VOLUME 16 NUMBER 3 May/June 2003
and clinical profile of osteomalacia in adolescent girls
in northern India:[PDF]
J. Rajeswari, K. Balasubramanian, V. Bhatia, V. P. Sharma, A.
Background. The adolescent age group is particularly prone to
nutritional rickets/osteomalacia due to an increased demand for
nutrients, especially calcium and vitamin D. Osteomalacia presents
with non-specific signs and symptoms because of which diagnosis
may be delayed. Vitamin D deficiency is unexpected in India,
which is a tropical country with abundant sunshine.
Methods. We prospectively studied the clinical presentation,
aetiology and social factors contributing to adolescent rickets/osteomalacia
in our region.
Results. We saw 21 symptomatic
adolescents with osteomalacia during the study period (November
2000–July 2002). All
were girls. Only 1 practised purda and 4 belonged to a low socioeconomic
class. The mean (SD) duration of illness before correct diagnosis
was 2.8 (2.1) years. Bone pains and muscular weakness were universally
present. Non-specific complaints (especially limb pains being
mistaken for joint involvement) led to a delay in diagnosis with
consequent morbidity. All but 1 patient had low serum 25-hydroxyvitamin
D levels (<10 ng/ml), with the mean (SD) being 4.9 (2.7) ng/ml.
Their mean dietary calcium intake was low [265 (199) mg/day,
range 40–810 mg/day]. Restricted outdoor activities (n=19)
and the traditional dress code (n=21) were contributory factors,
as they led to poor exposure to sunshine.
Conclusion. Nutritional osteomalacia among adolescents is a poorly
recognized entity. Even in non-purda practising communities in
the tropics, poor exposure to sunshine due to social factors,
compounded by low dietary calcium intake, can lead to osteomalacia
Natl Med J India 2003;16:139–42
More than a century after the aetiology and prevention of nutritional
rickets and osteomalacia were described, these conditions remain
prevalent both in developed and developing countries.1–6 The
reasons include lack of adequate sunshine in temperate regions,
skin pigmentation in darker races, and low calcium and vitamin
D consumption due to poverty or food fads. Adolescent osteomalacia
was first reported among Asian immigrants from India and Pakistan
to the UK.7–9 The rapid growth
rate during adolescence increases the requirement of vitamin
D and calcium. Poor exposure
to sunshine due to a temperate climate and/or excessive clothing
would be expected to further compound this problem. Recent studies
from Finland, northern France, Saudi Arabia and China have again
brought into focus the issue of vitamin D deficiency during adolescence.1–5,10
In India, we do not share some of the contributory factors postulated
in the above geographical regions, in as much as there is no
paucity of sunshine and only a minority practise purda. There
are no published data on osteomalacia among adolescents living
in India. We present our experience with symptomatic adolescent
girls with osteomalacia to highlight the varied presentations
of the illness in this age group, the aetiology in our sunny
country in a predominantly non-purda practising community and
the response to therapy.
SUBJECTS AND METHODS
We prospectively studied all adolescents clinically suspected
to have rickets/osteomalacia attending the outpatient services
of the Endocrinology Department, Sanjay Gandhi Postgraduate Institute
of Medical Sciences and the Department of Physical Medicine and
Rehabilitation (Rehabilitation and Artificial Limb Centre), Chatrapati
Sahuji Maharaj Medical University (formerly King George’s
Medical College), Lucknow (latitude 26.8° N), from November
2000 to July 2002. The former is a tertiary care centre attended
predominantly by the middle socioeconomic group and the latter
serves, in addition, people belonging to the low socio-economic
All adolescents in Tanner stage 2 or more of puberty, with onset
of symptoms prior to 18 years of age, were included in the study.
All patients with a clinical suspicion of rickets/osteomalacia
underwent estimation of serum alkaline phosphatase and X-rays
of the pelvis or any other clinically relevant site. The diagnosis
was confirmed by an alkaline phosphatase level >200 IU/L11 and
radiological features of osteomalacia. The serum alkaline phosphatase
level in normal adults in our assay is 30–90
IU/L. Children with renal, hepatic or generalized skin disease,
those with malabsorption, or on anticonvulsant or antitubercular
drugs prior to the onset of symptoms, or having a family history
suggestive of resistant rickets were excluded. Since early marriage
is common in this population, those who were pregnant or had
given birth to a child were also excluded.
Clinical details of bone or joint pains, muscular weakness, deformities,
seizures, tetany, fractures or gait disturbances were noted and
information was obtained, with special reference to dietary history
and exposure to sunshine. The anthropometric data are in reference
to Indian children of the upper socioeconomic class.12 Calcium
and vitamin D intake was assessed by a 3-day diet recall. Details
of sun exposure were obtained by the daily duration of time spent
outdoors during the various seasons of the year by a direct questionnaire.
