Skeletal Radiol (2015) 44:1529–1533 DOI 10.1007/s00256-015-2190-9
CASE REPORT
Osteosclerotic metaphyseal dysplasia with extensive interstitial pulmonary lesions: a case report and literature review Helin Zheng 1 & Jinhua Cai 1 & Longlun Wang 1 & Xiaoya He 1
Received: 7 February 2015 / Revised: 27 May 2015 / Accepted: 2 June 2015 / Published online: 18 June 2015 # ISS 2015
Abstract Osteosclerotic metaphyseal dysplasia (OMD) is a very rare sclerosing bone disorder. To date, four cases have been documented in three reports. Here, we present the case of a 12-year-old girl with a history of recurrent respiratory infections, hypotonia, developmental delay, genu valgum, and hepatosplenomegaly. Radiographs revealed profound, ivory-white sclerosis of the metaphyses and epiphyses of the long bones in both the upper and lower extremities. Sclerosis also affected the ends or margins of the flat bones, including the mandible, clavicles, scapulae, ribs, iliac crests, ischia, pubic bones, talus, calcaneus, and some vertebrae, to varying degrees. Based on the clinical, radiographic, and laboratory findings, a diagnosis of OMD was made. Our patient is the fifth case of OMD reported in the international literature and shares clinical and radiological similarities with four other reported cases of OMD. However, the extensive interstitial pulmonary lesions observed on computed tomography images in the present case have not been previously documented. This pulmonary disorder, which may be associated with OMD, should be evaluated in subsequently encountered cases.
Keywords Bone dysplasia . Sclerosis . Metaphysis . Respiratory infections
* Jinhua Cai [email protected] 1
Department of Radiology, Children’s Hospital of Chongqing Medical University, 136 Zhongshan 2 Road, Yuzhong District, Chongqing 400014, China
Introduction Osteosclerotic metaphyseal dysplasia (OMD) is a very rare sclerosing bone disease that is characterized by specific clinical manifestations, including early developmental delay, hypotonia, and/or later spastic paraplegia, and imaging features of multiple areas of very dense metaphyseal osteosclerosis. To date, only four cases have been reported in the English literature [1-3]. We present the fifth case of OMD in a 12year-old girl with recurrent respiratory infections. Radiographs revealed characteristic sclerosis in the growing bones. This characteristic was similarly observed in the other four reported cases. However, the extensive interstitial pulmonary lesions (which could explain the respiratory disorders) that were detected via chest computed tomography (CT) imaging have not been previously documented.
Case report We describe the case of a Chinese girl who presented to us at age 12. The girl was a term infant and remained in good health until the first onset of respiratory infection that was accompanied with a high-grade fever at 7 months of age. Initially, she was diagnosed with bronchitis and received antibiotic treatment (details unknown). Subsequently, she experienced repeated respiratory infections, more than 6 per year, particularly during periods of weather changes. This condition lasted 1– 2 weeks per onset. Antibiotic treatments (cephalosporins and azithromycin) were effective. At 6 years of age, the girl was admitted to our hospital for a relapsing respiratory infection. Hepatosplenomegaly was significant upon a physical examination. Blood cell counts indicated granulocytopenia, but the other cell counts were normal. Chest radiographs and CT imaging
1530
