Therapy in Idiopathic Juvenile Osteoporosis
Mineral Metabolism and Calcitriol
Giuseppe Saggese, MD; Silvano Bertelloni, MD; Giampiero I. Baroncelli, MD; Giuseppe Perri, MD; Andrea Calderazzi, MD
Idiopathic juvenile osteoporosis is a rare cause of osteoporosis during childhood. We examined four children (three boys and one girl, ranging in age from 2.3 to 12.6 years) with idiopathic juvenile osteoporosis. All of these patients had normal serum calcium, ionized calcium, phosmagnesium, 25-hydroxyvitamin D, intact parathyroid \s=b\
levels. phat e, and total and extractablelowcalcitonin three patients 1,25-Dihydroxyvitamin D values hormone,
were
in
and slightly decreased in one. Three children were treated with calcitriol (1,25 dihydroxycholecalciferol) (0.50 \g=m\g/d in two and 0.25 \g=m\g/din the other). The fourth patient was not treated because of parental refusal. Therapy reduced the fracture rate. Follow-up at 6 and 12 months showed a significant increase in bone mineralization, which reached normal values in two children after 12 months of treatment. No side effects of calcitriol therapy were observed. The untreated patient did not show an improvement of bone mineralization in the same time. -
(AJDC. 1991;145:457-462) I diopathic juvenile osteoporosis (IJO) is
a rare form of bone demineralization during childhood.1 The diagnosis is difficult since symptoms are not specific; it is based on the exclusion of known causes of osteoporosis in child¬ hood, mainly the mild forms of osteogenesis imperfecta.1 and of the Typical features are fractures of the long bones vertebrae, bone pain, difficulty in walking, and variable time to spontaneous recovery of bone mineralization, gen¬ erally within 3 to 4 years.2-4 In most patients, the onset of disease is just before puberty.3-4 Kooh et al5 and Exner et al6 described some cases in which symptoms became ev¬ ident before the age of 5 years. These periods of life, ie, the early years and peripuberty, are characterized by a high height velocity,7 and it is likely that IJO requires rapid clinically. growth to be manifest The pathogenesis of IJO is unknown.2 A negative calcium balance, detected in some3-8-9 but not in all patients,10 is the main metabolic abnormality observed. Marder and coworkers11 found low 1,25-dihydroxyvitamin D [l,25(OH)2D]
Accepted for publication August 23, 1990. From the Vitamin D Laboratory and Calcium Research Center, Endocrine Unit, Department of Pediatrics (Drs Saggese, Bertelloni, and Baroncelli), and Institute of Radiology (Drs Perri and Calderazzi), University of Pisa, Italy. Reprint requests to Vitamin D Laboratory and Calcium Research Center, Endocrine Unit, Department of Pediatrics, University of Pisa, Via Roma, 35, 56100 Pisa, Italy (Dr Saggese).
levels in
one
patient,
while
Leroy
et al12 found
high
concentrations associated with low levels of 25-hydroxyvitamin D (25-OH-D) and 24,25-dihydroxyvitamin D in the girl they observed. Recently, Jackson et al13 suggested a possible calcitonin deficiency in some cases. Therapeutic trials with vitamin D, calcium supplements,
l,25(OH)2D
calcitonin, and anabolic steroids failed to modify the natural course of IJO.313 Marder et al11 found that calcitriol (1,25dihydroxycholecalciferol) was effective, even if the same
group did not confirm this finding in another patient.13 Since the pathogenesis of IJO has been related to an impaired secretion of l,25(OH)2Dn or calcitonin,13 we studied serum basal and stimulated levels of l,25(OH)2D and calcitonin to clarify the relationships between these hormones and IJO. In this study, we evaluated both total plasma calcitonin (tCT) and extractable calcitonin (exCT) levels, since it has been demonstrated that the exCT mea¬ surement reflects more accurately the biologically relevant plasma monomeric calcitonin level than the tCT assay does.14 Moreover, we report bone mineralization, as¬ sessed by single photon absorptiometry (SPA), at diag¬ nosis and during 3 years of follow-up. In the first year of follow-up, three patients received calcitriol therapy; the fourth was not treated because of parental refusal.
