Case 1 - Ageing and Bones Flashcards
1
Q
The adult skeleton is composed of how many bones?
A
206
2
Q
Bones are classified according to
shape into four groups:
A
◦ Long
◦ Short
◦ Flat
◦ Irregular
3
Q
Bones (like all connective tissue) is made of:
A
cells
extracellular matrix
4
Q
what are the cells that make up bones?
A
Osteoblasts
Osteoclasts
Osteocytes
5
Q
The organic parts (especially the collagen fibers) provides for what for the bone?
A
provide for bone’s
flexibility and great tensile strength (ability to be stretched without
breaking).
6
Q
The calcium salts deposited in the matrix give bone?
A
The calcium salts deposited in the matrix give bone its hardness, which
resists compression.
7
Q
collagen is for [bone structure]
A
tensile strength
8
Q
minerals is for [bone structure]
A
compressive strength
9
Q
2 basic types of bone structure are?
A
Compact bone
dense, looks
smooth and,
homogeneous
Spongy bone-
spiky, open
appearance like
a sponge
10
Q
Spongy bone (Cancellous/trabecular bone)- composed of?
A
small needlelike pieces
of bone (trabeculae) and lots of “open” space filled by marrow, blood vessels and
nerves
11
Q
In compact bone (cortical bone), the mature bone cells (osteocytes) are found where?
A
within the bone matrix in tiny cavities (lacunae).
12
Q
The lacunae are arranged how?
A
in concentric circles (lamellae) around central canals (Haversian canals)
13
Q
what is an osteon (Haversian system)
A
A complex consisting of a central canal and matrix rings is called an osteon
(Haversian system), and is the structural and functional unit of compact bone.
14
Q
how do central canals run in bone structure?
A
Central canals run lengthwise
through the bony matrix, carrying
blood vessels and nerves to all
areas of the bone.
15
Q
structure of long bone
A
- Epiphysis
- Metaphysis
- Diaphysis
- Physis/epiphyseal
plate/growth plate (in
children and adolescents) or
epiphyseal line (in adults) - Periosteum
16
Q
In infants, medullary cavity is?
A
a storage area for red marrow-producing RBCs.
17
Q
what does red marrow contain
what does yellow marrow contain
A
red marrow - RBCs
yellow marrow - adipose (fat) tissue
18
Q
In adult bones, red marrow is where?
A
red marrow is
confined to cavities in the
spongy bone of the axial
skeleton, the hip bones, and
the epiphyses of long bones
such as the humerus and
femur
19
Q
what is osteogenesis/bone ossification
A
the process of bone formation.
[Starts in embryo, week 6-7 as embryo, but ossification continues throughout
growth and into the mid-twenties]
20
Q
bone formation/Osteogenesis/Ossification from embryo to foetus - 2 bullet points
A
in an embryo, hyaline cartilage model is completely covered with bone matrix (a bone “collar”) by osteoblasts.
So, for a short period fetus has cartilage
“bones” enclosed by actual bone
matrix.
Then, in the fetus, the enclosed hyaline
cartilage model is replaced by bone,
and the center is digested away, opening
up a medullary cavity within the newly
formed bone
21
Q
what are the 2 types of osteogenesis?
A
intramembranous and endochondral
* Each processes begins with a mesenchymal tissue precursor, but how it
transforms into bone differs.
22
Q
what is Intramembranous ossification
A
Intramembranous ossification directly converts the mesenchymal
tissue to bone and forms the flat bones of the skull, clavicle, and most of
the cranial bones.
23
Q
what about the process of Osteogenesis-Intramembranous
A
- Neural crest-derived mesenchymal cells differentiate into osteoblasts.
- Osteoblasts group into clusters and form ossification centre.
- Osteoblasts become trapped by the osteoid. they secrete osteoid, transforming them into osteocytes.
- Trabecular bone and periosteum form.
- Cortical bone forms superficially to the trabecular bone.
- Blood vessels form the red marrow.