revealed extensive interstitial pulmonary lesions bilaterally (Fig. 1). Radiographs of the skeleton revealed osteosclerosis involving the metaphyseal regions of the long bones in the upper and lower extremities (Fig. 2). The diagnosis upon discharge included pneumonia, granulocytopenia, possible immunodeficiency disease, and suspected lead poisoning. Three years later, at age 9, the girl developed an abnormal gait and genu valgum. At that time, a bone biopsy of the right proximal tibial metaphysis indicated diffuse hyperplasia of the bone trabeculae in a disordered organization with calcification (Fig. 3). This observation prompted us to consider the diagnosis of osteosclerotic metaphyseal dysplasia. Seven days prior to the latest admission, the girl developed a respiratory infection associated with fever, shortness of breath, and orthopnea. Upon admission, she was noted to be poorly nourished and demonstrated hypotonia. Her body weight and height indicated developmental delay. Her mental function was normal. Mild facial dysmorphism was observed, including a flat nasal bridge, hypotelerism, and thick lips. The cardiac examination was normal. The liver was moderately enlarged. Splenomegaly was also observed. Family and past histories were negative, and the family denied the possibility of genetic or infectious diseases. Fig. 1 CT images of the chest. a, b Lung window images showed extensive bilateral ground glass opacification and fibrosis with bronchial thickening. c, d Mediastinal window images revealed multiple lymphadenectasis in the mediastinum and bilateral pulmonary hila
Skeletal Radiol (2015) 44:1529–1533
Laboratory analysis An examination of peripheral blood cells revealed granulocytopenia and an elevated reticulocyte count. The Coombs test was positive. The previous two bone marrow aspirations did not indicate malignant hematopoietic disease or fibrosis. The antibody to hepatitis B core antigen (HBc-Ab) was slightly elevated (1.65 IU/mL). There was no evidence of infection with syphilis, HIV, tuberculosis, or other viruses or fungi. Imaging analysis The skeletal radiographs obtained at age 6 years demonstrated symmetrical, thick transverse sclerotic bands in the metaphyses and the margins of the epiphyses of the long bones in the upper and lower extremities. The sclerotic metaphyses were flared and striped longitudinally (Fig. 2a– d). Slight osteoporosis was observed in the thoracic and lumbar vertebrae (Fig. 2a, e). The skull appeared to be unaffected. The sclerotic metaphyseal changes progressed slightly between 6 and 12 years of age. Similar sclerosis involved the margins of the flat bones, including the mandible, clavicles, scapulae, sternum, ribs, iliac crests, ischia, pubic bones, talus, and calcaneus (varying degrees). Reconstructed spinal CT images indicated that some vertebrae were slightly involved,
Skeletal Radiol (2015) 44:1529–1533
1531
Fig. 2 Radiographs of the skeleton. Focal sclerosis was identified in the metaphyses and the margins of the epiphyses of the long bones in the a, b upper and c, d lower extremities. The sclerotic/ivory-white metaphyses were flared and striped longitudinally. Sclerosis also involved the epiphyseal cartilage of the pelvic bones, including b, c the ischia and
pubic bones, d the talus and calcaneus, e the clavicles, scapulae, ribs, and some vertebrae. f A reconstructed sagittal spinal CT image of the spine demonstrated focal sclerosis, primarily in the superior or inferior endplates of some vertebral bodies and a spinal process. Some sclerosis was also observed in the mandibula and sternum
predominantly in the superior and inferior endplates of the vertebral bodies and the tips of the spinal processes (Fig. 2f). Chest X-ray and CT revealed bilateral interstitial pulmonary lesions at age 6. Six years later, a chest CT indicated segmental consolidation of both lungs and interstitial changes with differing degrees of pulmonary fibrosis and bronchial wall thickening. Lymphadenopathy was noted in the mediastinum and bilateral pulmonary hila (Fig. 1). At 9 years of age, emission computed tomography (ECT) demonstrated hyperactive metabolism in the metaphyseal
portion of most tubular bones and at the ends or margins of the flat bones.