SUBJECTS AND METHODS Patients
We examined three boys and one girl with IJO (Table 1). Symp¬ toms were bone pain, recurrent fractures at the methaphyses of long bones in all but one (patient 2), and difficulty in walking. In none of the patients was there any history of nausea, vomiting,
diarrhea, steatorrhea, immobilization, bleeding ten¬ dency, familial osteogenesis imperfecta, or other metabolic bone disease. A detailed evaluation of diet showed an adequate intake of energy, protein, calcium, and phosphate. Roentgenographic films showed diffuse osteoporosis in the three boys only. No signs of rickets, ossa suturarum, or abnormalities of the lamina dura were present. More clinical details of these patients at di¬ agnosis were reported elsewhere.15 recurrent
All
Study Protocol
subjects were studied in the supine position after an over¬
night fast; blood samples were taken from an antecubital vein through an indwelling catheter between 8 and 9 am for the de¬ termination of calcium, phosphate, magnesium, alkaline phosphatase, osteocalcin (the major noncollagenous bone protein se¬ creted by osteoblasts),16 intact parathyroid hormone (PTH), tCT,
exCT, 25-OH-D, and l,25(OH)2D levels in basal condition. After
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Table 1.—Clinical and
Radiological Findings Patient No.
1
12.1/M
Age, y/sex Symptom
9.5
2.0/M 1.3
12.6/F
9.0/M
10.5
2.1
onset, age, y
Height, cm Height
148
91
148
126
50
75
10-25
10-25
Weight, kg Weight percentile*
44
14
40
25
75-90
50
25
25
Pubertal
G1PM
G1Ph1
B2Ph1
G1Ph1
percenti le*
yt 12.0
1.7
10.0
9.0
Family history
No
No
No
No
Bone
Diffuse
Knee, foot
Diffuse
Legs, spine
Walking difficulty Loss of height
Yes
No
Yes
No
No
No
Yes
Yes
Backache Pigeon chest
No
Yes
No
Yes
No
Yes
No
No
Fractures
Legs,
No
Hands, knees, Vertebrae,
pain
Fracture rate,
Methods Serum levels of calcium (normal range, 2.1 to 2.7 mmol/L), phosphate (1.2 to 2.0 mmol/L), magnesium (0.8 to 1.3 mmol/L), alkaline phosphatase (86 to 645 U/L), glucose (4.0 to 6.4 mmol/L), creatinine (
Mineral Metabolism and Calcitriol
Giuseppe Saggese, MD; Silvano Bertelloni, MD; Giampiero I. Baroncelli, MD; Giuseppe Perri, MD; Andrea Calderazzi, MD
Idiopathic juvenile osteoporosis is a rare cause of osteoporosis during childhood. We examined four children (three boys and one girl, ranging in age from 2.3 to 12.6 years) with idiopathic juvenile osteoporosis. All of these patients had normal serum calcium, ionized calcium, phosmagnesium, 25-hydroxyvitamin D, intact parathyroid \s=b\
levels. phat e, and total and extractablelowcalcitonin three patients 1,25-Dihydroxyvitamin D values hormone,
were
in
and slightly decreased in one. Three children were treated with calcitriol (1,25 dihydroxycholecalciferol) (0.50 \g=m\g/d in two and 0.25 \g=m\g/din the other). The fourth patient was not treated because of parental refusal. Therapy reduced the fracture rate. Follow-up at 6 and 12 months showed a significant increase in bone mineralization, which reached normal values in two children after 12 months of treatment. No side effects of calcitriol therapy were observed. The untreated patient did not show an improvement of bone mineralization in the same time. -
(AJDC. 1991;145:457-462) I diopathic juvenile osteoporosis (IJO) is
a rare form of bone demineralization during childhood.1 The diagnosis is difficult since symptoms are not specific; it is based on the exclusion of known causes of osteoporosis in child¬ hood, mainly the mild forms of osteogenesis imperfecta.1 and of the Typical features are fractures of the long bones vertebrae, bone pain, difficulty in walking, and variable time to spontaneous recovery of bone mineralization, gen¬ erally within 3 to 4 years.2-4 In most patients, the onset of disease is just before puberty.3-4 Kooh et al5 and Exner et al6 described some cases in which symptoms became ev¬ ident before the age of 5 years. These periods of life, ie, the early years and peripuberty, are characterized by a high height velocity,7 and it is likely that IJO requires rapid clinically. growth to be manifest The pathogenesis of IJO is unknown.2 A negative calcium balance, detected in some3-8-9 but not in all patients,10 is the main metabolic abnormality observed. Marder and coworkers11 found low 1,25-dihydroxyvitamin D [l,25(OH)2D]
Accepted for publication August 23, 1990. From the Vitamin D Laboratory and Calcium Research Center, Endocrine Unit, Department of Pediatrics (Drs Saggese, Bertelloni, and Baroncelli), and Institute of Radiology (Drs Perri and Calderazzi), University of Pisa, Italy. Reprint requests to Vitamin D Laboratory and Calcium Research Center, Endocrine Unit, Department of Pediatrics, University of Pisa, Via Roma, 35, 56100 Pisa, Italy (Dr Saggese).
