Bones, Joints and Soft Tissues Flashcards
1
Q
What type of collagen is found in the bone matrix?
A
Type I collagen
2
Q
What specific protein is found in bone?
A
osteopontin
aka osteocalcin
3
Q
What type of cell creates osteopontin (osteocalcin) that is found in bone?
A
osteoblasts
4
Q
What are the three major functions of osteoblasts?
A
- CALCIUM HOMEOSTASIS
- bone formation
- mineralization
5
Q
True or False: osteopontin (aka osteocalcin) is a sensitive and specific serum test that can be done to detect osteoblast activity.
A
True
6
Q
What inorganic compound is responsible for a bone’s hardness?
A
hydroxyapatite
7
Q
Bones harbor the majority of these two elements in the body.
A
- 99% of body’s calcium
- 85% of body’s phosphorus
8
Q
What are the two histologic forms of bone?
A
Woven: produced rapidly, fetal development, fracture repair; haphazard arrangement of collagen; abnormal finding in adults
Lamellar: slow production, parallel collagen, stronger
9
Q
What are osteocytes and their main role?
A
-inactive osteoblasts with decreased cytoplasm that are embedded in the matrix
- control calcium and phosphorus levels
- detect mechanical force and translate it to bioactivity
10
Q
What are canaliculi in the bone?
A
-tunnels that osteocyte dendritic processes use to network
11
Q
What are osteoclasts and their main role?
A
- MULTINUCLEATED macrophages derived from circulating monocytes
- bone resorption
12
Q
Describe how osteoclasts perform their bone resorption.
A
- in the resorption pit, osteoclasts utilize cell surface INTEGRINS to attach which creates a sealed extracellular trench
- secrete matrix metalloproteases (MMPs) that dissolve organic and inorganic bone components
13
Q
What are the two types of bone ossification?
A
Endochondral: long bones
-deposits new bone at bottom of growth plate for longitudinal growth
Intramembranous: flat bones
-new bone on preexisting surface for appositional growth
14
Q
True or False: the adult skeleton is constantly turning over
A
True; 10% of skeleton is replaced annually
15
Q
When is peak bone mass achieved?
A
- early adulthood after cessation of skeletal growth
- 4th decade: resorption > formation leads to decrease in skeletal mass
16
Q
What is RANK?
A
–receptor activator for NF-KB on osteoclast precursors
–when stimulated by RANK ligand, it activates NF-KB (a transcription factor) that is essential in generation and survival of osteoclasts that carry out bone breakdown
17
Q
What is RANKL?
A
–RANK ligand is expressed on osteoblasts and marrow stromal cells that binds to induce bone breakdown
18
Q
What is osteoprotegerin (OPG)?
A
- a “decoy” receptor made by osteoblasts
- binds RANKL
- PREVENT RANKL from interacting w/ RANK
- induces BUILDING of bone
19
Q
How is WNT/B-catenin involved in bone building and/or breakdown?
A
–WNT proteins are produced by osteoprogenitor cells and bind to receptors on osteoblasts
–triggers activation of B-catenin and production of OPG (osteoprotegerin)
20
Q
What is sclerostin?
A
- -produced by osteocytes
- -inhibits the WNT/B-catenin pathway
21
Q
What hormones/vitamins promote bone building?
A
- estrogen
- testosterone
- vitamin D
22
Q
What hormones/cytokines/substances promote bone breakdown?
A
- -PTH
- -IL-1
- -glucocorticoids
23
Q
How is M-CSF (monocyte colony stimulating factor) involved in bone breakdown?
A
–binding to an M-CSF receptor on osteoclast precursor stimulates tyrosine kinase cascade that generates osteoclasts
24
Q
How does the breakdown of bones stimulate the formation of bone, in return?
A
-breakdown liberates/activates matrix proteins, growth factors, cytokines, enzymes (some of which stimulate osteoblasts)
25
What happens when homeobox proteins are mutated?
-abnormal differentiation of osteoblasts and chondrocytes
26
What is brachydactyly Type D and E?
- short terminal phalanx of thumb and big toe
| - HOXD13 mutation
27
What are the characteristics of Cleidocranial Dysplasia, an autosomal dominant disorder caused by a RUNX2 mutation?
