Overview
Definition
Osteogenesis imperfecta (OI) is an inherited connective tissue Connective tissue Connective tissues originate from embryonic mesenchyme and are present throughout the body except inside the brain and spinal cord. The main function of connective tissues is to provide structural support to organs. Connective tissues consist of cells and an extracellular matrix. Connective Tissue disorder characterized by impaired bone Bone Bone is a compact type of hardened connective tissue composed of bone cells, membranes, an extracellular mineralized matrix, and central bone marrow. The 2 primary types of bone are compact and spongy. Structure of Bones formation and severe bone Bone Bone is a compact type of hardened connective tissue composed of bone cells, membranes, an extracellular mineralized matrix, and central bone marrow. The 2 primary types of bone are compact and spongy. Structure of Bones fragility.
Epidemiology
- Most common genetic cause of osteoporosis Osteoporosis Osteoporosis refers to a decrease in bone mass and density leading to an increased number of fractures. There are 2 forms of osteoporosis: primary, which is commonly postmenopausal or senile; and secondary, which is a manifestation of immobilization, underlying medical disorders, or long-term use of certain medications. Osteoporosis
- Incidence:
- Overall: 1 in 20,000 births
- Type I: 1 in 15,000 to 1 in 20,000 births
- Type II: 1 in 60,000 births
- Types III and IV: unknown, very low
- The distribution is similar worldwide.
- Males and females are equally affected.
Etiology
- Mutations in genes encoding collagen type 1 (COL1A1 and COL1A2):
- 90% of all cases
- Classified as types I–IV
- Other mutations (10%):
- Post-translational defects
- 3-prolyl-hydroxylation complex defects
- Other proteins involved in bone Bone Bone is a compact type of hardened connective tissue composed of bone cells, membranes, an extracellular mineralized matrix, and central bone marrow. The 2 primary types of bone are compact and spongy. Structure of Bones formation and homeostasis
| Type I | Type II | Type III | Type IV | |
|---|---|---|---|---|
| Mutated gene | COL1A1, COL1A2 (collagen type 1 alpha 1 and 2 chains) | COL1A1, COL1A2, and CRTAP ( cartilage Cartilage Cartilage is a type of connective tissue derived from embryonic mesenchyme that is responsible for structural support, resilience, and the smoothness of physical actions. Perichondrium (connective tissue membrane surrounding cartilage) compensates for the absence of vasculature in cartilage by providing nutrition and support. Cartilage-associated protein) | COL1A1, COL1A2 | COL1A1, COL1A2 |
| Inheritance modality | Autosomal dominant Autosomal dominant Autosomal inheritance, both dominant and recessive, refers to the transmission of genes from the 22 autosomal chromosomes. Autosomal dominant diseases are expressed when only 1 copy of the dominant allele is inherited. Autosomal Recessive and Autosomal Dominant Inheritance | Autosomal dominant Autosomal dominant Autosomal inheritance, both dominant and recessive, refers to the transmission of genes from the 22 autosomal chromosomes. Autosomal dominant diseases are expressed when only 1 copy of the dominant allele is inherited. Autosomal Recessive and Autosomal Dominant Inheritance AND autosomal recessive | Autosomal dominant Autosomal dominant Autosomal inheritance, both dominant and recessive, refers to the transmission of genes from the 22 autosomal chromosomes. Autosomal dominant diseases are expressed when only 1 copy of the dominant allele is inherited. Autosomal Recessive and Autosomal Dominant Inheritance | Autosomal dominant Autosomal dominant Autosomal inheritance, both dominant and recessive, refers to the transmission of genes from the 22 autosomal chromosomes. Autosomal dominant diseases are expressed when only 1 copy of the dominant allele is inherited. Autosomal Recessive and Autosomal Dominant Inheritance |
| Defect | Frameshift mutations in collagen type 1 alpha 1 and 2 chains leading to decreased amounts of normal collagen | Disrupted formation of the collagen triple helix structure, leading to little or no normal collagen | Mutations causing structural protein defects leading to severe pathology | Mutations causing structural protein defects leading to minimal or mild pathology |
Pathophysiology
- Mutations in alpha 1 or alpha 2 chains of type 1 collagen:
- Decreased amount of type 1 collagen (type I)
- Disruption of type 1 collagen triple helix (type II)
- Structural protein defects of type 1 collagen (type III and IV)
