The Impact of Three Siblings of Children With Severe Osteogenesis Imperfecta on Financial Burden for Infatient Care in a Hospital
H
HA
ASSIILL PPEEN
NEELLIITTIIA
AN
N
THE IMPACT OF THREE SIBLINGS OF CHILDREN WITH
SEVERE OSTEOGENESIS IMPERFECTA ON FINANCIAL
BURDEN FOR INPATIENT CARE IN A HOSPITAL
Hadyanto Lim1,2,3, Umar Zein4, Yahwardiah Siregar5,
Blondina Marpaung6, dan Jaminsen Sinaga7
1
Department of Pharmacology, Faculty of Medicine, Methodist University of Indonesia/
Methodist Susanna Wesley Hospital, Medan.
Jl. Setia Budi Psr II Tj Sari, Medan 20132
2
Biomedical Research, Postgraduate School, University of Nort Sumatra, Medan.
Jl. Civitas Akademika Kampus USU, Medan 20155
3
Cardiovascular Pharmacology, Mastery and Resident Programs, Faculty of Medicine,
University of Nort Sumatra, Medan.
Jl. Dr. Mansur No 5. Kampus USU, Medan 20155
4
Division of Tropical Medicine and Infectious Diseases, Department of Internal Medicine,
Faculty of Medicine, University of Nort Sumatra, Medan.
Jl. Dr. Mansur No 5. Kampus USU, Medan 20155
5
Department of Biochemistry, Faculty of Medicine, University of Nort Sumatra, Medan.
Jl. Dr. Mansur No 5. Kampus USU, Medan 20155
6
Division of Rheumatology, Department of Internal Medicine, Adam Malik General Hospital-Medan
Jl. Djamin Ginting, Medan
7
Department of Pediatrics, Faculty of Medicine, Methodist University of Indonesia/Methodist
Susanna Wesley Hospital, Medan
Jl. Setia Budi Psr II Tj Sari, Medan 20132
ABSTRACT
Osteogenesis imperfecta (OI) is a rare genetic skeletal disorder that has a major
impact to the financial status of the suffered’s family. We investigated the cost
expenditures of three siblings with OI after five admissions in a hospital. Three
siblings, two brothers and one young sister aged 1-6 years old were admitted to
Methodist Susanna Wesley Hospital in Medan. We reviewed the computerized
database capturing a variety of cost expenditures of diagnosis determinant,
medical treatment, and hospital charges for each admission. Total charges for five
admissions in the hospital were > Rp.31 millions, of which 21.25% was accounted
for by diagnosis determinant, 9.38% for treatment, and 69.37% for hospital stay.
The mean length of stay was 10 days for five admissions. The findings show that
there is enormous financial impact of osteogenesis imperfecta on inpatient care.
Keywords: Financial impact, Family, Osteogenesis imperfecta
INTRODUCTION
Osteogenesis
imperfecta
(OI), often referred to as "brittlebone disease," is a heritable genetic
disorder characterized in most
affected persons by either a reduction
in the production of normal type I
collagen or the synthesis of abnormal
collagen as a result of mutations in the type I
collagen genes (Glorieux et al. 1998). Its
hallmark feature is bone fragility, (Lang, 2003;
Rauch and Glorieux, 2004) with a tendency to
fracture from minimal trauma (Marini, 1998)
or from the work of bearing weight against
gravity.
Improved physician awareness may
lead to earlier diagnosis in patients with
Perbedaan Faktor Infeksi dengan Pemeriksaan PCR Serviks HPV (1–78)
19
Chatarina U.W.
Universitas Sumatera Utara
previously undiagnosed genetic
conditions
and
improved
management of patients with known
genetic disorders (Rauch and
Glorieux, 2004). Caring of patients
with these fractures is also very
expensive, and costs will continue to
rise as the frequency of fractures
increases in the future. To our
knowledge, no studies have detailed
the cost expenditures of OI patients
admitted to the hospital.
Methodist Susanna Wesley
Hospital, located in Medan, serves a
large diverse disease, either the
primary or specialty care. For many
families served in the hospital,
predominantly the poor family.
