OSR basic science Flashcards
(500 cards)
1
Q
From which cells do osteoblasts arise?
A
Undifferentiated mesenchymal stem cells (MSCs)
2
Q
What seven growth factors influence osteoblast differentiation?
A
Interleukins (ILs); Insulin-like growth factor (IGF-I); Platelet-derived growth factor (PDGF); Bone morphogenic proteins (BMPs); Transforming growth factor-_ (TGF-_); Osterix; Runx 2 (formerly Cbfa 1)
3
Q
What is the function of IGF?
A
Osteosynthesis
4
Q
Through what intracellular signaling pathway does it work?
A
Tyrosine kinase
5
Q
What is the function of PDGF?
A
Chemotaxis
6
Q
Through what intracellular signaling pathway does it work?
A
Tyrosine kinase
7
Q
What is the function of BMP?
A
Stimulates mesenchymal cell differentiation
8
Q
Through what intracellular signaling pathway does it work?
A
Serine/threonine kinase through SMAD proteins
9
Q
Is BMP osteoinductive or osteoconductive?
A
Osteoinductive
10
Q
TGF-b stimulates mesenchymal cells to produce what two substances?
A
Type II collagen; Proteoglycans
11
Q
TGF-b also indirectly stimulates osteoblasts to produce what?
A
Type I collagen
12
Q
Through what intracellular signaling pathway does it work?
A
Serine/threonine kinase
13
Q
What four substances do osteoblasts produce?
A
Alkaline phosphate; Type I collagen; Osteocalcin; RANK ligand
14
Q
Osteoblasts respond directly to what five factors?
A
Parathyroid hormone (PTH); Glucocorticoids; Prostaglandins; 1,25-vitamin D; Estrogen
15
Q
Which two of these favor osteogenesis?
A
1,25-vitamin D; Estrogen
16
Q
Which three favor resorption?
A
PTH (resorption releases calcium); Glucocorticoids; Prostaglandins
17
Q
What two factors upregulate adenylate cyclase at the cellular level?
A
PTH; Prostaglandins
18
Q
What factor downregulates adenylate cyclase?
A
Estrogen
19
Q
What factor also decreases calcium absorption at the level of the gut?
A
Glucocorticoids
20
Q
From what cells do osteoclasts arise?
A
Monocyte progenitors
21
Q
How do osteoclasts bind to the surface of bone?
A
With integrins (vibronectin)
22
Q
Where does resorption occur?
A
Howship’s lacunae
23
Q
What are the two products of osteoclasts?
A
Hydrogen ions (through carbonic anhydrase); Tartrate resistant acid phosphatase
24
Q
What do osteoclasts respond directly to?
A
Calcitonin
25
What is the effect of calcitonin on the osteoclast?
Inhibits osteoclast function
26
What is the effect of IL-1?
Stimulates osteoclast function
27
What is the effect of IL-10?
Inhibits osteoclast function
28
What is the effect of IL-11?
Increases production of RANK ligand
29
What is the function of RANK ligand?
Links osteoblast and osteoclast function
30
What cell contains RANK ligand?
Osteoblast
31
How does RANK ligand work?
Binds to and stimulates osteoclasts
32
What cofactor is required?
Macrophage colony-stimulating factor (M-CSF)
33
What inhibits the RANK stimulation of osteoclasts?
Osteoprotegerin
34
How?
Blocks RANK binding to the osteoclast, competitive inhibition
35
If considering estrogen replacement therapy, when should it be started for maximal benefit?
Within 5 to 10 years of menopause
36
Generally speaking, how does estrogen work?
Decreases both bony resorption and formation; But resorption is decreased much more than formation
37
What are two pharmacologic alternatives to estrogen therapy?
Alendronate; Raloxifene
38
What are osteocytes stimulated by?
Calcitonin
39
What are osteocytes inhibited by?
PTH
40
How does mechanical stimulation work?
Increases prostaglandin E2”_production (stimulus)
41
How are osteons connected to one another?
By haversian canals
42
What are the extensive networks of osteonal processes that allow communication?
Canaliculi
43
What is the outer osteonal border called?
Cement line
44
What lies in between osteons?
Interstitial lamellae
45
What is the principal organic component of bone?
Type I collagen
46
What is the composition of a collagen fibril?
Two _1”_chains; Two _2”_chains
47
How is collagen secreted?
Secreted as procollagen
48
Then what happens?
Cross-linked after secretion
49
What is the difference between a hole and a pore?
Holes are the spaces between the ends of collagen molecules; Pores are the spaces between the sides of the collagen molecules
50
What are the three noncollagenous matrix proteins of bone?
Osteocalcin; Osteonectin; Osteopontin
51
What stimulates osteocalcin production?
1,25-vitamin D
52
What inhibits osteocalcin production?
PTH
53
Osteocalcin attracts what cell type?
Osteoclasts
54
What are osteocalcin levels a marker of?
Bone metabolism
55
Bone mineralization consists of what two processes? What are the key features of each?
Initiation (sialoproteins, pores, high-energy requirement); Growth (osteocalcin, coalescing areas of mineralization)
56
What are the three laboratory markers of bone resorption?
Urinary hydroxyproline; Urinary pyridoline; N-telopeptide
57
What are the laboratory markers of bone formation?
Alkaline phosphate
58
Normal mature bone is of what type?
Lamellar
59
What is the defining characteristic of lamellar bone?
