MSK Module I Flashcards
1
Q
Cortical bone (compact bone) makes up how much of the human skeleton?
A
80%
2
Q
Does cortical bone (compact bone) have a slow or fast turnover rate?
A
Slow
3
Q
What is the makeup of cortical bone (compact bone)?
A
Dense, tightly packed osteons w/ Haversian canal system
4
Q
Cancellous bone (trabecular or spongy bone) makes up how much of the skeletal mass?
A
20%
5
Q
Does cancellous bone (trabecular or spongy bone) have a high or low turnover rate?
A
Higher turnover compared to compact
6
Q
Cancellous bone (trabecular or spongy bone) is less dense than cortical bone, but has what?
A
Large surface area
7
Q
Because of cancellous bone (trabecular or spongy bone) having a large surface area, it is more susceptible to what?
A
Bone density loss
8
Q
What is Wolff’s Law?
A
Mechanical stress/gravity stimulate bone remodeling
(mechanical stress increases bone density along “stress lines” or “gravity vectors”)
9
Q
The density of the femoral neck varies due to what?
A
Mechanical stress lines
10
Q
Areas not in the stress lines of the femoral neck may become susceptible to what?
A
Fracture
11
Q
What is the periosteum?
A
Thin, double-layered, tough fibrous membrane that surrounds all bone except at ligament or tendon insertion sites
12
Q
What is contained in the inner layer (cellular layer) of the periosteum?
A
-Sharpey’s fibers: anchor periosteum as well as tendons&ligaments to cortical bone
-Active and resting osteoblasts
13
Q
What is contained in the outer layer (fibrous layer) of the periosteum?
A
-Capillaries and nerves
14
Q
What is a periosteal reaction of the outer layer of the periosteum?
A
Fracture cortex or expanding tumor may disrupt periosteum and generate pain
15
Q
Where is myeloid tissue located in bone marrow?
A
In the cavities between osseous component of bone (myelos=marrow)
16
Q
What is the function of red (active) bone marrow?
A
Blood cell formation
-All RBCs, platelets, 60-70% of WBCs
17
Q
What produces the other 20-30% of WBCs?
A
Lymphatic tissue of spleen, lymph nodes, thymus
18
Q
Where is red (active) bone marrow located in adults?
A
Trabecular/Lymphatic tissue of spleen, lymph nodes, thymus bone of pelvic bones, vertebrae, cranium and mandible, sternum and ribs, proximal femur and humerus
19
Q
What does the “yellow” of yellow (inactive) bone marrow represent?
A
Presence of fatty acids
20
Q
Where is yellow (inactive) bone marrow located in adults?
A
Medullary cavity of long bones
21
Q
What is a bone scan? What will it show?
A
Tracer injected/accumulates in areas of high cell metabolism/turnover
Scan will show normal areas of red bone marrow as well as abnormal areas of bone cellular metabolism
(tumor, infection, fracture/bine repair, arthritis, etc.)
22
Q
What is apheresis?
A
Collection of stem cells by filtering blood for circulating blood cells (PBSC- peripheral blood stem cells)
23
Q
What is a bone marrow harvest?
A
Collection of stem cells directly out of bone
*pelvis and sternum MC sites to harvest bone marrow
24
Q
Stem cells can be filtered from blood in what structure after a baby is born?
A
Umbilical cord
25
Cellular components of bone?
Osteoblasts, Osteocytes, Osteoclasts, Osteoprogenitor cells
26
Extracellular components of bone?
Extracellular matrix: collagen, proteoglycans, ECM proteins, cytokines, GF, minerals, etc.
27
Osteoblasts originate from what?
Osteoprogenitor cells
28
Osteoblasts are located where in bone?
Along bone surfaces (trabecular, Harversian's canal, inner surface of periosteum)
*also located deeper in bone and activated y fracture or trauma
29
Function of osteoblasts?
Secrete bone matrix which forms new bone during bone remodeling/repair: type I collagen, osteonectin, osteocalcin, OPG (osteoprotegerin), Alkaline phosphate
30
Elevated lab levels of alkaline phosphate indicate what?
