Skeletal Disorders Flashcards
Bone matrix is osteoid made of this
Type I collagen
These cells form new bone on surface of osteoid
Osteoblasts
These cells become osteocytes when senescent
Osteoblasts
These cells secrete acids into resorption pit to absorb bone and release calcium
Osteoclasts
Osteoclasts are derived from this
Hematopoietic cells, monocyte/macrophage
Type of bone formation that occurs in long bones
Endochondral
Fibroblast growth factor 3 promotes differentiation of these
Chondrocytes
Type of bone formation where growing cartilage at epiphyseal plates have provisional mineralization
Apoptotic chondrocytes are replaced by ingrowth of osteoblasts
Endochondral
Fibroblast growth factor 3 promotes this type of bone formation
Endochondral
Type of bone formation that occurs in flat bones
Intramembranous
Type of bone formation where mesenchymal cells differentiate into osteoblasts and pre-existing matrix undergoes mineralization
Intramembranous
Before remodeling, initial bone is of this type
Woven
These cells are activated by WNT/Beta-catenin signaling
Osteoblasts
Calcium deposition is mediated by this
Alkaline phosphatase
Alkaline phosphatase mediates the deposition of this
Calcium
Osteoblasts are activated by signaling of this
WNT/Beta-catenin
Parathyroid hormone stimulates these cells
Osteoclasts
Stimulation of RANK receptor activates these cells
Osteoclasts
Osteoclasts are activated by stimulation of this receptor
RANK
These cells are activated by M-CSF
Osteoclasts
What effect does estrogen have on bone mass?
Is protective
What effects does Vitamin D have on Calcium?
Increases renal Ca reabsorption
Increases bone deposition of Ca
Vitamin D increases bone deposition of Ca via osteoblast production of this calcium binding protein
Osteocalcin
This increases bone deposition of Ca via osteoblast production of the Ca binding protein osteocalcin
Vitamin D
Vitamin D increases bone deposition of Ca via these cells producing osteocalcin (Ca binding protein)
Osteoblast
Alkaline phosphatase is increased when this is occuring
Increased in bone deposition/turnover
E.g. tumor
What effect does Parathyroid Hormone have on bone resorption?
Causes bone resorption
These are precursors to osteoblasts
Mesenchymal cells
Osteoblasts or Osteoclasts?:
Eccentric nuclei
Osteoblasts
Osteoblasts or Osteoclasts?:
On osteoid surface
Osteoblasts
Osteoblasts or Osteoclasts?:
Mineralize bone with alkaline phosphatase
Osteoblasts
Osteoblasts or Osteoclasts?:
Osteocyte is senescent form
Osteoblasts
Osteoblasts or Osteoclasts?:
Monocytes are precursors
Osteoclasts
These are precursors to Osteoclasts
Monocytes
Osteoblasts or Osteoclasts?:
Multinucleated
Osteoclasts
Osteoblasts or Osteoclasts?:
Form resorption pits
Osteoclasts
Osteoblasts or Osteoclasts?:
Release Ca and P into serum
Osteoclasts
Type of bone:
Newly formed bone, disorganized, not as strong
woven bone
Type of bone:
Mature bone after remodeling, increased strength, compact bone cortex, cancellous in medullary cavity
Lamellar bone
Bone marrow fills this part of bone
Medullary cavity
What effect does RANK/RANK-L have on bone?
Stimulates bone resorption by osteoclasts
RANK/RANK-L stimulates bone resorption by these
Osteoclasts
Decoy molecule that inhibits bone resorption
Protects bone
Osteoprotegerin
This promotes osteoclast mediated bone resorption via increased RANK/RANK-L
PTH
This decreases RANK/RANK-L, increases osteoprotegerin
Estrogen
Most common form of dwarfism
Achondroplasia
Inheritance pattern of Achondroplasia
Autosomal dominant
Condition caused by a gain of function in FGF3 receptor
Most are new sporadic paternal mutations (advanced paternal age)
Achondroplasia
Gain of function in this can cause Achondroplasia
FGF3
What effect does Achondroplasia have on long bones?
Promotes endochondral ossification, so there is presence of shortened long bones - short extremities
Normal flat bones
More severe, lethal form of dwarfism
Thanatophoric dysplasia
What causes Achondroplasia?
Gain of function in FGF3 receptor
What causes Thanatophoric dysplasia?
Gain of function FGF3 mutation with greater effect
This condition has similar features as Achondroplasia, but death occurs in neonatal period due to respiratory insufficiency
Thanatophoric dysplasia
What causes Osteogenesis Imperfecta?
