|Year : 2014 | Volume
| Issue : 2 | Page : 127-131
A rare case report of intermediate osteopetrosis and review of literature
Priyanka Verma1, Sonali Kadam1, Hemant Rangnath Umarji1, Varun Surya2
1 Department of Oral Medicine and Radiology, Government Dental College and Hospital, Mumbai, Maharashtra, India
2 Department of Oral Pathology and Microbiology, Government Dental College and Hospital, Mumbai, Maharashtra, India
|Date of Web Publication||2-Aug-2014|
Dr. Priyanka Verma
Room No. 23, Department of Oral Medicine and Radiology, Government Dental College and Hospital, Mumbai - 400 001, Maharashtra
Source of Support: None, Conflict of Interest: None
Osteopetrosis also known as "marble bone disease" is a group of rare genetic disorders caused by osteoclast failure, which ranges widely in severity. Osteopetrosis presents with a spectrum of craniofacial abnormalities such as frontal bossing, macrocephaly, hydrocephaly, and cranial hyperostosis. Osteopetrosis is caused by failure of osteoclast development or function and mutations in at least 10 genes have been identified as causative in humans, accounting for 70% of all cases. These conditions can be inherited as autosomal recessive, dominant or X-linked traits with the most severe forms being autosomal recessive. We present a rare case of osteopetrosis in a 10-year-old boy who reported with an unhealed socket after tooth extraction. The characteristic clinical and radiographic findings were suggestive of intermediate osteopetrosis.
Keywords: Craniofacial, osteopetrosis, osteomyelitis, radiographic, sclerosis
|How to cite this article:|
Verma P, Kadam S, Umarji HR, Surya V. A rare case report of intermediate osteopetrosis and review of literature. J Cleft Lip Palate Craniofac Anomal 2014;1:127-31
|How to cite this URL:|
Verma P, Kadam S, Umarji HR, Surya V. A rare case report of intermediate osteopetrosis and review of literature. J Cleft Lip Palate Craniofac Anomal [serial online] 2014 [cited 2020 Apr 10];1:127-31. Available from: http://www.jclpca.org/text.asp?2014/1/2/127/137919
| Introduction|| |
Osteopetrosis is a rare genetic disorder resulting from reduction in bone resorption relative to bone formation, which leads to generalized increased bone mass. Imbalanced bone turnover is a consequence of inadequate osteoclastic bone resorption, despite normal osteoblastic function. The disease is characterized by thickening of the cortical bones, decrease in the size of bone marrow spaces and generalized bone sclerosis. The estimated incidence of the disease is one in 100,000-500,000 of the population. 
The term osteopetrosis is derived from the Greek root "osteon" meaning bone and "petros", stone. Osteopetrosis is variably referred to as "brittle bone disease", "marble bone disease" and "Albers-Schönberg disease", after the German radiologist credited with the first description of the condition in 1904. 
Autosomal recessive osteopetrosis (ARO) is a rare disorder and reports of large groups of patients are scarce. Loría-Cortés  detailed a cross-sectional study of 26 patients from Costa Rica and Gerritsen's et al. have presented a retrospective longitudinal study of 33 patients. Intermediate ARO has the lowest incidence rate among all three types of osteopetrosis.  In a series of 79 patients, Armstrong et al.  have reported only three cases of this form. However, authors could not find any such case series from the Indian subcontinent.
| Case Report|| |
A 10-year-old male patient reported to our institution with the chief complaint of pain and swelling in lower left jaw since last 15 days. Patient gave a history of extraction of 75 (deciduous second molar) 2 months back. He also gave a history of progressive impairment of hearing and vision since early childhood.
On extraoral examination, skull appeared enlarged (macrocephaly) along with hypertelorism. Diffuse swelling was evident in the left mandibular region [Figure 1]. On palpation swelling was tender and firm to hard in consistency. Intraoral examination revealed unhealed socket in relation to 75 with purulent discharge and buccolingual expansion of the left alveolus [Figure 2].