Remodeled along lines of stress
60
What are the two subtypes of lamellar bone?
Cortical; Cancellous
61
In contrast, immature or pathologic bone is of what type?
Woven
62
Bone is strongest in what direction? Weakest in what direction?
Strongest in compression; Weakest in shear
63
When bone is under torsion, where is the greatest load experienced?
Maximum load experienced at 45 degrees to the long axis of the bone
64
What is the basic premise of Wolff's law?
Increased stress leads to increased bone formation
65
Piezoelectric charges: is compression electropositive or negative?
Compression results in a negative charge
66
The negative charge then leads to what process?
Bone formation
67
Is tension electropositive or negative?
Positive charge
68
What does the positive charge lead to?
Bone resorption
69
What is the Heuter-Volkmann law? Give an example of where this law applies.
Compression inhibits growth; Tension stimulates growth; Example: scoliosis
70
At what age is peak bone mass achieved?
End of the third decade of life (the 20s)
71
What is the annual rate of bone loss after peak?
0.3 to 0.5% per year
72
What is the annual rate of bone loss after menopause, without treatment?
2 to 3% per year for 6 to 10 years after menopause
73
Is the observed postmenopausal decline simply estrogen related?
Not just estrogen, but changes in calcium metabolism also; Decreased intestinal calcium absorption; Increased calcium losses
74
Is the nutrient system high or low pressure?
High pressure
75
What does it supply?
Inner two thirds of bone
76
Is the periosteal system high or low pressure?
Low pressure
77
What does it supply?
Outer one third of bone
78
In what direction does blood flow in the adult?
Nutrient to periosteal
79
In what direction does blood flow in immature bone?
Opposite direction of flow
80
What is the principal determinant of fracture healing?
Blood supply
81
What are the three components of the sequence of changes in blood supply after fracture?
Immediate decrease in blood supply; Increased vascularity (maximal at 2 weeks); Return to normal by 3 to 5 months
82
What is the effect of reaming?
Destroys endosteal blood supply
83
What are the three effects of nicotine on fracture healing?
Increased time to fracture healing; Increased risk of nonunion; Decreased fracture callus strength
84
Nicotine use is associated with increased risk of fractures at which locations?
Increases risk of wrist and hip fractures
85
How does smoking affect lumbar fusion rates?
Increases the pseudarthrosis rate of lumbar fusion by 500%
86
What is the two-step sequence of callus types formed after fracture?
Bridging (soft) callus within 2 weeks; Replaced by woven bone (hard callus)
87
Callus is ultimately remodeled over what period?
Remodeled to lamellar bone within 7 years
88
What two types of bone formation are seen with cast treatment of fracture?
Periosteal bridging callus; Enchondral ossification
89
Is there any difference with intramedullary (IM) nail treatment?
IM nail treatment also results in medullary callus formation late
90
Under what two conditions can intramembranous bone formation (no cartilage precursor) be seen after fracture?
Low strain; High oxygen tension
91
What type of chondrocytes are present in the first 10 days after fracture?
Proliferative chondrocytes
92
What collagen type do they produce?
Type II
93
What other collagen type is present in the chondroid phase?
Type IX: cross-linking function
94
After 14 days, what chondrocyte type is present?
Hypertrophic chondrocytes
95
What type of collagen do they produce?
Type X
96
What are the next three steps?
Calcification; Osteoclasts resorb matrix; Osteoblasts lay down new bone
97
How do hypertrophic nonunions heal?
Mineralization of fibrocartilage
98
What other treatment modality has a similar mechanism?
Pulsed electromagnetic field treatment (bone stimulator)
99
Rate the four tissue types from highest to lowest strain tolerances?
Granulation tissue (100% strain tolerance); Fibrous tissue; Cartilage; Bone
100
At what phase of fracture healing does direct current exert an effect?
Inflammatory-response phase
101
At what phase of fracture healing does alternating current exert an effect?
Repair phase (callus)
102
What is the effect of pulsed electromagnetic fields?
Initiates fibrocartilage calcification
103
What is the classic application of this technology?
Nonhealing pseudo-Jones fracture
104
What are the two benefits of pulsed low-intensity ultrasound?
Accelerated fracture healing; Increased callus strength
105
What are the two detrimental effects of radiation?
Decreased cellularity; Decreased callus strength
106
How long should the latency phase last?
5 to 7 days
107
What is the desired rate of distraction during distraction phase?
1 mm/day
108
What is the duration of the consolidation phase?
Twice as long as the distraction phase
109
What is the weight-bearing status throughout treatment?
Weight-bearing as tolerated (WBAT)
110
What changes are seen in blood vessels?
Proliferation of vasa vasorum
111
What is the oxygen tension with distraction osteogenesis?
High oxygen tension
112
So what type of bone formation is seen under these low-strain, high oxygen tension conditions?
Intramembranous bone formation (no cartilage precursor)
113
What is the daily calcium intake recommendation for healthy children and adults?
750 mg
114
What is the daily calcium intake recommendation for teenagers, pregnant women, and individuals with healing fractures?
1500 mg
115
What is the daily calcium intake recommendation for lactating mothers?
2000 mg
116
What is the mechanism of calcium absorption in the duodenum?
Active transport
117
What is the mechanism of calcium absorption in the jejunum?
Passive diffusion
118
What is the mechanism of calcium absorption in the kidney?
Proximal tubular resorption
119
What percentage of total body calcium is within plasma?
