Idiopathic Juvenile Osteoporosis Mohini Teotia, MD, DCH; Surendra P. S. Teotia, MD;
describe four children with idiopathic juvenile osteoporosis. All patients were initially seen between the ages of 10 and 13 years and spontaneously recovered following puberty. We review 27 similar cases reported in the literature. Theories on the cause of idiopathic osteoporosis in children are critically discussed. It may be that milder forms remain undiagnosed because of the self-limited course and the pain being confused with a variety of rheumatic disorders. It would be worth observing these cases to determine if they are otherwise prone to development of osteoporosis during pregnancy or in later life. (Am J Dis Child 133:894-900, 1979)
REPORT OF CASES
\s=b\ We
is an disease chil¬ that affects dren. It starts around the ages of 8 to 14 years and is characterized by arrest of growth, loss of height, joint pain, and varying degrees of generalized osteoporosis with vertebral collapse. The children recover spontaneously during later puberty. Teotia1 reported idiopathic juvenile osteoporosis the first time from India. We describe our further experience with the follow-up of these cases and review 27 similar cases reported in the literature.
osteoporosis Idiopathic juvenile previously healthy uncommon
self-limited
From the Department of Human Metabolism and Endocrinology, LLRM Medical College, Meerut, India. Reprints not available.
Raj K. Singh, MSc, PhD
Case l.-This
boy
was
born in 1956. His
prenatal, natal, and postnatal history was noncontributory. He was well and growing normally. He was brought to us in Novem¬
ber 1968 at the age of 12 years with the complaints of low back pain following a 1.8-m fall eight months previously. This constant dull ache was often aggravated by movements of his spine. A detailed dietary evaluation at this stage revealed a daily intake of 2,200 calories, 40 g of protein, 1,022 mg of calcium, and 86 IU of vitamin D. He had a normal appetite. There was no history of nausea, vomiting, recurrent diarrhea, or steatorrhea. There was no history of recent change in weight, altera¬ tion in facial appearance, ankle swelling,
muscular weakness, or bleeding tendency. His two brothers (aged 16 and 5 years) and a sister (aged 1 year) were normal. There was no family history of osteogenesis imperfecta or other metabolic bone disor¬ ders. Examination revealed a young boy of average build. His measurements were as follows: height, 127 cm (crown to pubis height, 57.5 cm; pubis to heel height, 69.2 cm), span, 127 cm, and weight, 27.3 kg. Apart from dorsal cyphosis and pigeon chest, no other abnormal findings could be detected on thorough physical examina¬ tion. Results of the
following investigations
normal: hemoglobin, total leukocyte count, differential leukocyte count, ESR, were
electrophoretic strip, serum sodium, serum potassium, serum chloride, serum bilirubin, prothrombin time, urine concentration,
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and dilution test, and amino acid chromatogram. The plasma calcium value was 9.8 mg/dL; phosphorus, 5.2 mg/dL; alkaline phosphatase, 22 King-Armstrong units/ dL; urinary excretion of calcium, 156 mg/
day; phosphorus excretion,
768
mg/day;
17-ketosteroid excretion, 3.2 mg/day; and 17-ketogenic steroid excretion, 11.0 mg/ day. The plasma cortisol level at 9 am was 12,8 Mg/dL, and at 12 midnight was 3.2 Mg/dL. Fat excretion on three consecutive days on a hospital diet was 1.8 g/day, which represented 95% absorption of the adminis¬ tered fat. X-ray films revealed a marked rarefraction of the whole skeleton, with collapse and wedging of the vertebral bodies that was most marked in the dorsal region. Metaphyseal bands of osteoporosis were visible in the tibia and fibula (Fig 1). No evidence of rickets or secondary hyperparathyroid¬ ism was seen. An intravenous pyelogram was normal. A four-day calcium balance test using copper thiocyanate as internal marker on a diet similar to his home diet showed that he had a negative calcium balance of 42 mg/ day, which is abnormal for his age (Table 1). He was observed in the metabolic ward on a diet supplying 1 g of calcium per day, supplemented by effervescent gluconate calcium, one tablet twice a day (500 mg of elemental calcium per tablet). He was given crutches for support while walking. After a period of four months, in March 1969, he was discharged and advised to carry on the treatment at home and to report to a follow-up clinic every three months. There was no clinical or radiologically
Fig 1 .—X-ray film of leg showing marked osteo¬ porosis and extremely thin cortex; submetaphyseal band of osteoporosis is visible in tibia (case 1).
Fig 2.—Pelvis, extreme rarefaction of bones, thin cortex, bilateral fracture of femoral necks (case 2).
Fig 3.—Pelvis after clinical recovery (case 2). Improvement density of bones and thickening of cortex is obvious.
evident improvement in the condition of the child at the time of discharge and on subsequent follow-up until July 1969, when his back pain started decreasing and he felt better. At this stage, his bone density also showed improvement. He was admitted for additional calcium balance tests; results indicated positive balance of 300 mg/day. Since then, he has been seen every six months and has shown steady improve¬ ment. In December of 1977, he had no back pain, his height was 147 cm, and his weight was 43 kg. His sexual development has been normal. Case 2.-A 10-year-old girl, first child of healthy unrelated parents, was well until June 1969, when she experienced pain in both feet and difficulty in walking. X-ray films of both feet showed marked osteopo¬ rosis. She was transferred to a metabolic ward for investigation of her osteoporosis. While she was in the ward, pain and swell¬ ing of the right knee joint developed, which further increased her difficulty in walking. At the same time, she experienced back¬ ache and generalized bone pains. Apart from these symptoms, she had good appe¬ tite, had not lost weight, and had no nausea or vomiting. A dietary assessment showed a daily intake of 2,300 calories, 60 g of protein, 110 g of fat, 260 g of carbohy¬ drates, 980 mg of calcium, and 80 IU of vitamin D. There was no family history of bone disease. On examination, her height was 127.5 cm; span, 128.8 cm; crown to pubis height, 60 cm; and pubis to heel height, 63.5 cm. Weight was 24.1 kg. With the two knees together, the internal malleoli were 8.5 cm apart. Cyphoscoliosis was present in the thoracic region. Bone tenderness, corneal
in
Fig
4.—Ankle shows
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porotic
bones and thin cortex
(case 2).