It was also confirmed indirectly from the details of school timings,
mode of transport, time spent in outdoor games, and outdoor and
indoor household activities. The socioeconomic factors evaluated
included the educational and occupational details of the parents,
per capita income and type of housing. Serum calcium, phosphorus
and 25-hydroxyvitamin D [25(OH)D] levels were also estimated.
The study was approved by our institutional ethics committee.
Serum calcium, phosphorus and alkaline phosphatase levels were
measured by commercial kits (Boehringer Mannheim, Mannheim, Germany)
using a spectrophotometer. Serum 25(OH)D level was measured by
radioimmunoassay kits (Incstar, Minnesota, USA). The limit of
detectability for 25(OH)D was 1.5 ng/ml and the interassay variation
in our laboratory was 17% at a 25(OH)D level of 15.1 ng/ml.
Treatment and follow up
All the subjects received a single oral dose of 600 000 U of
vitamin D and were advised adequate sun exposure. Elemental calcium
(as calcium carbonate) was given at a dose of 1 g daily, in three
divided doses for 12 months. Patients with multiple pseudofractures
of the pelvic bones were advised bed rest for 4–6 weeks.
The response was assessed at 1, 3 and 6 months from the start
of treatment, with repeat X-ray and estimation of alkaline phosphatase
levels at 3-monthly intervals until healing.
Twenty-five adolescents with osteomalacia presented during the
study period. Four were excluded from analysis as they had received
antitubercular therapy or irregular treatment with vitamin D
previously, rendering their biochemistry uninterpretable. All
were girls in whom the mean age at onset of symptoms was 13.6
years (range 9–16.5 years). The mean duration of symptoms
was 2.8 years (0.5–6 years). All were of urban origin.
Only 4 girls were from a low socioeconomic background; their
parents were either illiterate or had received only primary education
and there was evidence of overcrowding in the home. The majority
belonged to the middle socioeconomic class and their parents
were either professionals or businessmen. About 33% belonged
to the Muslim community.
|Table I. Presenting complaints in 21 adolescents
with Aetiology and clinicalosteomalacia
|Symptoms at presentation
|* 2 of the 4 patients who were excluded from the study
because of previous antitubercular therapy also had a recent
history of fracture
The clinical features are shown in Table I. Bone pain was the
most striking and distressing complaint. In 7 of them (33%),
the pain was excruciating, forcing them to restrict their daily
activities and discontinue schooling. In 6 patients, bone pain
was mistakenly attributed to joint pains resulting in unnecessary
investigations to uncover tuberculosis or a rheumatological
disorder. Two girls were referred to a cardiologist with a
diagnosis of rheumatic fever before osteomalcia was suspected,
and were on prophylaxis for rheumatic fever. Two patients had
received antitubercular treatment.
Muscular weakness was the next most prominent symptom and was
universally present. A minority (n=2) also complained of a waddling
gait. In 2 cases, predominant proximal muscle weakness led to
a suspicion of a primary neuromuscular disorder and these patients
were referred to the neurologist by their primary physician.
The combination of bone pains and muscular weakness with elevated
parathormone resulted in the referral diagnosis of primary hyperparathyroidism
in 3 girls. Deformities seen in 5 girls included genu valgum,
genu varum and coxa vara. Acute manifestations such as seizures
and tetany were infrequently seen, probably due to the patients
being in the stage when secondary hyperparathyroidism corrects
the hypocalcaemia. The mean height standard deviation score was
significantly lower than that for the reference population, though
weight standard deviation scores were comparable. None of the
patients had clinical evidence of other nutritional deficiencies.
Dietary calcium and sun exposure
The mean daily calcium intake was 265 (199) mg (recommended dietary
allowance 1200–1500 mg/day in adolescents).13 In 17 of
them it was stated to be due to personal preferences (distaste
for milk) rather than to economic reasons.
The mean exposure to sunlight was 5 (9) and 88 (103) minutes,
respectively, in summer and winter. None of the girls had participated
in outdoor games even at school, prior to their illness. Their
only exposure to the sun was on their way to and from school.
There was an even distribution of cases throughout the year.