Bone pathology
31
Osteoblasts also play a role in signaling what?
Osteoclast activity & function
32
Osteocytes are formed from what?
Osteoblasts
33
After osteoblast secretes bone matrix (osteoid), the matrix mineralizes and the osteoblast becomes what?
Osteocyte
34
Osteocytes located in a cavity are known as what?
Lacunae
35
Osteocytes make up how much of the cells in a mature human skeleton?
90%
36
Osteocytes have long cellular processes that communicate with with other bone cells through what?
Through the canaliculi
37
Do osteocytes have blood supply?
Yes, not "dead cells"
Blood supply via small capillaries
38
Osteocytes are very active in regulating what?
Mineralization homeostasis and bone remodeling
39
How do osteocytes maintain bone mineralization homeostasis?
By regulation of calcium & phosphorous concentrations
40
How do osteocytes regulate bone remodeling?
Detect physical stimuli & produce signals to regulate bone remodeling
Dissolve surrounding mineralized bone by secreted enzymes in prep for bone remodeling
41
If osteocytes are damaged, neighboring healthy osteocytes signal what?
RANKL production to stimulate bone remodeling
42
Stimuli of osteocyte regulation/remodeling?
Mechanical stress (positive or negative), hormones, drugs, cytokines, etc.
43
What cells are large, multinucleated, phagocytic cells that create resorptive pits (Howship's lacunae)?
Osteoclasts
44
What are resorptive pits/Howship's lacunae?
Microscopic depressions formed during bone modeling
*eventually get filled with new bone during remodeling
45
Function of osteoclasts?
Bone resorption, one of the initial steps of bone remodeling
46
How does bone resorption occur by osteoclasts?
Breaking down of mineralized bone and releasing calcium, phosphate, etc. that are resorbed into microvilli of osteoclast and secreted into plasma
47
What do osteoclasts secrete to break down/dissolve mineralized bone matrix?
Acid and lytic enzymes
48
Until they are needed again, osteoclasts undergo what?
Apoptosis or become dormant
49
According to NASA research, microgravity in space promotes what?
Osteoclast activity and bone density loss
50
Healthy bone is or is not constantly remodeling?
It is constantly remodeling
51
Healthy remodeling bone occurs in both ____ and ____ bone?
cortical and cancellous
52
Healthy remodeling of bone relies on what?
Balance between osteoclast and osteoblast activity
53
When does osteoporosis occur?
When osteoclast activity exceeds osteoblast activity
54
Activation of bone remodeling by hormones, drugs, physical stress, or trauma signaling the dormant osteoblasts to stimulate what?
Osteoclast maturation and activity
55
The resorption cavity follows what in compact bone?
Longitudinal axis of Haversian canals
56
The resorption cavity follows what in cancellous bone?
Surface of trebeculae
57
What is the reversal phase of bone remodeling?
Macrophages will clean up surface of the resorptive cavity to prep for laying down of new bone
58
What happens to osteoblasts in the formation phase of bone remodeling?
Mature and actively secrete bone matrix into the resorptive cavity
59
How is bone laid down in compact bone remodeling?
In concentric layers until a small canal is formed (Haversian canal)
60
How is bone formed in cancellous bone remodeling?
Trabeculae are broken down and new trabeculae are formed
61
What is the mineralization phase of bone remodeling?
New matrix mineralizes/ becomes new bone
62
What is the quiescence phase of bone remodeling?
Osteoblasts in the area of new bone formation are now at rest/dormant
63
Hormones, drugs, physical stress, or trauma signal resting osteoblasts to secrete what in order to stimulate osteoclast maturation/activity?
RANKL and M-CSF (cytokine)
64
When mature osteoblasts migrate to the cavity and secrete what?
-New bone matrix to fill cavity
-Osteoprotegerin (OPG) that inhibits osteoclast activity
65
What does OPG protect bone from?
Excess bone resorption by inhibition of osteoclast maturation/activity
66
Healthy bone remodeling and overall bone density relies on optimal _____ ratio?
OPG/RANKL
67
What does a high OPG/RANKL ratio promote?