calcification, blue sclerae, petechiae, striae, bruising, obesity, and hypertension were
notably absent on examination. Fat distri¬
bution and muscle power were normal. Laxity of the ligaments around wrists and ankles was present. The rest of the exami¬ nation results were normal. The plasma calcium level was 9.8 mg/dL;
plasma specific gravity, 1,026 to 1,027; plas¬ ma phosphorus, 4.6 mg/dL; alkaline phos¬ phatase, 22 King-Armstrong units/dL; 24hour urinary excretion of calcium, 180 mg; phosphorus, 1,156 mg/24 hr. The plasma sodium, potassium, chloride, bicarbonate, and total differential leukocyte count val¬ ues were normal. Peripheral blood smear showed no abnormal or immature cells. Maximum urinary specific gravity was 1,022, and dilution was 1,008. The urine contained no albumin, pus cells, RBCs or casts, and the culture was sterile. The 24-hour urinary 17-ketosteroid value was 7.3 mg, and the 17-ketogenic steroid value was 10.8 mg. The plasma cortisol value at 9 am was 10.8 Mg/dL and at midnight was 1.9 Mg/dL. On the second day of the adminis¬ tration of 40 IU of purified corticotropin intramuscularly, the 17-ketogenic steroid level rose to 30 mg/24 hr, and the plasma cortisol level rose to 48.6 Mg/dL five hours after the morning dose on second day of the administration of purified corticotro¬ pin. Following the administration of dexamethasone, 2 mg/day for two days, the plasma cortisol level dropped to 1.2 Mg/dL. Her mean daily fat excretion on three consecutive days was 1.3 g. X-ray films showed generalized severe osteoporosis. A lateral x-ray film of the thoracolumbar area of the spine showed a marked degree of vertebral collapse with widening of the intervertebral disk spaces. She had bilateral fractures of the femoral neck with extreme rarefaction of the pelvic bone. The ankle bones were grossly porotic with very thin cortices (Fig 2 to 5). The hands showed generalized osteoporosis and no evidence of subperiosteal bone résorp¬ tion. Calcium balance tests carried out during two periods showed she was in negative balance of 50 mg/day, which is abnormal for her age (Table 1). After the initial balance periods were over and while she was still receiving a balanced diet, therapy with vitamin D2, 10 drops per day, supply¬ ing 5,000 IU of vitamin D;,, and efferves¬ cent gluconate calcium, one tablet twice daily, was started. The next calcium balance test showed that she was in posi¬ tive balance of 100 mg/day. She was discharged from the metabolic ward in August 1969, and was advised to continue the same treatment at home and to attend the metabolic follow-up clinic every three
Fig 5.—X-ray film recovery (case 2).
of ankle after clinical
months. In March 1971, her back pain was less, and an x-ray film of the knee joints showed healing of the fractures, although the spine did not reveal any significant improvement. In July 1971, her serum
was 11 mg/dL. All therapy stopped, and she was readmitted to the metabolic ward. She had a positive calcium balance of 200 mg/day. Her serum calcium level gradually dropped to 9.2 mg/dL. She was discharged, but was advised to contin¬ ue her diet, which supplied 1 g of calcium per day and no medication. X-ray films taken in September 1972 showed marked improvement in bone density. Vertebral bodies now appeared normal in size and shape (Fig 3). She had her menarche in February 1973, and has shown an 8.5-cm gain in height during the period of follow-
calcium level was
up (December 1976). Case 3.—A 13-year-old boy was admitted to the metabolic ward in December 1970 with the complaints of excessive weight gain and backache for the past year, and pain in knee, ankle joints, and difficulty in walking for the last six months. Before the onset of these symptoms, he had been in good health. His other three siblings and parents were healthy. A detailed diet eval¬ uation showed an adequate intake of calo¬ ries, proteins, calcium, and vitamin D. Examination at this stage revealed his height and weight to be within the 50th percentile. He had pain and difficulty in
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Fig 6.—Lateral x-ray film of spine showing osteoporosis; vertebral bodies have thin pencilled outline (case 3).
severe
movements of his joints He had not fractured his long bones. There were no petechiae, striae, hypertension, or buffalo hump obe¬ sity. Results of the following investiga¬ tions were normal: hemoglobin; total and differential leukocyte and platelet counts; ESR; plasma electrolytes; urea; total pro¬ tein; electrophoretic strip; rheumatoid fac¬ tor; and bone marrow examination. His urinary 17-ketosteroid excretion was 2.5
walking. Passive were
painless.
steroid excre¬ tion was 11.8 mg/day. The plasma cortisol level at 9 am was 10.2 Mg/dL. His fecal fat excretion was 2.4 g/day. An x-ray film of his spine showed gener¬ alized rarefaction and flattening of the vertebral bodies, which had a thin pencilled outline. Growing ends of all the bones were grossly porotic. Rarefaction of the metaphyses of the ulna was more marked than in the radius. Similar porotic areas were seen around knee, ankle, lower pubic and ischial rami, superior surface of the femor¬ al neck, and greater trochanter. A chest x-ray film showed collapse of the thoracic cage, diminished width of ribs, and marked osteoporosis. Dental x-ray films showed
mg/day, and 17-ketogenic
intact lamina dura. An intravenous pyelogram showed normal findings. He was found to have a negative calcium balance. Since the known causes of osteo¬ porosis had been excluded by clinical exam¬
laboratory investigations, idio¬ pathic osteoporosis was diagnosed. Thera¬ py including a weight-reducing diet, 10,000 ination and
IU of vitamin
D», and
1 g of calcium
supplements per day was started. A balance study three months after starting this treatment showed that he still had a negative calcium balance of 20 mg/day. There was no change in the radiological density of long bones, or in the size and shape of the vertebral bodies. He was then discharged and was advised to avoid trau¬ matic activities, to continue the reducing diet, and to attend a metabolic follow-up clinic every three months. Nine months after the discharge his backache was still persistent, but pain in knees and ankles had almost disappeared. Roentgenograms did not reveal any change in his skeleton. In November 1971, his back pain lessened and some improvement in the density of the bones was noted for the first time. At present (August 1977), he has shown marked improvement in the mineralization of his spine. The areas of osteoporosis at the ends of the long bones and pelvis have almost disappeared. He has grown 6 cm and has for the last two months started taking part in games. Case 4.—A 12-year-old boy, the second son of healthy parents, was brought to us in January 1971 with the complaints of gradually increasing pains in the dorsal areas of his feet that had gradually curtailed his physical activity for the last five months. He had enjoyed excellent health in the past and was a good
gymnast.
He could walk slowly, with a shuffling gait, and complained of pain in his heels and knee joints. His general condition was good. A detailed general and systemic examination showed normal findings. His height was 128 cm and weight was 23 kg. His hemoglobin level was 13.8 g/dL; total
WBC count was 5,000/cu mm with a normal differential count. The following values were also obtained: plasma calcium, 9.1 mg/dL; phosphorus, 4.8 mg/dL; alkaline phosphatase, 20 King-Armstrong units/
dL; sodium, 142 mEq/L, potassium, 6 mEq/ L; and bicarbonate, 21 mEq/L. Liver and kidney function tests, including tubular reabsorption of phosphorus and amino acid chromatogram, showed normal results.
Urinary 17-ketosteroid excretion was 4.0 mg/day; 17-ketogenic steroid excretion was 11.6 mg/day. The plasma cortisol value at 9 am was 10.2 Mg/dL, and at midnight it was 1.8 Mg/dL. Urinary excretion of
Fig 7.—Pelvis shows grossly fractures of femur (case 4).
porotic bones, pencilled outline
of femoral cortex, and two
Table 1 —Calcium Balance in Cases With Idiopathic Juvenile Osteoporosis* Calcium
Intake, mg/ Day
Case
Urine, mg/ Day
Feces, mg/ Day
Balance, mg/ Day
1_1,052_1_56_938_-42_ 980
2
180
850
-50
3_1,020_1^5_91_5_^60_
"
4 1,040 Balance at time of admission.