SUBJECTS AND METHODS
Between October 2006 and
May 2007, three siblings of children
(aged 1-6 years) with previously
suspected of osteoporosis were
admitted to Methodist Susanna
Wesley Hospital in Medan for
determining the causes of their bone
fractures. The clinical, biochemistry,
and radiograph examinations were
done to confirm the diagnosis.
The computerized database
capturing a variety cost expenditures
of diagnosis determinant, medical treatment,
and hospital charges for each admission was
maintained by the financial department at the
Methodist Susanna Wesley Hospital. These
records formed the total expenditures during
the five admissions at a different timeframe at
this hospital.
RESULTS
Table 1 shows the gender, ages,
height, and biochemistry measurements and
the drug (zoledronic acid) used for treating the
patients. The initial dose was 0.015 mg/kg,
followed by 0.025 mg/kg 12 weeks after the
first dose, and the third dose was increased to
0.05mg/kg thereafter every 3 months. The
alkaline phosphatase levels were increased,
indicating increased bone formation. The
urinary
type
I
collagen
Ntelopeptidase/creatinine was also increased
compared to the normal range, suggesting
increased bone resorption (Rauch et al. 2003).
Taken together, the biochemistry changes
confirmed the diagnosis of OI.
Table 2 and Figure 1 show the
radiological findings of osteopenia and
fractures, the hallmark of severe osteogenesis
imperfecta, (Glorieux et al. 1998), probably
results from structural abnormalities in bone
tissues (Sykes, 1990) and a reduced rate of
osteogenesis (Glorieux, 1994).
Table 1. The biochemistry characteristics of patients with osteogenesis imperfecta
Patients No Age
(y,m)
Height
(cm)
Serum Alkaline
Urinary Type I Collagen
Phosphatase
N-Telopeptidase/creatinine
(Unit/liter) (Ref.. R)* (nMBCE/mM)(Ref..R)#
Zoledronic Acid
Treatment
(mg/kg)
Boy
1
5.7
80
552 (115-391)
2890 (13-78)
0.015
Boy
2
3.9
70
514 (115-391)
4221 (13-78)
0.015
Girl
3
1.10
70
417 (115-460)
2387 (14-74)
0.015
* Ref. R indicates reference range as established in the accredited laboratory.
Ref. R indicates reference range as established in the specialty laboratory (Valencia, CA, USA).
#
Table 2. The radiological findings of patients with osteogenesis imperfecta
Patient
Spine Abnormalities
Boy
Biconcave vertebra
Yes
Bowing extremities,
Bulbous distal
Boy
Biconcave vertebra
Yes
Bowing extremities,
fractures
20
Osteopenia
Deformity
The Impact of Three Siblings of Children with Severe Osteogenesis (19– 23)
Hadyanto Lim, Umar Zein, Yahwardiah Siregar, Blondina Marpaung, dan Jaminsen Sinaga
Universitas Sumatera Utara
Girl
Biconcave vertebra
Yes
(A)
Bowing extremities,
fractures
(B)
(C)
Figure 1. (A) Bulbous distal metaphysic (patient 1). (B) Lower extremity showing fracture, and
bowing (patient 2). (C) Lumbal spine showing biconcave configuration and multiple lytic
lesions (patient 3)
Table 3. Costs of expenditure of patients with OI in hospital stay
1st Adm
Types of service
(6 d)
2nd Adm
(13 d)
3 rd Adm
(10 d)
4 th Adm
(9 d)
5 th Adm
(12 d)
4.427.550
3.911.150
4.180.900 19.636.800
-
Total
(in Rp)
Inpatient
Hospital
2.372. 300
4.744.900
Diagnostic
Radiology
2.365.000
-
-
Biochemical
Measurements
3.600.000
-
-
1.960.000
-
-
-
Physician
Visits
Medications
126.200
132.300
921.200
1.081.700
-
2.365.000
360.000
5. 920.000
1.163.400 3.424.800
Abbreviations: Adm = admission; d = day; Rp = rupiah.