Switch of glycine with non-gly amino acid in type I collagen
Impairs formation of triple helix
Condition caused by a switch of glycine with a non-gly amino acid in collagen, impairing the formation of the triple helix
Osteogenesis Imperfecta
What type of collagen is affected in Osteogenesis Imperfecta?
Type I
What is the inheritance pattern of Osteogenesis Imperfecta?
Dominant negative
Condition that is also called Brittle bone disease
Osteogenesis Imperfecta
Condition where fusion of conductive ossicles may occur, leading to conductive hearing loss
Osteogenesis Imperfecta
Condition that can have thin, transparent sclera with visualization of underlying choroid vasculature = blue sclera
Osteogenesis Imperfecta
Blue sclera is seen in this condition
Osteogenesis Imperfecta
Diffuse skeletal sclerosis due to defective osteoclast absorption
Osteopetrosis
Osteopetrosis is diffuse skeletal sclerosis due to a defect in this
Osteoclast absorption
Condition where defective osteoclast absorption results in no bony remodeling
Osteopetrosis
Carbonic Anhydrase deficiency may cause this skeletal condition
Osteopetrosis
Why can Carbonic Anhydrase deficiency cause Osteopetrosis?
Deficiency results in lack of acidic environment in resorption pit
(also results in renal tubular acidosis)
Condition were there is a lack of bone resorption, so bone is DENSE
Osteopetrosis
Condition where neural foramen may be occluded, causing cranial nerve defects
Osteopetrosis
Condition where there is extremely sclerotic bone with no medullary cavity for hematopoiesis, leading to low platelet, WBC, etc. counts
Osteopetrosis
What is the treatment for Osteopetrosis?
Bone marrow transplant
What are the levels of platelets and WBCs in Osteopetrosis?
Low
Extremely sclerotic bone has no medullary cavity for hematopoiesis
Extramedullary hematopoiesis may occur
Condition described by a bone density less than 2.5 std below mean peak bone density of young adults
Osteoporosis
What race is most affected by Osteoporosis?
Caucasians
Much less common in African races
Risk of Osteoporosis is determined by these two factors
Peak bone mass at early adulthood
Rate of age-related bone loss
Primary or secondary Osteoporosis?:
Senile - males especially
Post-menopausal (estrogen deficiency)
Primary
Primary or secondary osteoporosis:
Can be caused by hyperparathyroidism, neoplasm, intestinal disorders with malabsorption, chronic steroid use, hypogonadism
Secondary Osteoporosis
Chronic steroid use increases risk of this condition
Secondary Osteoporosis
Condition where there is normal bone but less of it
Most significant change at lumbar/thoracic vertebral bodies
Osteoporosis
What are the levels of Ca, PTH, and Alkaline phosphatase in Osteoporosis?
All normal
Biphosphonates inhibit these and can be used as treatment for Osteoporosis
Osteoclasts
Biphosphonates inhibit osteoclasts and can be used as treatment for this condition
Osteoporosis
Condition characterized by normal amount of bone matrix but inadequate mineralization
Rickets/Osteomalacia
Usually caused by Vitamin D deficiency
In children, does Rickets affect endochondral or membranous bone?
Both
What are the levels of Ca, Phosphate, Alk phos, and PTH in Rickets/Osteomalacia?
