1
Q
What is bone?
A
Ridged inflexible mineralised connective tissue
2
Q
What is bone mineralised by?
A
Calcium and phosphate salts
3
Q
Why are bones important?
A
- Provides physical integrity/ support
- Protects squishy organs
- Allows for insertion of muscles and tendons
- Provides minerals
- Important in haematopoiesis
4
Q
What minerals does bone provide
A
- Calcium
- Phosphorous
- Magnesium
5
Q
What is haematopoiesis?
A
It is the formation, development and maturation of blood cells in adult bone marrow
6
Q
Where does haematopoiesis occur in adults?
A
Bone marrow
7
Q
Name the parts that make up bone
A
- Non cellular mineralised matrix
2. Cells that maintain the matrix
8
Q
What is the matrix that makes up bone made up of?
A
- Type I collagen- osteoid
- Calcium phosphate (calcium hydroxyapatite)
- Regulatory protein and growth factors
9
Q
What is type 1 collagen in bone called?
A
Osteoid
10
Q
List the cells that maintain the matrix in bone
A
- Osteoblasts
- Osteocytes
- Osteoclasts
11
Q
Why is mineralisation critical?
A
The osteoid would be soft and bendy if it wasn’t mineralised
12
Q
What do osteoblasts do?
A
They build up the bone
13
Q
What is the origin of osteoblasts
A
Mesenchymal origin
14
Q
What is the function of osteoblasts?
A
- They secrete osteoid
2. Needed for mineralisation
15
Q
What are osteocytes
A
Inactive osteoblasts that are trapped in the bone
16
Q
What is the origin of osteoclasts
A
Macrophage lineage
17
Q
What do osteoclasts do?
A
They are involved in bone resorption and remodelling
18
Q
How can bone be categorised?
A
- Maturity type
2. Location type
19
Q
Name the different types of bone based on maturity
A
- Woven bone (immature bone)
2. Lamellar bone
20
Q
Describe woven bone
A
It is immature bone as the osteoid collagen is random
It is remodelled into lamellar bone
21
Q
What causes the random osteoid formation in woven bones?
A
Rapid bone turnover by osteoblasts
22
Q
What is woven bone remodelled into?
A
Lamellar bone
23
Q
Where is woven bone found?
A
In fractures
Fetal developemt
24
Q
Describe lamellar bone
A
Made up of parallel bands/ sheets of lamellae
25
Where is lamellar bone found?
Makes up the majority of normal healthy adult bone
26
What are the two different types of lamellar bone?
Compact (CB)
| Cancellous (T)
27
Which type of bone is stronger? WHY?
Lamellar bone is much stronger due to regular arrangement of lamellae
28
Name the different types of bone based on location?
1. Cortical/ compact
| 2. Cancellous. trabecular
29
Describe Cortical bone
Has a hard outer shell and regular shape
It is highly organised
Follows the Haversian system
30
What system does cortical bone follow?
The Haversian system
31
What is the Haversian system
Columns of lamellar bone (v compact and dense)
32
Describe cancellous/ trabecular bone
Spongy non structural "filler" bone
33
What is found in the spaces between cancellous bone?
Bone marrow
34
How are the different bone types organised?
Cortical bone surrounds cancellous bone
35
Why is bone remodelling important?
1. To maintain bone strength as your bones constantly suffer from trauma like micro fractures through the day
2. To be able to release metabolites
36
List the stages of the bone remodelling cycle
1. Activation
2. Resorption
3. Reversal
4. Formation
37
How is bone remodelling activated?
By hormones or damage
38
What happens when bone remodelling is activated by hormones of damage>
1. Osteoblasts are activated
2. Cytokines are released
3. Osteoclasts stick to the surface of the bone
39
What is the next stage after activation in the bone remodelling cycle
Resorption
40
What happens in the Resorption stage of the bone remodelling cycle
1. Mono nuclear osteocytes that are stuck to the surface of bone secrete substances
2. These substances resorb bone
3. Create pits on the surface
4. Mono nuclear osteocytes undergo apoptosis or migrate
41
What is the next stage after Resorption in the bone remodelling cycle
Reversal
42
What happens in the reversal stage of the bone remodelling cycle
Monocytes clear debris for bone formation
43
What is the next stage after reversal in the bone remodelling cycle
formation
44
What happens in the formation stage of the bone remodelling cycle
1. Osteoblasts are recruited
2. They secrete osteoid matrix and initiate mineralisation
3. Osteoblasts sit on the new bone
4. some undergo apoptosis and some are incorporated as osteocytes
45
What is another name for immature bones?