Table 3 shows the total charges of
the five admissions in the hospital were Rp.
31,346,600, in which Rp.8.285.000 (26.43%)
was accounted for by diagnosis determinant
(diagnostic radiology and biochemical
measurements), Rp. 3.424.800 (10.92%) for
medications, and Rp. 19.636.800 (62.65%)
for hospital stay. The mean length of hospital
stay in five admissions was 10 days.
DISCUSSION
This study begins to quantify the
enormous impact of the osteogenesis
imperfecta on financial burden in inpatient
care. We found that, in five admissions, the
total cost expenditures in the hospital were
substantially high for the poor family of six
children with the last three affected this
genetic bone disease. The total cost would be
higher than that calculated if the hospital did
not provide the social beds for the poor. This
study also confirms what Hall et al, found
>25 years ago-that the cost to individual and
society for treating genetic disorders is high
(Hall, et al. 1978).
The first admission was to improve
the general conditions and to confirm
diagnosis of the patients. The second
admission were intended to improve the
The Impact of Three Siblings of Children with Severe Osteogenesis (19– 23)
21
Hadyanto Lim, Umar Zein, Yahwardiah Siregar, Blondina Marpaung, dan Jaminsen Sinaga
Universitas Sumatera Utara
whole health status and giving supplemental
calcium prior to given intravenous
antiresorptive drugs. The third to fifth
admissions were given zoledronic acid, the
antiresorptive agent, for strengthening the
bone by reducing bone pain and fracture. Not
surprisingly, the longer hospital stay was
similar to that reported for children who are
admitted for genetic disorders. (Hall, et al.
1978; McCandless et al. 2004). To our
knowledge, this is the first report regarding
financial burden for three siblings with
severe osteogenesis imperfecta. Further
studies should extend on a larger sample on
diverse genetic bone disorders concerning
socioeconomic burden in families.
There are several drawbacks to the
current study. First, only three siblings of
children in a single family were analyzed.
Second, the financial burden was imposed by
a generous hospital; and third, the billings
were paid by a foundation. In spite of these
drawbacks, the findings are consistent with
those of Hall et al. in an entirely different
hospital setting and provide a unique case in
a single family.
Osteogenesis imperfecta is a rare
genetic skeletal disease, so that the healthcare provider could miss the diagnosis. The
fourth child was undiagnosed in inpatient
care in a hospital in Medan when his parents
had noted the spontaneous femoral fracture
while he was lifted up. Subsequently, the
fifth and sixth children were born with the
same symptoms related to osteogenesis
imperfecta. The previous undiagnosed
genetic conditions is also encountered in the
primary even the tertiary provided health
care hospital (Kumar et al. 2001).
CONCLUSION
The financial burden of the
osteogenesis imperfecta in inpatient care is
high and has a longer hospital stay. The data
set were based and analyzed by capturing a
variety cost expenditures of diagnosis
determinant, medical treatment, and hospital
charges for each admission at the financial
department of the Methodist Susanna Wesley
Hospital in Medan.
SUGGESTION
22
Improved physician awareness may
lead to earlier diagnosis of osteogenesis
imperfecta, which leads to improved
management of patients with known genetic
disorders. Every person providing care to
children will need to be competent to explain
these complexities to anxious public and to
discuss their implications with affected
families due to enormous impact on their
families in terms of financial burden and
their subsequent risks of giving birth of
genetic disorders.
ACKNOWLEDGEMENT
The authors would like to thank the
Yayasan Lestari Indo Makmur (Marga LIM)
in Medan for funding the hospitalization of
the three siblings of children at the Methodist
Susanna Wesley Hospital, Medan.
REFERENCES
Glorieux FH, Bishop NJ, Plotkin H, Chabot
G, Lanoue G, Travers R. Cyclic
administration of pamidronate in
children with severe osteogenesis
imperfecta. N Eng J Med. 1998; 339:
947-952.
Glorieux FH, Travers R, Chabot G, Lanoue
G. Bone histomorphometric analysis in
osteogenesis imperfecta. J Bone Miner
Res 1994;9:Suppl 1:S226-S226
Hall JG, Powers EK, Mcllvaine RT, Ean VH.