24
Q
the process of Osteogenesis-Endochondral
A
- Mesenchymal cells differentiate into chondrocytes and form cartilage
model for bone - Chondrocytes near centre of model hypertrophy and alter contents of the matrix they secrete, enabling mineralization
- Chondrocytes undergo apoptosis due to decreased nutrient availability, blood vessels invade and bring osteogenic cells
- Primary ossification centre forms in diaphyseal region of periosteum
called the periosteal collar - Secondary ossification centres develop in the epiphyseal region after
birth
25
where does Primary ossification centre form?
in the diaphyseal region of the periosteum and when the Primary ossification centre forms here, it's called periosteal collar
26
when does Secondary ossification centres develop
in the epiphyseal region after
birth
27
what does Osteoclast do
Breaks down bone (bone resorption)
Large, multinucleated cells
Important for bone remodeling
"Clast = Crash"
28
Osteoblast
Builds new bone
Secretes bone matrix (collagen + minerals)
"Blast = Build"
Eventually becomes osteocyte
29
Osteocyte
Mature bone cell
Maintains bone tissue
Lives in a lacuna
Derived from osteoblasts
30
Periosteum
Outer membrane covering bone (except at joints)
Contains nerves and blood vessels
Helps with growth, repair, and nourishment
31
Chondrocyte
Cartilage cell
Maintains cartilage matrix
Lives in lacunae (like osteocytes)
Found in joints, ear, nose, etc.
32
Physis/epiphyseal plate/growth plate - tell me about reserve zone
* Storage for lipids, glycogen, proteoglycan
33
Physis/epiphyseal plate/growth plate - tell me about proliferative zone
* Proliferating chondrocytes leading to longitudinal growth
34
Physis/epiphyseal plate/growth plate - tell me about hypertrophic zone
* Chondrocytes mature and prepare a matrix for calcification; then degenerate allowing calcium release for matrix calcification.
35
Physis/epiphyseal plate/growth plate - tell me about osteogenic zone
Primary Spongiosa
* Mineralization to form woven bone
* Vascular invasion occurs
Secondary Spongiosa
* Internal modeling with the replacement of immature bone with lamellar bone
36
By birth or shortly after
, most hyaline cartilage models have
been converted to bone except for two regions, which are
the articular cartilages (that cover the bone ends) and the epiphyseal plates.
37
what occurs for bones to increase in length as the infant grows into a child
new cartilage is formed continuously on the external face (joint side) of the articular cartilage and on the epiphyseal plate
surface that faces the bone end (is farther away from the medullary cavity). Simultaneously, the old cartilage (adjacent to the internal face of the articular cartilage and the medullary cavity) is broken down
and replaced by bony matrix.
38
Endosteum
Thin membrane lining the inside of bones
Covers the inner surface of the bone marrow cavity
Contains osteoblasts & osteoclasts
Helps with bone growth, repair, and remodeling
"Endo" = inside
39
hypertrophy
Increase in cell size (not number)
Leads to enlarged tissue or organs
Common in muscle growth from strength training
Can also occur in the heart or other organs
"Hyper" = more, "trophy" = growth
40
process of bone growth-widening
*Growing bones also widen as they lengthen to maintain proper proportion.
*Osteoblasts in the periosteum add bone matrix to the outside of the diaphysis.
*Osteoclasts in the endosteum remove bone from the inner face of the diaphysis wall,
enlarging the medullary cavity.
* Because these two processes occur at about the same rate, the circumference of the long
bone expands, and the bone widens.
41
appositional growth and what hormones involved in this?
process by which bones increase in diameter is called appositional growth
* The most important hormones here are growth hormone and, during puberty, the sex hormones.
[this process ends during adolescence, when the epiphyseal plates are completely converted to bone.]
42
clinical sign of rickets
bowed legs
43
rickets is caused by
* Most commonly caused by a
vitamin D deficiency.
* Leads to the softening and
weakening of bones in children.
* The main mechanism is
insufficient
calcification at the growth plate
during bone formation
44
what is a fracture
“Break in the structural
continuity of bone”
45
fracture can be caused by?