- Increased amounts of type III and IV collagen in bone Bone Bone is a compact type of hardened connective tissue composed of bone cells, membranes, an extracellular mineralized matrix, and central bone marrow. The 2 primary types of bone are compact and spongy. Structure of Bones tissue
- Increased activity of osteoclasts and abnormal osteoblast differentiation
- Poor deposition of hydroxyapatite crystals and paradoxic bone Bone Bone is a compact type of hardened connective tissue composed of bone cells, membranes, an extracellular mineralized matrix, and central bone marrow. The 2 primary types of bone are compact and spongy. Structure of Bones hypermineralization
- Globally abnormal bone Bone Bone is a compact type of hardened connective tissue composed of bone cells, membranes, an extracellular mineralized matrix, and central bone marrow. The 2 primary types of bone are compact and spongy. Structure of Bones growth: decreased bone Bone Bone is a compact type of hardened connective tissue composed of bone cells, membranes, an extracellular mineralized matrix, and central bone marrow. The 2 primary types of bone are compact and spongy. Structure of Bones trabeculae and cortical thickness
- Fractures with normal movement and very low-impact activities, with a normal healing process
Clinical Presentation
- Variable severity
- Type II die in utero or early infancy.
- Present to a
variable
Variable
Variables represent information about something that can change. The design of the measurement scales, or of the methods for obtaining information, will determine the data gathered and the characteristics of that data. As a result, a variable can be qualitative or quantitative, and may be further classified into subgroups.
Types of Variables extent in types I, III, and IV:
- Excess or atypical fractures
- Short stature
- Scoliosis Scoliosis Scoliosis is a structural alteration of the vertebral column characterized by a lateral spinal curvature of greater than 10 degrees in the coronal plane. Scoliosis can be classified as idiopathic (in most cases) or secondary to underlying conditions. Scoliosis
- Basilar skull Skull The skull (cranium) is the skeletal structure of the head supporting the face and forming a protective cavity for the brain. The skull consists of 22 bones divided into the viscerocranium (facial skeleton) and the neurocranium. Skull deformities (may cause nerve compression)
- Blue sclerae
- Hearing loss Hearing loss Hearing loss, also known as hearing impairment, is any degree of impairment in the ability to apprehend sound as determined by audiometry to be below normal hearing thresholds. Clinical presentation may occur at birth or as a gradual loss of hearing with age, including a short-term or sudden loss at any point. Hearing Loss
- Dentinogenesis imperfecta (opalescent teeth Teeth Normally, an adult has 32 teeth: 16 maxillary and 16 mandibular. These teeth are divided into 4 quadrants with 8 teeth each. Each quadrant consists of 2 incisors (dentes incisivi), 1 canine (dens caninus), 2 premolars (dentes premolares), and 3 molars (dentes molares). Teeth are composed of enamel, dentin, and dental cement. Teeth)
- Increased laxity of ligaments
- Wormian bones (small bones near cranial sutures)
- Easy bruising
| Type I | Type II | Type III | Type IV | |
|---|---|---|---|---|
| Description | Non-deforming with blue sclerae | Perinatally lethal | Progressively deforming | Variable with normal sclerae |
| Severity | Mild | Perinatal lethal | Severe | Mild to moderate |
| Fractures | < 100 | > 100 | > 100 | > 100 |
| Bone deformity | Uncommon | Severe | Moderate to severe | Mild to moderate |
| Stature | Normal to mildly reduced | Severely reduced | Reduced | Variable |
| Dentogenesis imperfecta | Variable | Common | Common | Variable |
| Color of sclerae | Blue | Dark blue | Blue | Normal to gray |
| Hearing loss Hearing loss Hearing loss, also known as hearing impairment, is any degree of impairment in the ability to apprehend sound as determined by audiometry to be below normal hearing thresholds. Clinical presentation may occur at birth or as a gradual loss of hearing with age, including a short-term or sudden loss at any point. Hearing Loss | Present in approximately 50% | — | Frequent | Variable |
Diagnosis
History
- History of fractures:
- Multiple and recurrent fractures during very low-impact activities (e.g., diaper change)
- Specific
bone
Bone
Bone is a compact type of hardened connective tissue composed of bone cells, membranes, an extracellular mineralized matrix, and central bone marrow. The 2 primary types of bone are compact and spongy.