200
+5
835
Table 2.—Features Distinguishing Idiopathic Juvenile Osteoporosis From
Osteogenesis Imperfecta Idiopathic Juvenile Osteoporosis Family history Onset Duration Course Roe ntgenog rams
Calcium balances Connective tissue defects
None 2-3 yr before puberty. Clinical and roentgenological normality before onset of disease 1-4 yr
Acuteness of process when it does manifest followed by spontaneous healing Overall width of shaft of long bones and ribs normal, although cortices were extremely thin; metaphyseal fractures common Negative in acute phase Some have loose joints
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Osteogenesis Imperfecta May be positive Present from birth
Lifelong Lifelong Abnormally
narrow
long bones,
diminished width of ribs; metaphyseal fractures rare
Slightly positive Loose joints, blue sclerae
deafness, abnormal teeth common
Table
3.—Summary of the Clinical, Radiological, and Biochemical Findings and Therapeutic Regimens in Reported Cases of
Age,
Sex
yr
No. of
Year
1938
Author
Cases
Schippers2
Mean
Range M
F
7-1/2
12
1965 Berglund and
Llndquist3
1965 Dent and
9-1/2
8-11
3
3
Friedman4
1966 Fanconi et al5
15
1967 Cloutier et
1
12-1/2
al6
1
1
Main Clinical Presentation
Radiologie
Important Investigations
Features
Generalized pain, loss of height
Multiple fractures of legs, vertebrae
Foot and back pain, difficulty in walking, fractures
Generalized decrease
Recurrent fractures, backache, pain in arms and legs
Widespread Calcium balance osteoporosis, vertebral compression; negative in 3 cases; adrenal functions multiple fractures
Bone pains
Severe generalized
Back pain
in density of skeleton; compression of thoracic and lumbar vertebrae
Kinetic studies (47Ca) showed normal rate of bone formation
normal
osteoporosis; multiple fractures
Osteoporosis of the whole spinal column; compression of
thoracic and lumbar vertebrae
Hypercalcuria;
decreased response of 17-oxysteroids to
corticotropin
Quantitative microradiography showed increased bone
résorption, normal bone formation
1969
1
Goding
15
and Ball7
1969
1971
Gorgenyi8
1
10
Lapatasonis
10
8-12
Pain in left hip, loss of height
Generalized
Backache following a minor fall
Marked osteoporosis of the thoracic and lumbar vertebrae
17-ketosteroid and oxysteroid excretion normal
Pain in ankle and toe; difficulty and unsteadiness in
Marked osteoporosis of spine and foot; rarefaction of long bones
Negative calcium
walking 1975 Brenton and Dent10 (includes 6 cases
and
17
10-1/2
8-13
Back pain; general¬ ized aches; pain in joints; loss of
of Dent
osteoporosis; dorsal kyphosis
Tetracycline labeling
showed red uced rate of bone formation
balance in both cases
Widespread osteopo¬ rosis; metaphyseal impaction; fractures
height
Friedman,
1965)4
1979 Teotiaetal
(present report)
11-1/2
10-13
3
1
Backache; difficulty
in walking; pain in knee, ankles, and feet
Generalized
severe
osteoporosis; neoosseous porosis;
spontaneous fractures
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Urinary 17-ketosterold; 17-ketogenic steroid; plasma cortisol normal; calcium balance negative in 3/4
was 200 mg/day (normal range for laboratory at this age is 80 to 120 mg/day). His fecal fat excretion was 3.0 g/day. Calcium balance showed that his intake was equal to excretion (Table 1).
Idiopathic Juvenile Osteoporosis
calcium
and recovery coincided with onset of
our
puberty.
A roentgenogram revealed marked os¬ the thoracic and the lumbar vertebral bodies. The cortical pattern was sharp. Intervertébral disks were swollen. Marked osteoporosis of the pelvis, feet, and hands was also seen (Fig 7). Metaphyseal ends of almost all the long bones showed rarefaction. He was observed for three months in the metabolic ward. His clinical and radiologi¬ cal condition remained the same during this period. He was discharged with the advice to avoid traumatic activities and to attend a metabolic follow-up clinic every three months. In March 1972, his backache and pains in the feet decreased and he felt better. His skeletal x-ray films showed some improvement in density of the bones. At present (August 1977), he has no back¬ ache or bone pains, and he has grown 7.5
teoporosis involving Recovery and Follow-up
Treatment
Calcium, vitamin D
Recovery after 2yr
Physiotherapy,
6
calcium, vitamins, norethandrolone
Dihydrotachysterol, sex
hormone,
calcium
mo
and 1 yr
follow-up
Recovery within 6 mo to
2 yr;
majority showed good growth after recovery
curve
cm.
Orthopedic
treatment;
4 yr after onset
of symptoms
physiotherapy
No treatment;
spontaneous remission
High doses of calcium, vitamin D
Recovery after 1-1/2 yr
Back pain and general weak¬
continued; radiological improvement ness
no
until 1 yr Anabolic steroids, calcium
Follow-up4yrlater
showed vertebral
bodies of normal
shapeand height Calcium and vitamin D
Clinical improve¬ ment 10-18 mo after starting treatment
None In mildly affected patients; minimal mobili¬ zation after fractures
Good in mild cases; slow
suggested
covery
re¬
(3-4 yr)
often incom¬ plete with deformities, in severe cases
Calcium and vitamin D
Improvement after 9 mo to 1 yr;
follow-up 5yr
after the clinical
improvement
COMMENT
Marked osteoporosis was a constant characteristic radiological finding in all four cases. The detailed history, clinical examination, and biochemical investigations ruled out the known causes of osteoporosis in this group. Therefore, the diagnosis of idiopathic juvenile osteoporosis was made. Idio¬ pathic juvenile osteoporosis has a superficial resemblance to osteogene¬ sis imperfecta. The important differ¬ entiating features between the two conditions are summarized in Table 2. Of the four, one patient did not receive any treatment and showed spontaneous recovery after one year. The remaining three patients received calcium and vitamin D supplements, and their conditions improved after nine months to one year. We believe that their recovery was also indepen¬ dent of the supplements they re¬ ceived. Their spontaneous recovery further confirmed the diagnosis of
idiopathic juvenile osteoporosis. Twenty-seven similar cases of idio¬ pathic juvenile osteoporosis have been reported in the literature.-1" The clin¬ ical symptoms, signs, and radiological and biochemical investigations of the cases reported are summarized in Table 3. All of these patients had clinical disease at fairly uniform age,
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Eleven
cases
of transient childhood
osteoporosis of unknown origin in patients between the ages of 19 months to 12 years have been reported by Kooh et al." These were identical to the cases of idiopathic juvenile osteoporosis regarding their symp¬ toms, signs, radiological and biochem¬ ical investigations, and course of
disease. However, because of the widely varying age of presentation unrelated to puberty, a likelihood of different underlying cause could not be excluded. Therefore, these cases have not been included in Table 3. The mechanism of development of
idiopathic juvenile osteoporosis re¬ mains largely a matter of speculation.