Low/normal Ca
Low phosphate
High alk phos
High PTH
Normal levels of Ca, PTH, and alk phos but with low bone density indicate this condition
Osteoporosis
Low/normal levels of Ca, low phosphate, and high Alk phos and PTH are typical labs seen in this condition
Rickets/Osteomalacia
Epiphyseal cartilage overgrowth due to inadequate mineralization and failure of chondrocyte maturation is seen in this condition
Rickets
Growth plate cartilage and osteoid continues to expand laterally but does not mineralize or mature into bone is seen in this condition
Rickets
Skeletal deformation due to lack of structural rigidity is seen in this condition
Windswept deformity, bowing of legs (varus and valgum deformities), Pigeon breast, lumbar lordosis
Rickets
Condition where radiographs show widening of growth plates and fraying of collagen
Rickets
Fraying of cartilage as seen on radiograph indicates this condition
Rickets
Looser zones that are transverse areas of lucency due to microfractures and/or vascular channel erosion are seen on radiograph in this condition
Rickets
A row of beadlike prominences at the junction of a rib and its cartilage (i.e., enlarged costochondral joints), resembling a rosary, is seen in this condition
Rickets
Most characteristic diagnostic features of Rickets are seen in this type of bone
Long bones
Does still affect bones with intramembranous ossification though (frontal bossing of skull)
Vitamin D dependent rickets (type 1) is caused by a deficiency in this
1 alpha hydroxylase
A deficiency in 1 alpha hydroxylase causes this condition
Vitamin D dependent rickets (type 1)
Inheritance pattern of Vitamin D dependent rickets (type 1)
Autosomal recessive
Vitamin D dependent rickets (type 1) involves this gene
CYP2R1
CYP2R1 gene is involved in this condition
Vitamin D dependent rickets (type 1)
Type of Rickets where patients develop the condition by age 1 year
Vitamin D dependent rickets (type 1)
Vitamin D supplements help this type of Rickets
Vitamin D dependent rickets (type 1)
Type of Rickets caused by VDR mutations (Vit D receptor)
Vitamin D dependent rickets (type 2)
Mutations in VDR (Vit D receptor) cause this condition
Vitamin D dependent rickets (type 2)
Inheritance pattern of Vitamin D dependent rickets (type 2)
Autosomal recessive
Type of Rickets where patients develop the condition in adolescence usually
Vitamin D dependent rickets (type 2)
When do patients with Vitamin D dependent rickets (type 2) develop the condition?
In adolescence usually
When do patients with Vitamin D dependent rickets (type 1) develop the condition?
By age 1 year
IV calcium helps this type of Rickets
Vitamin D dependent rickets (type 2)
Type of Rickets caused by PHEX mutation on X chromosome
X-linked hypophosphatemia (Vit D resistant Rickets)
PHEX mutation on the X chromosome causes this condition
X-linked hypophosphatemia (Vit D resistant Rickets)
What are the levels of Ca and phosphate in X-linked hypophosphatemia (Vit D resistant Rickets)?
Normal/high Ca
VERY LOW phosphate
What are the levels of Alk Phos and PTH in X-linked hypophosphatemia (Vit D resistant Rickets)?
HIGH alk phos
normal PTH
What is the effect of X-linked hypophosphatemia (Vit D resistant Rickets) on males?
Early rickets
What is the effect of X-linked hypophosphatemia (Vit D resistant Rickets) on females?
Isoalted hypophosphatemia usually
2 supplements used to treat X-linked hypophosphatemia (Vit D resistant Rickets)
1,25 dihydroxy vitamin D and phosphate
Loss of 1ɑ hydroxylase activity in proximal renal tubules leads to this
Chronic renal disease
Condition where renal dysfunction leads to loss of phosphate, glucose, bicarbonate, amino acids
Results in renal tubular acidosis (Rickets/osteomalacia)
Fanconi syndrome
Fanconi syndrome can lead to this condition due to its associated hypophosphatemia
Rickets/osteomalacia
Condition of inadequate mineralization of bone in remodeling of mature skeleton due to low Vitamin D
Osteomalacia
Areas of overgrowth in weak bones are seen in Rickets or Osteomalacia?
Rickets
Morphological widening of osteoid seams (gap between new collagen and zone of mineralization) is seen in this condition
Osteomalacia
This condition causes excess production of PTH resulting in excess bone resorption
Hyperparathyroidism
Hyperparathyroidism causes excess production of this, resulting in excess bone resorption
PTH
Type of Hyperparathyroidism due to autonomous (neoplastic) secretion
Primary
Type of neoplasm that most commonly causes primary Hyperparathyroidism
Parathyroid adenoma
Levels of calcium in Primary Hyperparathyroidism
High
Type of Hyperparathyroidism that is a response to renal loss of calcium in chronic renal disease
Secondary
Levels of calcium in Secondary Hyperparathyroidism
Low
Low Ca leads to high PTH, which compensates and causes normalish Ca
Type of Hyperparathyroidism that is a secondary form which has become autonomous
Tertiary
Level of alk phos in Hyperparathyroidism
High
Brown tumors of bone are complications of this condition
Hyperparathyroidism
Microfractures resulting in reactive hypervascularity, hemorrhage and fibrosis and osteoclast accumulation
Brown tumors
Seen in Hyperparathyroidism
Osteoporosis with cystic change
Form brown tumors (due to hemosiderin)
Seen in Hyperparathyroidism
Osteitis Fibrosa Cystica
Osteitis Fibrosa Cystica is a complication of this condition
Hyperparathyroidism
Constellation of skeletal changes due to chronic renal failure
Renal Osteodystrophy
Secondary hyperparathyroidism, osteopenia/osteoporosis, and osteomalacia are changes due to chronic renal failure seen in this condition
Renal Osteodystrophy
How does secondary hyperparathyroidism occur due to renal failure in Renal Osteodystrophy?