* Single traumatic event
* Repetitive stress
* Pathological fracture - abnormal weakness in bone
46
what is a simple/closed fracture
A fracture in which the bone breaks
cleanly but does not penetrate the
skin
47
what is an open/compound fracture
When the broken bone ends
penetrate through the skin
48
Common types of fractures - name 2 or 3
comminuted - bone breaks into 3 or more fragments
compression - bone is crushed
depression - broken bone portion is pressed inward
impacted - broken bone ends are forced into each other
spiral - ragged break occurs when excessive twisting forces are applied to a bone
greenstick - bone breaks incompletely, much in the way a green twig breaks
49
average healing time of simple bone fracture
6-8 weeks
50
Salter-Harris classification - what are Salter-Harris fractures?
* Salter-Harris fractures are
fractures of the epiphyseal
plate.
* Can result in decreased
longitudinal growth, angular
deformity, and altered joint
mechanics.
* Type I to V: increasing in
severity in children
* (Eg: Type I has less effect on
bone growth and heals well.
Type V has compression)
51
Salter-Harris fracture classification - what are types I to V?
* Type I: separation through the physis
* Type II: fracture enters the plane of the
physis and exits through the metaphysis
* Type III: fracture enters the plane of the
physis and exits through the epiphysis
* Type IV: fracture crosses the physis and
extends from metaphysis to epiphysis
* Type V: fracture is a crush injury
52
what are the 2 things bone remodeling consists of?
1. Osteoclastic resorption
2. Osteoblast deposit new bone
53
Bones are dynamic and active tissue and are remodeled continually in
response to changes in two factors:
(1) the calcium ion level in the blood and
(2) the pull of gravity and muscles on the skeleton.
54
what happens when there's low blood calcium levels [bone remodeling]
parathyroid hormone (PTH) is released
PTH activates osteoclasts >> release calcium ions into the blood
In hypercalcemia >> calcium is deposited in bone matrix by osteoblasts
55
In bedridden or physically inactive people, what happens to the bone
bone tends to lose mass and to atrophy because they are no longer subjected to
stress.
56
Fracture repair is the biological response to..
and it results in?
traumatic bone injury
It results in activation of the same processes which contribute to
the development and growth of the skeleton i.e.
−Cell proliferation
−Tissue differentiation
57
Bone Healing: stages
Stages of ‘natural’ bone healing:
◦ Haematoma
◦ Inflammation
◦ Granulation
◦ Callus
◦ Consolidation
◦ Remodelling
58
‘natural’ bone healing - Haematoma
* Blood vessel tearing
* Local bleeding
* Defect between fracture
ends filled with blood clots
59
‘natural’ bone healing - Inflammation
* The injury results in acute
inflammation.
* Disposal of dead tissue by
phagocytes
60
‘natural’ bone healing - Granulation
* In-growth of new capillaries
(granulation tissue)
* By day 5, the granulation tissue
has replaced the clot and
extends into the marrow cavity
61
‘natural’ bone healing - Callus
* Islands of cartilage appear (especially
near the periosteum)
* The fracture ends are now united by a
sleeve of vascularised granulation
tissue and cartilage = provisional
callus
* Act to “splint” the broken bone,
closing the gap
62
Consolidation: Bony callus formation
* By the end of week 1: Calcium is deposited
in the cartilage.
* Osteoblasts start to produce a seam of
osteoid across the fracture.
* As more osteoblasts and osteoclasts
migrate into the area and multiply, the
provisional callus is gradually replaced by
the bony callus made of spongy bone.
* The callus calcifies and the ends unite with
bony callus
63
‘natural’ bone healing - Remodelling
*Woven bone (immature)
replaced by lamellar bone
(osteoblasts and osteoclasts)
*Excess bone is slowly resorbed
*Takes years
*Often incomplete
64
Osteoporosis WHO definition
“Metabolic bone disorder
characterised by low bone
mass and microstructural
deterioration in bone tissue,
leading to increasing bone
fragility, thus increasing the
risk of fracture"
65
type of osteoporosis
Primary:
* Post menopausal
* Age related
Secondary:
* Drug related
* Comorbidities
66
diagnosis of osteoporosis
Bone density scan (DEXA) is
the gold standard in the
diagnosis of osteoporosis,
measured in the spine and hip.