- patent fontanelles
- delayed closure of cranial sutures
- Wormian Bones (extra bones along cranial sutures)
- delayed eruption of secondary teeth
- primitive clavicles
- short stature
28
What is the gene mutation in achondroplasia (the most common skeletal dysplasia)?
- FGFR3 gain of fxn (autosomal dominant)
| - 90% are new mutations (almost always paternal)
29
What are the physical characteristics of achondroplasia?
- slow cartilage growth
- short proximal extremities
- NORMAL TRUNK LENGTH
- enlarged head w/ bulging forehead
- depression of the root of the nose
- NORMAL longevity, intellect and reproduction
30
What is the gene mutation in Thanatophoric Dysplasia (the most common lethal form of dwarfism)?
-FGFR3 gain of fxn
| different mutation than achondroplasia
31
What are the physical characteristics of Thanatophoric Dysplasia?
- -diminished proliferation of chondrocytes
- -disorganization in Zone of Proliferation
- -micromelic shortening of limbs
- -frontal bossing w/ relative macrocephaly
- -SMALL CHEST CAVITY (respiratory insufficiency)
- -bell-shaped abdomen
- -die at birth or shortly afterward
32
What gene can be mutated that results in abnormal bone density?
LRP5
-depending on the defect, either osteoporosis OR osteopetrosis can be the result
33
What would a mutation in RANKL cause?
-decreased or absent osteoclasts
34
What component of connective tissue is abnormal in Osteogenesis Imperfecta (the most common inherited disorder of connective tissue)?
Type I collagen
- -alpha-1 and alpha-2 chains
- -no triple helix formation
35
What is the least severe type of Osteogenesis Imperfecta?
Type I (most common type)
- normal life span and stature
- childhood fractures, but decrease after puberty
- increased joint mobility
- normal collagen structure, just smaller amount
- blue sclera
- brittle teeth
- hearing loss (in 20's and 30's)
36
What is the most severe type of Osteogenesis Imperfecta?
Type II
- uniformly fatal in utero or shortly after birth
- small stature
- underdeveloped lungs (resp. problems)
- extraordinary bone fragility, intrauterine fractures
37
What are possible treatments of Osteogenesis Imperfecta?
- surgical "rodding" of long bones
- exercise
- healthy weight
- good nutrition
- no smoking
- no steroids
38
What mutation causes Osteopetrosis (aka Marble Bone Dz)?
-CLCN7 that encodes proton pumps in osteoclasts
- Carbonic Anhydrase 2 (CA2) deficiency
- -impaired fxn of osteoclasts
- -acidifies the resorption pit and solubilizes hydroxyapatite
--prevents acidification of urine, causing RTA
39
What is the physical clinical manifestation of Osteopetrosis?
- abnormally brittle bones that fracture easily
- bones lack medullary cavity
- anemia d/t lack of hematopoietic tissue
- bulbous ends of long bones (Erlenmeyer flask)
- nerve compression
40
Explain the characteristics of the autosomal recessive form of Osteopetrosis vs the autosomal dominant form of the disease.
Recessive: severe infantile; optic atrophy, DEAFNESS, facial paralysis; postpartum mortality d/t fractures, anemia and hydrocephalus
Dominant: mild adult; repeated fractures
41
In what category are the major of enzymes affected by mucopolysaccharidoses and what types of diseases are they?
- acid hydrolase enzymes
| - lysosomal storage diseases
42
How do mucopolysaccharidoses affect the joints?
- mucopolysaccharides accumulate in chondrocytes and the extracellular space in joints since chondrocytes are a type of mesenchymal cell that normally degrades them
- apoptosis of chondrocytes leading to structural defects in articular cartilage
43
What can be seen on physical exam of patients suffering from a form of mucopolysaccharidosis?
- short stature
- chest wall abnormality
- malformed bones
44
What is the difference in bone density between the categories of osteopenia and osteoporosis?
Osteopenia: 1.0-2.5 SD below the mean peak bone mass in young adults
Osteoporosis: at least 2.5 SD below the mean peak bone mass in young adults
45
What is the main clinical feature that signifies osteoporosis?