levels in
one
patient,
while
Leroy
et al12 found
high
concentrations associated with low levels of 25-hydroxyvitamin D (25-OH-D) and 24,25-dihydroxyvitamin D in the girl they observed. Recently, Jackson et al13 suggested a possible calcitonin deficiency in some cases. Therapeutic trials with vitamin D, calcium supplements,
l,25(OH)2D
calcitonin, and anabolic steroids failed to modify the natural course of IJO.313 Marder et al11 found that calcitriol (1,25dihydroxycholecalciferol) was effective, even if the same
group did not confirm this finding in another patient.13 Since the pathogenesis of IJO has been related to an impaired secretion of l,25(OH)2Dn or calcitonin,13 we studied serum basal and stimulated levels of l,25(OH)2D and calcitonin to clarify the relationships between these hormones and IJO. In this study, we evaluated both total plasma calcitonin (tCT) and extractable calcitonin (exCT) levels, since it has been demonstrated that the exCT mea¬ surement reflects more accurately the biologically relevant plasma monomeric calcitonin level than the tCT assay does.14 Moreover, we report bone mineralization, as¬ sessed by single photon absorptiometry (SPA), at diag¬ nosis and during 3 years of follow-up. In the first year of follow-up, three patients received calcitriol therapy; the fourth was not treated because of parental refusal.
SUBJECTS AND METHODS Patients
We examined three boys and one girl with IJO (Table 1). Symp¬ toms were bone pain, recurrent fractures at the methaphyses of long bones in all but one (patient 2), and difficulty in walking. In none of the patients was there any history of nausea, vomiting,
diarrhea, steatorrhea, immobilization, bleeding ten¬ dency, familial osteogenesis imperfecta, or other metabolic bone disease. A detailed evaluation of diet showed an adequate intake of energy, protein, calcium, and phosphate. Roentgenographic films showed diffuse osteoporosis in the three boys only. No signs of rickets, ossa suturarum, or abnormalities of the lamina dura were present. More clinical details of these patients at di¬ agnosis were reported elsewhere.15 recurrent
All
Study Protocol
subjects were studied in the supine position after an over¬
night fast; blood samples were taken from an antecubital vein through an indwelling catheter between 8 and 9 am for the de¬ termination of calcium, phosphate, magnesium, alkaline phosphatase, osteocalcin (the major noncollagenous bone protein se¬ creted by osteoblasts),16 intact parathyroid hormone (PTH), tCT,
exCT, 25-OH-D, and l,25(OH)2D levels in basal condition. After
Downloaded From: http://archpedi.jamanetwork.com/ by a University of Manitoba User on 06/20/2015
Table 1.—Clinical and
Radiological Findings Patient No.
1
12.1/M
Age, y/sex Symptom
9.5
2.0/M 1.3
12.6/F
9.0/M
10.5
2.1
onset, age, y
Height, cm Height
148
91
148
126
50
75
10-25
10-25
Weight, kg Weight percentile*
44
14
40
25
75-90
50
25
25
Pubertal
G1PM
G1Ph1
B2Ph1
G1Ph1
percenti le*
yt 12.0
1.7
10.0
9.0
Family history
No
No
No
No
Bone
Diffuse
Knee, foot
Diffuse
Legs, spine
Walking difficulty Loss of height
Yes
No
Yes
No
No
No
Yes
Yes
Backache Pigeon chest
No
Yes
No
Yes
No
Yes
No
No
Fractures
Legs,
No
Hands, knees, Vertebrae,
pain
Fracture rate,
Methods Serum levels of calcium (normal range, 2.1 to 2.7 mmol/L), phosphate (1.2 to 2.0 mmol/L), magnesium (0.8 to 1.3 mmol/L), alkaline phosphatase (86 to 645 U/L), glucose (4.0 to 6.4 mmol/L), creatinine (