Panoramic radiograph showed unhealed socket in 75 region obscured by generalized opacity involving mandible. A dull gray shadow was seen close to the lower border of mandible suggestive of periosteal reaction. The margins of inferior alveolar nerve canal on both sides were not traceable. There was an absence of cortication at the lower border of mandible [Figure 3]. Lateral skull radiograph revealed overall increased density of maxilla, base, and vault of the cranium [Figure 4].
|Figure 3: Orthopantogram showing multiple unerupted and carious teeth with prominent osteosclerotic changes|
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Suspecting a generalized condition, other radiographs were advised. Posteroanterior chest X-ray revealed a uniform increase in bone density throughout the clavicular bones, thoracic cage, and vertebrae [Figure 5]. Lateral spine radiograph showed sclerosis of vertebral endplates resulting in "sandwich vertebrae" appearance [Figure 6] and hand (wrist) radiograph showed "bone-within-bone" appearance [Figure 7].
|Figure 6: Lateral spine radiograph showing sclerosis of vertebral endplates (arrows) resulting in "sandwich vertebrae" appearance|
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|Figure 7: Hand wrist X-ray shows bone-within-bone appearance and diffuse sclerosis of bone|
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Radiographic examination of the visualized skeletal bones showed generalized increased bone density. Distal end of the femur exhibited absence of normal contour and presented with flask shaped enlargement termed as "Erlenmeyer flask deformity" [Figure 8].
|Figure 8: Erlenmeyer flask deformity of distal femur and proximal tibiae|
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Cone beam computer tomography of maxilla, mandible, and skull bones showed complete absence of maxillary, frontal, and sphenoidal sinuses along with hypoplastic ethmoidal sinuses. Narrowing of all the foramina and increased density of various skull bones were noted in axial, sagittal, and coronal planes. In the area of chief complaint, periosteal reaction was appreciated, suggestive of osteomyelitis of left mandible [Figure 9], [Figure 10] and [Figure 11].
|Figure 9: Coronal section showing extensive sclerosis, absence of maxillary sinus and frontal sinus with periosteal reaction on left side of the mandible. Narrowing of inferior alveolar canal is also noted|
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|Figure 10: Sagittal section showing absence of sphenoid sinus, reduction in the size of sella turcica and diffuse sclerosis of bones including cervical vertebrae|
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|Figure 11: Axial section showing diffuse sclerosis of the bones and narrowing of all the foramina|
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Patient was referred to a tertiary care center for further management, where he was subjected to various investigations. All the laboratory values of serum calcium (10.3 mg%), serum phosphorous (4.3 mg/dl) and alkaline phosphatase (11.0 KAU) were within normal limits except hemoglobin (6.7 g%), which was very low thus suggestive of severe anemia. Computed tomography scan of the brain showed moderate dilation of lateral and third ventricles suggestive of congenital hydrocephalus [Figure 12].
|Figure 12: Axial section of computed tomography scan of brain showing moderate dilation of lateral and third ventricle|
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Optic atrophy and papilledema were confirmed by an ophthalmologist on fundus examination. Audiometry test confirmed mild to moderate sensory hearing loss. Bone marrow biopsy revealed markedly diminished marrow spaces, widened bony trabeculae and absence of hematopoietic cells, which were consistent with osteopetrosis. The final diagnosis of intermediate osteopetrosis was made considering the overall clinical, radiographic, and histopathological findings.
After two blood transfusions and prescription of medications, the patient was discharged from the hospital as he was hemodynamically stable. But, unfortunately after a week, patient sustained traumatic craniocerebral injuries due to fall from height, which resulted in cerebral hematoma and eventually death.
| Discussion|| |
Osteopetrosis has been reported in three clinical forms:
- Malignant infantile form with poor prognosis and autosomal recessive inheritance
- Benign adult form with autosomal dominant inheritance and associated with few symptoms
- Autosomal recessive intermediate form with clinical manifestations similar to malignant form and lowest incidence rate. 
Craniofacial findings in osteopetrosis
The increased bone mass can result in phenotypes such as macrocephaly and altered craniofacial morphology.  Hydrocephaly, peculiar facies, cranial hyperostosis, skull base osteosclerosis, and choanal stenosis are noted. Nerve compression of cranial nerves II, VII, and VIII are seen with mental retardation. Other findings include blindness, hypertelorism, strabismus, and nystagmus. 