Woven bone
46
What is another name for mature bones
Lamellar bone
47
Compact and cancellous bone are both what type of bone?
Lamellar bone
48
What is osteoarthritis?
Progressive erosion of articular cartridge
49
Is osteoarthritis just erosion?
No it is a complex imbalance of damage and repairs
50
What happens in osteoarthritis
Underlying bone is exposed
This leads to damage and the formation of cysts / osteophytes causing inflammation pain
This ultimately leads to narrowing joint space
51
What are osteophytes
Abnormal growth in bone
52
How common is osteoarthritis?
uptown 80% of over 65s have evidence of having osteoarthritis
53
What are some of the symptoms of osteoarthritis
1. Pain/ functional limitation
| 2. Morning stiffness
54
What are some of the signs of osteoarthritis
1. Crepitus (crunchy)
2. Restricted movements
3. Bony enlargement
4. Instability/ muscle wasting
55
What are the differences between signs and symptoms
Signs are something you observe as a clinical
| Symptoms are things patients present with
56
What is a primary cause for disease?
Unknown cause or unknown origin for a disease
| no underlying cause for the disease
57
Give some secondary causes of osteoarthritis
1. Pre existing joint damage
2. Metabolic disease
3. Systemic disease
58
How do you investigate osteoarthritis
1. Blood tests to make sure rheumatoid factor is negative and to look for bone markers
2. X-tay will show cartilage loss. joint space narrowing and cysts
59
What would a raised rheumatoid factor suggests?
the patient may have rheumatoid arthritis
60
How do we manage osteoarthritis
1. Physical: weight loss, hydrotherapy
2. Medications: NSAIDS, steroids
3. Surgery: joint replacement
61
What is rheumatoid arthritis?
It is an autoimmune disease consisting of persistent inflammation (synovitis) leading to chronic symmetrical
62
List the 3 factors that strongly influences the progression of rheumatoid arthritis
1. Gender: women at higher risk
2. Genetic: associated with human leucocyte antigen (HLA)
3. Environmental: periodontal disease may contribute to it
63
Who is most affected by rheumatoid arthritis?
Younger (30-50) women
64
What does synovitis
Inflammation
65
What happens in rheumatoid arthritis
Citrullination of self antigens leading to loss of normal tolerance as the antigens are no longer recognised as self cells
Auto immune response occurs leading to inflammation leading to damage
66
What is citrullination?
Protein modification from arginine to citrulline
67
What are the differences between rheumatoid arthritis and osteoarthritis?
Rheumatoid arthritis is an autoimmune synovitis leading to mass formation and sticking of joins together
Osteoarthritis is just breakdown of cartridge leading to damage to bone
68
What is ankylosis
Abnormal stiffening/ immobility in joint due to bony fusion
69
How do we investigate rheumatoid arthritis
1. Blood tests: bony markers present and look for anti citrullinated peptide antibodies. Can also look for rheumatoid factor
2. X rays show synovitis and joint damage
70
How do we manage rheumatoid arthritis
Theres no cure
| Can give them anti inflammatories, steroids, anti-TNF, disease modifying anti rheumatic drugs (DMARD)
71
What is Paget's disease?
A disorder of bone turnover/ remodelling
72
Wjay happens in paget's disease?
Increased osteoclastic bone resorption leading to increased new bone formation
Formation happens at a faster rate than resorption but woven bone is made
73
What is the problem with increased formation of woven bone?
Woven bone is weaker than lamellar bone
| This can leaf to deformity and increased risk of fracture
74
What is the aetiology of paget's disease
Unknown aetiology
Suggested to be a combination of environmental and genetic
Mutation in osteoblast gene
75
How is paget's disease presented in most people?
60-80% asymptomatic
| Some present with bone pain/ joint pain or bone deformities
76
If Paget's disease is mainly asymptotic how is it diagnosed?
Usually patients come in for an X-ray and the x ray shows changes
77
Describe how the bone in patients with Paget's disease may look
Cotton wool like appearance (hypercementosis)
78
What are some of of the side effects of having Paget's disease?
1. Nerve compression leading to deafness
2. Spinal stenosis
3. Hydrocephalus
4. Cardiac failure, myocardial hypertrophy due to increased blood flow
5. Pathological fractures
6. Osteosarcoma
79
What is hypercementosis
Excessive cementum on the roots of teeth
80
Name the stages of paget's disease
1. Hot osteolytic phase
2. Mixed phase
3. Cold osteosclerotic phase
81
What happens in the hot osteolytic phase of Paget's disease?
Osteoclasts are breaking down bone
82
What happens in the mixed phase of Paget's disease?