Fig. 3 Pathological findings revealed via a biopsy of the right proximal tibial metaphysis (hematoxylin–eosin staining, original magnification× 400). Microscopic imaging showed diffuse hyperplasia of the bone trabeculae in a disordered organization with calcification
Discussion Osteosclerotic metaphyseal dysplasia (OMD) is a very rare bone disease. Only 4 cases have been reported to date. This report documents the first case of OMD in a Chinese population and the fifth case described internationally. The first cases, two Japanese siblings born to first-degree cousin parents, were reported by Nishimura and Kozlowski in 1993 [1]. Next, the case of a 23-month-old Hispanic male was described by Mennel and John in 2003 [2], and the 4th case, a 12-monthold Turkish male, was reported by Kasapkara et al. in 2013 [3]. These cases demonstrated developmental delay, hypotonia, and/or later spastic paraplegia, and multiple metaphyseal osteosclerosis at specific locations. The clinical features and imaging findings from these four cases are summarized in Tables 1 and 2. In our patient, the clinical (Table 1) and radiographic (Table 2) findings, particularly the location, morphology, and density of metaphyseal sclerosis, had some similarities with the findings from the four previously reported patients with OMD. In addition, the bone biopsy performed at 9 years of age revealed diffuse hyperplasia of the bone
1532 Table 1
Skeletal Radiol (2015) 44:1529–1533 Clinical review of osteosclerotic metaphyseal dysplasia reported in the literature
Author/reference
Nishimura and Kozlowski [1]
Mennel and John [2] Kasapkara et al. [3]
Our patient
Case number
Case 1
Case 3
Case 4
Case 5
Family history
Normal
Normal
Parental consanguinity Pregnancy
A sister of their mother was mentally Normal retarded and had walking difficulties Yes No 41 weeks 34 weeks 36 weeks
No 36 weeks
No 38 weeks
Conditions of delivery Initial development
Normal Normal
Respiratory distress Normal
Normal Normal
Respiratory distress Normal
Normal Normal
Facial dysmorphism
(−)
(−)
(−)
(−)
(+)
Hypotonia Respiratory infections
(+) At 11 months
(+) At 12 months
(+) Not mentioned
(+) (+) Mentioned but the age is unknown Recurrent from 7 months
Hepatosplenomegaly (−) Later spastic paraplegia No follow-up
(−) (+)
(−) (−)
(−) (−)
(+) (−)
Epilepsy
(+)
(+)
(−)
(−)
(−)
Case 2
trabeculae exhibiting disordered organization with calcification. Thus, we believe that this is the first case of OMD reported in a Chinese population and the fifth case described internationally. Although the present case shared some similarities regarding the clinical and imaging findings, it differed from the other four cases in some aspects. The most notable difference was the presence of interstitial pulmonary disease. In our case, repeated respiratory infections occurred throughout the entire course of the disease and appeared to be a remarkable clinical feature during the early stage. A follow-up CT revealed progressive interstitial pulmonary lesions, including fibrosis and bronchiectasis. These imaging findings could explain the clinical respiratory manifestations. Interestingly, a respiratory disorder was mentioned in all previous reports except for the 2003 case. In cases 1, 2, and 4, bone abnormalities were all detected incidentally via chest radiographs that were performed for respiratory tract infections. Because of the unique Table 2
imaging findings in the thorax, these reports focused on osteosclerosis and did not describe the respiratory manifestations in detail. Although there has been no direct evidence to date, we believe that the respiratory disorder is associated with OMD. Another difference was the presence of granulocytopenia and hepatosplenomegaly, which were present in our case, but were not mentioned in the previous cases. In addition, data regarding paraplegia and the elevation of serum alkaline phosphatase present in the previous cases were not present in our patient at 12 years of age. In the first reported case, paraplegia did not occur until age 15, suggesting that it is a late-stage manifestation of this disorder. Osteosclerotic metaphyseal dysplasia was first suggested by Nishimura and Kozlowski [1] owing to the unique imaging findings of osteosclerosis in a specific location. Currently, OMD is a diagnosis based on the imaging features, and the etiology remains unknown. The two Japanese siblings whose parents were first-degree cousins suggest autosomal recessive
Sclerotic skeletal involvement in cases of OMD