Sun exposure was longer in winters due to a propensity for people
to sit in direct sunlight during this season. None of the girls
used sunscreens. Only one girl used purda. Even among the Hindus,
only the head, neck, forearm and hands were uncovered.
|Table II. Baseline clinical and biochemical
features of 21 patients with adolescent osteomalacia
|Age at presentation (years)
|Age at onset of symptoms (years)
|Religion (Hindu/Muslim) (n)
|Sun exposure† (min/day)
||5 (9)/ 88(103)
|Calcium intake (mg/day)
|Serum alkaline phosphatase (IU/L)
(adult normal 30–90 IU/L)
|Serum calcium (mg/dl)
(normal 8.5–10 mg/dl)
|Serum phosphorus (mg/dl)
(normal 3.5–5 mg/dl)
|25-hydroxyvitamin D (ng/ml)
(normal >10 ng/ml)
|* Standard deviation scores (SDS) with reference
to Indian children of higher socioeconomic class12
Area exposed included head, forearm, hands and feet in summer,
and only head and hands in winter
All but 1 patient had vitamin D deficiency with a mean 25(OH)D
of 4.9 (2.7) ng/ml. The mean 25(OH)D levels in the 14 ambulatory
patients was 5.9 (2.6) ng/ml, higher than the 7 non-ambulatory
patients [3.4 (2.4) ng/ml] and the difference was significant
(p=0.04). Nevertheless, both values were below normal (<10
ng/ml) (Table II).
Looser zones (pseudofractures) were seen at the upper end of
long bones, and/or pubic or ischial rami (n=10) (Fig. 1). Another
common finding was a wide and irregular pubic symphysis (n=12),
which became normal on follow up. Brown tumour was seen in 1
patient who presented with a fracture through the cyst, with
delayed union (Fig. 2). A triradiate pelvis was seen in 2 patients.
Response to therapy
All the patients showed clinical improvement on oral vitamin
D and calcium supplementation at 1 month of follow up. Proximal
myopathy and bone pain improved and all were ambulatory at 1
month. Radiological healing was complete by 3–6 months
and the alkaline phosphatase levels became normal between 1 and
9 months (Table III).
|Table III. Follow up serum alkaline phosphatase
|Duration of therapy
Mean SAP (range)*
|* SAP levels of patients with values outside
the normal range
Our study highlights the high index of suspicion necessary to
make an early diagnosis of osteomalacia in the absence of rickety
deformities. Misdiagnosis as arthritis, myopathy or psycho-
somatic illness in these young girls resulted in a delay in diagnosis
with associated severe morbidity. As the institutions from which
the patients were drawn were referral in nature, mildly affected
patients from the community must have been missed. Our study
also highlights the socioeconomic reasons that preclude many
Indians, particularly girls, from taking advantage of the abundant
sunshine available. Adolescent girls are discouraged from outdoor
activities (in comparison to boys), so that even non-purda practising
girls, who would otherwise be able to expose the face, neck,
forearms, arms and hands to sunshine, suffer from severe vitamin
D deficiency rickets/osteomalacia. This gender bias is witnessed
by the fact that during the period of the study, we did not encounter
a single male adolescent patient. The preponderance of girls
has been commented on in other reports on adolescent rickets/osteomalacia
from tropical middle eastern countries4–6 but not in reports
from temperate western countries.1,3 El-Haji Fuleihan et
al.6 observed in a multivariate analysis of Lebanese school-children
10–16 years of age that female gender predicted a low 25(OH)D
level, independent of the socioeconomic status and season. However,
these studies were carried out in communities observing purda.
In our study, a low level of 25(OH)D was universal in the adolescent girls with
osteomalacia. The cutaneous synthesis of vitamin D depends on the age, melanin
pigmentation and the angle of incidence of the sun’s rays (which in turn
depends on the latitude and season). Thus, synthesis is most efficient under
the overhead sun, in the summer season, in less pigmented races and in young
people. In our subjects, who were considerably more pigmented than Caucasians,
sun exposure was probably inadequate during the summer season. As regards winter,
Webb et al.14 have demonstrated cutaneous vitamin D production to continue throughout
the year at Los Angeles (latitude 34º N), though with a lower efficiency
in winter. In our subjects, however, though the duration of exposure in winter
was greater, the surface area exposed was less than that in summer. It is also
pertinent to mention here that studies on the intensity of ultraviolet-B rays
reaching the earth’s surface in winter in Lucknow showed that the intensity
was half that in summer (0.42 v. 0.82 mW/cm2, respectively).15 Our study could
not address the issue of seasonal changes in serum vitamin D levels. Goswami
et al.16 reported significantly lower vitamin D levels in winter than in summer
in a group of 19 physicians and nurses in New Delhi (latitude 28º N).
Low dietary calcium intake was also a pertinent factor in almost all our patients.
Dietary calcium deficiency has been shown to cause secondary vitamin D deficiency.17This relationship has also been noted in a study of 1248 Chinese adolescents
in whom low dietary calcium predicted the development of subclinical hypovitaminosis
D.10 The authors concluded that it was the low dietary calcium intake of rural
subjects that kept their serum vitamin D levels low in spite of better sun exposure
as compared to urban subjects. It is worth noting that except in 4 girls in our
study, it was not economic considerations but dislike for milk that led to low
calcium intake. Moncrieff et al.7 also noted this to be a pertinent fact among
immigrant Asians in the UK. At the same time, however, we must point out that
estimation of calcium intake by a 7-day recall or weighing food items during
home visits and during various seasons of the year would have been a better method
than a 3-day recall, which is a limitation of our study.