Results of routine blood examination, electrophoretic strip, blood and bone marrow smear for abnormal cells, renal and liver function tests, serum electrolyte determinations, routine urine examination, and 24-hour stool fat studies have been reported to be normal. Plasma calcium, phosphorus, and alkaline phosphatase levels are generally within normal range. Dur¬ ing the active phase of disease, hypercalcuria and a negative calcium bal¬ ance have been seen in the majority of the patients. Urine chromatograms show no abnormal aminoaciduria. In view of the possibility that this condition is a variant of Cushing's disease, Dent and Friedman4 exten¬ sively studied the adrenal function in their six patients. Two had a slightly increased cortisol production rate. Both adrenal glands were found to be of normal size at laporotomy in one, while the other one showed sponta¬ neous remission of bone disease on follow-up. Results of plasma cortisol, 24-hour urinary 17-ketosteroid and 17ketogenic steroid, ACTH stimulation, and dexamethasone suppression tests were within normal limits in the four cases studied by us. The radioactive iodine uptake and thyroid scan showed normal findings in one case reported by Gooding and Ball.7 Quantitative microradiography in seven cases of idiopathic juvenile osteoporosis12 showed normal bone formation and increased bone résorp¬ tion. The width of the osteoid tissue
was
less than that found in normal
age-matched controls. The bone showed no quantitative abnormality. The large number of investigations done so far have not suggested the mechanism of its development. The negative calcium balance during the acute phase of disease may suggest a possibility of temporary calcium malabsorption from gut at an age when the demands for calcium are high, eventually leading to secondary hy¬ perparathyroidism and bone disease clinically manifesting as idiopathic juvenile osteoporosis. Serum immunoreactive parathyroid hormone levels reported1- in one case was 19 µ!· equiv¬ alents per milliliter, compared with
normal individuals, with serum cal¬ cium levels between 10.0 and 10.2 mg/ dL and parathyroid hormone levels of 18 mL equivalent per milliliter. Jowsey and Jhonson1- suggest that the value was within normal range, but inappro¬ priately high for a serum calcium level. The finding of increased bone résorption on quantitative microradiography of the bone biopsy speci¬ mens could further suggest parathy¬ roid overactivity. Grossly porotic areas at the metaph¬ yseal ends of long bones were seen in our cases and have also been reported by Brenton and Dent1" in some of their cases. Since the metaphyses, the growing ends of the long bones, are most porotic and constitute a charac¬ teristic roentgenological finding in
idiopathic juvenile osteoporosis,
we
have
the term "neoemphasize the involvement of the newly formed bone in this disease. Similar areas of neoosseous porosis have been earlier described by us in children with endemic skeletal fluorosis,:' who also had raised levels of serum immunoreactive parathyroid hormone. Probably development of secondary hyperpara¬ thyroidism may be a causative factor in the radiological manifestation of neo-osseous porosis in the growing children in the two conditions. Hahn et al," using a photon absorption tech¬ nique, reported a greater degree of bone loss at the distal metaphyseal sites in patients with primary hyper¬ parathyroidism and corticosteroidinduced osteopenia than in controls and cases with senile osteoporosis. They suggested that increased para¬ thyroid activity may play a signifi¬ cant role in the bone loss associated with chronic corticosteroid therapy. Probably the areas of metaphyseal erosions seen in idiopathic juvenile osteoporosis could also be the result of
preferred to porosis"
osseous
use
to
secondary parathyroid overactivity
and similar to the cases of corticosteroid-induced osteopenia. Dent and Friedman4 gave infusions of plasma taken from a case of adult marble-bone disease to one of their patients. Plasma infusions in this case changed the initial negative calcium balance of 114 mg/day to a positive balance of 100 mg/day. These authors suggested that the beneficial effect
that followed the plasma infusions might be due to the presence of an unknown factor in pooled plasma that had induced calcium accretion. Most patients with idiopathic juve¬ nile osteoporosis have a fairly con¬ stant age of presentation and show spontaneous remission with the onset of puberty. It is likely that some hormonal imbalance related to the
pubertal growth spurt acts as a trig¬ ger for the clinical disease at this criti¬ cal period of growth; this imbalance is corrected by the onset of puberty. In view of the recently described abnormalities of skin collagen in
osteogenesis imperfecta1'—an inher¬ ited form of osteoporosis in children— a study of the collagen metabolism may prove helpful in uncovering the pathogenesis of baffling problems of idiopathic juvenile osteoporosis.
Because of the self-limited course, many of the milder cases of idiopathic juvenile osteoporosis that undergo spontaneous recovery may be missed without the clinical diagnosis of the underlying disorder ever being made. It is suggested that a previously healthy child with an unexplained limp or back pain should be carefully evaluated to rule out the presence of this disease. A follow-up study of a larger number of such cases may unveil the underlying cause. It would be worthwhile to watch these patients for development of idiopathic osteo¬ porosis during pregnancy or senile osteoporosis at a later age.
References 1. Teotia SPS: Idiopathic juvenile osteoporosis, abstracted. International Symposium on Clinical Aspects of Metabolic Bone Disease\p=m-\HenryFord Hospital, Detroit, Michigan, USA, 1972. 2. Schippers JC: A case of spontaneous general osteoporosis in girl 10 years old. Maandschr
Kindergeneek 8:109-111, 1938. 3. Berglund G, Lindquist B: Osteopenia in adolescence. Clin Orthop 17:259-264, 1960. 4. Dent CE, Friedman M: Idiopathic juvenile osteoporosis. Q J Med 34:177-210, 1965. 5. Fanconi A, Illig R, Poley JR, et al: Idiopathic transitorische osteoporose in pubertatsalter. Helv
Paediatr Acta 6:531-547, 1966. 6. Cloutier MD, Hayles AB, Higgs BL, et al: Juvenile osteoporosis. Report of a case including a description of some metabolic and microradio-
graphic studies. Pediatrics 40:649-652, 1967. 7. Gooding CA, Ball JH: Idiopathic juvenile osteoporosis. Radiology 93:1349-1351, 1969. 8. Gorgenyi A: Idiopathic juvenile osteoporosis. Acta Pediatr Acad Sci Hung 10:315-321, 1969. 9. Lapatsanis
P, Kavadias A, Vretos K: JuveChild 47:66-71, 1971. 10. Brenton DP, Dent CE: Idiopathic juvenile
nile
osteoporosis. Arch Dis
osteoporosis in inborn errors of calcium and bone
metabolism, in Bickel H, Stern J (eds): Proceedings of the 12th Symposium of the Society for the Study of Inborn Errors of Metabolism. MTP Press Limited, pp 222-238,1976. 11. Kooh SW, Cumming WA, Fraser D, et al: Transient childhood osteoporosis of unknown cause, in Clinical Aspects of Metabolic Bone
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Disease. Amsterdam, Excerpta Medica, 1973, pp 329-332. 12. Jowsey J, Jhonson KA: Juvenile osteoporosis: Bone findings in seven patients. J Pediatr 81:511-517, 1972. 13. Teotia M, Teotia SPS, Kunwar KB: Endemic skeletal fluorosis. Arch Dis Child 46:686-691, 1971. 14. Hahn TJ, Beisseau VC, Avioli AL: Effect of chronic corticosteroid administration on diaphyseal and metaphyseal bone mass. J Clin Endocrinol Metab 39:274-282, 1974. 15. Francis MJO, Smith R, Bauze RJ: Instability of polymeric skin collagen in osteogenesis imperfecta. Br Med J 1:421-424, 1974.