Structure of Bones fractures:
- Olecranon process
- Transverse humerus
- Diaphyseal humerus
- Fractures before or during birth
- History of extra-skeletal symptoms:
- Hearing loss Hearing loss Hearing loss, also known as hearing impairment, is any degree of impairment in the ability to apprehend sound as determined by audiometry to be below normal hearing thresholds. Clinical presentation may occur at birth or as a gradual loss of hearing with age, including a short-term or sudden loss at any point. Hearing Loss
- Easy bruising
- Family history of the disease or findings suggestive of undiagnosed disease in relatives:
- Family history of multiple fractures
- Family history of extra-skeletal symptoms:
- Hearing loss Hearing loss Hearing loss, also known as hearing impairment, is any degree of impairment in the ability to apprehend sound as determined by audiometry to be below normal hearing thresholds. Clinical presentation may occur at birth or as a gradual loss of hearing with age, including a short-term or sudden loss at any point. Hearing Loss
- Dentinogenesis imperfecta
- Lack of family history does not rule out disease.
- History of child abuse Child abuse Child abuse is an act or failure to act that results in harm to a child's health or development. The abuse encompasses neglect as well as physical, sexual, and emotional harm. Seen in all subsets of society, child abuse is a cause of significant morbidity and mortality in the pediatric population. Child Abuse: important to rule out in cases of fractures
Physical examination
- Skeletal findings:
- Dentinogenesis imperfecta: translucent teeth Teeth Normally, an adult has 32 teeth: 16 maxillary and 16 mandibular. These teeth are divided into 4 quadrants with 8 teeth each. Each quadrant consists of 2 incisors (dentes incisivi), 1 canine (dens caninus), 2 premolars (dentes premolares), and 3 molars (dentes molares). Teeth are composed of enamel, dentin, and dental cement. Teeth with amber, blue, or gray coloration
- Genu varum Genu varum Genu varum is a deformation of the knee joint(s) that creates angulation of the lower limb(s) away from the midline in the coronal plane. Children ages 1-5 years are commonly affected. Genu Varum (bow legs): outward bowing at the knees
- Scoliosis Scoliosis Scoliosis is a structural alteration of the vertebral column characterized by a lateral spinal curvature of greater than 10 degrees in the coronal plane. Scoliosis can be classified as idiopathic (in most cases) or secondary to underlying conditions. Scoliosis
- Loose joints
- Limb deformity (particularly bowing of the femur)
- Extra-skeletal findings:
- Prolonged bleeding from injured areas
- Easy bruising
- Blue-colored sclera
- Breathing problems/fatigue
- Hypoacusia that can be conductive, sensorineural, or mixed (deficient ossification of the middle ear)
- Muscle weakness
- Short stature (more common in severe cases)
Blue-colored sclera associated with OI
Image: “Blue sclera” by the Department of Medical Oncology, Ankara University School of Medicine, 06300 Ankara, Turkey. License: CC BY 3.0.