1.00%
120
What are the relative proportions of bound vs. unbound plasma calcium?
Bound = unbound
121
What are the two principal regulators of plasma calcium concentration?
PTH; 1,25-vitamin D
122
What are the relative proportions of bound vs. unbound plasma phosphate?
Unbound predominates
123
What is the principal site of phosphate resorption within the kidney?
Proximal tubule
124
What type of molecule is parathyroid hormone (PTH)?
Peptide
125
Where is PTH produced?
Chief cells of the parathyroid gland
126
What is the stimulus for release of PTH?
Low plasma calcium concentration
127
What receptor detects calcium concentration?
Calcium sensing receptor (CaSR)
128
In what organ and gland can this receptor be found?
Kidney; Parathyroid gland
129
What type of receptor is CaSR?
G-protein-coupled receptor
130
What are the three effects of CaSR activation within the parathyroid gland?
PTH secretion; PTH gene expression; Cellular proliferation
131
In what organ and in what cells can PTH receptors be found?
Kidney; Osteoblasts
132
What are PTH's two actions on the kidney?
Increase 1,25-vitamin D production; Decrease resorption of renal phosphate
133
What are PTH's three actions on the bone?
Stimulate osteoblasts; Osteoblasts produce RANK ligand; RANK ligand stimulates osteoclasts
134
What is the net effect of PTH on plasma calcium and phosphate concentrations?
Increased plasma calcium; Decreased plasma phosphate
135
What type of molecule is 1,25-vitamin D?
Steroid
136
As vitamin D is activated to 1,25-vitamin D, what are the two sites of hydroxylation?
First: liver; Second: kidney
137
What are the three stimuli for release of 1,25-vitamin D?
Low serum calcium concentration; Low serum phosphate concentration; Elevated PTH levels
138
What are the two effects of 1,25-vitamin D?
Increased intestinal absorption of calcium and phosphate; Increased osteoclast activity
139
What is the net effect of 1,25-vitamin D on plasma calcium and phosphate concentrations?
Increased plasma calcium; Increased plasma phosphate
140
What type of molecule is calcitonin?
Peptide
141
Where is calcitonin produced?
Clear cells (parafollicular cells) of the thyroid gland
142
What is the stimulus for release of calcitonin?
Elevated serum calcium
143
What is the effect of calcitonin?
Inhibits osteoclast activity
144
What is a common cause of primary hyperparathyroidism?
Adenoma of one parathyroid gland
145
If four glands are affected, what diagnosis must be considered?
Multiple endocrine neoplasia (MEN) syndrome
146
What is the effect of primary hyperparathyroidism on 1,25-vitamin D levels?
Increased 1,25-vitamin D
147
What is the effect of primary hyperparathyroidism on serum calcium concentration?
Increased serum calcium
148
What is the effect of primary hyperparathyroidism on serum phosphate concentration?
Decreased serum phosphate
149
What is the hydration status of hypercalcemic patients?
Generally dehydrated as hypercalcemia leads to polyuria
150
What is osteitis fibrosa cystica?
Resorption of bone due to PTH overactivity and replacement with fibrous tissue
151
What are the two characteristic histologic features of brown tumors?
Giant cells; Hemosiderin
152
What are the other systemic effects of hypercalcemia?
Renal stones; Psychiatric disorders; Abdominal pain
153
What are the four available hypercalcemia treatment methods?
Saline hydration; Loop diuretics; Dialysis; Mobilization
154
What is the most common cause of hypoparathyroidism?
Iatrogenic
155
What is the effect on serum calcium concentration?
Decreased serum calcium
156
What is the effect on serum phosphate concentration?
Increased serum phosphate (because low PTH levels)
157
What is the effect on 1,25-vitamin D levels?
Decreased 1,25-vitamin D
158
What is the characteristic radiographic finding on skull films?
Calcification of the basal ganglia
159
What is the cause of pseudohypoparathyroidism?
No PTH effect at target cells
160
Inheritance?
X-linked dominant (XLD)
161
Quick review: what other disorder has a similar inheritance pattern?
Hypophosphatemic rickets
162
What gene is involved?
GNAS1
163
Mutation?
G_ subunit
164
Quick review: in what two other clinical situations do G-proteins play a vital role?
Fibrous dysplasia; CaSR function
165
What is the PTH level in pseudohypoparathyroidism?
Normal or high
166
What is the serum calcium concentration?
Low serum calcium
167
What is the serum phosphate concentration?
Elevated serum phosphate (again, no PTH effect)
168
What is the effect on 1,25-vitamin D levels?
Low 1,25-vitamin D
169
Give an example of a disorder associated with pseudohypoparathyroidism?
Albright syndrome
170
What are the four characteristic features of pseudohypoparathyroidism?
Short metacarpals; Bony exostoses; Obesity; Mental retardation
171
Quick review: what is another disorder that is associated with obesity and mental retardation?
Prader-Willi
172
Pseudopseudohypoparathyroidism is phenotypically similar to what?
Pseudohypoparathyroidism
173
What is the serum calcium concentration?
Normal
174
What is the target cell response to PTH?
Normal
175
What are the two general types of renal failure osteodystrophy?
High turnover; Low turnover (excess aluminum leads to decreased metabolic activity)
176
With the high turnover type, what is the serum phosphate level?
Elevated due to renal failure/inability to dump phosphate
177
_ the serum calcium level?