The frequency andfinancial burdern of
genetic disease in aa pediatric hospital.
Am J Med Genet. 1978; i:417-436.
Kumar PJ, Radakrishnan J, Chowdary MA,
Giampietro PF. Prevalence and pattern
of presentation of genetic disorders in a
pediatric emergency department. Mayo
Clin Proc. 2001; 76: 777-783.
Lang CB. Improvement of bone in patients
with osteogenesis imperfecta treated
with
pamidronate-lesson
from
biochemistry. J Clin Endocrionol
Metab 2003; 88: 984-985.
Marini JC. Osteogenesis imperfecta:
managing brittle bone. N Eng J Med.
1998; 339:986-987.
McCandless SE, Brunger JW, Cassidy SB.
The burden of genetic disease on
inpatient care in a children’s hospital.
Am J Hum Genet. 2004; 74: 121-127.
The Impact of Three Siblings of Children with Severe Osteogenesis (19– 23)
Hadyanto Lim, Umar Zein, Yahwardiah Siregar, Blondina Marpaung, dan Jaminsen Sinaga
Universitas Sumatera Utara
Rauch F, Glorieux FH. Osteogenesis
imperfecta. Lancet 2004; 363: 13771385.
Rauch F, Plotkin H, Travers R, Zeitlin L,
Glorieux FH. Osteogenesis imperfecta
types I, III, and IV: effect of
pamidronate therapy on bone and
mineral metabolism. J Clin Endocrinol
Metab 2003; 88:98-992.
Sykes B, Ogilvie D, Wordsworth P, et al.
Consistent linkage of dominantly
inherited osteogenesis imperfecta to
the type I collagen loci: COL1A1 and
COL1A2. Am J Hum Genet
1990;46:293-307.
The Impact of Three Siblings of Children with Severe Osteogenesis (19– 23)
23
Hadyanto Lim, Umar Zein, Yahwardiah Siregar, Blondina Marpaung, dan Jaminsen Sinaga
Universitas Sumatera Utara
HA
ASSIILL PPEEN
NEELLIITTIIA
AN
N
THE IMPACT OF THREE SIBLINGS OF CHILDREN WITH
SEVERE OSTEOGENESIS IMPERFECTA ON FINANCIAL
BURDEN FOR INPATIENT CARE IN A HOSPITAL
Hadyanto Lim1,2,3, Umar Zein4, Yahwardiah Siregar5,
Blondina Marpaung6, dan Jaminsen Sinaga7
1
Department of Pharmacology, Faculty of Medicine, Methodist University of Indonesia/
Methodist Susanna Wesley Hospital, Medan.
Jl. Setia Budi Psr II Tj Sari, Medan 20132
2
Biomedical Research, Postgraduate School, University of Nort Sumatra, Medan.
Jl. Civitas Akademika Kampus USU, Medan 20155
3
Cardiovascular Pharmacology, Mastery and Resident Programs, Faculty of Medicine,
University of Nort Sumatra, Medan.
Jl. Dr. Mansur No 5. Kampus USU, Medan 20155
4
Division of Tropical Medicine and Infectious Diseases, Department of Internal Medicine,
Faculty of Medicine, University of Nort Sumatra, Medan.
Jl. Dr. Mansur No 5. Kampus USU, Medan 20155
5
Department of Biochemistry, Faculty of Medicine, University of Nort Sumatra, Medan.
Jl. Dr. Mansur No 5. Kampus USU, Medan 20155
6
Division of Rheumatology, Department of Internal Medicine, Adam Malik General Hospital-Medan
Jl. Djamin Ginting, Medan
7
Department of Pediatrics, Faculty of Medicine, Methodist University of Indonesia/Methodist
Susanna Wesley Hospital, Medan
Jl. Setia Budi Psr II Tj Sari, Medan 20132
ABSTRACT
Osteogenesis imperfecta (OI) is a rare genetic skeletal disorder that has a major
impact to the financial status of the suffered’s family. We investigated the cost
expenditures of three siblings with OI after five admissions in a hospital. Three
siblings, two brothers and one young sister aged 1-6 years old were admitted to
Methodist Susanna Wesley Hospital in Medan. We reviewed the computerized
database capturing a variety of cost expenditures of diagnosis determinant,
medical treatment, and hospital charges for each admission. Total charges for five
admissions in the hospital were > Rp.31 millions, of which 21.25% was accounted
for by diagnosis determinant, 9.38% for treatment, and 69.37% for hospital stay.