In the most severe and fatal form, marrow spaces decrease, leading to hematological failure including anemia, and pancytopenia. Even extra medullary hematopoiesis is unable to compensate for the reduction in medullary blood cell production with resultant hepatosplenomegaly, hypersplenism, and hemolysis. Neuropathies related to cranial nerve entrapment occur, leading to visual and hearing deterioration. 
Visual disturbances are the most common cranial nerve dysfunction of osteopetrosis caused by the optic nerve compression leading to enlargement of the subarachnoid space around the optic nerve and papilledema.  Our case also complained of impaired hearing and vision.
Autosomal recessive intermediate form of osteopetrosis is milder than malignant condition with significantly lower rate of occurrence. Patients are usually asymptomatic with only radiographic signs.  Saeedinia et al.  also stated that intermediate osteopetrosis is less symptomatic, and usually shows manifestations in childhood. Our case was also asymptomatic since birth, but radiographic examinations revealed characteristic findings of osteopetrosis.
Del Fattore et al.  stated that life expectancy is reduced in this condition; nevertheless, our patient died at the age of 10 due to cerebral hematoma following parietal and occipital bone fractures.
Intermediate osteopetrosis patients present with abnormal stature and tend to exhibit manifestations at the end of the first decade. Some of the osteopetrosis patients show cranial nerve deficits, macrocephaly, mild to moderate or severe anemia and dental changes that may predispose to the development of osteomyelitis of jaws.  All of these features were apparent in our case.
The dental changes reported to be associated with osteopetrosis include disturbance of tooth eruption due to impaired alveolar bone resorption of osteoclasts, hypodontia, malformed teeth, multiple caries, enamel hypoplasia, abnormal pulp chambers, and hypercementosis. The increased bone density, initially presented as thickening of lamina dura, obscures the roots. 
Osteomyelitis is a well-described complication of osteopetrosis taking place in approximately 10% of cases, mostly in the mandible. Impaired white blood cell function and reduced vascular supply have been considered key factors associated with its development. In addition, the decreased blood supply limits the availability of antibiotics at the sites of infection.  In our case, osteomyelitis was initiated after extraction of deciduous second molar.
The diagnosis of osteopetrosis is based on radiological and clinical features, and these findings are sufficiently characteristic to make a definite diagnosis, and it is not necessary to perform a genetic study to confirm the disease.  In the absence of typical radiographic findings, raised concentrations of the creatine kinase BB isoenzyme and tartrate resistant acid phosphatase can be helpful in making the diagnosis. 
| Treatment|| |
Since the hematological origin of osteoclasts was discovered, the disease has been treated with hematopoietic stem cell transplantation (HSCT), which in most cases improves but does not to fully rescue the phenotype. This approach has mostly been used to treat ARO, with >50% of successful engraftment and several undesired effects, including the progression of neural failure with vision deterioration.  The results of pharmacological treatments with corticosteroids, vitamin D/calcium supplementation, parathyroid hormone or gamma-interferon are inconsistent and generally cannot substitute for HSCT, with a very few exceptions. 
Management of osteomyelitis in patients with osteopetrosis is controversial. Main therapeutic approach is antibiotic therapy combined with complete debridement of necrotic tissue and suturing of soft tissue. Hyperbaric oxygen therapy has been recommended for management of chronic osteomyelitis. Higher oxygen content induces angiogenesis, promotes neutrophil-mediated defense, and stimulates collagen formation. 
Our patient was given appropriate antibiotics with irrigation and curettage of the lesion was planned, but unfortunately patient expired due to trauma before the appointment.
| Conclusion|| |
Intermediate osteopetrosis is the least common type of osteopetrosis, which might be characterized by an asymptomatic clinical picture. Therefore, a proper clinical and radiographic investigation is essential for accurate diagnosis. Moreover, because of the high infection risk and increased susceptibility to jaw fracture in these patients, careful treatment planning is important to avoid secondary complications of the disease.
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[Figure 1], [Figure 2], [Figure 3], [Figure 4], [Figure 5], [Figure 6], [Figure 7], [Figure 8], [Figure 9], [Figure 10], [Figure 11], [Figure 12]