Dentinogenesis imperfecta:
Image: “Anterior teeth Teeth Normally, an adult has 32 teeth: 16 maxillary and 16 mandibular. These teeth are divided into 4 quadrants with 8 teeth each. Each quadrant consists of 2 incisors (dentes incisivi), 1 canine (dens caninus), 2 premolars (dentes premolares), and 3 molars (dentes molares). Teeth are composed of enamel, dentin, and dental cement. Teeth showing brownish discoloring” by the Division of Oral Radiology, Department of Clinical Dentistry, Federal University of Ceará, Rua Alexandre Baraúna 949, 60430-160 Fortaleza, CE, Brazil. License: CC BY 3.0.
Anterior teeth Teeth Normally, an adult has 32 teeth: 16 maxillary and 16 mandibular. These teeth are divided into 4 quadrants with 8 teeth each. Each quadrant consists of 2 incisors (dentes incisivi), 1 canine (dens caninus), 2 premolars (dentes premolares), and 3 molars (dentes molares). Teeth are composed of enamel, dentin, and dental cement. Teeth show a brownish discoloration (upper dental arch (a), lower arch (b), and dental occlusion(c)).
Intraoral photograph showing yellowish discoloration and chipping of the dentition: A 4-year-old male child with OI (type IV)
Image: “Chipping of the dentition” by the Department of Oral Medicine and Radiology, AB Shetty Memorial Institute of Dental Sciences, Nitte University, Mangalore 575018, India. License: CC BY 3.0.
Infant with OI: Notice the deformity of the limbs, an indication of possible fractures during inspection.
Image: “Congenita A type of osteogenesis imperfecta” by the Maria Sklodowska Curie Clinical Emergency Hospital for Children, Bucharest, Romania. License: CC BY 2.0.
Laboratory testing
- Bloodwork:
- Usually normal
- Alkaline phosphatase may be increased.
- ↓ Markers of bone Bone Bone is a compact type of hardened connective tissue composed of bone cells, membranes, an extracellular mineralized matrix, and central bone marrow. The 2 primary types of bone are compact and spongy. Structure of Bones formation, ↑ markers of bone Bone Bone is a compact type of hardened connective tissue composed of bone cells, membranes, an extracellular mineralized matrix, and central bone marrow. The 2 primary types of bone are compact and spongy. Structure of Bones resorption
- Urine: Hypercalciuria with normal renal function may be present.
- Biopsy:
- Collagen: In vitro fibroblast culturing shows abnormal organization/structure.
- Bone histology:
- Shows disorganized bone Bone Bone is a compact type of hardened connective tissue composed of bone cells, membranes, an extracellular mineralized matrix, and central bone marrow. The 2 primary types of bone are compact and spongy. Structure of Bones structure
- Decreased size and number of bony trabeculae
- Increased osteoblasts and osteoclasts
- Genetic studies:
- No widely available commercial tests
- Genomic DNA DNA The molecule DNA is the repository of heritable genetic information. In humans, DNA is contained in 23 chromosome pairs within the nucleus. The molecule provides the basic template for replication of genetic information, RNA transcription, and protein biosynthesis to promote cellular function and survival. DNA Types and Structure testing for mutations in COL1A1 and COL1A2
- Prenatal testing:
- Chorionic villus sampling
- Amniocentesis
Imaging
- Prenatal ultrasound: evidence of bony deformities
- X-ray findings suggestive of OI:
- Multiple fractures in various states of healing
- Thin bone Bone Bone is a compact type of hardened connective tissue composed of bone cells, membranes, an extracellular mineralized matrix, and central bone marrow. The 2 primary types of bone are compact and spongy. Structure of Bones cortices and widened metaphysis
- Low bone Bone Bone is a compact type of hardened connective tissue composed of bone cells, membranes, an extracellular mineralized matrix, and central bone marrow. The 2 primary types of bone are compact and spongy. Structure of Bones density