Bone formation and increases bone density
68
What does a low OPG/RANKL ratio promote?
Bone resorption and decreases bone density
69
OPG/RANKL ratio is often used in research as a biomarker for what?
Bone mass/skeletal integrity
70
What can stimulate the release of RANKL?
PTH
71
Transient short-term PTH signaling on healthy bone will stimulate a short-term release in what?
Ca2+ from bone fluid
72
Sustained PTH signaling on healthy bone will stimulate what?
RANKL (stimulates osteoclast activity/bone resorption)
73
Do normal PTH levels create excess osteoclastic activity?
No, part of ongoing signaling which maintains a healthy bone density
74
Does excess PTH signaling disrupt bone density?
Yes, causes excess osteoclast activity leading to excessive bone resorption/loss of bone density
75
What can cause excess PTH secretion and may lead to osteoporosis?
Hyperparathyroidism
76
What can cause excess PTH and leads to osteolytic bone lesions?
Cancers
77
How can a total joint replacement recruit RANKL?
Periprosthetic osteolysis can loosen joint replacement hardware, microdebris from the loosened hardware stimulate PGE2 production and promote RANKL expression/increases osteoclast activity
78
What is the role of interleukin 6 (IL-6), IL-1 and other IL's in a loosened total joint implant?
IL-1 stimulates RANKL
IL-6 promotes PGE2 synthesis which increases RANKL osteoclast activity
79
What form of vitamin D stimulates RANKL?
1,25 dihydroxy vitamin D (active vitamin D)
***Although it stimulates RANKL, also inhibits osteoclasts, net result: promotion of bone formation
80
What hormone promotes OPG release and inhibits RANKL release?
Estrogen, increases OPG/RANKL ratio --> protective effect on bone density
81
What is directly related to post-menopausal estrogen loss?
Post-menopausal bone density loss
82
What kind of exercise promotes OPG/inhibits RANKL, increases OPG/RANKL ratio, and has protective effect on bone?
Weight bearing/resistance exercise
83
What inhibits OPG expression and promotes RANKL expression, decreases OPG/RANKL ratio, and promotes loss of bone density?
PTH (overall negative effect on bone density)
84
Calcitonin interacts directly with which cells via cell-surface receptors?
Osteoclasts
85
Effect of calcitonin on osteoclasts?
Inhibit bone resporption by decreasing # and activity of osteoclasts
86
What is an initial fracture?
Disruption of periosteum and blood vessels in cortex/marrow
*causes fracture pain
87
Characteristics of primary (direct) bone healing?
-Bone stabilization is very rigid
-No callus formation
-Longer time until stable
88
Characteristics of secondary (indirect) bone healing?
-Bone stabilization is less rigid
-Callus formation
-Callus will provide quicker stability
89
Three phases of secondary bone healing?
Inflammatory, reparative, remodeling
90
How long does the inflammatory phase of secondary bone healing last?
days to 1-2 weeks
91
Process of inflammatory phase of secondary bone healing?
increased blood flow to area after acute immune response to fracture--> hematoma forms --> osteoclast activity removes damaged bone --> GF promote initial fibroblast/osteoblast activity in area of damaged bone
92
Imaging/x-ray of inflammatory phase of secondary bone healing?
Fracture line becomes more visible as necrotic tissue is removed from site
93
How long does the reparative phase of secondary bone healing last?
up to several months
94
Process of reparative phase of secondary bone healing?
Fibroblasts secrete fibrocollagenous matrix which forms a sioft fibrous callus at beginning --> osteoclasts secrete bony matrix which forms hard callus at end *considered immature bone that is stable but weaker than mature bone
95
Imaging/x-ray of reparative phase of secondary bone healing?
Fracture line begins to disappear as hard callus forms
96
How long does the remodeling phase of secondary bone healing last?
months to years
97
Process of remodeling phase of secondary bone healing?
Immature bone gradually replaced by organized mature bone, bone returns to original shape
98
Imaging/x-ray of remodeling phase of secondary bone healing?
Fracture line has disappeared and bone gradually remodels
99
Whose fractures heal faster: children or adults?