Low because with elevated phosphate, calcium precipitates out of solution
178
_ the PTH level?
Elevated, because high phosphate levels lead to secondary hyperparathyroidism
179
What are the two components of the treatment for high turnover renal osteodystrophy?
Phosphate binders (antacids); Activated oral vitamin D
180
With the low turnover type, what is the serum calcium level?
Normal
181
_ the serum phosphate level?
Normal
182
_ the PTH level?
Low
183
_ the 1,25-vitamin D level?
Low because of impaired renal hydroxylase
184
With renal osteodystrophy, what is the clinical appearance of the spine?
Rugger jersey spine
185
What other disorder also exhibits a rugger jersey spine?
Osteopetrosis
186
What other generalized bony changes are present?
Osteitis fibrosa cystica due to secondary hypoparathyroidism
187
Chronic dialysis treatment also leads to what disorder?
Amyloidosis
188
With renal tubular acidosis, what two ions are lost in the urine?
Sodium; Calcium
189
What is the key lab value for diagnosis?
Urine calcium > serum calcium
190
What is the treatment of renal tubular acidosis?
Alkalinize the urine
191
Renal tubular acidosis is phenotypically similar to what disorder?
Rickets
192
Quick review: What are three other situations in which calcium losses can exceed intake?
Postmenopausal woman (increased urine calcium, decreased absorption); Elevated glucocorticoids (increased urine calcium); Osteogenic rickets (fibroblast growth factor-23 [FGF-23])
193
What is the suggested daily intake of vitamin D for healthy adults?
200 international units (IU)
194
What is the suggested daily intake of vitamin D for children, pregnant women, and lactating mothers?
400 IU
195
What is the only natural dietary source of vitamin D?
Oily fish
196
What is the serum calcium level with vitamin D deficiency?
Decreased (due to decreased absorption)
197
What is the resulting effect on PTH?
Increased (in response to low calcium)
198
What two clinical features of nutritional rickets are most sensitive and specific?
Wrist enlargement; Costochondral enlargement
199
What is the serum phosphate level?
Decreased (due to high PTH)
200
What does treatment of vitamin D deficiency rickets consist of?
5000 IU per day of vitamin D
201
Deficient calcium intake has what effect on PTH levels?
PTH levels become elevated
202
What effect does this have on vitamin D levels?
Increases vitamin D levels (attempt to absorb greater amounts of calcium, phosphate)
203
What are serum phosphate levels?
May actually be low (due to elevated PTH)
204
What is the treatment of calcium deficiency rickets?
750 mg/day of calcium
205
Deficient phosphate intake has what effect on PTH levels?
None (PTH responds only to high phosphate)
206
What effect does low serum phosphate have on vitamin D levels?
Increases vitamin D levels (attempt to absorb greater amounts of phosphate)
207
What is the treatment of phosphate deficiency rickets?
Oral phosphate supplementation
208
Inheritance?
Autosomal recessive (AR)
209
Mutation?
Defect in renal 1,25-hydroxylase
210
What is the effect of defective hydroxylase?
No conversion of inactive vitamin D to active form
211
What is the characteristic clinical feature?
Rachitic rosary responsive to vitamin D
212
What is the resulting serum calcium level?
Decreased
213
What is the resulting serum phosphate level?
Decreased (due to decreased absorption)
214
What is the resulting serum PTH level?
Elevated (in response to low calcium)
215
What is the treatment of vitamin D-dependent rickets (VDDR) type I?
Oral activated vitamin D
216
Defect?
No receptor for 1,25-vitamin D at target cells
217
What is the serum level of 1,25-vitamin D?
Very high
218
What is the serum level of active vitamin D in type I?
Very low in type I
219
What are the two characteristic clinical features?
Alopecia; Rachitic rosary unresponsive to vitamin D therapy
220
What is the treatment of VDDR type II?
Vitamin D analogue
221
What is the relative severity of both types of vitamin D dependent rickets vs. nutritional rickets?
Vitamin D dependent rickets I and II are more severe
222
What is the relative frequency of hypophosphatemic rickets as a cause of rickets?
Most common cause in the United States
223
What is the inheritance?
XLD
224
What is the mutation?
Impaired renal tubular absorption of phosphate
225
What is the gene?
PHEX
226
This disorder is also known as what?
Vitamin D resistant rickets
227
What is the serum phosphate level?
Low, because a lot of phosphate is lost in the urine
228
What is the resulting PTH level?
Normal (no PTH response to low serum phosphate)
229
What is the serum calcium level?
Normal
230
What is the classic triad of clinical features?
Short child; Lower limb deformities; Low serum phosphate
231
What are the two components of treatment of hypophosphatemic rickets?
High-dose phosphate replacement; High-dose vitamin D (to facilitate phosphate absorption)
232
What is the inheritance?
AR
233
What is the defect?
Enzymatic deficiency leads to low levels of alkaline phosphate
234
Clinical features are similar to what group of disorders?
Nutritional rickets
235
How is hypophosphatasia diagnosed?
Elevated urinary phosphoethanolamine
236
What is the treatment of hypophosphatasia?
No good options exist
237
High-turnover renal osteodystrophy displays clinical features similar to what other disorder?
Primary hyperparathyroidism (for example, osteitis fibrosa cystica)
238
The renal osteodystrophy spine has what appearance?
Rugger jersey spine
239
This spine appearance is also associated with what other disorder?