- Bowed femurs
- “Wormian” bones
- “Codfish” vertebrae
- Saber shins
- Coxa vara
- Kyphoscoliosis
- Platyspondyly
| Type I | Type II | Type III | Type IV | |
|---|---|---|---|---|
| Skull radiographic findings | Intra-sutural bones | Undermineralization; calcified areas | Intra-sutural bones | Intra-sutural bones (sometimes) |
| Spine radiographic findings | Biconcave vertebrae (adults) | Widened vertebral bodies (platyspondyly) | Biconcave vertebrae; kyphoscoliosis | Biconcave vertebrae |
| Extremity radiographic findings | Thin cortices | Severely deformed femurs | Flared metaphyses, bowing, thin cortices | Thin cortices |
| Other radiographic findings | Osteopenia | Small, beaded ribs (pathognomonic) | Thin ribs, severe osteoporosis Osteoporosis Osteoporosis refers to a decrease in bone mass and density leading to an increased number of fractures. There are 2 forms of osteoporosis: primary, which is commonly postmenopausal or senile; and secondary, which is a manifestation of immobilization, underlying medical disorders, or long-term use of certain medications. Osteoporosis | Protrusio acetabuli in a subset |
Prenatal ultrasound diagnosing OI:
Image: “Prenatal ultrasound” by the Department of Bone and Osteogenesis Imperfecta, Kennedy Krieger Institution, Johns Hopkins University, Baltimore, MD, USA. License: CC BY 2.5.
This prenatal ultrasound at 22 weeks’ gestation shows bowing of the femur (the crosshairs show the extremities of the femur).
Radiograph showing OI:
Image: “Fig. 260” by Bryant, Joseph D. License: Public domain.
periosteal dysplasia, almost complete absence of cortical bone Bone Bone is a compact type of hardened connective tissue composed of bone cells, membranes, an extracellular mineralized matrix, and central bone marrow. The 2 primary types of bone are compact and spongy. Structure of Bones, and numerous fractures
Chest radiograph showing long and narrow thorax (barrel-shaped chest) with anterior compression
Image: “Barrel-shaped chest” by the Department of Oral Medicine and Radiology, AB Shetty Memorial Institute of Dental Sciences, Nitte University, Mangalore 575018, India. License: CC BY 3.0.
Radiograph of the lower limbs showing bowing of the femur, with widening of the metaphases:
Image: “Bowing of the femur” by the Department of Oral Medicine and Radiology, AB Shetty Memorial Institute of Dental Sciences, Nitte University, Mangalore 575018, India. License: CC BY 3.0.
a 4-year-old boy with OI (type IV)
Radiograph showing a bowing tibia and fibula (saber shins):
Image: “Radiograph showing bowing tibia and fibula” by the Department of Oral Medicine and Radiology, AB Shetty Memorial Institute of Dental Sciences, Nitte University, Mangalore 575018, India. License: CC BY 3.0.
a 4-year-old boy with OI (type IV)
Biconcave deformities in the lower thoracic and lumbar vertebrae in a 15-year-old patient with OI (“codfish” vertebrae)
Image: “Osteogenesis imperfecta” by the 1st Department of Orthopaedic Surgery, School of Medicine, University of Athens, “Attikon” Hospital, Rimini 1 Haidari 12462, Athens, Greece. License: CC BY 2.0.Radiographs of a 19-year-old woman with OI: Fragile bones, short trunk, severe kyphoscoliosis, and platyspondyly are noticed.
Image: “Biconcavity deformities” by the Department of Endocrine and Metabolic Diseases, Qilu Hospital, Shandong University, Jinan, Shandong 250012, P.R. China. License: CC BY 3.0.
Human skull Skull The skull (cranium) is the skeletal structure of the head supporting the face and forming a protective cavity for the brain. The skull consists of 22 bones divided into the viscerocranium (facial skeleton) and the neurocranium. Skull with wormian bones in a 21-year-old man
Image: “Wormian bones” by E. Barclay-Smith. License: Public domain.
