as yet) behave the same way. Bluegills and tree frogs, pigeons, and rabbits, all show a febrile response. It is no recently evolved ability of our kind; even crayfish develop fever! The act of infection, probably associated with the tell-tale proteins, seem to set every animal thermostat up a few degrees . ..fever is in fact adaptive, a regulatory response acquired over 400 million years of animal evolution . ..Moderate fevers . . .seem to inhibit infection, perhaps both by their
effect on microorganisms and by modifying the responses of the host. The
ancient wisdom of the phylum is not to be gainsaid. Even the noble aspirin ought to be used with discretion, under the dictate of the wise Thomas Syden-ham, physician and friend to Robert Boyle, who wrote ‘Fever is Nature’s engine which she brings into the field to remove her enemy.”
From P. Morrison in book review of Kiuger MJ: Fever: Its Biology, Evolution, and Function.