- renal Ca loss secondary to tubular dysfunction
- compensatory PTH secretion
- Ca/P resorbed from bone = fibrosis and cyst formation (Osteitis Fibrosa Cystica)
How does Osteopenia/osteoporosis result from chronic renal failure in Renal Osteodystrophy?
1 of 3 ways:
1. high PTH
2. renal Ca loss
3. renal tubules don’t excrete H+ (= metabolic acidosis = Ca is resorbed as a buffer)
Generalized loss of Ca from bone
How does Osteomalacia result from Renal Osteodystrophy?
Renal failure results in inability to convert inactive Vitamin D to active 1,25 Vitamin D form
(leads to inability to mineralize osteoid)
Condition characterized by increased, but dysfunctional, bone mass due to increased osteoclast activity and osteoblast response
Paget disease
Condition where morphology shows bone resorption with increased numbers of large, multinucleated osteoclasts
Paget disease
Condition characterized by bone deposition without remodeling
Paget disease
Condition characterized by thick lamellar bone with prominent cement lines
Paget disease
Thick lamellar bone with prominent cement lines are seen in this condition
Paget disease
Mosaic pattern of lamellar bone is seen in this condition
Paget disease
Morphology of Paget disease involves increased numbers of this cell type with increased numbers of nuclei
Osteoclasts
Do osteoblasts or osteoclasts initially have increased activity in Paget disease?
Osteoclasts
Then compensatory increase of osteoblast activity
Condition that may initially be due to osteoclastic viral infection or increased RANK or NFk-B activity
Paget disease
Condition characterized by the following 3 phases:
Osteolytic, Mixed osteoclastic-osteoblastic, osteosclerotic
Paget disease
Condition involving:
1. increased osteoclast activity and bone resorption
2. compensatory increased osteoblast activity and bone deposition
3. burnt out osteoclasts with continued bone deposition by osteoblasts
Paget Disease
In Paget disease, there is increased bone density with no remodeling, leading to this type of bone
Weaker woven bone
Radiographs showing thickened cortices, cotton wool appearance and bowing of weight bearing bones is seen in this condition
Paget disease
Cotton wool appearance of bones seen radiographically are characteristic of this condition
Paget disease
A patient with a history of increasing hat size or hearing loss may have this condition
Paget disease
Paget disease is relatively common in these populations
European/Anglo
Bone enlargement and weakness are seen in this condition
Also bowing of weight bearing bones and compression of nerve roots or cranial contents
(skull, femur, axial skeleton are common sites)
Paget disease
Levels of Alk phos in Paget disease
Elevated
Levels of Ca and P in Paget disease
Both normal
Osteosarcoma and Osteoblastic hypermetabolic state are complications of this condition
Paget disease
Complication of Paget disease due to increased blood flow requirement causing increased demand on heart
Exacerbates heart disease and may produce high output cardiac failure in extensive disease
Osteoblastic hypermetabolic state
This condition may exacerbate heart disease and produce high output cardiac failure in extensive disease
Paget disease
Rupture of blood vessels forms this during healing of a fracture
Hematoma
In the healing of a fracture, formation of granulation tissue produces this scaffold
Fibrin scaffold
Fibroblasts, WBCs, capillaries grow into hematoma
During fracture healing, osteoid is deposited similar to this type of ossification during the formation of soft callus
Intramembranous
During fracture healing, chondroid matrix is ossified similar to this type of ossification during the formation of soft callus
Endochondral
This is the final stage of fracture healing
Remodeling
Why is resumption of weight bearing so critical during healing of fractures?
Non-stressed parts of callus are resorbed
Stressed parts of callus are remodeled to new lamellar bone
Physical stress on bone helps bone remodel to produce new bone
In a fracture with non-union, ingrowth of synovium may produce this
Pseudoarthrosis
Type of fracture:
Overlying skin is intact
Simple (closed)
Type of fracture:
Bone communicates with skin surface
Risk of osteomyelitis
Compound (open)
Type of fracture:
Bone is fragmented
Comminuted
Type of fracture:
Fracture along long axis
Associated with torsional injuries
Spiral
Type of fracture:
Fracture due to axial load
Compression (impacted)
Type of fracture:
Fracture perpendicular to long axis
Transverse
Type of fracture:
Tendinous insertion pulled off bone
Avulsion
Type of fracture:
Ends of bone are not aligned
Displaced
Type of fracture:
Slow developing fracture due to repeated trauma and microfractures
Stress
Type of fracture:
Fracture extends partially through bone
Mostly in pediatrics
Greenstick
Why is it called a Greenstick fracture?