Management
There is no definitive cure for OI.
Goals of therapy
- Reduce pain Pain Pain has accompanied humans since they first existed, first lamented as the curse of existence and later understood as an adaptive mechanism that ensures survival. Pain is the most common symptomatic complaint and the main reason why people seek medical care. Physiology of Pain
- Reduce fractures
- Reduce bone Bone Bone is a compact type of hardened connective tissue composed of bone cells, membranes, an extracellular mineralized matrix, and central bone marrow. The 2 primary types of bone are compact and spongy. Structure of Bones deformity
- Increase ambulation/independence
Lifestyle modifications
- Controlled weight carrying
- Safe exercises to improve muscle and bone Bone Bone is a compact type of hardened connective tissue composed of bone cells, membranes, an extracellular mineralized matrix, and central bone marrow. The 2 primary types of bone are compact and spongy. Structure of Bones strength
- Diet rich in calcium and vitamin D
- Avoidance of alcohol and caffeine
- Steroids are contraindicated.
- Avoidance of active or passive inhalation of cigarette smoke
Supportive management
- Casts and splints
- Braces
- Physical therapy
- Implantation of rods in legs or arms
- Dental workup
- Hearing aids
- Crowns for brittle teeth Teeth Normally, an adult has 32 teeth: 16 maxillary and 16 mandibular. These teeth are divided into 4 quadrants with 8 teeth each. Each quadrant consists of 2 incisors (dentes incisivi), 1 canine (dens caninus), 2 premolars (dentes premolares), and 3 molars (dentes molares). Teeth are composed of enamel, dentin, and dental cement. Teeth
- Mobility aids (e.g., crutches, canes, wheelchairs, walkers)
- Supplemental oxygen
- Genetic counseling for parents considering future pregnancies
Bisphosphonates (pamidronate)
- Inhibit bone Bone Bone is a compact type of hardened connective tissue composed of bone cells, membranes, an extracellular mineralized matrix, and central bone marrow. The 2 primary types of bone are compact and spongy. Structure of Bones turnover/resorption
- Have been shown to reduce fracture Fracture A fracture is a disruption of the cortex of any bone and periosteum and is commonly due to mechanical stress after an injury or accident. Open fractures due to trauma can be a medical emergency. Fractures are frequently associated with automobile accidents, workplace injuries, and trauma. Overview of Bone Fractures rates
- Long-term effect on other skeletal symptoms (scoliosis, deformity) is unclear.
Surgical therapy
- Fracture repair
- Deformity correction
Prognosis
- Severe functional limitation and decreased quality of life
- Type I cases can attain a full lifespan.
- Type II cases die prenatally or within the 1st year of life.
- Type III and IV cases require walking aids, but can attain household and community ambulation skills.
Differential Diagnosis
- Child abuse: defined by the U.S. government as “any recent act or failure to act on the part of a parent or caretaker, which results in death, serious physical or emotional harm, sexual abuse Sexual Abuse Sexual abuse and assault are major public health problems that affect many people from all walks of life, including people of all ages and genders, but it is more prevalent in women and girls, with reports of up to 1 in 3 experiencing sexual assault at some time in their life. Sexual Abuse or exploitation, or an act or failure to act which presents an imminent risk of serious harm.” Physically abused children may present with recurrent fractures and visits to the emergency department (ED). Old and recent signs of inflicted trauma are more indicative of the diagnosis of child abuse Child abuse Child abuse is an act or failure to act that results in harm to a child's health or development. The abuse encompasses neglect as well as physical, sexual, and emotional harm. Seen in all subsets of society, child abuse is a cause of significant morbidity and mortality in the pediatric population. Child Abuse.