[* Relying on this alone
underestimates the number
who go on to bony fracture]
67
what about a DEXA scan - how does it work
T-score
* An Objective score
* Measures standard deviation
(SD) comparing a normal
healthy adult in their 20s of
the same sex
68
DEXA scan in osteoporosis
* Osteoporosis is diagnosed at the T-score of
less than or equal to minus five SDs
or
* patient onset fragility fracture whatever the
T-score is.
69
DEXA scan in Osteopaenia
* When the T-score is minus one to minus 2.5
SD, it is called osteopenia.
70
name 3 risk factors of osteoporosis
* Female
* >50y
* No children
* Post-menopausal
* Early menopause
* Caucasian/ Asian
* Sedentary lifestyle
* Slim
* Alcohol
* Smoking
* Thyroid
* Hypogonadism
* Some drugs e.g. proton
pump inhibitors
71
low levels of oestrogen in osteoporosis
* Low levels cause increase in
osteoclast : osteoblast
* Cause apoptosis of
osteoclast normally
* Lower levels of oestrogen in Caucasian
and Asians
72
signs of osteoporosis (name 3)
* Shorter than they were
* Skeletal tenderness
* Kyphosis
* Hump
* Unsteady
* Whether they are
wearing a plaster (on a
current fracture)
73
tests for osteoporosis
* X-ray: Is there a fracture?
* DEXA
* Full blood count
* Bone profile
* Renal test
* Liver function test
* Thyroid function test
The blood tests will be normal in idiophathic osteoprosis
74
NICE definition of Osteoporotic Fracture
NICE: “a fragility fracture is caused by a force which would not normally break a bone. (Low energy trauma)"
75
WHO definition of Osteoporotic Fracture
WHO: “low energy trauma causing osteoporotic fracture is equivalent to falling from standing height or less.”
76
what bone is Commonest reason of fragility fractures
femur
77
what about Stresses on bone
* Thinning of the cortex reduces
the bone’s ability to withstand
flexion and compression
forces.
* These cortical lines become
less dense as osteoporosis
progresses.
78
other than femur, what other bones have fragility fractures
humerus
wrist
spine
79
predictors of osteoporosis (name 1)
* Any recent fracture in over 50 should
prompt osteoporosis investigation.
* Strongest predictor of fragility fracture
is previous fracture.
* New fragility fracture usually soon after
the first
80
Osteoporosis Treatment - Primary prevention & Prohpylaxis
* Weightbearing and strengthening exercise
* Stop smoking
* Reduce alcohol
* Healthy diet
* Calcium and vitamin D
81
Osteoporosis Treatment - medications & Secondary prevention
Secondary prevention: post
menopausal with history of
fracture
* Bisphosphonates
* Strontium
* SERMS
* PTH
* Calcium and vitamin D
* HRT
82
Osteoporosis Treatment - what about Bisphosphonates
* First line drugs
* Alendronate: reduces vertebral, wrist, hip fracture risk by 35-39%.
* Works by preferential binding to calcium (so collects in high
concentrations in bone) and mimics pyrophosphate (so inhibit enzymes
which use it).
* Inhibits bone absorption by encouraging osteoclasts to die by
apoptosis and so slows bone loss.
* May be stopped after 5y in low risk, 10y in high risk.
83
side effects of Bisphosphonates in Osteoporosis treatment - name 2
stomach, AF, jaw osteonecrosis, bisphosphonate fracture
84
other medications, other than Bisphosphates for Osteoporosis and how they work
* Calcium and vitamin D reduces fracture risk but recent studies show little evidence their use
* Strontium – increases bone deposit by osteoblasts and reduces absorption by
osteoclasts so a dual action bone agent (DABA) but high risk of MI identified
in 2013 so restricted use.
* SERM– raloxifene reduces vertebral fracture risk. Selective (o)Estrogen Receptor Modulator
* PTH– teriparatide (recombinant parathyroid hormone) triggers new bone formation. But theoretical risk of osteosarcoma
85