describe four children with idiopathic juvenile osteoporosis. All patients were initially seen between the ages of 10 and 13 years and spontaneously recovered following puberty. We review 27 similar cases reported in the literature. Theories on the cause of idiopathic osteoporosis in children are critically discussed. It may be that milder forms remain undiagnosed because of the self-limited course and the pain being confused with a variety of rheumatic disorders. It would be worth observing these cases to determine if they are otherwise prone to development of osteoporosis during pregnancy or in later life. (Am J Dis Child 133:894-900, 1979)
REPORT OF CASES
\s=b\ We
is an disease chil¬ that affects dren. It starts around the ages of 8 to 14 years and is characterized by arrest of growth, loss of height, joint pain, and varying degrees of generalized osteoporosis with vertebral collapse. The children recover spontaneously during later puberty. Teotia1 reported idiopathic juvenile osteoporosis the first time from India. We describe our further experience with the follow-up of these cases and review 27 similar cases reported in the literature.
osteoporosis Idiopathic juvenile previously healthy uncommon
self-limited
From the Department of Human Metabolism and Endocrinology, LLRM Medical College, Meerut, India. Reprints not available.
Raj K. Singh, MSc, PhD
Case l.-This
boy
was
born in 1956. His
prenatal, natal, and postnatal history was noncontributory. He was well and growing normally. He was brought to us in Novem¬
ber 1968 at the age of 12 years with the complaints of low back pain following a 1.8-m fall eight months previously. This constant dull ache was often aggravated by movements of his spine. A detailed dietary evaluation at this stage revealed a daily intake of 2,200 calories, 40 g of protein, 1,022 mg of calcium, and 86 IU of vitamin D. He had a normal appetite. There was no history of nausea, vomiting, recurrent diarrhea, or steatorrhea. There was no history of recent change in weight, altera¬ tion in facial appearance, ankle swelling,
muscular weakness, or bleeding tendency. His two brothers (aged 16 and 5 years) and a sister (aged 1 year) were normal. There was no family history of osteogenesis imperfecta or other metabolic bone disor¬ ders. Examination revealed a young boy of average build. His measurements were as follows: height, 127 cm (crown to pubis height, 57.5 cm; pubis to heel height, 69.2 cm), span, 127 cm, and weight, 27.3 kg. Apart from dorsal cyphosis and pigeon chest, no other abnormal findings could be detected on thorough physical examina¬ tion. Results of the
following investigations
normal: hemoglobin, total leukocyte count, differential leukocyte count, ESR, were
electrophoretic strip, serum sodium, serum potassium, serum chloride, serum bilirubin, prothrombin time, urine concentration,
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and dilution test, and amino acid chromatogram. The plasma calcium value was 9.8 mg/dL; phosphorus, 5.2 mg/dL; alkaline phosphatase, 22 King-Armstrong units/ dL; urinary excretion of calcium, 156 mg/
day; phosphorus excretion,
768
mg/day;
17-ketosteroid excretion, 3.2 mg/day; and 17-ketogenic steroid excretion, 11.0 mg/ day. The plasma cortisol level at 9 am was 12,8 Mg/dL, and at 12 midnight was 3.2 Mg/dL. Fat excretion on three consecutive days on a hospital diet was 1.8 g/day, which represented 95% absorption of the adminis¬ tered fat. X-ray films revealed a marked rarefraction of the whole skeleton, with collapse and wedging of the vertebral bodies that was most marked in the dorsal region. Metaphyseal bands of osteoporosis were visible in the tibia and fibula (Fig 1). No evidence of rickets or secondary hyperparathyroid¬ ism was seen. An intravenous pyelogram was normal. A four-day calcium balance test using copper thiocyanate as internal marker on a diet similar to his home diet showed that he had a negative calcium balance of 42 mg/ day, which is abnormal for his age (Table 1). He was observed in the metabolic ward on a diet supplying 1 g of calcium per day, supplemented by effervescent gluconate calcium, one tablet twice a day (500 mg of elemental calcium per tablet). He was given crutches for support while walking. After a period of four months, in March 1969, he was discharged and advised to carry on the treatment at home and to report to a follow-up clinic every three months. There was no clinical or radiologically
Fig 1 .—X-ray film of leg showing marked osteo¬ porosis and extremely thin cortex; submetaphyseal band of osteoporosis is visible in tibia (case 1).
Fig 2.—Pelvis, extreme rarefaction of bones, thin cortex, bilateral fracture of femoral necks (case 2).
Fig 3.—Pelvis after clinical recovery (case 2). Improvement density of bones and thickening of cortex is obvious.
evident improvement in the condition of the child at the time of discharge and on subsequent follow-up until July 1969, when his back pain started decreasing and he felt better. At this stage, his bone density also showed improvement. He was admitted for additional calcium balance tests; results indicated positive balance of 300 mg/day. Since then, he has been seen every six months and has shown steady improve¬ ment. In December of 1977, he had no back pain, his height was 147 cm, and his weight was 43 kg. His sexual development has been normal. Case 2.-A 10-year-old girl, first child of healthy unrelated parents, was well until June 1969, when she experienced pain in both feet and difficulty in walking. X-ray films of both feet showed marked osteopo¬ rosis. She was transferred to a metabolic ward for investigation of her osteoporosis. While she was in the ward, pain and swell¬ ing of the right knee joint developed, which further increased her difficulty in walking. At the same time, she experienced back¬ ache and generalized bone pains. Apart from these symptoms, she had good appe¬ tite, had not lost weight, and had no nausea or vomiting. A dietary assessment showed a daily intake of 2,300 calories, 60 g of protein, 110 g of fat, 260 g of carbohy¬ drates, 980 mg of calcium, and 80 IU of vitamin D. There was no family history of bone disease. On examination, her height was 127.5 cm; span, 128.8 cm; crown to pubis height, 60 cm; and pubis to heel height, 63.5 cm. Weight was 24.1 kg. With the two knees together, the internal malleoli were 8.5 cm apart. Cyphoscoliosis was present in the thoracic region. Bone tenderness, corneal
in
Fig
4.—Ankle shows
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porotic
bones and thin cortex
(case 2).