Author/reference
Nishimura and Kozlowski [1]
Mennel and John [2]
Kasapkara et al. [3]
Our patient
Case number
Case 1
Case 2
Case 3
Case 4
Case 5
Metaphyses of the extremity long bones Epiphyses of the extremity long bones Margin of the pelvic bones Ends of the ribs Talus and calcaneus Skull Vertebrae Metaphyses flared and frayed Diaphyseal osteopenia
(+) (+) (+) Not mentioned (+) (+) Not mentioned (+) (+)
(+) (+) (+) (+) Not mentioned (−) (+) (+) (+)
(+) (+) (+) (+) (+) (−) (−) (+) (+)
(+) (+) (+) (+) (+) (−) (+) (+) (+)
(+) (+) (+) (+) (+) (−) (+) (+) (+)
Skeletal Radiol (2015) 44:1529–1533
inheritance. In our patient, some facial dysmorphia was observed, which could be attributed to a congenital disease. Multiple systems were involved, and the disorder became more extensive and severe with increasing age. All the above evidence prompted the consideration of an inherited disorder. In addition, the bone biopsy revealed diffuse hyperplasia of bone trabeculae in a disordered organization with calcification, which agreed with the histopathological findings also found in osteopetrosis. Other diseases causing metaphyseal sclerosis, hypotonia, and developmental delay were considered in the differential diagnosis of the patient. Lead intoxication, a common cause of metaphyseal sclerosis in young children, was suspected initially. A careful analysis of the metaphyseal bone changes can enable differentiation between the two diseases. A band of focal sclerosis can be observed in the metaphyses of the long bones in the extremities of individuals with chronic lead poisoning [4–6]. However, the metaphyseal bands of sclerosis resulting from OMD are thicker than those associated with lead intoxication. Meanwhile, the marginal epiphyseal sclerosis detected in OMD patients has not been observed in patients with lead intoxication. Additionally, no history of lead poisoning or gastrointestinal symptoms was observed, and the blood and urine heavy metal assay results were normal. Osteopetrosis [7], pyknodysostosis [8], spondylometaphyseal dysplasia, and idiopathic hypercalcemia [9] all have clinical and radiographic features that are clearly different from the features observed in patients with OMD.
Conclusion To date, the underlying cause of OMD is unknown. However, the diagnosis can be made by the combination of clinical, laboratory, and radiographic findings. In particular, the radiographic appearance of the skeleton is remarkable and a unique characteristic that helps to distinguish OMD from other causes
1533
of metaphyseal sclerosis in children. To our knowledge, this is the first case of OMD reported in a Chinese population and the fifth case described in the international literature. The pulmonary disorder was a remarkable manifestation in our case that may be associated with OMD and should be noted in subsequently encountered cases.
Funding This work is partially supported by the National Natural Science Foundation of China (No. 81171387). Conflict of interest This work is partially supported by the National Natural Science Foundation of China (No. 81171387). The authors declare that they have no conflict of interest.
References 1.
Nishimura G, Kozlowski K. Osteosclerotic metaphyseal dysplasia. Pediatr Radiol. 1993;23(6):450–2. 2. Mennel EA, John SD. Osteosclerotic metaphyseal dysplasia: a skeletal dysplasia that may mimic lead poisoning in a child with hypotonia and seizures. Pediatr Radiol. 2003;33(1):11–4. 3. Kasapkara CS, Küçükçongar A, Boyunağa O, Bedir T, Oncü F, Hasanoğlu A, et al. An extremely rare case: osteosclerotic metaphyseal dysplasia. Genet Couns. 2013;24(1):69–74. 4. Blickman JG, Wilkinson RH, Graef JW. The radiologic "lead band" revisited. AJR Am J Roentgenol. 1986;146(2):245–7. 5. Raber SA. The dense metaphyseal band sign. Radiology. 1999;211(3):773–4. 6. Palaniappan PL, Krishnakumar N, Vadivelu M, Vijayasundaram V. The study of the changes in the biochemical and mineral contents of bones of Catla catla due to lead intoxication. Environ Toxicol. 2010;25(1):61–7. 7. El-Tawil T, Stoker DJ. Benign osteopetrosis: a review of 42 cases showing two different patterns. Skeletal Radiol. 1993;22(8):587–93. 8. Soliman AT, Ramadan MA, Sherif A, Aziz Bedair ES, Rizk MM. Pycnodysostosis: clinical, radiologic, and endocrine evaluation and linear growth after growth hormone therapy. Metabolism. 2001;50(8):905–11. 9. Singleton EB. The radiographic features of severe idiopathic hypercalcemia of infancy. Radiology. 1957;68(5):721–6.