- Rickets Rickets Rickets and osteomalacia are disorders of decreased bone mineralization. Rickets affects the cartilage of the epiphyseal growth plates in children. Although most cases of rickets are due to vitamin D deficiency, other genetic and nutritional disorders as well as medications can cause these disorders. Rickets commonly presents with skeletal deformities and growth abnormalities. Osteomalacia and Rickets: a disease of the growing bone Bone Bone is a compact type of hardened connective tissue composed of bone cells, membranes, an extracellular mineralized matrix, and central bone marrow. The 2 primary types of bone are compact and spongy. Structure of Bones caused by inadequate bone Bone Bone is a compact type of hardened connective tissue composed of bone cells, membranes, an extracellular mineralized matrix, and central bone marrow. The 2 primary types of bone are compact and spongy. Structure of Bones mineralization due to vitamin D deficiency. Rickets Rickets Rickets and osteomalacia are disorders of decreased bone mineralization. Rickets affects the cartilage of the epiphyseal growth plates in children. Although most cases of rickets are due to vitamin D deficiency, other genetic and nutritional disorders as well as medications can cause these disorders. Rickets commonly presents with skeletal deformities and growth abnormalities. Osteomalacia and Rickets presents with recurrent fractures, limb deformities, increased alkaline phosphatase, and dental abnormalities in some cases, but does not display hearing loss and blue sclerae.
- Osteomalacia Osteomalacia Rickets and osteomalacia are disorders of decreased bone mineralization. Osteomalacia affects the sites of bone turnover in children and adults. Although most cases are due to vitamin D deficiency, other genetic and nutritional disorders as well as medications can cause these disorders. Osteomalacia can present with bone pain, difficulty with ambulation and pathologic fractures. Osteomalacia and Rickets: a condition of decreased bone Bone Bone is a compact type of hardened connective tissue composed of bone cells, membranes, an extracellular mineralized matrix, and central bone marrow. The 2 primary types of bone are compact and spongy. Structure of Bones density in adults that tends to appear prior to the development of osteoporosis Osteoporosis Osteoporosis refers to a decrease in bone mass and density leading to an increased number of fractures. There are 2 forms of osteoporosis: primary, which is commonly postmenopausal or senile; and secondary, which is a manifestation of immobilization, underlying medical disorders, or long-term use of certain medications. Osteoporosis. Osteomalacia Osteomalacia Rickets and osteomalacia are disorders of decreased bone mineralization. Osteomalacia affects the sites of bone turnover in children and adults. Although most cases are due to vitamin D deficiency, other genetic and nutritional disorders as well as medications can cause these disorders. Osteomalacia can present with bone pain, difficulty with ambulation and pathologic fractures. Osteomalacia and Rickets shows fractures and increased alkaline phosphatase, but no hearing loss or blue sclerae.
- Paget’s disease of the bone Bone Bone is a compact type of hardened connective tissue composed of bone cells, membranes, an extracellular mineralized matrix, and central bone marrow. The 2 primary types of bone are compact and spongy. Structure of Bones: a disorder characterized by increased and abnormal remodeling of bone Bone Bone is a compact type of hardened connective tissue composed of bone cells, membranes, an extracellular mineralized matrix, and central bone marrow. The 2 primary types of bone are compact and spongy. Structure of Bones tissue that presents with fractures, bone Bone Bone is a compact type of hardened connective tissue composed of bone cells, membranes, an extracellular mineralized matrix, and central bone marrow. The 2 primary types of bone are compact and spongy. Structure of Bones deformity, bowing of long bones, increased alkaline phosphatase, and conductive hearing loss. However, 20% of cases are asymptomatic and diagnosis may be made incidentally as these patients are investigated for something else.