calcification, blue sclerae, petechiae, striae, bruising, obesity, and hypertension were
notably absent on examination. Fat distri¬
bution and muscle power were normal. Laxity of the ligaments around wrists and ankles was present. The rest of the exami¬ nation results were normal. The plasma calcium level was 9.8 mg/dL;
plasma specific gravity, 1,026 to 1,027; plas¬ ma phosphorus, 4.6 mg/dL; alkaline phos¬ phatase, 22 King-Armstrong units/dL; 24hour urinary excretion of calcium, 180 mg; phosphorus, 1,156 mg/24 hr. The plasma sodium, potassium, chloride, bicarbonate, and total differential leukocyte count val¬ ues were normal. Peripheral blood smear showed no abnormal or immature cells. Maximum urinary specific gravity was 1,022, and dilution was 1,008. The urine contained no albumin, pus cells, RBCs or casts, and the culture was sterile. The 24-hour urinary 17-ketosteroid value was 7.3 mg, and the 17-ketogenic steroid value was 10.8 mg. The plasma cortisol value at 9 am was 10.8 Mg/dL and at midnight was 1.9 Mg/dL. On the second day of the adminis¬ tration of 40 IU of purified corticotropin intramuscularly, the 17-ketogenic steroid level rose to 30 mg/24 hr, and the plasma cortisol level rose to 48.6 Mg/dL five hours after the morning dose on second day of the administration of purified corticotro¬ pin. Following the administration of dexamethasone, 2 mg/day for two days, the plasma cortisol level dropped to 1.2 Mg/dL. Her mean daily fat excretion on three consecutive days was 1.3 g. X-ray films showed generalized severe osteoporosis. A lateral x-ray film of the thoracolumbar area of the spine showed a marked degree of vertebral collapse with widening of the intervertebral disk spaces. She had bilateral fractures of the femoral neck with extreme rarefaction of the pelvic bone. The ankle bones were grossly porotic with very thin cortices (Fig 2 to 5). The hands showed generalized osteoporosis and no evidence of subperiosteal bone résorp¬ tion. Calcium balance tests carried out during two periods showed she was in negative balance of 50 mg/day, which is abnormal for her age (Table 1). After the initial balance periods were over and while she was still receiving a balanced diet, therapy with vitamin D2, 10 drops per day, supply¬ ing 5,000 IU of vitamin D;,, and efferves¬ cent gluconate calcium, one tablet twice daily, was started. The next calcium balance test showed that she was in posi¬ tive balance of 100 mg/day. She was discharged from the metabolic ward in August 1969, and was advised to continue the same treatment at home and to attend the metabolic follow-up clinic every three
Fig 5.—X-ray film recovery (case 2).
of ankle after clinical
months. In March 1971, her back pain was less, and an x-ray film of the knee joints showed healing of the fractures, although the spine did not reveal any significant improvement. In July 1971, her serum
was 11 mg/dL. All therapy stopped, and she was readmitted to the metabolic ward. She had a positive calcium balance of 200 mg/day. Her serum calcium level gradually dropped to 9.2 mg/dL. She was discharged, but was advised to contin¬ ue her diet, which supplied 1 g of calcium per day and no medication. X-ray films taken in September 1972 showed marked improvement in bone density. Vertebral bodies now appeared normal in size and shape (Fig 3). She had her menarche in February 1973, and has shown an 8.5-cm gain in height during the period of follow-
calcium level was
up (December 1976). Case 3.—A 13-year-old boy was admitted to the metabolic ward in December 1970 with the complaints of excessive weight gain and backache for the past year, and pain in knee, ankle joints, and difficulty in walking for the last six months. Before the onset of these symptoms, he had been in good health. His other three siblings and parents were healthy. A detailed diet eval¬ uation showed an adequate intake of calo¬ ries, proteins, calcium, and vitamin D. Examination at this stage revealed his height and weight to be within the 50th percentile. He had pain and difficulty in
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Fig 6.—Lateral x-ray film of spine showing osteoporosis; vertebral bodies have thin pencilled outline (case 3).
severe
movements of his joints He had not fractured his long bones. There were no petechiae, striae, hypertension, or buffalo hump obe¬ sity. Results of the following investiga¬ tions were normal: hemoglobin; total and differential leukocyte and platelet counts; ESR; plasma electrolytes; urea; total pro¬ tein; electrophoretic strip; rheumatoid fac¬ tor; and bone marrow examination. His urinary 17-ketosteroid excretion was 2.5
walking. Passive were
painless.
steroid excre¬ tion was 11.8 mg/day. The plasma cortisol level at 9 am was 10.2 Mg/dL. His fecal fat excretion was 2.4 g/day. An x-ray film of his spine showed gener¬ alized rarefaction and flattening of the vertebral bodies, which had a thin pencilled outline. Growing ends of all the bones were grossly porotic. Rarefaction of the metaphyses of the ulna was more marked than in the radius. Similar porotic areas were seen around knee, ankle, lower pubic and ischial rami, superior surface of the femor¬ al neck, and greater trochanter. A chest x-ray film showed collapse of the thoracic cage, diminished width of ribs, and marked osteoporosis. Dental x-ray films showed
mg/day, and 17-ketogenic
intact lamina dura. An intravenous pyelogram showed normal findings. He was found to have a negative calcium balance. Since the known causes of osteo¬ porosis had been excluded by clinical exam¬
laboratory investigations, idio¬ pathic osteoporosis was diagnosed. Thera¬ py including a weight-reducing diet, 10,000 ination and
IU of vitamin
D», and
1 g of calcium
supplements per day was started. A balance study three months after starting this treatment showed that he still had a negative calcium balance of 20 mg/day. There was no change in the radiological density of long bones, or in the size and shape of the vertebral bodies. He was then discharged and was advised to avoid trau¬ matic activities, to continue the reducing diet, and to attend a metabolic follow-up clinic every three months. Nine months after the discharge his backache was still persistent, but pain in knees and ankles had almost disappeared. Roentgenograms did not reveal any change in his skeleton. In November 1971, his back pain lessened and some improvement in the density of the bones was noted for the first time. At present (August 1977), he has shown marked improvement in the mineralization of his spine. The areas of osteoporosis at the ends of the long bones and pelvis have almost disappeared. He has grown 6 cm and has for the last two months started taking part in games. Case 4.—A 12-year-old boy, the second son of healthy parents, was brought to us in January 1971 with the complaints of gradually increasing pains in the dorsal areas of his feet that had gradually curtailed his physical activity for the last five months. He had enjoyed excellent health in the past and was a good
gymnast.
He could walk slowly, with a shuffling gait, and complained of pain in his heels and knee joints. His general condition was good. A detailed general and systemic examination showed normal findings. His height was 128 cm and weight was 23 kg. His hemoglobin level was 13.8 g/dL; total
WBC count was 5,000/cu mm with a normal differential count. The following values were also obtained: plasma calcium, 9.1 mg/dL; phosphorus, 4.8 mg/dL; alkaline phosphatase, 20 King-Armstrong units/
dL; sodium, 142 mEq/L, potassium, 6 mEq/ L; and bicarbonate, 21 mEq/L. Liver and kidney function tests, including tubular reabsorption of phosphorus and amino acid chromatogram, showed normal results.
Urinary 17-ketosteroid excretion was 4.0 mg/day; 17-ketogenic steroid excretion was 11.6 mg/day. The plasma cortisol value at 9 am was 10.2 Mg/dL, and at midnight it was 1.8 Mg/dL. Urinary excretion of
Fig 7.—Pelvis shows grossly fractures of femur (case 4).
porotic bones, pencilled outline
of femoral cortex, and two
Table 1 —Calcium Balance in Cases With Idiopathic Juvenile Osteoporosis* Calcium
Intake, mg/ Day
Case
Urine, mg/ Day
Feces, mg/ Day
Balance, mg/ Day
1_1,052_1_56_938_-42_ 980
2
180
850
-50
3_1,020_1^5_91_5_^60_
"
4 1,040 Balance at time of admission.