Both osteoclasts and osteoblasts are working
83
What happens in the Cold osteosclerotic phase of Paget's disease?
Burn out inactive phase but bone is still weak and woven
84
How do we treat paget's disease?
With biphosphonates
85
How do biphosphonates work?
1. Inhibit osteoclasts recruitment
2. Inhibit osteoclast activity
3. Slow bone loss
86
Other than Paget's disease what else can biphosphonates treat?
Used in osteoporosis
87
What is a serious side effect of using biphosphonates?
Osteonecrosis of the Jaw
88
What is osteomyelitis?
Inflammation of bone / bone marrow
89
What is osteomyelitis almost always due to?
Virtually always secondary to infection
90
How do most people develop osteomyelitis
1. Haematogenous spread (through blood)
2. Extension from adjacent site
3. Direct implantation
91
What is the most common cause for children developing osteomyelitis
Haematogenous spread
92
What is the most common cause for adults developing osteomyelitis?
Fractures
Surgical infections
Diabetic foot
93
Describe the clinical presentation of osteomyelitis
1. Fever
2. Localised bone pain
3. Overlying tenderness/ erythema
94
How do you diagnose osteomyelitis
1. MRI / bone scan
2. Blood cultures
3. Bone culture and sensitivity test
95
How do we treat osteomyelitis
Immobilise
Antibiotics
Can drain or make excision
96
How common is chronic osteomyelitis
Occurs in 5-25% of cases
97
What os the cause of osteomyelitis of the jaw and when does it happen?
It has a poly microbial cause and is secondary to odontogenic infection
98
Name some different types of osteomyelitis
1. Chronic osteomyelitis
2. Osteomyelitis of the jaw
3. Tuberculosis osteomyelitis
99
Name some historical subtypes of osteomyelitis
1. Focal sclerosing
2. Diffuse sclerosing
3. Proliferative periostitis
100
Define fractures
Loss of bone integrity
101
What can fractures be caused by?
Mechanical injury and/or diminished bone strength
102
Give examples of different types of fractures
1. Simple
2. Compound
3. Comminuted
4. Displaced
5. Stress
6. Greenstick
7. Pathologic
103
What is a compound fracture?
A fracture where bone is exposed
104
What is a stress fracture
A slow developing fracture due to repeated repetitive loads
105
What is a greenstick fracture
Partial fracture through bone
106
What is a pathologic fracture
Weakened bone due to existing disease
107
List the 3 phases of fracture healing
1. Inflammatory phase
2. Reparative phase
3. Remodelling phase
108
What is another name for the reparative phase of fracture healing
Endochondral
109
What happens in the inflammatory phase of fracture healing
1. Haematoma forms
2. Macrophages, neutrophils and platelets release cytokines
3. Fibroblasts and mesenchymal cells go to fracture site
4. Granulation tissue forms around the fracture ends
5. Neurovascularisation
6. Osteoblasts, chondrocytes, fibroblasts proliferate
110
What are the benefits of a haematoma forming?
Stems blood flow from site of injury and is also a source of haemopoietic cells and growth factors
111
What is granulation tissue?
Vascular tissue
112
What does the inflammatory phase ultimately lead to the formation of?
A callus
113
What happens in the reparative phase of bone healing
1. Primary callus forms quickly
2. Cartilage provides provisional stabilisation
3. Endochondral ossification converts soft callus to hard callus
114
Why is the reparative phase also known as the endochondral phase
As endochondral ossification converts soft callus into hard callus
115
What is soft callus?
Cartilage
116
What is hard callus
Woven bone
117
What happens in the remodelling phase of bone healing
1. Bony callus tissue is resorbed
| 2. Osteoblast and osteoclast remodel to bones original cortex structure
118
What is osteonecrosis?
Infarction of bone/marrow
119
What is osteonecrosis also known as?
Avascular, aseptic or ischaemic necrosis
120
What are most cases of osteonecrosis due to?
Alcohol
Steroids
Fractures
121
What is the underlying cause of ALL cases of osteonecrosis?
Vascular insufficiency through mechanical injury to blood vessels, thromboembolism, external pressure
122
Is osteonecrosis due to infection?
NO it is aseptic
123
What do patients with osteonecrosis osteoarthritis display?
```
Joint pain (shoulder or hip)
Can be asymptomatic
```
124
What will an MRI of osteonecrosis show?
Bone marrow oedema / plain x ray
125
How do we manage osteonecrosis
1. Surgical decompression
2. Grafts
3. Joint replacement
126
What controls serum calcium in the body
Vitamin D
| Parathyroid hormone
127
What is released if calcium levels are low?