CASE REPORT
Osteosclerotic metaphyseal dysplasia with extensive interstitial pulmonary lesions: a case report and literature review Helin Zheng 1 & Jinhua Cai 1 & Longlun Wang 1 & Xiaoya He 1
Received: 7 February 2015 / Revised: 27 May 2015 / Accepted: 2 June 2015 / Published online: 18 June 2015 # ISS 2015
Abstract Osteosclerotic metaphyseal dysplasia (OMD) is a very rare sclerosing bone disorder. To date, four cases have been documented in three reports. Here, we present the case of a 12-year-old girl with a history of recurrent respiratory infections, hypotonia, developmental delay, genu valgum, and hepatosplenomegaly. Radiographs revealed profound, ivory-white sclerosis of the metaphyses and epiphyses of the long bones in both the upper and lower extremities. Sclerosis also affected the ends or margins of the flat bones, including the mandible, clavicles, scapulae, ribs, iliac crests, ischia, pubic bones, talus, calcaneus, and some vertebrae, to varying degrees. Based on the clinical, radiographic, and laboratory findings, a diagnosis of OMD was made. Our patient is the fifth case of OMD reported in the international literature and shares clinical and radiological similarities with four other reported cases of OMD. However, the extensive interstitial pulmonary lesions observed on computed tomography images in the present case have not been previously documented. This pulmonary disorder, which may be associated with OMD, should be evaluated in subsequently encountered cases.
Keywords Bone dysplasia . Sclerosis . Metaphysis . Respiratory infections
* Jinhua Cai [email protected] 1
Department of Radiology, Children’s Hospital of Chongqing Medical University, 136 Zhongshan 2 Road, Yuzhong District, Chongqing 400014, China
Introduction Osteosclerotic metaphyseal dysplasia (OMD) is a very rare sclerosing bone disease that is characterized by specific clinical manifestations, including early developmental delay, hypotonia, and/or later spastic paraplegia, and imaging features of multiple areas of very dense metaphyseal osteosclerosis. To date, only four cases have been reported in the English literature [1-3]. We present the fifth case of OMD in a 12year-old girl with recurrent respiratory infections. Radiographs revealed characteristic sclerosis in the growing bones. This characteristic was similarly observed in the other four reported cases. However, the extensive interstitial pulmonary lesions (which could explain the respiratory disorders) that were detected via chest computed tomography (CT) imaging have not been previously documented.
Case report We describe the case of a Chinese girl who presented to us at age 12. The girl was a term infant and remained in good health until the first onset of respiratory infection that was accompanied with a high-grade fever at 7 months of age. Initially, she was diagnosed with bronchitis and received antibiotic treatment (details unknown). Subsequently, she experienced repeated respiratory infections, more than 6 per year, particularly during periods of weather changes. This condition lasted 1– 2 weeks per onset. Antibiotic treatments (cephalosporins and azithromycin) were effective. At 6 years of age, the girl was admitted to our hospital for a relapsing respiratory infection. Hepatosplenomegaly was significant upon a physical examination. Blood cell counts indicated granulocytopenia, but the other cell counts were normal. Chest radiographs and CT imaging
1530