200
+5
835
Table 2.—Features Distinguishing Idiopathic Juvenile Osteoporosis From
Osteogenesis Imperfecta Idiopathic Juvenile Osteoporosis Family history Onset Duration Course Roe ntgenog rams
Calcium balances Connective tissue defects
None 2-3 yr before puberty. Clinical and roentgenological normality before onset of disease 1-4 yr
Acuteness of process when it does manifest followed by spontaneous healing Overall width of shaft of long bones and ribs normal, although cortices were extremely thin; metaphyseal fractures common Negative in acute phase Some have loose joints
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Osteogenesis Imperfecta May be positive Present from birth
Lifelong Lifelong Abnormally
narrow
long bones,
diminished width of ribs; metaphyseal fractures rare
Slightly positive Loose joints, blue sclerae
deafness, abnormal teeth common
Table
3.—Summary of the Clinical, Radiological, and Biochemical Findings and Therapeutic Regimens in Reported Cases of
Age,
Sex
yr
No. of
Year
1938
Author
Cases
Schippers2
Mean
Range M
F
7-1/2
12
1965 Berglund and
Llndquist3
1965 Dent and
9-1/2
8-11
3
3
Friedman4
1966 Fanconi et al5
15
1967 Cloutier et
1
12-1/2
al6
1
1
Main Clinical Presentation
Radiologie
Important Investigations
Features
Generalized pain, loss of height
Multiple fractures of legs, vertebrae
Foot and back pain, difficulty in walking, fractures
Generalized decrease
Recurrent fractures, backache, pain in arms and legs
Widespread Calcium balance osteoporosis, vertebral compression; negative in 3 cases; adrenal functions multiple fractures
Bone pains
Severe generalized
Back pain
in density of skeleton; compression of thoracic and lumbar vertebrae
Kinetic studies (47Ca) showed normal rate of bone formation
normal
osteoporosis; multiple fractures
Osteoporosis of the whole spinal column; compression of
thoracic and lumbar vertebrae
Hypercalcuria;
decreased response of 17-oxysteroids to
corticotropin
Quantitative microradiography showed increased bone
résorption, normal bone formation
1969
1
Goding
15
and Ball7
1969
1971
Gorgenyi8
1
10
Lapatasonis
10
8-12
Pain in left hip, loss of height
Generalized
Backache following a minor fall
Marked osteoporosis of the thoracic and lumbar vertebrae
17-ketosteroid and oxysteroid excretion normal
Pain in ankle and toe; difficulty and unsteadiness in
Marked osteoporosis of spine and foot; rarefaction of long bones
Negative calcium
walking 1975 Brenton and Dent10 (includes 6 cases
and
17
10-1/2
8-13
Back pain; general¬ ized aches; pain in joints; loss of
of Dent
osteoporosis; dorsal kyphosis
Tetracycline labeling
showed red uced rate of bone formation
balance in both cases
Widespread osteopo¬ rosis; metaphyseal impaction; fractures
height
Friedman,
1965)4
1979 Teotiaetal
(present report)
11-1/2
10-13
3
1
Backache; difficulty
in walking; pain in knee, ankles, and feet
Generalized
severe
osteoporosis; neoosseous porosis;
spontaneous fractures
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Urinary 17-ketosterold; 17-ketogenic steroid; plasma cortisol normal; calcium balance negative in 3/4
was 200 mg/day (normal range for laboratory at this age is 80 to 120 mg/day). His fecal fat excretion was 3.0 g/day. Calcium balance showed that his intake was equal to excretion (Table 1).
Idiopathic Juvenile Osteoporosis
calcium
and recovery coincided with onset of
our
puberty.
A roentgenogram revealed marked os¬ the thoracic and the lumbar vertebral bodies. The cortical pattern was sharp. Intervertébral disks were swollen. Marked osteoporosis of the pelvis, feet, and hands was also seen (Fig 7). Metaphyseal ends of almost all the long bones showed rarefaction. He was observed for three months in the metabolic ward. His clinical and radiologi¬ cal condition remained the same during this period. He was discharged with the advice to avoid traumatic activities and to attend a metabolic follow-up clinic every three months. In March 1972, his backache and pains in the feet decreased and he felt better. His skeletal x-ray films showed some improvement in density of the bones. At present (August 1977), he has no back¬ ache or bone pains, and he has grown 7.5
teoporosis involving Recovery and Follow-up
Treatment
Calcium, vitamin D
Recovery after 2yr
Physiotherapy,
6
calcium, vitamins, norethandrolone
Dihydrotachysterol, sex
hormone,
calcium
mo
and 1 yr
follow-up
Recovery within 6 mo to
2 yr;
majority showed good growth after recovery
curve
cm.
Orthopedic
treatment;
4 yr after onset
of symptoms
physiotherapy
No treatment;
spontaneous remission
High doses of calcium, vitamin D
Recovery after 1-1/2 yr
Back pain and general weak¬
continued; radiological improvement ness
no
until 1 yr Anabolic steroids, calcium
Follow-up4yrlater
showed vertebral
bodies of normal
shapeand height Calcium and vitamin D
Clinical improve¬ ment 10-18 mo after starting treatment
None In mildly affected patients; minimal mobili¬ zation after fractures
Good in mild cases; slow
suggested
covery
re¬
(3-4 yr)
often incom¬ plete with deformities, in severe cases
Calcium and vitamin D
Improvement after 9 mo to 1 yr;
follow-up 5yr
after the clinical
improvement
COMMENT
Marked osteoporosis was a constant characteristic radiological finding in all four cases. The detailed history, clinical examination, and biochemical investigations ruled out the known causes of osteoporosis in this group. Therefore, the diagnosis of idiopathic juvenile osteoporosis was made. Idio¬ pathic juvenile osteoporosis has a superficial resemblance to osteogene¬ sis imperfecta. The important differ¬ entiating features between the two conditions are summarized in Table 2. Of the four, one patient did not receive any treatment and showed spontaneous recovery after one year. The remaining three patients received calcium and vitamin D supplements, and their conditions improved after nine months to one year. We believe that their recovery was also indepen¬ dent of the supplements they re¬ ceived. Their spontaneous recovery further confirmed the diagnosis of
idiopathic juvenile osteoporosis. Twenty-seven similar cases of idio¬ pathic juvenile osteoporosis have been reported in the literature.-1" The clin¬ ical symptoms, signs, and radiological and biochemical investigations of the cases reported are summarized in Table 3. All of these patients had clinical disease at fairly uniform age,
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Eleven
cases
of transient childhood
osteoporosis of unknown origin in patients between the ages of 19 months to 12 years have been reported by Kooh et al." These were identical to the cases of idiopathic juvenile osteoporosis regarding their symp¬ toms, signs, radiological and biochem¬ ical investigations, and course of
disease. However, because of the widely varying age of presentation unrelated to puberty, a likelihood of different underlying cause could not be excluded. Therefore, these cases have not been included in Table 3. The mechanism of development of
idiopathic juvenile osteoporosis re¬ mains largely a matter of speculation.