Osteopetrosis
240
Hypophosphatasia displays clinical features similar to what other disorder?
Nutritional rickets
241
The spine has what appearance in hypophosphatasia?
Rachitic rosary (like rickets)
242
What are three proposed viral etiologies for Paget's disease?
Respiratory syncytial virus (RSV); Paramyxovirus; Canine distemper virus
243
What is the typical clinical presentation of Paget's?
Bone pain
244
Within a given bone, how does Paget's progress?
Starts at one end and progresses to the other
245
What is the radiographic appearance of progression?
Leading _lytic flame_
246
Laboratory findings include increased levels of what four substances?
Alkaline phosphate; Urinary hydroxyproline; Osteocalcin; N-telopeptide
247
What are the three key histologic features?
Osteoclasts with viral inclusion bodies (paramyxovirus); Cement lines; Relative osteoblastic or osteoclastic appearance depends on phase of disease
248
What is the treatment of Paget's disease?
Bisphosphonates
249
What other clinical conditions occur secondary to Paget's disease in the spine?
Spinal stenosis
250
What other clinical conditions occur secondary to Paget's disease in the heart?
High output cardiac failure
251
What other clinical conditions occur secondary to Paget's disease in the auditory system?
Deafness
252
What does the new onset of severe pain and swelling in a patient with known Paget's suggest?
Malignant osteosarcoma
253
How often does this occur?
In 10% of patients
254
What effect does aging have on stomach acidity?
Decreased acidity
255
What effect does the change in acidity have on calcium absorption?
Decreased calcium absorption
256
What effect does aging have on vitamin D requirements?
Increased vitamin D requirements with age
257
Is osteoporosis a quantitative or qualitative deficiency of bone?
Quantitative (not enough bone)
258
What are the common laboratory findings in patients with osteoporosis?
Generally normal
259
What is the definition of osteoporosis in terms of T-score?
T-score of -2.5 or less
260
What are the two indications for treatment of osteoporosis?
T score of -2.5
261
Compare the definitions of T-score and Z-score?
T-score is the number of standard deviations away from mean peak bone mass (comparison to 25-year-old population)
262
What two imaging modalities are most commonly used to arrive at a T-score?
Dual-energy x-ray absorptiometry (DEXA) scan
263
How much bone must be lost before a change in plain x-ray appearance is evident?
30.0%
264
Does a DEXA scan evaluate cancellous and cortical bone individually?
No, together
265
Does a quantitative CT scan evaluate cancellous and cortical bone individually?
Yes, can separate
266
What is the downside of quantitative CT?
Increased radiation
267
What test is the most accurate for determining bone density?
Quantitative CT
268
What test is the most reliable for predicting fracture risk?
DEXA scan
269
What are the two general types of osteoporosis?
Type I: postmenopausal
270
With type I osteoporosis, what type of bone is principally affected?
Trabecular bone (cancellous)
271
Give two examples of typical type I fractures?
Vertebral body fractures
272
With type II osteoporosis, what type of bone is principally affected?
Trabecular and cortical bone
273
Give two examples of typical type II fractures?
Hip fracture
274
How do bisphosphonates affect osteoclast microstructure?
Disrupt microtubules within the ruffled border
275
How do they disrupt macrostructure?
Disrupt protein prenylation
276
What disadvantageous effect do high-dose bisphosphonates have?
Disrupt calcium deposition also, not just resorption
277
Over what period of time does the peak bone loss occur?
First 16 months after injury
278
After that period of time, how much bone mass remains?
Two thirds of the preinjury bone mass
279
What anatomic region is most affected by bone loss?
Knee
280
What anatomic region is most spared by bone loss?
Skull
281
What are the two products of stem cell division?
Another stem cell
282
Why is it desirable to select out stem cells from other cells within grafts?
Because the greater the total number of cells, the greater the metabolic needs
283
What is the main advantage of fresh allograft?
Contains osteoinductive BMPs
284
What is the main disadvantage?
Immunogenic
285
Is fresh allograft osteoconductive or inductive?
Both
286
What are the two advantages of fresh frozen allograft?
Still contains osteoinductive BMPs
287
Is fresh frozen allograft osteoconductive or inductive?
Both
288
What is the main advantage of freeze-dried allograft?
Lowest immunogenicity
289
What are the two main disadvantages?
Does not contain BMPs
290
How does freeze-dried stiffness and compactability compare to fresh allograft?
Same maximal stiffness
291
Based on recent literature, what type of allograft results in superior stem fixation?
Freeze-dried has superior stem fixation
292
What does the recent literature on use of freeze-dried allograft in adolescent idiopathic scoliosis surgery indicate?
Significantly lowers fusion rates
293
What is demineralized bone matrix?
Digested allograft and BMP
294
Is it osteoconductive or inductive?
Both
295
What are the three key points to know about BMP mechanism of osteoinductivity?
Serine/threonine kinase intracellular signaling pathway
296
What is the main disadvantage of osteochondral allografts?
Cartilage is immunogenic
297
How does cryogenic preservation affect chondrocyte number?
Very few remain
298
After implantation of osteochondral allograft, what happens to host chondrocytes?
Not preserved
299
How long is transplanted cartilage preserved?
2 to 3 years
300
What is the histological appearance thereafter?
Transplanted cartilage covered by fibrocartilage
301
Bottom line: How does the strength of cortical and cancellous grafts change over time?