Children
100
Pathological fractures may or may not heal, and are a risk for what?
Complications
101
What is gap healing in primary bone healing?
Rigid fixation w/ small gaps but NO movement or micro-movement at fracture site
102
Phase 1 of gap healing in primary bone healing?
New bone laid down vertically to serve as initial stabilization, necrosis along fracture ends
103
Phase 2 of gap healing in primary bone healing?
Longitudinal reconstruction of Haversian organization of bone-->osteoclasts create a cutting zone across fracture site --> capillary formation (angiogenesis) follows pathway of cutting zones--> capillaries deliver osteoblast precursors to area new bone is laid down
104
What is contact healing in direct bone healing?
Rigid fixation with NO gaps and NO movement or micro-movement at fracture site
105
What is the one phase of contact healing in direct bone healing?
Longitudinal reconstruction of Haversian organization of bone-->osteoclasts create a cutting zone across fracture site --> capillary formation (angiogenesis) follows pathway of cutting zones--> capillaries deliver osteoblast precursors to area new bone is laid down
**same as gap healing but skips phase 1
106
Is determining when a fracture is healed an absolute science?
No
107
Healing time of fractures vary with what?
Age and type of fracture
108
Criteria for balancing between fracture healing vs. negative consequences of immobilization?
-Clinical judgement
-Radiographs (callus formation w/ disappearance of fx line, cortex outline restores)
-Anatomical location (different bones heal at different rates)
109
Distal radial fractures take approximately how long to heal?
6-8 weeks
110
Mid-diaphyseal fractures take approximately how long to heal?
3 months
111
Fracture immobilization strategies?
Cast
Intramedullary rods/nails Pins,wires,screws
Compression plate
External fixator
112
Which immobilization strategies allow for secondary bone healing with periostal callus formation?
Cast, Pins/wires/screws, Intramedullary rods/nails
113
Which immobilization strategy allows for primary bone healing with NO periostal callus formation? Why do LE fxs need a longer period of non-weight bearing with primary healing?
Compression plate (primary healing is slower-->longer period of non-weight bearing NWB if lower extremity)
114
Which type of bone healing will occur with a less rigid external fixator?
Secondary healing with callus formation
115
Which type of bone healing will occur with a very rigid external fixator?
Primary healing with NO callus formation
116
In addition to fracture itself there is also concern for damage to what in pediatric fractures?
Damage to growth plate, future growth impairment
117
What % of pediatric fractures involve the growth plate?
15-30%
118
What % of pediatric injuries that involve the growth plate have growth impairment of the bone?
estimated 1-10%
119
Salter-Harris classification for pediatric fractures Type 1?
Disruption of the growth plate (distraction or slip injury)
*SCFE (slipped capital femoral epiphysis) is a type 1 Salter Harris injury
120
Salter-Harris classification for pediatric fractures Type 2?
Fracture line through growth plate and metaphysis
121
Salter-Harris classification for pediatric fractures Type 3?
Fracture line through growth plate and epiphysis
122
Salter-Harris classification for pediatric fractures Type 4?
Fracture through metaphysis, growth plate, and epiphysis
123
Salter-Harris classification for pediatric fractures Type 5?
Compression injury of the growth plate
124
What is the classification of low bone mass (osteopenia)?
Low bone mineral density but not severe enough to be considered osteoporosis (BD between 1-2.5 SD below young adult men)
125
What is the classification of osteoporosis?
Severe decrease in BMD
(BD < or = 2.5 SD of young adult men)
126
What is the classification of osteomalacia?
Softening of the bone
127
What is the classification of osteopetrosis?
Increased bone density
128
What is primary osteoporosis?
Low BD unrelated to any underlying disease/condition
129
What is secondary osteoporosis?
Low BD secondary to medication or disease/condition
130
What is Type-1 primary osteoporosis? What kind of bone does it affect?
Post-menopausal, primarily affects cancellous bone
131
What is Type-2 primary osteoporosis? What kind of bone does it affect?
Age-related (typical in >75 y/o), affects both cancellous and cortical bone
132
What is peak bone mass?