The mean length of stay was 10 days for five admissions. The findings show that
there is enormous financial impact of osteogenesis imperfecta on inpatient care.
Keywords: Financial impact, Family, Osteogenesis imperfecta
INTRODUCTION
Osteogenesis
imperfecta
(OI), often referred to as "brittlebone disease," is a heritable genetic
disorder characterized in most
affected persons by either a reduction
in the production of normal type I
collagen or the synthesis of abnormal
collagen as a result of mutations in the type I
collagen genes (Glorieux et al. 1998). Its
hallmark feature is bone fragility, (Lang, 2003;
Rauch and Glorieux, 2004) with a tendency to
fracture from minimal trauma (Marini, 1998)
or from the work of bearing weight against
gravity.
Improved physician awareness may
lead to earlier diagnosis in patients with
Perbedaan Faktor Infeksi dengan Pemeriksaan PCR Serviks HPV (1–78)
19
Chatarina U.W.
Universitas Sumatera Utara
previously undiagnosed genetic
conditions
and
improved
management of patients with known
genetic disorders (Rauch and
Glorieux, 2004). Caring of patients
with these fractures is also very
expensive, and costs will continue to
rise as the frequency of fractures
increases in the future. To our
knowledge, no studies have detailed
the cost expenditures of OI patients
admitted to the hospital.
Methodist Susanna Wesley
Hospital, located in Medan, serves a
large diverse disease, either the
primary or specialty care. For many
families served in the hospital,
predominantly the poor family.
SUBJECTS AND METHODS
Between October 2006 and
May 2007, three siblings of children
(aged 1-6 years) with previously
suspected of osteoporosis were
admitted to Methodist Susanna
Wesley Hospital in Medan for
determining the causes of their bone
fractures. The clinical, biochemistry,
and radiograph examinations were
done to confirm the diagnosis.
The computerized database
capturing a variety cost expenditures
of diagnosis determinant, medical treatment,
and hospital charges for each admission was
maintained by the financial department at the
Methodist Susanna Wesley Hospital. These
records formed the total expenditures during
the five admissions at a different timeframe at
this hospital.
RESULTS
Table 1 shows the gender, ages,
height, and biochemistry measurements and
the drug (zoledronic acid) used for treating the
patients. The initial dose was 0.015 mg/kg,
followed by 0.025 mg/kg 12 weeks after the
first dose, and the third dose was increased to
0.05mg/kg thereafter every 3 months. The
alkaline phosphatase levels were increased,
indicating increased bone formation. The
urinary
type
I
collagen
Ntelopeptidase/creatinine was also increased
compared to the normal range, suggesting
increased bone resorption (Rauch et al. 2003).
Taken together, the biochemistry changes
confirmed the diagnosis of OI.
Table 2 and Figure 1 show the
radiological findings of osteopenia and
fractures, the hallmark of severe osteogenesis
imperfecta, (Glorieux et al. 1998), probably
results from structural abnormalities in bone
tissues (Sykes, 1990) and a reduced rate of
osteogenesis (Glorieux, 1994).
Table 1. The biochemistry characteristics of patients with osteogenesis imperfecta
Patients No Age
(y,m)
Height
(cm)
Serum Alkaline
Urinary Type I Collagen
Phosphatase
N-Telopeptidase/creatinine
(Unit/liter) (Ref.. R)* (nMBCE/mM)(Ref..R)#
Zoledronic Acid
Treatment
(mg/kg)
Boy
1
5.7
80
552 (115-391)
2890 (13-78)
0.015
Boy
2
3.9
70
514 (115-391)
4221 (13-78)
0.015
Girl
3
1.10
70
417 (115-460)
2387 (14-74)
0.015
* Ref. R indicates reference range as established in the accredited laboratory.