Cortical grafts are strongest day 1; then resorbed and remodeled
302
What is the two-step sequence of chemical conversion of tricalcium phosphate (TCP)?
TCP rapidly broken down
303
Is TCP osteoconductive or inductive?
Osteoconductive only
304
Is TCP immunogenic?
No
305
What is the ideal ceramic pore size?
150 _m
306
What two factors determine the extent of allograft incorporation?
Cellularity
307
What cells mediate the immune response?
T cells
308
What surface structure on transplanted cells is recognized by host immune cells?
Surface glycoprotein
309
Mechanical properties of allograft change at what dose of radiation?
3 Mrad
310
What four growth factors act on chondrocytes?
IGF-I
311
What is the effect of IGF-I on the chondrocyte?
Stimulates matrix production
312
TGF-_ has what three effects on the chondrocyte?
Stimulates production of proteoglycans
313
Quick review: what other commonly tested role do Smads have?
Facilitate signaling and activity of BMPs
314
What are the two other key points about BMP?
Intracellular signaling through serine/ threonine kinase pathway
315
What is the net effect of FGF on chondrocytes?
Synthetic
316
PDGF is particularly important in what clinical situation?
Osteoarthritis
317
What is the predominant collagen type in articular cartilage?
Type II
318
What is the principal function of type II collagen?
Provides tensile strength
319
What three other collagen types may also be present in articular cartilage?
Type VI
320
Are type VI collagen levels higher with normal aging or with osteoarthritis?
Osteoarthritis
321
In what situation are type X collagen levels particularly elevated?
During enchondral ossification
322
Type X collagen is produced by what cells?
Hypertrophic chondrocytes
323
When does this occur?
>14 days after fracture
324
Type X collagen is generally associated with what process?
Calcification of cartilage
325
Type X collagen is deficient in what inherited syndrome?
Schmid metaphyseal chondrodysplasia
326
What is the principal function of type XI collagen?
Acts as an adhesive holding collagen together
327
What is the principal function of proteoglycans?
Provide compressive strength
328
How do they achieve this function?
By maintaining water within the matrix
329
What limits the total water content of normal cartilage?
The ordered structure of proteoglycan and collagen
330
What are proteoglycan subunits called?
Glycosaminoglycans (GAGs)
331
What are three commonly tested GAGs?
Chondroitin 4 sulfate
332
What GAG increases most significantly in concentration with normal aging?
Keratan sulfate
333
What GAG increases most significantly with osteoarthritis development?
Chondroitin 4 sulfate
334
What GAG concentration remains relatively constant despite aging or osteoarthritis?
Chondroitin 6 sulfate
335
How are GAGs bound to the protein core?
Sugar bonds
336
GAGs and the protein core form what molecules?
Aggrecan
337
What is the role of link proteins?
Stabilize aggrecan molecules to hyaluronic acid (HA)
338
Several aggrecan molecules stabilized to HA form what?
Proteoglycan aggregate
339
What is the half-life of a proteoglycan aggregate?
3 months
340
How can mature cartilage be differentiated from immature cartilage?
Mature cartilage has no stem cell population
341
What are the five zones of articular cartilage?
Gliding zone (superficial)
342
In general, where is water content the highest?
At the surface
343
In general, where is proteoglycan concentration the highest?
In the deep layers
344
Within the gliding zone, what is the fiber orientation?
Tangential
345
What is the function of this zone?
Resists shear
346
What is the level of metabolic activity?
Low
347
Within the transitional zone, what is the fiber orientation?
Oblique
348
What is the function of this zone?
Resists compression
349
What is the level of metabolic activity?
High
350
Within the radial zone, what is the fiber orientation?
Vertical
351
What is the function of this zone?
Resists compression
352
What is the collagen size?
Large
353
Within the tidemark, what is the fiber orientation?
Tangential
354
What are the two functions of this zone?
Resists shear
355
Is the tidemark seen best in adults or children?
Adults
356
Is the tidemark present in cartilaginous exostoses?
No, joints only (articular cartilage)
357
In the calcified zone, what is the key component?
Hydroxyapatite crystals
358
What is the function?
Acts as an anchor
359
How do these zones make cartilage biphasic?
Fluid layers shield solid matrix from stress
360
What two cell types are present within synovium?
Type A: responsible for phagocytosis
361
Does synovium have a basement membrane?
No; facilitates fluid transport
362
What three components of plasma are absent in synovial fluid?
Red blood cells
363
Compare complement levels in synovial fluid with rheumatoid arthritis and ankylosing spondylitis.
Rheumatoid arthritis: decreased levels of complement
364
How does the viscosity of synovial fluid change with shear? What does that say about synovial fluid?
Viscosity increases as shear decreases
365
Under conditions of high strain, what two things happen to the hyaluronan within synovial fluid?
Becomes entangled and forms a relatively solid cushion
366
Under conditions of instability, what happens to the hyaluronan within synovial fluid?
Hyaluronan content and efficacy decrease
367
Under conditions of disuse, what happens to the hyaluronan within synovial fluid?
No change
368
What are the two key lubricating components of synovial fluid?
Lubricin: a glycoprotein
369
What is hydrodynamic lubrication?
A thin film completely separates two articulating surfaces
370
What is elastic lubrication?
Articular surfaces deform slightly when loaded to create pockets of fluid
371
What is the primary method by which normal articular cartilage is lubricated?