From birth to 20's the rate of bone formation occurs at faster rate than bone resorption, and bone mass will peak at 25-30 y/o
133
Peak bone mass plateuas for how long?
~3.5 years
134
Modifiable risk factors for low peak bone mass?
Smoking, alcohol, physical inactivity, poor nutrition
135
The rate of bone loss is the same for men and women until what occurs?
Menopause
136
Age-related bone loss in men and women starts at what age?
in the 30's sometime after 3-5 yr plateau
137
Normal age related bone loss rate for men and women before menopause?
0.5-1%/year
138
Women reach osteoporotic levels faster than men due to what?
Menopause and men starting with a higher peak bone mass
139
Rate of bone loss after menopause is most rapid when?
during the first decade post-menopause
140
Rate of bone loss the first decade post-menopause?
increases up to 3-5%/year
141
What % of bone mass is lost in the first decade post-menopause? What % of expected lifetime bone density loss does this amount account for?
After first decade 15% lost, accounts for 40-50% of lifetime density lost
142
After the first decade post-menopause the rate of bone loss slows and returns to what rate?
"normal" age related loss of 1%/year
143
Pathogenesis of post-menopausal osteoporosis?
Loss of estrogen-->reduces OPG--> decreases OPG/RANKL ratio--> favors osteoclast activity/promotes bone loss
144
How does Raloxifine work for osteoporosis tx?
Stimulates OPG production
145
How does Denosumab work for osteoporosis tx?
Inhibits RANKL
146
How do Bisphosphates work for osteoporosis tx?
Inhibit bone resorption itself
147
Pathogenesis of age-related osteoporosis?
Many factors contribute:
OPG/RANKL ratio gradually decreases
GH, IGF, androgens decrease with age
Lifestyle- inactivity w/ less mechanical stimulation, poor nutrition w/ little Vit. D/calcium, Tobacco inhibits OPG, Alcohol lowers OPG/RANKL ratio
148
How does long term glucocorticoid use decrease bone mass?
Decrease OPG/RANKL ratio,
Inhibit OPG
Stimulate RANKL/osteoclasts
149
The largest rate of bone loss occurs at what point of glucocorticoid use?
Initial 6 months of daily use, and then rate slows
150
What is a significant concern in managing patients with osteoporosis?
Fracture risk
151
Which bone is affected first by osteoporosis? What kind of fractures does this lead to?
Cancellous bone (vertebra, long bone metaphysis), lead to wrist, hip, and compression fxs
152
Gold standard to measure bone density?
Dual energy x-ray absorptiometry (DEXA or DXA scan)
*this alone does not identify patients w/ highest fracture risk
153
What is the online questionaire used to assess fracture risk (developed by Univeristy of SHeffield in association with the WHO)? What does it predict?
FRAX- Fracture Risk Assessment Tool, predicts 10-year likelihood of having a minimal trauma fracture
154
What is osteomalacia?
Insufficient mineralization of bone (no bone loss occurs)
155
Etiologies of osteomalacia?
-Poor Vit. D intake
-Intestinal dz impairing absorption
-Renal dz, meds, tumors
156
What is Rickets?
Childhood osteomalacia
157
Imaging/x-ray appearance of osteomalacia?
"Looser's zones" or Milkman's pseudofractures: lesions that resemble fxs but are actually poorly mineralized osteoid matrix oriented perpedicular/do not completely cross the full width
Deformed bowing of long bones
158
What is Paget's Disease of bone?
Severe bone deformation causing associated complications
159
Onset of Paget's disease? Prevalence in males/females?
>50 y/o, M>F (ratio 8:1)
160
Pathology of Paget's disease?
Osteoblast/osteoclast signaling disrupted, causes rapid and abnormal bone remodeling leading to enlarged or deformed bone of poor quality
(disorganized collagen fibers, poor mineralization)
161
Potential complications of Paget's disease?
Fracture, deformity, arthritis, nerve dysfunction if compressed in skull, pain
162
The term osteochondrosis refers to what?
bone growth disorders that involve ossification centers (osteonecrosis, apophysitis)
163
Osteochrondrosis may result from what?
abnormal growth, injury, overuse of developing growth plate/surrounding ossification centers
*can be self limiting depending on age, severity, stress removal, etc.
