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Osteopetrosis encompasses rare inherited metabolic bone disorders with defect in the osteoclast activity. Severe forms of presentation such as malignant infantile osteopetrosis are seen in infants and milder forms in older children. The clinical presentation includes failure to thrive, severe pallor, optic atrophy and hepatosplenomegaly. The disorder is characterised by dense bone on radiography, hence the name marble bone disease. A 10-month-old boy who presented with developmental delay, failure to thrive, nystagmus (which the mother described as wandering eye movements), splenomegaly of 16 cm and hepatomegaly of 8 cm. Investigations demonstrated severe anaemia (5.7 g/dL) and thrombocytopenia (34 x 109/L). Radiological signs which help in the diagnosis include diffuse sclerosis, bone within bone appearance, sandwich vertebrae and Erlenmeyer flask deformity. Plain radiography is an easily available and cost effective tool which can aid in the diagnosis of osteopetrosis.

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INTRODUCTION: Osteopetrosis is a rare hereditary disease that can be transmitted in an autosomal recessive or autosomal dominant. CASE REPORT: Here, we report a case of trochanteric fracture in an 18-year-old boy with an anatomical plate. At the last follow-up, 24 months after surgery, the fracture had healed well, and the patient was not restricted in his activities. DISCUSSION: Osteopetrosis is a rare bone disease that is mainly caused by osteoclast dysfunction. It results from a remodelling defect that leads to hypermineralization of the skeleton, resulting in bone fragility. Both surgical and nonsurgical management have advantages and disadvantages. Thus, open reduction and anatomic plate fixation remain effective management modalities for trochanteric fractures in osteopetrosis patients. CONCLUSION: For our patient and as described in the literature, the complication rate decreases as some principles are respected with better consolidation of the osteoporotic fracture.

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Moyamoya angiopathy (MMA) is a progressive vasculopathy characterized by slowly progressive stenosis involving the proximal portions of the major intracranial arteries, resulting in strokes and intracranial hemorrhages. If it occurs secondary to a known cause, it is called Moyamoya syndrome (MMS). Here, we describe the case of a five-year-old male child who presented to us with symptoms of stroke and, upon evaluation, revealed Moyamoya angiopathy. He was further evaluated, and it was found that MMA occurred as a complication of undetected beta-thalassemia. Thalassemia is an autosomal recessive blood disorder where there is a defect in hemoglobin production. It affects 100 to 150 thousand children in the Indian subcontinent. It is classified into two main types: alpha thalassemia and beta thalassemia, depending on which globin chain is affected. It primarily presents with symptoms of anemia such as easy fatiguability, dizziness, jaundice, or breathlessness. The occurrence of Moyamoya syndrome in beta-thalassemia is extremely rare, and it is extremely important to identify MMS at the earliest as it can cause long-term disabilities. We describe the imaging findings in MMS and the various classical skeletal radiographic findings in thalassemia that were seen in our patient.

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Osteopetrosis (OPT) denotes the consequences from failure of osteoclasts to resorb bone and chondroclasts to remove calcified physeal cartilage throughout growth. Resulting impairment of skeletal modeling, remodeling, and growth compromises widening of medullary spaces, formation of the skull, and expansion of cranial foramina. Thus, myelophthisic anemia, raised intracranial pressure, and cranial nerve palsies complicate OPT when severe. Osteopetrotic bones fracture due to misshaping, failure of remodeling to weave the collagenous matrix of cortical osteons and trabeculae, persistence of mineralized growth plate cartilage, "hardening" of hydroxyapatite crystals, and delayed healing of skeletal microcracks. Teeth may fail to erupt. Now it is widely appreciated that OPT is caused by germline loss-of-function mutation(s) usually of genes involved in osteoclast function, but especially rarely of genes necessary for osteoclast formation. Additionally, however, in 2003 we published a case report demonstrating that prolonged excessive dosing during childhood of the antiresorptive aminobisphosphonate pamidronate can sufficiently block osteoclast and chondroclast activity to recapitulate the skeletal features of OPT. Herein, we include further evidence of drug-induced OPT by illustrating osteopetrotic skeletal changes from repeated administration of high doses of the aminobisphosphonate zoledronic acid (zoledronate) given to children with osteogenesis imperfecta.

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Discovery in 1904 of the disorder initially called "marble bones", then in 1926 more appropriately referred to as "osteopetrosis", is attributed to Heinrich E. Albers-Schönberg (1865-1921), the first radiologist. He used the new technique of "Röntgenographie" to report in a young man the radiographic hallmarks of this osteopathy. Clinical descriptions of lethal forms of osteopetrosis had apparently been published earlier by others. In 1926, "osteopetrosis" (stony or petrified bones) replaced "marble bone disease" because the skeletal fragility resembled limestone more than marble. In 1936, despite fewer than 80 reported patients, a fundamental defect in hematopoiesis, secondarily impacting the entire skeleton, was hypothesized. By 1938, the signature histopathological finding of osteopetrosis was recognized -- persistence of unresorbed calcified growth plate cartilage. Also, it was apparent that besides lethal autosomal recessive osteopetrosis a less severe form was "handed down directly from generation to generation". In 1965, quantitative, but also qualitative, defects in osteoclasts became apparent. Here, I review the discovery and early understanding of osteopetrosis. Characterization of this disorder commencing at the beginning of the past century would support the aphorism of Sir William Osler (1849-1919): "Clinics Are Laboratories; Laboratories Of The Highest Order". As featured in this special issue of Bone, the osteopetroses would prove remarkably informative about the formation and function of the cells responsible for skeletal resorption.