Elastohydrodynamic: a combination of elastic and hydrodynamic lubrication
372
Comparison/review: What is the primary lubrication method for hard-on-soft articular bearings?
Boundary method
373
Comparison/review: What is the primary lubrication method for hard-on-hard articular bearings?
Mixed: hydrodynamic and boundary methods
374
What does _weeping_ refer to?
Under conditions of loading, fluid shifts to loaded areas of articular cartilage
375
What is the half-life of articular cartilage?
117 years
376
Because cartilage has such a long half-life, what is the rate of cartilage synthesis in adulthood?
Markedly diminished relative to earlier in life
377
What is the basic mechanism by which normal cartilage ages?
Passive glycation
378
What is the net effect of this process?
Increased cartilage stiffness (modulus of elasticity)
379
With aging, what changes are seen in chondrocyte number?
Decreases
380
What changes are seen in chondrocyte size?
Increases
381
What changes are seen in collagen variability?
Increases
382
What changes are seen in total proteoglycan concentration?
Decreases
383
What is the corresponding change in water content?
Decreases
384
In normal aging, what happens to chondroitin 4 concentration as a percentage of total chondroitin?
Decreases
385
What happens to keratan sulfate concentration?
Increases
386
Again, what is the net effect on modulus of elasticity?
Increased (increased cartilage stiffness)
387
Do superficial cartilage lacerations heal?
No, because cartilage is avascular
388
Do lacerations deep to the tidemark heal?
Yes, blood supply is available
389
What cell type is involved in healing?
Mesenchymal cells produce fibrocartilage
390
Is motion beneficial or detrimental to the healing of deep lacerations?
Beneficial
391
After BMP-7 application, what effect is seen at 4 weeks? At 8 months?
4 weeks: accelerated healing observed
392
Is there an observed difference in outcomes between microfracture and autologous chondrocyte implantation?
No demonstrated difference
393
What sequence of three steps is involved in autologous chondrocyte implantation?
Harvest cartilage
394
What is the maximum defect area for which this technology is applicable?
8 cm
395
What are the two potential benefits of hyaluronic acid injection?
Stimulation of fibroblasts
396
Have any chondroprotective effects been proven?
No
397
What location is the most reliable for successful injection into the knee?
Superolaterally
398
What two families of enzymes are involved with the development of osteoarthritis?
Metalloproteinases
399
What are three examples of metalloproteinases? What is a common factor among them?
Collagenase
400
What are the roles of tumor necrosis factor-a (TNF-a) and interleukin-1 (IL-1)?
Catabolic
401
What is more detrimental to articular cartilage: shear or compression?
Shear (e.g., instability)
402
With osteoarthritis development, what changes are seen in collagen order and relative concentration?
Increasingly disordered
403
What changes are seen in DNA within the chondrocytes?
No change; remains essentially normal
404
What changes are seen in rate of proteoglycan degradation?
Markedly increased
405
What changes are seen in proteoglycan concentration?
Decreases
406
What changes are seen in water content?
Increases
407
So, if a proteoglycan concentration determines water content, why does the water content increase in osteoarthritis when proteoglycan concentration decreases?
Because the ordered structure of proteoglycan and cartilage in normal cartilage limits total water content
408
In osteoarthritis, what happens to chondroitin 4 concentration as a percentage of total chondroitin?
Increases
409
What happens to keratan sulfate concentration?
Decreases
410
What happens to modulus of elasticity?
Decreases (decreased stiffness)
411
What joint is most commonly affected by osteoarthritis?
Knee
412
What are two subchondral changes?
Sclerosis
413
How do gross changes in cartilage appear?
As microfractures
414
What is the four-part Outerbridge classification of cartilage injury?
I: cartilage softening
415
With rheumatoid arthritis, what are the two key associated enzymes?
IL-1
416
What are the two key human leukocyte antigen (HLA) associations?
DR4
417
What virus may possibly be associated with rheumatoid arthritis development?
Epstein-Barr virus
418
What cell type is responsible for inciting inflammatory response?
T-cell
419
What cell type is responsible for the associated destruction?
Monocyte
420
What are the two key elements of the history and exam?
Morning stiffness
421
What four laboratory findings may be present in rheumatoid arthritis?
Elevated erythrocyte sedimentation rate (ESR)
422
What is rheumatoid factor?
An immunoglobulin M (IgM) antibody against IgG
423
What are the two classic radiographic findings of rheumatoid arthritis?
Periarticular erosions
424
What are the four classic disease-modifying antirheumatologic agents (DMARDs)?
Methotrexate
425
What drug is anti IL-1?
Anakinra
426
What three drugs are anti-TNF-a?
Etanercept: may be associated with demyelination as side effect
427
What drug is anti-B-cell?
Rituximab
428
What are the three characteristics of Felty's syndrome?
Rheumatoid arthritis
429
What are the three characteristics of Still's disease?
Acute fever
430
By definition, symptoms must last for how long to be considered juvenile rheumatoid arthritis (JRA)?
At least 6 weeks
431
What is the age criterion for JRA diagnosis?
16 years old or less
432
What joint is most commonly affected?
Knee
433
Are most JRA patients rheumatoid factor positive or negative?
Negative
434
What is the significance of rheumatoid factor positive JRA?
Increased likelihood of developing adult form of rheumatoid arthritis
435
How many joints must be affected for JRA to be considered polyarticular?