- atraumatic fractures
| - vertebral compression fractures
46
What are the two most common forms of osteoporosis?
- senile
| - postmenopausal
47
What are important factors that contribute to the development or non-development of osteoporosis?
- physical activity
- muscle strength
- diet
- hormonal state
48
How does aging contribute to osteoporosis?
-decreased proliferative and biosynthetic potential
--age-related osteoporosis is the "low turnover variant"
49
How does decreased physical activity contribute to osteoporosis?
- mechanical forces stimulate bone remodeling
- resistance exercises are better (load magnitude)
-immobility, paralysis, zero gravity environments lead to bone loss
50
How does the calcium nutritional state contribute to osteoporosis?
- if adolescents (particularly girls) have insufficient calcium intake during a period of rapid growth, it can restrict the peak bone mass achieved
- decreased vitamin D also contributes to this
51
How do hormones contribute to osteoporosis?
- estrogen deficiency leads to accelerated bone loss in postmenopausal women
- hormonal osteoporosis is the "high turnover variant"
52
Which cytokines are implicated in post-menopausal osteoporosis?
- -IL-6
- -TNF-alpha
- -IL-1
--decreased estrogen increases secretion of these inflammatory cytokines and increases RANKL
53
What drug used to treat breast cancer increases the risk of osteoporosis?
-tamoxifen
| a selective estrogen receptor modulator, SERM
54
What is the morphology of bone in postmenopausal osteoporosis?
- increased osteoclast activity
| - trabeculae thin
55
`What is the morphology of bone in senile osteoporosis?
-cortex thinned by periosteal and endosteal resorption
56
What material inside the bone increases with age as a normal part of the aging process?
fat
57
What demographic is most at risk for osteoporosis?
- Caucasian
- light hair
- light eyes
58
What food, when consumed in excess, can contribute to osteoporosis?
- phosphorus (milk, cheese, dried beans, peas, SODA)
| - SMOKE also contributes to osteoporosis
59
What test can be used to detect osteoporosis?
DEXA-scan
--baseline scan should be done around age 55
60
What is the purpose of blood tests when diagnosing osteoporosis?
- to check for secondary causes of osteoporosis
| ex: renal or hepatic failure, hyperthyroidism
61
What areas of the spine are more susceptible to fractures due to osteoporosis?
- thoracic
| - lumbar
62
What changes do you see in the curvature of the spine d/t osteoporosis?
- increased lumbar lordosis
- kyphoscoliosis
-contributes to loss of height
63
What are visceral complications of vertebral compression fractures?
- PNA
- respiratory issues
-trunk height is shortened
64
What are possible treatments for osteoporosis?
- -bisphosphonates (decrease osteoclast activity)
- -hormone therapy to reduce DVT's and strokes
- -denosumab (anti-RANKL)
65
What is Paget's Disease (aka osteitis deformans)?
- acquired disorder that causes increased bone mass, but it's disordered and structurally unsound
- average age at Dx is 70yrs
66
Does Paget's Disease tend to involve one bone or many bones?
- polyostotic
| - usually the axial skeleton and femur
67
What is the pathogenesis of Paget's Disease?
- both genetic and environmental factors
- 50% is familial
- 10% is d/t sporadic mutations in SQSTM1 gene
- -increased activity of NF-KB, which leads to increased osteoclast activity
68
What is seen on radiograph of a patient w/ Paget's Disease?
- "cotton wool"
- patchy density
- extremely thickened skull bones
69
What is seen on histology of a patient w/ Paget's Disease?
- mosaic pattern of lamellar bone, seen in sclerotic phase (final stage)
- "jigsaw" appearance w/ prominent cement lines (haphazardly oriented units of lamellar bone)
70
What are the three phases of Paget's Disease?
1) Lytic phase: large osteoclasts w/ 100 nuclei
2) Mixed phase: clasts persist, but lots of blasts also
3) Final phase: burned-out quiescent osteosclerotic stage
71
True or False: Paget's Disease often transforms into cancer
False; only 1% transforms, but when it does, it usually transforms to OSTEOSARCOMA (or fibrosarcoma)
72
What happens to the weight-bearing bones in the body of Paget's Disease patients?