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Carbonic anhydrase II deficiency (OMIM # 259730), initially called "osteopetrosis with renal tubular acidosis and cerebral calcification syndrome", reveals an important role for the enzyme carbonic anhydrase II (CA II) in osteoclast and renal tubule function. Discovered in 1972 and subsequently given various names, CA II deficiency now describes >100 affected individuals encountered predominantly from the Middle East and Mediterranean region. In 1983, CA II deficiency emerged as the first osteopetrosis (OPT) understood metabolically, and in 1991 the first understood molecularly. CA II deficiency is the paradigm OPT featuring failure of osteoclasts to resorb bone due to inability to acidify their pericellular milieu. The disorder presents late in infancy or early in childhood with fracturing, developmental delay, weakness, short stature, and/or cranial nerve compression and palsy. Mental retardation is common. The skeletal findings may improve by adult life, and CA II deficiency can be associated with a normal life-span. Therefore, it has been considered an "intermediate" type of OPT. In CA II deficiency, OPT is uniquely accompanied by renal tubular acidosis (RTA) of proximal, distal, or combined type featuring hyperchloremic metabolic acidosis, rarely with hypokalemia and paralysis. Cerebral calcification uniquely appears in early childhood. The etiology is bi-allelic loss-of-function mutations of CA2 that encodes CA II. Prenatal diagnosis requires mutational analysis of CA2. Although this enzymopathy reveals how CA II is important for the skeleton and kidney tubule, the pathogenesis of the mental subnormality and cerebral calcification is less well understood. Several mouse models of CA II deficiency have shown growth hormone deficiency, yet currently there is no standard pharmacologic therapy for patients. Treatment of the systemic acidosis is often begun when growth is complete. Although CA II deficiency is an "osteoclast-rich" OPT, and therefore transplantation of healthy osteoclasts can improve the skeletal disease, the RTA and central nervous system difficulties persist.

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The prevalence of Gaucher disease (GD) in Japan is much lower than that in Western countries; therefore, data on Japanese pediatric patients with GD type 1 are currently limited. The present study reports on the case of a Japanese pediatric patient with GD type 1 who was diagnosed when she presented with hepatosplenomegaly, thrombocytopenia and slight anemia at the age of 2 years. Serology tests revealed high levels of acid phosphatase (ACP) and angiotensin-converting enzyme (ACE). A bone marrow biopsy revealed the presence of Gaucher cells. Abdominal MRI indicated huge hepatosplenomegaly. Erlenmeyer flask deformity was observed on X-ray examination. MRI of the femora featured a high-intensity area within the diaphysis region. The enzymatic activity of leukocyte ß-glucosidase, the measurement of which is necessary for a definitive diagnosis of GD, had decreased to 186.7 nmol/h/mg (reference range, 1,424.0-2,338.0 nmol/h/mg). Based on these results, the patient was clinically diagnosed with GD. Glucocerebrosidase gene analysis identified the compound heterozygote mutation of F213I (c.754T>A) on exon 7 and L444P (c.1448T>C) on exon 11. Enzyme replacement therapy (ERT) along with an intravenous infusion of 60 U/kg of imiglucerase every other week was initiated following diagnosis. Hemoglobin levels and the platelet count gradually improved and normalized after two years. ACP and ACE levels, biomarkers of the progression of GD, also improved. Abdominal MRI at six months after the initiation of ERT revealed a decrease in the size of the liver and spleen, which normalized after 1 year. Conversely, MRI of the femora indicated no improvement in the high-intensity area within the diaphysis region for 10 years.

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The Erlenmeyer flask deformity is a common skeletal modeling deformity, but current classification systems are binary and may restrict its utility as a predictor of associated skeletal conditions. A quantifiable 3-point system of severity classification could improve its predictive potential in disease. Ratios were derived from volumes of regions of interests drawn in 50 Gaucher's disease patients. ROIs were drawn from the distal physis to 2 cm proximal, 2 cm to 4 cm, and 4 cm to 6 cm. Width was also measured at each of these boundaries. Two readers rated these 100 femurs using a 3-point scale of severity classification. Weighted kappa indicated reliability and one-way analysis of variance characterized ratio differences across the severity scale. Accuracy analyses allowed determination of clinical cutoffs for each ratio. Pearson's correlations assessed the associations of volume and width with a shape-based concavity metric of the femur. The volume ratio incorporating the metaphyseal region from 0 to 2 cm and the diametaphyseal region at 4-6 cm was most accurate at distinguishing femurs on the 3-point scale. Receiver operating characteristic curves for this ratio indicated areas of 0.95 to distinguish normal and mild femurs and 0.93 to distinguish mild and severe femurs. Volume was moderately associated with the degree of femur concavity. The proposed volume ratio method is an objective, proficient method at distinguishing severities of the Erlenmeyer flask deformity with the potential for automation. This may have application across diseases associated with the deformity and deficient osteoclast-mediated modeling of growing bone.

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We report a 14-month-old male with craniometaphyseal dysplasia (CMD). The patient presented with a history of diminishing vision and hearing loss. Cranial computed tomography scan showed diffuse calvarial and skull base hyperostosis with excessive bone narrowing the internal auditory canals and skull base foramina. A subsequent skeletal survey revealed other skeletal abnormalities, which led to the diagnosis of CMD. This was later confirmed by ANKH mutation. CMD is a rare genetic disorder that belongs to the group of craniotubular bone dysplasias. It is important to recognize this condition from other causes of craniotubular bone dysplasias to institute early treatment and explain prognosis.