Ref. R indicates reference range as established in the specialty laboratory (Valencia, CA, USA).
#
Table 2. The radiological findings of patients with osteogenesis imperfecta
Patient
Spine Abnormalities
Boy
Biconcave vertebra
Yes
Bowing extremities,
Bulbous distal
Boy
Biconcave vertebra
Yes
Bowing extremities,
fractures
20
Osteopenia
Deformity
The Impact of Three Siblings of Children with Severe Osteogenesis (19– 23)
Hadyanto Lim, Umar Zein, Yahwardiah Siregar, Blondina Marpaung, dan Jaminsen Sinaga
Universitas Sumatera Utara
Girl
Biconcave vertebra
Yes
(A)
Bowing extremities,
fractures
(B)
(C)
Figure 1. (A) Bulbous distal metaphysic (patient 1). (B) Lower extremity showing fracture, and
bowing (patient 2). (C) Lumbal spine showing biconcave configuration and multiple lytic
lesions (patient 3)
Table 3. Costs of expenditure of patients with OI in hospital stay
1st Adm
Types of service
(6 d)
2nd Adm
(13 d)
3 rd Adm
(10 d)
4 th Adm
(9 d)
5 th Adm
(12 d)
4.427.550
3.911.150
4.180.900 19.636.800
-
Total
(in Rp)
Inpatient
Hospital
2.372. 300
4.744.900
Diagnostic
Radiology
2.365.000
-
-
Biochemical
Measurements
3.600.000
-
-
1.960.000
-
-
-
Physician
Visits
Medications
126.200
132.300
921.200
1.081.700
-
2.365.000
360.000
5. 920.000
1.163.400 3.424.800
Abbreviations: Adm = admission; d = day; Rp = rupiah.
Table 3 shows the total charges of
the five admissions in the hospital were Rp.
31,346,600, in which Rp.8.285.000 (26.43%)
was accounted for by diagnosis determinant
(diagnostic radiology and biochemical
measurements), Rp. 3.424.800 (10.92%) for
medications, and Rp. 19.636.800 (62.65%)
for hospital stay. The mean length of hospital
stay in five admissions was 10 days.
DISCUSSION
This study begins to quantify the
enormous impact of the osteogenesis
imperfecta on financial burden in inpatient
care. We found that, in five admissions, the
total cost expenditures in the hospital were
substantially high for the poor family of six
children with the last three affected this
genetic bone disease. The total cost would be
higher than that calculated if the hospital did
not provide the social beds for the poor. This
study also confirms what Hall et al, found
>25 years ago-that the cost to individual and
society for treating genetic disorders is high
(Hall, et al. 1978).
The first admission was to improve
the general conditions and to confirm
diagnosis of the patients. The second
admission were intended to improve the
The Impact of Three Siblings of Children with Severe Osteogenesis (19– 23)
21
Hadyanto Lim, Umar Zein, Yahwardiah Siregar, Blondina Marpaung, dan Jaminsen Sinaga
Universitas Sumatera Utara
whole health status and giving supplemental
calcium prior to given intravenous
antiresorptive drugs. The third to fifth
admissions were given zoledronic acid, the
antiresorptive agent, for strengthening the
bone by reducing bone pain and fracture. Not
surprisingly, the longer hospital stay was
similar to that reported for children who are
admitted for genetic disorders. (Hall, et al.
1978; McCandless et al. 2004). To our
knowledge, this is the first report regarding
financial burden for three siblings with
severe osteogenesis imperfecta. Further
studies should extend on a larger sample on
diverse genetic bone disorders concerning
socioeconomic burden in families.
There are several drawbacks to the
current study. First, only three siblings of
children in a single family were analyzed.
Second, the financial burden was imposed by
a generous hospital; and third, the billings
were paid by a foundation. In spite of these
drawbacks, the findings are consistent with
those of Hall et al. in an entirely different
hospital setting and provide a unique case in
a single family.