Results of routine blood examination, electrophoretic strip, blood and bone marrow smear for abnormal cells, renal and liver function tests, serum electrolyte determinations, routine urine examination, and 24-hour stool fat studies have been reported to be normal. Plasma calcium, phosphorus, and alkaline phosphatase levels are generally within normal range. Dur¬ ing the active phase of disease, hypercalcuria and a negative calcium bal¬ ance have been seen in the majority of the patients. Urine chromatograms show no abnormal aminoaciduria. In view of the possibility that this condition is a variant of Cushing's disease, Dent and Friedman4 exten¬ sively studied the adrenal function in their six patients. Two had a slightly increased cortisol production rate. Both adrenal glands were found to be of normal size at laporotomy in one, while the other one showed sponta¬ neous remission of bone disease on follow-up. Results of plasma cortisol, 24-hour urinary 17-ketosteroid and 17ketogenic steroid, ACTH stimulation, and dexamethasone suppression tests were within normal limits in the four cases studied by us. The radioactive iodine uptake and thyroid scan showed normal findings in one case reported by Gooding and Ball.7 Quantitative microradiography in seven cases of idiopathic juvenile osteoporosis12 showed normal bone formation and increased bone résorp¬ tion. The width of the osteoid tissue
was
less than that found in normal
age-matched controls. The bone showed no quantitative abnormality. The large number of investigations done so far have not suggested the mechanism of its development. The negative calcium balance during the acute phase of disease may suggest a possibility of temporary calcium malabsorption from gut at an age when the demands for calcium are high, eventually leading to secondary hy¬ perparathyroidism and bone disease clinically manifesting as idiopathic juvenile osteoporosis. Serum immunoreactive parathyroid hormone levels reported1- in one case was 19 µ!· equiv¬ alents per milliliter, compared with
normal individuals, with serum cal¬ cium levels between 10.0 and 10.2 mg/ dL and parathyroid hormone levels of 18 mL equivalent per milliliter. Jowsey and Jhonson1- suggest that the value was within normal range, but inappro¬ priately high for a serum calcium level. The finding of increased bone résorption on quantitative microradiography of the bone biopsy speci¬ mens could further suggest parathy¬ roid overactivity. Grossly porotic areas at the metaph¬ yseal ends of long bones were seen in our cases and have also been reported by Brenton and Dent1" in some of their cases. Since the metaphyses, the growing ends of the long bones, are most porotic and constitute a charac¬ teristic roentgenological finding in
idiopathic juvenile osteoporosis,
we
have
the term "neoemphasize the involvement of the newly formed bone in this disease. Similar areas of neoosseous porosis have been earlier described by us in children with endemic skeletal fluorosis,:' who also had raised levels of serum immunoreactive parathyroid hormone. Probably development of secondary hyperpara¬ thyroidism may be a causative factor in the radiological manifestation of neo-osseous porosis in the growing children in the two conditions. Hahn et al," using a photon absorption tech¬ nique, reported a greater degree of bone loss at the distal metaphyseal sites in patients with primary hyper¬ parathyroidism and corticosteroidinduced osteopenia than in controls and cases with senile osteoporosis. They suggested that increased para¬ thyroid activity may play a signifi¬ cant role in the bone loss associated with chronic corticosteroid therapy. Probably the areas of metaphyseal erosions seen in idiopathic juvenile osteoporosis could also be the result of
preferred to porosis"
osseous
use
to
secondary parathyroid overactivity
and similar to the cases of corticosteroid-induced osteopenia. Dent and Friedman4 gave infusions of plasma taken from a case of adult marble-bone disease to one of their patients. Plasma infusions in this case changed the initial negative calcium balance of 114 mg/day to a positive balance of 100 mg/day. These authors suggested that the beneficial effect
that followed the plasma infusions might be due to the presence of an unknown factor in pooled plasma that had induced calcium accretion. Most patients with idiopathic juve¬ nile osteoporosis have a fairly con¬ stant age of presentation and show spontaneous remission with the onset of puberty. It is likely that some hormonal imbalance related to the
pubertal growth spurt acts as a trig¬ ger for the clinical disease at this criti¬ cal period of growth; this imbalance is corrected by the onset of puberty. In view of the recently described abnormalities of skin collagen in
osteogenesis imperfecta1'—an inher¬ ited form of osteoporosis in children— a study of the collagen metabolism may prove helpful in uncovering the pathogenesis of baffling problems of idiopathic juvenile osteoporosis.
Because of the self-limited course, many of the milder cases of idiopathic juvenile osteoporosis that undergo spontaneous recovery may be missed without the clinical diagnosis of the underlying disorder ever being made. It is suggested that a previously healthy child with an unexplained limp or back pain should be carefully evaluated to rule out the presence of this disease. A follow-up study of a larger number of such cases may unveil the underlying cause. It would be worthwhile to watch these patients for development of idiopathic osteo¬ porosis during pregnancy or senile osteoporosis at a later age.
References 1. Teotia SPS: Idiopathic juvenile osteoporosis, abstracted. International Symposium on Clinical Aspects of Metabolic Bone Disease\p=m-\HenryFord Hospital, Detroit, Michigan, USA, 1972. 2. Schippers JC: A case of spontaneous general osteoporosis in girl 10 years old. Maandschr
Kindergeneek 8:109-111, 1938. 3. Berglund G, Lindquist B: Osteopenia in adolescence. Clin Orthop 17:259-264, 1960. 4. Dent CE, Friedman M: Idiopathic juvenile osteoporosis. Q J Med 34:177-210, 1965. 5. Fanconi A, Illig R, Poley JR, et al: Idiopathic transitorische osteoporose in pubertatsalter. Helv
Paediatr Acta 6:531-547, 1966. 6. Cloutier MD, Hayles AB, Higgs BL, et al: Juvenile osteoporosis. Report of a case including a description of some metabolic and microradio-
graphic studies. Pediatrics 40:649-652, 1967. 7. Gooding CA, Ball JH: Idiopathic juvenile osteoporosis. Radiology 93:1349-1351, 1969. 8. Gorgenyi A: Idiopathic juvenile osteoporosis. Acta Pediatr Acad Sci Hung 10:315-321, 1969. 9. Lapatsanis
P, Kavadias A, Vretos K: JuveChild 47:66-71, 1971. 10. Brenton DP, Dent CE: Idiopathic juvenile
nile
osteoporosis. Arch Dis
osteoporosis in inborn errors of calcium and bone
metabolism, in Bickel H, Stern J (eds): Proceedings of the 12th Symposium of the Society for the Study of Inborn Errors of Metabolism. MTP Press Limited, pp 222-238,1976. 11. Kooh SW, Cumming WA, Fraser D, et al: Transient childhood osteoporosis of unknown cause, in Clinical Aspects of Metabolic Bone
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Disease. Amsterdam, Excerpta Medica, 1973, pp 329-332. 12. Jowsey J, Jhonson KA: Juvenile osteoporosis: Bone findings in seven patients. J Pediatr 81:511-517, 1972. 13. Teotia M, Teotia SPS, Kunwar KB: Endemic skeletal fluorosis. Arch Dis Child 46:686-691, 1971. 14. Hahn TJ, Beisseau VC, Avioli AL: Effect of chronic corticosteroid administration on diaphyseal and metaphyseal bone mass. J Clin Endocrinol Metab 39:274-282, 1974. 15. Francis MJO, Smith R, Bauze RJ: Instability of polymeric skin collagen in osteogenesis imperfecta. Br Med J 1:421-424, 1974.