revealed extensive interstitial pulmonary lesions bilaterally (Fig. 1). Radiographs of the skeleton revealed osteosclerosis involving the metaphyseal regions of the long bones in the upper and lower extremities (Fig. 2). The diagnosis upon discharge included pneumonia, granulocytopenia, possible immunodeficiency disease, and suspected lead poisoning. Three years later, at age 9, the girl developed an abnormal gait and genu valgum. At that time, a bone biopsy of the right proximal tibial metaphysis indicated diffuse hyperplasia of the bone trabeculae in a disordered organization with calcification (Fig. 3). This observation prompted us to consider the diagnosis of osteosclerotic metaphyseal dysplasia. Seven days prior to the latest admission, the girl developed a respiratory infection associated with fever, shortness of breath, and orthopnea. Upon admission, she was noted to be poorly nourished and demonstrated hypotonia. Her body weight and height indicated developmental delay. Her mental function was normal. Mild facial dysmorphism was observed, including a flat nasal bridge, hypotelerism, and thick lips. The cardiac examination was normal. The liver was moderately enlarged. Splenomegaly was also observed. Family and past histories were negative, and the family denied the possibility of genetic or infectious diseases. Fig. 1 CT images of the chest. a, b Lung window images showed extensive bilateral ground glass opacification and fibrosis with bronchial thickening. c, d Mediastinal window images revealed multiple lymphadenectasis in the mediastinum and bilateral pulmonary hila
Skeletal Radiol (2015) 44:1529–1533
Laboratory analysis An examination of peripheral blood cells revealed granulocytopenia and an elevated reticulocyte count. The Coombs test was positive. The previous two bone marrow aspirations did not indicate malignant hematopoietic disease or fibrosis. The antibody to hepatitis B core antigen (HBc-Ab) was slightly elevated (1.65 IU/mL). There was no evidence of infection with syphilis, HIV, tuberculosis, or other viruses or fungi. Imaging analysis The skeletal radiographs obtained at age 6 years demonstrated symmetrical, thick transverse sclerotic bands in the metaphyses and the margins of the epiphyses of the long bones in the upper and lower extremities. The sclerotic metaphyses were flared and striped longitudinally (Fig. 2a– d). Slight osteoporosis was observed in the thoracic and lumbar vertebrae (Fig. 2a, e). The skull appeared to be unaffected. The sclerotic metaphyseal changes progressed slightly between 6 and 12 years of age. Similar sclerosis involved the margins of the flat bones, including the mandible, clavicles, scapulae, sternum, ribs, iliac crests, ischia, pubic bones, talus, and calcaneus (varying degrees). Reconstructed spinal CT images indicated that some vertebrae were slightly involved,
Skeletal Radiol (2015) 44:1529–1533
1531
Fig. 2 Radiographs of the skeleton. Focal sclerosis was identified in the metaphyses and the margins of the epiphyses of the long bones in the a, b upper and c, d lower extremities. The sclerotic/ivory-white metaphyses were flared and striped longitudinally. Sclerosis also involved the epiphyseal cartilage of the pelvic bones, including b, c the ischia and
pubic bones, d the talus and calcaneus, e the clavicles, scapulae, ribs, and some vertebrae. f A reconstructed sagittal spinal CT image of the spine demonstrated focal sclerosis, primarily in the superior or inferior endplates of some vertebral bodies and a spinal process. Some sclerosis was also observed in the mandibula and sternum
predominantly in the superior and inferior endplates of the vertebral bodies and the tips of the spinal processes (Fig. 2f). Chest X-ray and CT revealed bilateral interstitial pulmonary lesions at age 6. Six years later, a chest CT indicated segmental consolidation of both lungs and interstitial changes with differing degrees of pulmonary fibrosis and bronchial wall thickening. Lymphadenopathy was noted in the mediastinum and bilateral pulmonary hila (Fig. 1). At 9 years of age, emission computed tomography (ECT) demonstrated hyperactive metabolism in the metaphyseal
portion of most tubular bones and at the ends or margins of the flat bones.