- -bowing of the femurs and tibia
- -femoral head distortion
- -secondary arthritis
- -chalk-stick type fractures of long bones in the leg
73
Besides osteoporosis, what other disease is known to cause compression fractures of the spine?
- Paget's Dz
| - -can cause spinal cord injury and kyphosis
74
What is a characteristic of vascularity in the bones of patients with Paget's Disease?
-hypervascularity of the bone warms overlying skin
- increased blood flow acts as AV shunt
- -causes high-output heart failure
75
What will happen to the level of serum alk phosphatase, calcium, and phosphorus in patients with Paget's Disease?
-elevated alk phos
- normal calcium
- normal phosphorus
76
What are the possible treatments for Paget's Disease?
- calcitonin
| - bisphosphonates
77
What causes Rickets in kids and Osteomalacia in adults?
Vitamin D deficiency
Rickets: interferes w/ deposition of bone in the growth plate
Osteomalacia: bone formed during remodeling is undermineralized (predisposed to fracture)
78
What can be seen on physical exam of a child with Rickets?
- -frontal bossing and squared-off head
- -RACHITIC ROSARY OF RIBS
- -anterior protrusion of chest (pigeon breast deformity)
- -lumbar lordosis
- -bowed legs
79
How does hyperparathyroidism affect serum calcium levels?
- PTH has a central role in calcium homeostasis
- -increases serum calcium
- -activates osteoclasts (unabated activity)
- -increases calcium resorption by renal tubules
- -increases urinary excretion of phosphates
- -increases synthesis of active vitamin D
80
What is the cause of primary hyperparathyroidism?
-autonomous parathyroid secretion
81
What is the cause of secondary hyperparathyroidism?
-underlying renal disease
--chronic renal insufficiency doesn't synthesize adequate amounts of active vitamin D
--renal failure results in hyperphosphatemia which suppresses renal alpha-hydroxylase and further impairs synthesis of active vitamin D
82
Describe the three types of skeletal abnormalities found in hyperparathyroidism?
OSTEOPOROSIS
DISSECTING OSTEITIS: clasts tunnel and dissect centrally along the length of trabeculae creating a "railroad track" appearance
BROWN TUMOR: microfractures elicit influx of macrophages and ingrowth of reparative fibrous tissue, creating a mass of reactive tissue (brown d/t hemorrhage and hemosiderin deposition)
83
What is von Recklinghausen disease of bone?
- severe hyperparathyroidism
- increased bone cell activity
- peritrabecular fibrosis
- GENERALIZED OSTEITIS FIBROSIS CYSTICA
84
What are the skeletal changes that occur in Renal Osteodystrophy (d/t chronic renal disease)?
- osteopenia/osteoporosis
- osteomalacia
- secondary hyperparathyroidism
- growth retardation
85
What are the possible types of histologic bone changes seen in Renal Osteodystrophy?
--high-turnover osteodystrophy: increased bone resorption and bone formation, but the resorption is greater than the formation
--low-turnover dystrophy: adynamic bone
--mixed pattern: areas of high turnover and areas of low turnover
86
How does renal tubular acidosis affect bone?
- associated low pH dissolves hydroxyapatite
- demineralization of matrix
- osteomalacia
87
How are serum levels of phosphate and calcium affected by generalized renal failure?
- hyperphosphatemia
| - hypocalcemia
88
How is vitamin D affected by kidney disease?
-the kidney normally converts vitamin D to its active form
89
Describe the first stage of bone healing post-fracture?
--ruptured blood vessels form a hematoma to fill gap and surround area of bone injurty
--fibrin mesh of clotted blood seals site and creates a framework for influx of inflammatory cells and ingrowth of fibroblasts, new capillaries, etc
--degranulated platelets and migrating inflammatory cells release PDGF, TGF-B, and FGF to activate osteoprogenitors
--by the end of the first week, soft tissue callus formed
90
Describe the second stage of bone healing post-fracture.