Parathyroid hormone
128
How does the parathyroid hormone help increase calcium levels
1. Increased osteoclast bone resorption
2. Increased intestinal calcium absorption
3. Increased renal tubular resorption Ca
4. Increased renal excretion of PO4
129
How does vitamin D increase calcium levels?
Increases intestinal absorption of calcium which increases mineralisation of bone
130
What effect does serum calcium on vitamin D?
Vitamin D increases bone respiration with LOW serum calcium
BUT
decreases bone resorption with HIGH serum calcium
131
What is another term for rickets
Osteomalacia
132
What causes rickets?
Defective mineralisation
133
What is rickets
Defective mineralisation of epiphyseal plate in children that can lead to weakened (bendy) bones
134
What is osteomalacia?
Defective mineralisation of epiphyseal plate in adults that can lead to weak bone formation during remodelling and makes the patient vulnerable to fractures
135
What is the aetiology of rickets/ osteomalacia
Anything that interferes with bone mineralisation Eg
1. Deficient intake or absorption of vitamin D
2. Defective 1alpha hydroxylation eg renal failure
3. Primary renal phosphate wasting
4. Inhibitors or mineralisation
5. Defective vitamin D receptors
136
What causes vitamin D deficiency?
1. Nutritional (dietary, inadequate exposure to sunlight)
2. Malabsorption due to coeliac disease
3. Vitamin D dependent rickets type 1 and 2
137
What happens in vitamin D deficiency?
1. Reduced serum calcium phosphate
2. Parathyroid hormone secreted causing bone to demineralise
3. Increased serum calcium
4. Bone is now poorly mineralised
138
Give some dentinal complications of rickets
1. Familial hypophospataemia
2. Hypoplasia
3. Missing teeth
139
Give some signs and symptoms of Familial hypophospataemia
1. Abnormally large pulp chamber
2. Thin enamel
3. Dentinal defects/ globular dentin
4. Dentinal abscesses more common
140
What is hyperparathyroidism?
Anything that causes pathological increase of parathyroid hormone
141
What can increased parathyroid hormone lead to ?
1. Increased osteoclast bone resorption
2. Increased intestinal calcium absorption
3. Increased synthesis of D3
4. Increased renal tubular resorption of calcium
5. Increased renal excretion of PO4
142
Name the 3 types of hyperparathyroidism
1. Primary: Autonomous hyperparathyroidism
2. Secondary: Compensatory hyper secretion
3. Tertiary: persistent hyperparathyroidism even when decreased calcium corrected
143
What is primary hyperparathyroidism the most common cause of?
Asymptomatic hypercalcemia
144
What is primary hyperparathyroidism caused by?
1. Adenoma
2. Hyperplasia
3. Malignancy
145
What symptoms do patients with primary hyperparathyroidism present with?
1. Bone disease/ bone pain (BONE)
2. Renal stones (STONES)
3. GI disturbances including constipation, nausea, peptic ulcers (GROANS)
4. CNS alterations eg depression and seizures(MOANS)
146
What is secondary hyperparathyroidism categorised by?
Any condition that causes reduced calcium leading to increased para thyroid hormone
147
What is osteogenesis imperfecta also known as?
Brittle bone disease
148
What is osteogenesis imperfecta caused by?
Gene mutation affecting the type 1 collagen gene (osteoid)
149
What is osteogenesis imperfecta usually presented with?
Increased fractures (can start in utero)
150
List some dentinal manifestations of osteogenesis imperfecta
Dentinogeneisis imperfecta type II
151
Name the 2 types of ossification
1. Endochondral
| 2. Intramembranous
152
Which type of ossification occurs in the maxilla and mandible?
Intramembranous ossification
153
What is Intramembranous ossification
Deposition of bone within primitive mesenchymal tissue
154
What is achondroplasia due to?
FGFR3 gene mutation
155
What is the purpose of the FGFR 3 gene
It inhibits endochondral growth
156
What happens with the FGFR 3 gene undergoes gene mutation?
Can impair cartilaginous growth
157
What does FGFR3 stand for
Fibroblast growth factor receptor
158
What can patients with achondroplasia present with|?
Short limbs
| Normal skull/ trunk
159
List some craniofacial issues patients with achondroplasia may suffer from
1. Macrocephaly / prominent forehead
2. Flattened/ depressed nasal bridge
3. Hypoplasia of midfacial structures
4. Maxilarry hypoplasia
5. Relative overgrowth of the mandible
6. Narrowing of anterior palate, open Bute
7. Orthodontic intervention
3rd yr- IWB- Pathology
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