Fracture extends partially through bone
Like a green twig - bends but does not break through full thickness
Type of fracture:
Fracture of bone weakened by underlying bone disease
Pathologic
Infarction of bone and marrow
Avascular necrosis
Aka Osteonecrosis
What is the most common site of Avascular necrosis?
Femoral head
Avascular necrosis resolves with this, resulting in dense bone seen on radiology
Ingrowth of new bone
Avascular necrosis is repaired by this
Creeping substitution
Condition with empty lacunae, bone that often appears denser, and subchondral linear lucency later
Avascular necrosis
How does bone appear in Avascular necrosis?
Often appears denser
Subchondral linear lucency later
Idiopathic avascular necrosis of femoral head epiphysis
Legg-Calve-Perthes Disease
Who is more likely to have Legg-Calve-Perthes Disease, male or female?
Male, 4:1
What does a patient with Legg-Calve-Perthes Disease present with?
Limp +/- pain
Pain often present at thigh or knee
What is the treatment for Legg-Calve-Perthes Disease?
Leg immobilization
Allows remineralization so that femoral head heals to conform to shape of acetabulum
Legg-Calve-Perthes Disease is idiopathic avascular necrosis of this
Femoral head epiphysis
Legg-Calve-Perthes Disease is uncertain etiology of this
Avascular necrosis
Infection of bone and bone marrow
Osteomyelitis
2 routes by which Osteomyelitis may occur
Hematogenous
Direct extension or traumatic implantation
This is the most common route of Osteomyelitis in pediatrics
Hematogenous
This is the most common location of Osteomyelitis in pediatrics
Metaphysis (due to slowing of circulation)
Most common organism that causes Osteomyelitis in pediatrics
S. aureus
Direct extension causing Osteomyelitis in pediatrics may occur with these 2 things
Otitis, open fractures
Most common route of Osteomyelitis in adults
Direct extension
Hematogenous route of Osteomyelitis in adults tends to occur in this part of the body
Vertebra (bodies)
Most common organism that causes Osteomyelitis in all populations
S. aureus
Common organism that causes Osteomyelitis in IV drug users
S. aures
Common organism that causes Osteomyelitis in Sickle Cell anemia
Salmonella
Salmonella can cause Osteomyelitis in patients with this
Sickle Cell anemia
3 Common organisms that cause Osteomyelitis in UTI/GI
E. coli
Pseudomonas
Klebsiella
Common organism that causes Osteomyelitis in Potts disease
M. tuberculosis involvement of vertebra
M. tuberculosis involvement of vertebra is a common cause of Osteomyelitis in patients with this
Potts disease
Necrotic focus of infected bone as seen in Osteomyelitis
Sequestrum
Sclerotic reactive bone that surrounds sequestrum, as seen in Osteomyelitis
Involucrum
Complication of Osteomyelitis that is a persistent infection in an involucrum
Brodie Abscess
Brodie Abscess is a persistent infection in an involucrum and is a complication of this
Osteomyelitis
Condition where radiology may show lucency with surrounding sclerosis or dense central nidus
Osteomyelitis
This may become Chronic Osteomyelitis
Due to inadequate antibiotic duration or type, inadequate debridement, delayed diagnosis
Pyogenic Osteomyelitis
Brodie abscess/sequestrum may form and recur, sometimes decades later, from this condition
Chronic Osteomyelitis
Draining sinuses, AA amyloidosis, and malignancy are complications of this
Chronic Osteomyelitis
AA amyloidosis is a complication of this condition
Chronic Osteomyelitis
This is the most common, classic location for Tuberculosis Osteomyelitis
Vertebral bodies
This condition is more destructive and difficult to eradicate that pyogenic osteomyelitis
Tuberculosis Osteomyelitis
Type of Osteomyelitis established by metastatic spread, usually from lung
Tuberculosis Osteomyelitis
Long term infection with Osteomyelitis may result in malignancy, such as this
Squamous cell carcinoma of draining sinus tract
Squamous cell carcinoma of draining sinus tract is a malignancy that can be a complication of this condition
Chronic Osteomyelitis
Potts disease is another name for this
Tuberculosis Osteomyelitis
