Genetic & Metabolic Bone Disorders Flashcards
What are the two general components of bone?
Organic and inorganic
What are the components of the organic component of bone?
Cells and matrix proteins
What are the cells that are in the organic part of bone? (4)
Osteoprogenitor cells
Osteoblasts
Osteocytes
Osteoclasts
What are the components of the matrix in organic bone?
Collagen type I
Non-collagenous proteins
What is the main component of inorganic bone?
calcium hydroxyapatite
What is unmineralized bone called?
Osteoid
What are osteoprogenitor cells?
Pluripotential mesenchymal cells that can form osteoblasts
What is the function of osteoblasts?
Synthesize and transport protein and osteoprotegerin, and initiate mineralization
What is the function of the RANK-L protein?
receptor on osteoblasts that binds to RANK receptor on osteoclasts to stimulate osteoclastic bone resorption
What is the precursor cell to osteoclasts?
Hematopoietic progenitor cells (fused monocytes/ Macrophages)
What is the role of osteoprotegerin?
Decoy receptor for RANKL, to prevent osteoclast activation
What are osteocytes? What is their function?
- Osteoblasts that have become surrounded by matrix
- Regulate daily serum Ca levels
How do osteoclasts appear histologically?
Multiple nuclei
Where is osteoprotegerin found?
Osteoclasts
How do osteocytes communicate with one another?
canaliculi
What is osteoid?
Unmineralized organic matrix that is lined by osteoblasts
What are the lacunae in which osteoclasts reside?
Howship lacunae
What part of the bone do osteoclasts not resorb?
Bone lined by osteoid or unmineralized cartilage
What is woven bone and laminar bone?
Woven bone = Collagen deposited in a random arrangement
Lamellar bone = bone deposited in an orderly, parallel arrangement
Where is woven bone usually present?
Fetal skeleton, at the growth plates, and in processes where there is very rapid bone production
True or false: Woven bone is almost always pathologic in adults
True
Where is lamellar bone located?
Only type of bone in adults
What are the 4 types of lamellar bone?
- Concentric
- Interstitial
- Inner circumferential
- Outer circumferential
Which is more sturdy–lamellar bone or woven bone?
Lamellar bone
What type of bone comprises calluses?
Woven bone
What are the causes of woven bone deposition in adults?
- calluses
- Fibrous dysplasia
- Areas surrounding tumors or infection
Which has more osteocytes: woven or lamellar bone?
Lamellar bone
What is an osteon?
Haversian canal + surrounding circular lamellar bone
What lines woven bone?
Osteoblasts
What are type I - IV of collagen?
I = bone II = cartilage III = reticular IV = BM
What, generally, is achondroplasia?
Fusion of the epiphyseal plates before full maturity
What is the genetic cause of achondroplasia?
Reduction in the proliferation of chondrocytes in developing growth plates d/t pt mutation in FGFR3
What is the normal role of FGFR3?
Inhibition of normal proliferation of chondrocytes at the growth plate (this is constitutively active in achondroplasia)
True or false: achondroplasia is usually inherited
false–most are sporadic mutations
If achondroplasia is inherited, what inheritance pattern does it follow?
AD
True or false: homozygotes for FGFR3 mutation is lethal
True–Small chest wall = respiratory failure
What happens to the ones of proliferation in achondroplasia?
hypertrophied, narrowed, and disorganized
Which bones are usually short in achondroplasia?
All bones from formed cartilage
True or false: mental and reproductive development in achondroplasia is usually normal
True
What happens to the trunk with achondroplasia?
Normal length
What are the five zones of normal epiphyseal plate growth?
- Reserve zone
- proliferation
- hypertrophy
- Mineralization
- Spongiosa
What happens to the zones of epiphyseal plates with achondroplasia?
Disorganization with transverse bars of bone sealing of plate growth
How is the head relative to the rest of the body with achondroplasia?
Enlarged with frontal bossing
What is the defect with osteogenesis imperfecta?
Abnormalities of type I collagen synthesis results in extreme bone fragility and thinning of bone cortex and trabeculae
What is the genetic cause of osteogenesis imperfecta, and what is the inheritance pattern?
Mutations in alpha 1 and 2 collagen chains
AD
What is type I OI?
increased risk of fracture, but is usually not deforming
What is type II OI?
Lethal–multiple fractures in utero with fetal demise
What is OI type III and IV?
Progressive deformities
What happens to the bone with OI?
Thinning of the cortex and trabeculae, with reduced numbers of trabeculae
What are the eye findings with OI?
Blue sclerae
What are the dental findings of patients with OI?
Amber, yellowish brown or translucent
What may happen to hearing with OI?
Decreased
True or false: patients with OI have a normal survival rate
True
What happens to the bones in type III and IV OI?
Bowing and breaking
What is osteopetrosis?
Marble bone disease–group of genetic diseases caused by decreased osteoclastic bone resorption, leading to diffuse skeletal sclerosis
What is the inheritance pattern of Osteopetrosis?
AR malignant
AD benign
What is the major cellular issue with osteopetrosis?
Defective osteoclastic activity, leading to abnormally thickened, heavily mineralized, and brittle bone
What causes the hematological abnormalities with osteopetrosis?
Encroachment on the bone marrow leads to reduced cellular proliferation
What are the features of the clinical presentation of osteopetrosis?
- Anemia/ thrombocytopenia
- Increased fractures
- CN palsies from compression
- Increased infx susceptibility
What is the role of bone marrow transplant with osteopetrosis?
helpful–provides progenitor cells which produce normal osteoclasts, which can reverse many of the skeletal abnormalities
What are the primary causes of osteoporosis?
Menopause
Age
What are the common secondary causes of osteoporosis?
Glucocorticoid induced
Immobilization induced
What, generally, is the pathophysiology of osteoporosis?
Reduction of bone mass
What are the histological findings of osteoporosis?
- Cortex and trabeculae are thinned, but remain of normal composition
- Increase porosity of the bone
By the time you’re able to diagnose osteoporosis be x-ray, what percent of bone is lost?
40%
What bones are particularly affected with osteoporosis?
Trabecular bone, such as, weight bearing bones
what is the role of estrogen in preventing bone formation?
- Increased production of osteoprotegerin
- Increase in collagen synthesis by osteoblasts
What happens when estrogen levels fall with bone formation?
- Increased production of RANKL
- Decreased osteoprotegerin
What are wedge fractures?
When the anterior column of the vertebral body is compressed, leading to kyphosis, but usually with preservation of the spinal cord
What are burst fractures?
Axial load disrupts the anterior, middle, and/or posterior columns, frequently leading to disruption of the spinal cord
What happens to the vertebral bodies with osteoporosis?
Shorten
How do glucocorticoids cause osteoporosis? (3)
Increase in osteoclast survival, decrease in osteoblastogenesis, and increased apoptosis of osteocytes
What causes rickets and osteomalacia?
Defective mineralization caused by vit D deficiency
What is the effect of rickets in children?
heaping of unmineralized matrix leads to softening of bones and increased fractures
What are the causes of Vit D deficiency in the developed world?
malabsorption syndromes
Liver/kidney disease
What are the s/sx of osteomalacia?
- generalized pain
- fractures
- Mottled areas of bone lucency
What are the s/sx of rickets?
- bowing of the legs
- Frontal bossing
- Pectus carinatum
What is the Rachitic rosary? What causes it?
- The prominent knobs of bone at the costochondral joints of rickets patients
- Bones grow in thickness, but not length
What happens histologically with osteomalacia?
More osteoid, causing a more malleable bone