Five
436
What gender is most affected by early-onset pauciarticular JRA?
Female
437
What is the usual age at onset?
2 to 3 years old
438
What are two associated conditions to watch for?
Iridocyclitis
439
What gender is most affected by late-onset pauciarticular JRA?
Male
440
What is the usual age at onset?
Teenage years
441
What is the classic treatment for JRA?
High-dose aspirin
442
Ankylosing spondylitis (AS) patients generally feel stiffest at what time of day?
Morning
443
What joint is most often the first affected?
Sacroiliac joint
444
What physical exam finding is most specific for AS?
Decreased chest wall expansion
445
What are the two classic ocular findings?
Iritis
446
What two associated conditions may also severely complicate AS?
Pulmonary fibrosis
447
What two tests can be used to evaluate bone density in ankylosing spondylitis patients?
DEXA scan of the hip
448
What are the three classic spine findings of AS?
Bamboo spine
449
What is the two-part treatment for low-energy neck trauma in AS patients? Why?
Strict immobilization
450
What additional test may be beneficial in excluding an occult fracture?
Bone scan
451
Cervical spine fractures in AS patients may be associated with what complication? How can this be evaluated?
Epidural hemorrhage
452
What are two treatment options for cervical fractures in ankylosing spondylitis?
Halo vest
453
In general, surgical intervention on the spine of AS patients requires what approach?
Combined anterior and posterior approaches
454
What is the preferred osteotomy for treatment of AS-related kyphosis?
Pedicle subtraction osteotomy
455
What is the general rule for the amount of correction this osteotomy can give you?
30 degrees per level
456
At which level should cervical kyphosis generally be corrected?
C7-T1
457
At which levels should umbar kyphosis generally be corrected?
L2 or below
458
Quick review of syndesmophytes: What are the two key characteristics of the syndesmophytes associated with AS and inflammatory bowel diseases?
Marginal
459
What are the two key characteristics of the syndesmophytes associated with Reiter syndrome and psoriasis syndesmophytes?
Nonmarginal
460
What are the two aspects of the classic radiographic appearance of disseminated idiopathic skeletal hyperostosis (DISH)?
Nonmarginal syndesmophytes
461
What is the composition of the crystals associated with gout?
Monosodium urate
462
What are the two aspects of the appearance of crystals under plane-polarized light?
Yellow
463
Where do articular erosions generally appear in patients with gout?
Generally away from the joint surface itself
464
What is the drug of choice to inhibit associated inflammatory mediators?
Colchicine
465
What two drugs act to inhibit phagocytosis?
Phenylbutazone
466
What is the mechanism of action of allopurinol? When it is indicated?
Xanthine oxidase inhibition
467
What is the relationship between myeloproliferative syndrome (MPS) and gout?
Chemotherapy for MPS may precipitate an attack of gout
468
What are five potential causes of chondrocalcinosis?
Calcium pyrophosphate deposition disease (CPPD, positively birefringent crystals)
469
What is the primary site of arthritic involvement with systemic lupus erythematosus (SLE)?
Hands and wrists
470
What is the classic clinical feature of SLE?
Malar (butterfly) rash
471
What are the two key lab values?
Generally ANA+
472
How is SLE treated?
Generally the same as rheumatoid arthritis
473
Mortality from SLE is generally due to what?
Renal disease
474
Quick review: In general, when given a patient with avascular necrosis (AVN), what should always be in the differential diagnosis?
AVN secondary to chronic steroid therapy
475
What are two commonly tested disorders that may present this way?
Systemic lupus erythematosus
476
What is the associated mutation?
Homogentisic acid oxidase deficiency
477
This deficiency results in the accumulation of what substance?
Homogentisic acid, which is then deposited within joints
478
In what two ways is alkaptonuria diagnosed?
Urine is black
479
What are two characteristics of the associated spondylitis?
Disk space narrowing
480
What is the classic clinical presentation of relapsing polychondritis?
Episodic attacks of arthritic pain
481
What patient population is most commonly affected?
Elderly
482
Other clinical manifestations include what two organs?
Ears
483
What organism is responsible for acute rheumatic fever?
Group A streptococcus
484
What are the two relevant diagnostic tests?
Antistreptolysin O (ASO) titer
485
What is the key point about the resultant arthritis?
Migratory
486
Acute rheumatic fever preferentially involves joints of what size?
Large
487
Other systemic manifestations include what process in the heart?
Carditis
488
_ in the skin?
Erythema marginatum
489
_ in the neurologic system?
Chorea (movement disorder)
490
What is the classic triad of Reiter's syndrome?
Arthritis
491
What is the key clinical feature of the hand and wrist?
Tenosynovitis of the dorsal hand and wrist (especially if gonorrhea)
492
What is the key clinical feature of the skin?
Pustular lesions on palms and soles
493
What is the key clinical feature of the mucosal surfaces?
Oral ulcers
494
How frequently are the sacroiliac joints involved?
In 60% of patients
495
How often are Reiter syndrome patients HLA-B27 positive?
80 to 90%
496
What are the characteristic synovial fluid findings of tuberculosis?
Rice bodies (fibrin globules)
497
What is the smallest functional unit of muscle?
The sarcomere
498
What is the function of tropomyosin?
Prevents actin cross-bridge binding
499
What is the function of troponin?
Modifies tropomyosin to allow cross-bridge binding
500
Troponin function is sensitive to what?
Changes in calcium level