Fig. 3 Pathological findings revealed via a biopsy of the right proximal tibial metaphysis (hematoxylin–eosin staining, original magnification× 400). Microscopic imaging showed diffuse hyperplasia of the bone trabeculae in a disordered organization with calcification
Discussion Osteosclerotic metaphyseal dysplasia (OMD) is a very rare bone disease. Only 4 cases have been reported to date. This report documents the first case of OMD in a Chinese population and the fifth case described internationally. The first cases, two Japanese siblings born to first-degree cousin parents, were reported by Nishimura and Kozlowski in 1993 [1]. Next, the case of a 23-month-old Hispanic male was described by Mennel and John in 2003 [2], and the 4th case, a 12-monthold Turkish male, was reported by Kasapkara et al. in 2013 [3]. These cases demonstrated developmental delay, hypotonia, and/or later spastic paraplegia, and multiple metaphyseal osteosclerosis at specific locations. The clinical features and imaging findings from these four cases are summarized in Tables 1 and 2. In our patient, the clinical (Table 1) and radiographic (Table 2) findings, particularly the location, morphology, and density of metaphyseal sclerosis, had some similarities with the findings from the four previously reported patients with OMD. In addition, the bone biopsy performed at 9 years of age revealed diffuse hyperplasia of the bone
1532 Table 1
Skeletal Radiol (2015) 44:1529–1533 Clinical review of osteosclerotic metaphyseal dysplasia reported in the literature
Author/reference
Nishimura and Kozlowski [1]
Mennel and John [2] Kasapkara et al. [3]
Our patient
Case number
Case 1
Case 3
Case 4
Case 5
Family history
Normal
Normal
Parental consanguinity Pregnancy
A sister of their mother was mentally Normal retarded and had walking difficulties Yes No 41 weeks 34 weeks 36 weeks
No 36 weeks
No 38 weeks
Conditions of delivery Initial development
Normal Normal
Respiratory distress Normal
Normal Normal
Respiratory distress Normal
Normal Normal
Facial dysmorphism
(−)
(−)
(−)
(−)
(+)
Hypotonia Respiratory infections
(+) At 11 months
(+) At 12 months
(+) Not mentioned
(+) (+) Mentioned but the age is unknown Recurrent from 7 months
Hepatosplenomegaly (−) Later spastic paraplegia No follow-up
(−) (+)
(−) (−)
(−) (−)
(+) (−)
Epilepsy
(+)
(+)
(−)
(−)
(−)
Case 2
trabeculae exhibiting disordered organization with calcification. Thus, we believe that this is the first case of OMD reported in a Chinese population and the fifth case described internationally. Although the present case shared some similarities regarding the clinical and imaging findings, it differed from the other four cases in some aspects. The most notable difference was the presence of interstitial pulmonary disease. In our case, repeated respiratory infections occurred throughout the entire course of the disease and appeared to be a remarkable clinical feature during the early stage. A follow-up CT revealed progressive interstitial pulmonary lesions, including fibrosis and bronchiectasis. These imaging findings could explain the clinical respiratory manifestations. Interestingly, a respiratory disorder was mentioned in all previous reports except for the 2003 case. In cases 1, 2, and 4, bone abnormalities were all detected incidentally via chest radiographs that were performed for respiratory tract infections. Because of the unique Table 2
imaging findings in the thorax, these reports focused on osteosclerosis and did not describe the respiratory manifestations in detail. Although there has been no direct evidence to date, we believe that the respiratory disorder is associated with OMD. Another difference was the presence of granulocytopenia and hepatosplenomegaly, which were present in our case, but were not mentioned in the previous cases. In addition, data regarding paraplegia and the elevation of serum alkaline phosphatase present in the previous cases were not present in our patient at 12 years of age. In the first reported case, paraplegia did not occur until age 15, suggesting that it is a late-stage manifestation of this disorder. Osteosclerotic metaphyseal dysplasia was first suggested by Nishimura and Kozlowski [1] owing to the unique imaging findings of osteosclerosis in a specific location. Currently, OMD is a diagnosis based on the imaging features, and the etiology remains unknown. The two Japanese siblings whose parents were first-degree cousins suggest autosomal recessive
Sclerotic skeletal involvement in cases of OMD