--after 2wks, soft tissue callus becomes a bony callus (reaches max width by week 2 or 3)
--osteoprogenitor cells deposit subperiosteal trabeculae of woven bone oriented perpendicular to cortical axis and within the medullary cavity
--newly formed cartilage along fracture line undergoes endochondral ossification
--callus subjected to weight-bearing forces; parts not physically stressed are resorbed
--callus is reduced in size and the outlines of the fractured bone are re-established as lamellar bone
--healing becomes complete w/ restoration of medullary cavity
91
What is osteonecrosis (avascular necrosis) and what causes the majority of cases?
- infarction of the bone and marrow (common site: hip)
| - most cases d/t fracture or corticosteroids
92
What are the characteristics of subchondral infarcts in avascular necrosis (osteonecrosis)?
- -initially cause pain only associated w/ activity
- -then becomes constant
- -triangle or wedge-shaped
-often collapse and lead to secondary severe osteoarthritis (cartilage sloughs off, but remains viable since it obtains nutrients from synovial fluid)
93
What are the characteristics of medullary infarcts in avascular necrosis (osteonecrosis)?
-usually small and clinically silent, except when they occur as part of a larger disease such as Gaucher, "bends", or sickle cell
94
Why is the bone cortex usually not affected during a medullary infarct of the bone?
-the cortex has collateral flow, so the medullary infarct remains geographic, involving only the trabecular bone and marrow
95
How does pyogenic osteomyelitis occur in kids?
-hematogenous spread from trivial mucosal injuries such as defecation, chewing hard foods, or minor skin infections
96
How does pyogenic osteomyelitis occur in adults?
- complication of open fractures or surgeries
| - diabetic foot infections
97
What pyogenic bacteria is responsible for the major of osteomyelitis infections?
-Staph aureus (80-90%)
--expresses cell wall proteins that bind to bone matrix components and facilitates adherence of bacteria to the bone
98
Osteomyelitis caused by E. coli, Klebsiella, or Pseudomonas is most often associated with what medical conditions?
- genitourinary tract infections
| - IV drug abuse
99
What pathogen that can cause osteomyelitis is often associated with sickle cell patients?
-Salmonella
100
What pathogen that can cause osteomyelitis is often associated w/ patients who have a MAC deficiency?
Neisseria
101
How does osteomyelitis progress in kids?
- periosteum is loosely attached, so subperiosteal abscesses can form and dissect for long distances along the bone surface
- the lifting of the periosteum d/t the abscess impairs blood supply and contributes to necrosis
102
What is a sequestrum in osteomyelitis?
- dead bone following a subperiosteal abscess
| - the periosteum ruptures, becomes a draining sinus
103
What is a complication of osteomyelitis in infants?
- epiphyseal infection spreads through the articular surface and may result in septic arthritis
- destruction of articular cartilage creates a permanent disability
104
What is an involucrum in chronic osteomyelitis?
-newly deposited bone that forms a shell of living tissue around the segment of devitalized bone
105
What is a Brodie Abscess in chronic osteomyelitis?
-small, interosseous abscess that frequently involves the cortex and is walled off by reactive bone
106
What is Sclerosing Osteomyelitis of Garre?
- occurs in the jaw
| - extensive new bone formation that obscures the underlying osseous structure
107
What are the characteristics of mycobacterial osteomyelitis?
- usually bloodborne, originating from a focus of visceral disease during initial stages of primary infection; or can be a direct extension
- bone infection may perist for years before being detected
108
What are the symptoms of mycobacterial osteomyelitis?
- -localized pain
- -low-grade fever
- -chills
- -weight loss
109
What is seen on histology of mycobacterial osteomyelitis?
- caseous necrosis
| - granulomas
110
True or False: mycobacterial osteomyelitis is more resistant and destructive than pyogenic osteomyelitis?
True
111
What is Tuberculous Spondylitis (Pott Disease)?
- spine
- permanent compression fractures
- arthritis
- amyloidosis
- psoas abscess
112
What are the skeletal implications of congenital syphilis?
- bones lesions appear around 5mos gestation and are fully developed at birth
- Saber Shin: massive reactive periosteal bone deposition of medial and anterior tibial surfaces)
113
What are the skeletal implications of acquired syphilis?
- bone disease may begin early in tertiary stage (2-5yrs after initial infection
- Saddle Nose, palate, skull, and extremities (especially long tubular bones like the tibia)