164
What is osteonecrosis?
Bone death due to loss of blood supply
165
Clinical signs of osteonecrosis (avascular necrosis/AVN) ?
early: often no sx
chronic: gradual pain onset
Acute pain sx if fracture in area of necrosis
166
Common sites of AVN/osteonecrosis?
Femoral head **MC
Scaphoid
Proximal humerus
Tibial plateau
Small bones of wrist/ankle
167
Common causes of AVN/osteonecrosis?
post-traumatic, steroid use, alcohol use, idipopathic
168
What is apophysitis?
Traction on secondary ossification center
169
What is Osgood-Schlatter disease (Apophysitis)?
Patella ligament traction on tibial tuberosity
170
What is Sinding-Larsen-Johansson disease (Apophysitis)?
Patella ligament traction on distal patella
171
Apophysitis of the elbow is common in what population?
Young throwing athletes
172
What is olecranon apophysitis?
Traction from triceps tendon
173
What is medial epicondyle apophysitis?
Traction from common flexor tendon
*Little Leaguer's Elbow
174
What is Sever's Disease (Apophysitis)?
Achilles tendon traction (pulling) on the secondary ossification center of the calcaneus
175
What can cause osteomyelitis?
Microstructure of bone contains regions that make bone susceptible to infection if bacteria/foreign invaders gain access
176
Adult inflammatory response to osteomyelitis?
Inflammation eventually disrupts bone cortex --> potential for pathological fracture
177
Child inflammatory response to osteomyelitis?
Subperiosteal abscess: inflammation may lift off periosteum sequestrum (area of necrosis)
Involucrum formation: lifting off of periosteum causing increase in osteoblastic activity resulting in new bone growth
178
Anatomical location of osteomyelitis in adults?
Lumbar spine
179
Anatomical location of osteomyelitis in children?
Metaphysis near growth plate in long bones:
-distal femur
-proximal humerus
-tibia
-radius
180
Signs/sx of osteomyelitis in adults?
Back pain w/ low grade fever
181
Signs/sx of osteomyelitis in children?
High fever, local pain, redness, swelling
182
Cells of benign primary bone tumors?
Well differentiated, look more like normal cells, tend to be slower growing
183
Bone attempts to contain growth of benign primary bone tumors by forming what?
Sclerotic rim around the tumor
184
In general, do benign primary bone tumors produce constant progressive bone pain?
No
185
Examples of benign bone tumors?
Osteoid (osteoid osteoma, osteoblastoma)
Chronoid (enchondroma)
Fibrous (non-ossifying fibroma)
Mixed (osteochondroma)
186
Radiographic characteristics of benign primary bone tumors that help provide helpful ddx info?
-Location of tumor (diaphysis, metaphysis, etc)
-Borders of tumor (benign: well defined small borders, malignant: ill-defined wide zone of transition)
-Morphology/matrix of tumor (recognizing patterns associated w/ cartilage, bone small round cell, giant cell, fibrogenic, vascular, chordoma helps assess tumor origin)
187
What periosteal reaction refers to thickened callus formation caused by benign bone tumors that never occurs in malignant tumors?
Solid benign reaction
188
What periosteal reaction refers to pushed out or lifted off of the bone appearance consistent with malignant bone tumors?
Onion skin (lamellated)
189
What periosteal reaction refers to fast perpendicular growth that extends through the periosteum consistent with malignant bone tumors?
Spiculated (sunburst)
190
What periosteal reaction refers to periosteum lifting from the bone consistent with malignant bone tumors?
Codman's triangle
191
What bone destruction pattern refers to well defined margins surrounding clear lytic area consistent with benign bone tumors?
Geographic pattern
192
What bone destruction pattern refers to less defined margins surrounding lytic or partially lytic area consistent with malignant bone tumors?
Moth eaten pattern
193
What bone destruction pattern refers to poorly defined margins with abnormal lytic bone merged throughout bone consistent with malignant bone tumors?
Permeative pattern
