Spectrum of Skeletal Imaging Features in Osteopetrosis: Inheritance Pattern and Radiological Associations

Abstract

Osteopetrosis (from the Greek “osteo”: bone; “petrosis”: stone) is a clinically and genetically heterogeneous group of rare diseases of the skeleton, sharing the same main characteristic of an abnormally increased bone density. Dense bones in radiological studies are considered the hallmark of these diseases, and the reason for the common term used: “Marble bone disease”. Interestingly, a radiologist, Dr. Albers-Schonberg, described this disease for the first time in Germany in 1904. Indeed, radiology has a key role in the clinical diagnosis of osteopetrosis and is fundamental in assessing the disease severity and complications, as well as in follow-up controls and the evaluation of the response to treatment. Osteopetrosis includes a broad spectrum of genetic mutations with very different clinical symptoms, age onset, and prognosis (from mild to severe). This diversity translates into different imaging patterns related to specific mutations, and different disease severity. The main recognized types of osteopetrosis are the infantile malignant forms with autosomal recessive transmission (ARO—including the rarer X-linked recessive form); the intermediate autosomal recessive form (IAO); and the autosomal dominant ones ADO, type I, and type II, the latter being called ‘Albers-Schonberg’ disease. Imaging features may change among those distinct types with different patterns, severities, skeletal segment involvement, and speeds of progression. There are several classical and well-recognized radiological features related to osteopetrosis: increased bone density (all types with different degrees of severity assuming a ‘Marble Bone Appearance’ especially in the ARO type), different metaphyseal alterations/enlargement including the so-called ‘Erlenmeyer flask deformity’ (particularly of femoral bones, more frequent in ADO type 2, and less frequent in ARO and IAO), ‘bone in bone’ appearance (more frequent in ADO type 2, less frequent in ARO and IAO), and ‘rugger-jersey spine’ appearance (typical of ADO type 2). After conducting an overview of the epidemiological and clinical characteristic of the disease, this review article aims at summarizing the main radiological features found in different forms of osteopetrosis together with their inheritance pattern.

Osteopetrosis complicated by multilevel spondylolysis

“…In the spine, the classic imaging appearance is of a “sandwich vertebrae” formed by diffuse endplate (and posterior element) sclerosis and lucency of the center of the vertebral body resulting in a “rugger jersey spine”. These findings are similarly translated to MRI as diffusely low signal on T1 and T2 weighted images in the region of sclerosis along the peripheral endplates and relatively increased central signal [6] .…”

“…Although the process of osteoclast differentiation and bone deposition/resorption are biochemically complex, 4 main types of osteopetrosis have been identified based on molecular pathogenesis and clinical features. These types include the autosomal recessive infantile/malignant form, the intermediate autosomal recessive form, type I autosomal dominant form and type II autosomal dominant form (also called Albert-Schoenberg disease) [ 6 , 7 ]. Type II is overall the most common form and is the genetic diagnosis in this case.…”

“…The infantile and intermediate forms most commonly affect children in the first year of life and during the first decade, respectively, with the infantile form often leading to mortality early in childhood. The intermediate form is a milder autosomal recessive form, often presenting with pathologic fractures and cranial nerve compressive neuropathies and is associated with defects in the carbonic anhydrase II protein [ 6 , 7 ]. The autosomal dominant forms (type I and type II) are more indolent and often asymptomatic, with type II presenting with pathologic fractures, arthritis, bone pain, and/or nerve compression in adulthood.…”

“…In the imaging evaluation of patients with osteopetrosis, some of the potential complications to evaluate include pathologic fractures, foraminal stenosis impinging on the cranial nerves at the nerve roots, and the potential paradoxical development of rickets secondary to low serum calcium related to sequestration of calcium in the bones [5] , [6] , [7] .…”

Brittle Bone Imaging: Diagnostic Procedures in Adults

“…Pycnodysostosis, secondary to chromosome-1 involvement, induces severe brittle bone, with disharmonious dwarfism, micrognathia, bilateral clavicular dysplasia, and acro-osteolysis. 24 Some rare forms of dysplasia are associated with local or general BMD elevation in a broad malformation syndrome: metaphyseal dysplasia or Pyle's disease, craniometaphyseal dysplasia, craniodiaphyseal dysplasia, frontometaphyseal dysplasia, and oculo-dental-osseous dysplasia.…”