Fibrous dysplasia of the bone can involve one or
several bones and is characterized by bone deformities, pain and
fractures. The bony lesions of fibrous dysplasia are characterized by
proliferation of fibroblast like cells that in some areas have features
of osteoblasts and in other areas have features of chondrocytes. There
is also an associated increase in osteoclastic bone resorption. The
lesions are usually focal and may be monoostotic or polyostotic and have
a radiolucent appearance. The disorder occurs with equal frequency in
both sexes(1) and in some individuals may have distinctive areas of skin
pigmentation and precocious puberty (McCune Albright syndrome).
Fractures and skeletal deformities are common and early onset disease is
usually more severe.
In the past 10 years, the bisphosphonate pamidronate
has been used as an intravenous infusion in fibrous dysplasia of the
bone(2). Oral bisphosphonate is a cheaper alternative and is also easy
to administer, hence its applicability in Indian circumstances is more.
We report a case of polyostotic fibrous dysplasia in a three-year-old
child who was given oral alendronate and showed significant improvement
in the bone mineral content while on this therapy.
Three-year-old male child, fifth product of a non-consanguinous
marriage presented with repeated fractures of the left femur, pain while
walking and asymmetry of the lower limbs. He was fully immunized and had
normal intellectual development but had delayed sitting and walking. By
the time he was five years old he had 5 fractures of the left femur
requiring surgical corrections. During this time his pain continued and
so did the asymmetry. Clinical examination showed unequal lower
extremity length, joint laxity, hyper-extensible joints, tibial
deformity and genu valgum. Rest of his systemic and general examination
was normal. His biochemistry showed calcium 8.5 mg/dL, serum protein 7.4
g/dL, serum albumin of 3.9 g/dL, serum phosphorus was 1.9 mg/dL,
alkaline phosphatase was 310 µ/L (50-350 µ/L) and parathormone was 69.5
pg/mL (12-72 pg/mL). Renal function was normal with a blood urea of 6.4
mg/dL, creatinine of 0.3 mg/dL, serum sodium was 137.6 mmol/L and
potassium was 3.1 mmol/L, uric acid was 2.7 mg/dL, CPK was 53 µ
(24-190/µL). Hemo-gram was normal. Routine urine examination was normal.
Radiography showed radiolucent areas in phalanges and in the metacarpals
and Looser’s zones at metaphyseal ends of long bones. Abdominal and
renal sonography was normal. No parathyroid mass was seen on USG. Whole
body scan using Technetium 99 suggested polyostotic fibrous dysplasia
localizing the distribution of the lesions to the left axial skeleton
and left side of pelvis, skull and facial bones. His bone biopsy was
consistent with a diagnosis of fibrous dysplasia. DEXA scan of the
lumbar spine showed low bone mineral density (BMD) with a Z score of
–2.51. BMD of left hip was much lower (0.241 g/cm2) as compared to that
of the right hip (0.403 g/cm2). He was treated with oral alendronate in
a dose of 5 mg per day. A repeat DEXA scan following 9 months of
alendronate therapy showed that BMD at lumbar spine and both hips had
significantly increased with a Z score of –1.68. The BMD in the lumbar
spine increased by 0.067 g/cm2 accounting for almost 8% bone mass gain.
BMD at right and left hip increased by 0.054 g/cm2 and 0.023 g/cm2
respectively. The next follow-up DEXA scan of the lumbar spine done
after 18 months of therapy showed a further increase in BMD at lumbar
spine and both hips with a Z score of –1.27. The BMD at lumbar spine
increased by 0.041g/cm2 and that at the right and left hip (in the
region of femoral neck) increased by 0.057 g/cm2 and 0.007 g/cm2
Calcium and vitamin D supplementation (elemental
calcium 1000 mg and vitamin D 3,500 IU/day) was also given during
alendro-nate therapy. His bone pain was significantly reduced and he did
not have any further fractures while on treatment with alendronate,
although asymmetry was persistent. During the course of therapy no side
effects were reported and therapy was tolerated well.
The main biologic action of bisphospho-nates consists
of the inhibition of osteoclastic bone resorption and hence they play a
major role in conditions that are characterized by an increased bone
resorption(1). Primary and secondary osteoporosis, symptomatic Paget
disease of bone, osteogenesis imperfecta both in children and adults and
fibrous dysplasia are currently the major indications for
bisphospho-nates. In the future, they might be used in rheumatoid
arthritis and osteoarthritis(3).
Pamidronate is poorly absorbed and may have a local
irritant effect on the upper gastrointestinal tract(1). The main
published studies describe the effects of intravenous pamidronate at a
daily dose of 1.5-3.0 mg/kg body weight for three days every four to six
months for 1-5 years in children with severe osteogenesis
imperfecta(3,4). In fibrous dysplasia it has been used by infusion (two
courses per year) with good results with respect to pain and osteolytic
lesion(3). The cost of the drug, its intravenous route of administration
and hence the necessity for hospitalization significantly reduces the
usage of the bisphosphonates in India.
Alendronate is at present indicated for use in
prevention and treatment of osteoporosis and Paget’s disease. It should
be used in conjunction with adequate amounts of vitamin D and calcium in
the prevention of progressive loss of bone mass. As yet very few studies
have looked at the use of oral alendronate in resorptive bone disorders
in children(5). Our patient with fibrous dysplasia had an improvement in
BMD and marked reduction in bone pain after 18 months on treatment with
oral alendronate. Based on these early observations we feel that
clinical trials of oral bisphosphonates should be carried out so that
its safety and efficacy in children can be evaluated.
Contributors: VVK and AVK planned and conducted
the study: AVK and GBM collected the data and drafted the manuscript.
VVK will act as guarantor of the study.
Funding: HCJMRI, Jehangir Hospital, Pune.
Competing interests: None stated.