Adolescence is a period of life particularly prone to vitamin D deficiency, as
are infancy and pregnancy. Low dietary calcium intake may precipitate clinically
significant hypovitaminosis D in these vulnerable groups, in the presence of
marginal sun exposure. Investigators in temperate regions such as northern France
and Finland have recommended vitamin D supplementation during winter for adolescents.2,18,19Investigators working in tropical and near-tropical latitudes (Saudi Arabia,
Lebanon, Beijing) have also made similar recommendations, as the prevalent sociocultural
factors cannot be easily changed.5,6,10
In conclusion, adolescents with osteomalacia present with non-specific symptoms,
and early recognition requires a high index of suspicion. The importance of public
health measures to stress the benefits of adequate sun exposure and dietary calcium
intake cannot be overemphasized. This would not only prevent pubertal osteomalacia,
but would safeguard against future osteoporosis and complicated pregnancies as
a consequence of pelvic deformity, as well as neonatal hypocalcaemia and infantile
Ala-Houhala, Parviainen MT, Pyykko K, Visakorpi JK.
Serum 25-hydroxyvitamin D levels in Finnish
children aged 2–17 years. Acta Pediatr
Lehtonen-Veromaa M, Mottonen T, Irjala
K, Karkkainen M, Lamberg-Allardt C, Hakola P, et al.
intake is low and hypovitaminosis D common in healthy
9–15-year-old Finnish girls. Eur J Clin Nutr 1999;53:746–51.
Guillemant J, Cabrol S, Allemandou
A, Peres G, Guillemant S. Vitamin D dependent seasonal
variation in PTH
in growing male adolescents.
Narchi H, EI Jamil M, Kulaylat N.
Symptomatic rickets in adolescence. Arch Dis Child 2001;84:501–3.
Narchi H. Case–control study of diet and sun exposure in adolescents
with symptomatic rickets. Ann Trop Paediatr 2000;20:217–21.
El-Haji Fuleihan G, Nabulsi M, Choucair
M, Salamoun M, Haji Shahine C, Kizirian A, et al. Hypovitaminosis
D in healthy
Moncrieff MW, Lunt HRW, Arthur LJH.
Nutritional rickets at puberty. Arch Dis Child 1973;48:221–4.
Ford JA, Colhoun EM, McIntosh WB,
Dunnigan MG. Rickets and osteomalacia in the Glasgow
1962–1971. BMJ 1972;2:677–80.
Ford JA, Colhoun EM, McIntosh WB,
Dunnigan MG. Biochemical response of late rickets
to a chupatty-free
diet. BMJ 1972;3:446–7.
Du X, Greenfield H, Fraser DR, Ge
K, Trube A, Wang Y. Vitamin D deficiency
girls in Beijing.
Am J Clin Nutr 2001;74:494–500.
Bowers GN Jr, McComb RB. Measurement
of total alkaline phosphatase
activity in human
Clin Chem 1975;21:1988–95.
Agarwal DK, Agarwal KN, Upadhyay
SK, Mittal R, Prakash R,
Rai S. Physical and sexual
from 5 to 18 years of
age. Indian Pediatr 1992;29:1203–68.
Baker SS, Cochran WJ,
Flores CA, Georgieff
MK, Jacobson MS,
T, et al. American
of infants, children
and adolescents. Pediatrics 1999;104:1152–7.
Webb AR, Kline L,
Holick MF. Influence
of season and
on the cutaneous
synthesis of vitamin
sunlight in Boston
and Edmonton will not promote
D3 synthesis in human
skin. J Clin
Endocrinol Metab 1988;67: 373–8.
Ray RS. Studies
drugs with emphasis
and skin care
products. PhD thesis
Goswami D, Marwaha
N. Prevalence and
subjects in Delhi. Am
J Clin Nutr 2000;2:472– 5.
Odievre M. Vitamin
tolerance of vitamin
Vol. 21. New York:Raven
Sanjay Gandhi Postgraduate Institute of Medical Sciences,
Lucknow 226014, Uttar Pradesh, India
J. Rajeswari, K. Balasubramanian, V. Bhatia
Department of Endocrinology
Chatrapati Sahuji Maharaj Medical University, Lucknow, Uttar Pradesh,
V. P. Sharma, A. K. Agarwal Department of Physical Medicine and
Rehabilitation (Rehabilitation and Artificial Limb Centre)
Correspondence to V. Bhatia; email@example.com