References
- Stankovits, L. M., M.D., & Lopyan, A.H., M.D., M.S. (2020). Genetic and metabolic conditions. Pediatric Clinics of North America, 67(1), 23-43. doi:http://dx.doi.org/10.1016/j.pcl.2019.09.005
- Marini, J. C. (2020). Osteogenesis imperfecta. In R. M. Kliegman MD, J. W. St Geme MD, N. J. Blum MD, Shah, Samir S., MD, MSCE, Tasker, Robert C., MBBS, MD & Wilson, Karen M., MD, MPH (Eds.), Nelson textbook of pediatrics (pp. 3736-3740.e1). https://www.clinicalkey.es/#!/content/3-s2.0-B9780323529501007215
- Forlino, A., PhD., & Marini, J.C., Dr. (2016). Osteogenesis imperfecta. Lancet, The, 387(10028), 1657-1671. doi:http://dx.doi.org/10.1016/S0140-6736(15)00728-X
- Prockop, D. J., & Bateman, J. F. (2018). Heritable disorders of connective tissue Connective tissue Connective tissues originate from embryonic mesenchyme and are present throughout the body except inside the brain and spinal cord. The main function of connective tissues is to provide structural support to organs. Connective tissues consist of cells and an extracellular matrix. Connective Tissue. In J. L. Jameson, A. S. Fauci, D. L. Kasper, S. L. Hauser, D. L. Longo & J. Loscalzo (Eds.), Harrison’s principles of internal medicine, 20e (). New York, NY: McGraw-Hill Education. accessmedicine.mhmedical.com/content.aspx?aid=1160017759
- Forlino, A., Cabral, W. A., Barnes, A. M., & Marini, J. C. (2011). New perspectives on osteogenesis imperfecta. Nature reviews. Endocrinology.
- Moscote-Salazar, L. R., Koller, O., Valenzuela, S., Narvaez-Rojas, A., Satyarthee, G. D., Mo-Carrascal, J., & Maraby, J. (2018). Neurosurgical Implications of Osteogenesis Imperfecta in a Child after Fall: Case Illustration. Journal of pediatric neurosciences, 13(4), 459–461.
- Dubowitz, H., & Lane, W. G. (2020). Abused and neglected children. In R. M. Kliegman MD et al., Nelson textbook of pediatrics (pp. 98-111.e1). https://www.clinicalkey.es/#!/content/3-s2.0-B978032352950100016X
- Greenbaum, L. A. (2020). Vitamin D deficiency (rickets) and excess. In R. M. Kliegman MD et al., Nelson textbook of pediatrics (pp. 375-385.e1). doi:http://dx.doi.org/10.1016/B978-0-323-52950-1.00064-X. Retrieved from https://www.clinicalkey.es/#!/content/3-s2.0-B978032352950100064X
- Ralston, S. H. (2020). Paget disease of bone Bone Bone is a compact type of hardened connective tissue composed of bone cells, membranes, an extracellular mineralized matrix, and central bone marrow. The 2 primary types of bone are compact and spongy. Structure of Bones. In L. Goldman MD, & A. I. Schafer MD (Eds.), Goldman-Cecil medicine (pp. 1623-1626.e2). https://www.clinicalkey.es/#!/content/3-s2.0-B9780323532662002332
- Marini, J.C. (2004). Osteogenesis imperfecta: Comprehensive management. Adv Pediatr. 1988;35:391-426. PMID: 3055864.
- Niyibizi, C., Wang, S., Mi MI MI is ischemia and death of an area of myocardial tissue due to insufficient blood flow and oxygenation, usually from thrombus formation on a ruptured atherosclerotic plaque in the epicardial arteries. Clinical presentation is most commonly with chest pain, but women and patients with diabetes may have atypical symptoms. Myocardial Infarction, Z. et al. (2004). Gene therapy approaches for osteogenesis imperfecta. Gene Ther 11, 408–416. https://doi.org/10.1038/sj.gt.3302199
- Steiner, R.D., Pepin, M.G., & Byers, P.H. (2005). Osteogenesis Imperfecta. Gene Reviews at GeneTests: Medical Genetics Genetics Genetics is the study of genes and their functions and behaviors. Basic Terms of Genetics Information Resource.