Author/reference
Nishimura and Kozlowski [1]
Mennel and John [2]
Kasapkara et al. [3]
Our patient
Case number
Case 1
Case 2
Case 3
Case 4
Case 5
Metaphyses of the extremity long bones Epiphyses of the extremity long bones Margin of the pelvic bones Ends of the ribs Talus and calcaneus Skull Vertebrae Metaphyses flared and frayed Diaphyseal osteopenia
(+) (+) (+) Not mentioned (+) (+) Not mentioned (+) (+)
(+) (+) (+) (+) Not mentioned (−) (+) (+) (+)
(+) (+) (+) (+) (+) (−) (−) (+) (+)
(+) (+) (+) (+) (+) (−) (+) (+) (+)
(+) (+) (+) (+) (+) (−) (+) (+) (+)
Skeletal Radiol (2015) 44:1529–1533
inheritance. In our patient, some facial dysmorphia was observed, which could be attributed to a congenital disease. Multiple systems were involved, and the disorder became more extensive and severe with increasing age. All the above evidence prompted the consideration of an inherited disorder. In addition, the bone biopsy revealed diffuse hyperplasia of bone trabeculae in a disordered organization with calcification, which agreed with the histopathological findings also found in osteopetrosis. Other diseases causing metaphyseal sclerosis, hypotonia, and developmental delay were considered in the differential diagnosis of the patient. Lead intoxication, a common cause of metaphyseal sclerosis in young children, was suspected initially. A careful analysis of the metaphyseal bone changes can enable differentiation between the two diseases. A band of focal sclerosis can be observed in the metaphyses of the long bones in the extremities of individuals with chronic lead poisoning [4–6]. However, the metaphyseal bands of sclerosis resulting from OMD are thicker than those associated with lead intoxication. Meanwhile, the marginal epiphyseal sclerosis detected in OMD patients has not been observed in patients with lead intoxication. Additionally, no history of lead poisoning or gastrointestinal symptoms was observed, and the blood and urine heavy metal assay results were normal. Osteopetrosis [7], pyknodysostosis [8], spondylometaphyseal dysplasia, and idiopathic hypercalcemia [9] all have clinical and radiographic features that are clearly different from the features observed in patients with OMD.
Conclusion To date, the underlying cause of OMD is unknown. However, the diagnosis can be made by the combination of clinical, laboratory, and radiographic findings. In particular, the radiographic appearance of the skeleton is remarkable and a unique characteristic that helps to distinguish OMD from other causes
1533
of metaphyseal sclerosis in children. To our knowledge, this is the first case of OMD reported in a Chinese population and the fifth case described in the international literature. The pulmonary disorder was a remarkable manifestation in our case that may be associated with OMD and should be noted in subsequently encountered cases.
Funding This work is partially supported by the National Natural Science Foundation of China (No. 81171387). Conflict of interest This work is partially supported by the National Natural Science Foundation of China (No. 81171387). The authors declare that they have no conflict of interest.
References 1.
Nishimura G, Kozlowski K. Osteosclerotic metaphyseal dysplasia. Pediatr Radiol. 1993;23(6):450–2. 2. Mennel EA, John SD. Osteosclerotic metaphyseal dysplasia: a skeletal dysplasia that may mimic lead poisoning in a child with hypotonia and seizures. Pediatr Radiol. 2003;33(1):11–4. 3. Kasapkara CS, Küçükçongar A, Boyunağa O, Bedir T, Oncü F, Hasanoğlu A, et al. An extremely rare case: osteosclerotic metaphyseal dysplasia. Genet Couns. 2013;24(1):69–74. 4. Blickman JG, Wilkinson RH, Graef JW. The radiologic "lead band" revisited. AJR Am J Roentgenol. 1986;146(2):245–7. 5. Raber SA. The dense metaphyseal band sign. Radiology. 1999;211(3):773–4. 6. Palaniappan PL, Krishnakumar N, Vadivelu M, Vijayasundaram V. The study of the changes in the biochemical and mineral contents of bones of Catla catla due to lead intoxication. Environ Toxicol. 2010;25(1):61–7. 7. El-Tawil T, Stoker DJ. Benign osteopetrosis: a review of 42 cases showing two different patterns. Skeletal Radiol. 1993;22(8):587–93. 8. Soliman AT, Ramadan MA, Sherif A, Aziz Bedair ES, Rizk MM. Pycnodysostosis: clinical, radiologic, and endocrine evaluation and linear growth after growth hormone therapy. Metabolism. 2001;50(8):905–11. 9. Singleton EB. The radiographic features of severe idiopathic hypercalcemia of infancy. Radiology. 1957;68(5):721–6.