Osteogenesis imperfecta is a rare
genetic skeletal disease, so that the healthcare provider could miss the diagnosis. The
fourth child was undiagnosed in inpatient
care in a hospital in Medan when his parents
had noted the spontaneous femoral fracture
while he was lifted up. Subsequently, the
fifth and sixth children were born with the
same symptoms related to osteogenesis
imperfecta. The previous undiagnosed
genetic conditions is also encountered in the
primary even the tertiary provided health
care hospital (Kumar et al. 2001).
CONCLUSION
The financial burden of the
osteogenesis imperfecta in inpatient care is
high and has a longer hospital stay. The data
set were based and analyzed by capturing a
variety cost expenditures of diagnosis
determinant, medical treatment, and hospital
charges for each admission at the financial
department of the Methodist Susanna Wesley
Hospital in Medan.
SUGGESTION
22
Improved physician awareness may
lead to earlier diagnosis of osteogenesis
imperfecta, which leads to improved
management of patients with known genetic
disorders. Every person providing care to
children will need to be competent to explain
these complexities to anxious public and to
discuss their implications with affected
families due to enormous impact on their
families in terms of financial burden and
their subsequent risks of giving birth of
genetic disorders.
ACKNOWLEDGEMENT
The authors would like to thank the
Yayasan Lestari Indo Makmur (Marga LIM)
in Medan for funding the hospitalization of
the three siblings of children at the Methodist
Susanna Wesley Hospital, Medan.
REFERENCES
Glorieux FH, Bishop NJ, Plotkin H, Chabot
G, Lanoue G, Travers R. Cyclic
administration of pamidronate in
children with severe osteogenesis
imperfecta. N Eng J Med. 1998; 339:
947-952.
Glorieux FH, Travers R, Chabot G, Lanoue
G. Bone histomorphometric analysis in
osteogenesis imperfecta. J Bone Miner
Res 1994;9:Suppl 1:S226-S226
Hall JG, Powers EK, Mcllvaine RT, Ean VH.
The frequency andfinancial burdern of
genetic disease in aa pediatric hospital.
Am J Med Genet. 1978; i:417-436.
Kumar PJ, Radakrishnan J, Chowdary MA,
Giampietro PF. Prevalence and pattern
of presentation of genetic disorders in a
pediatric emergency department. Mayo
Clin Proc. 2001; 76: 777-783.
Lang CB. Improvement of bone in patients
with osteogenesis imperfecta treated
with
pamidronate-lesson
from
biochemistry. J Clin Endocrionol
Metab 2003; 88: 984-985.
Marini JC. Osteogenesis imperfecta:
managing brittle bone. N Eng J Med.
1998; 339:986-987.
McCandless SE, Brunger JW, Cassidy SB.
The burden of genetic disease on
inpatient care in a children’s hospital.
Am J Hum Genet. 2004; 74: 121-127.
The Impact of Three Siblings of Children with Severe Osteogenesis (19– 23)
Hadyanto Lim, Umar Zein, Yahwardiah Siregar, Blondina Marpaung, dan Jaminsen Sinaga
Universitas Sumatera Utara
Rauch F, Glorieux FH. Osteogenesis
imperfecta. Lancet 2004; 363: 13771385.
Rauch F, Plotkin H, Travers R, Zeitlin L,
Glorieux FH. Osteogenesis imperfecta
types I, III, and IV: effect of
pamidronate therapy on bone and
mineral metabolism. J Clin Endocrinol
Metab 2003; 88:98-992.
Sykes B, Ogilvie D, Wordsworth P, et al.
Consistent linkage of dominantly
inherited osteogenesis imperfecta to
the type I collagen loci: COL1A1 and
COL1A2. Am J Hum Genet
1990;46:293-307.
The Impact of Three Siblings of Children with Severe Osteogenesis (19– 23)
23
Hadyanto Lim, Umar Zein, Yahwardiah Siregar, Blondina Marpaung, dan Jaminsen Sinaga
Universitas Sumatera Utara