T3 - L4 Diseases of the bone and new markers Flashcards
What is the purpose of bone?
- structural support for the body
- protection of vital organs
- blood cell production (bone marrow)
- storage bank for minerals (especially calcium)
What is cortical bone and trabecular bone?
Cortical bone = hard, outer layer
Trabecular bone = spongy, inner layer
What 2 types of cells are associated with bone?
Bone forming cells (osteoblasts)
bone reabsorbing cells (osteoclasts)
What is the extracellular component of bone composed of?
- organic matrix = mainly type 1 collagen
- inorganic components; hydroxyapatite and minerals
What is the name for bone before it has mineralised?
Osteoid
Bone matrix is mineralised by what? (to form mature bone tissue)
Hydroxyapatite (calcium-phosphate-hydroxide salt)
what do osteoblasts do?
- make osteoid
- communicate with other bone cells
- make hormones (e.g. osteocalcin), matrix proteins and alkaline phosphatase
- Prerequisite for mineralisation
what are features of osteoclasts?
- large surface area
- multi nucleated
- ruffled-resorption border
Describe some features of bone as a dynamic tissue
- extracellular matrix
- protein and mineral
- mainly collagen
- constant remodelling
- highly vascular tissue
- metabolically active
What does collagen do?
Provides tensile strength
What are osteoblasts?
Terminally differentiated products of mesenchymal stem cells that make osteoid
What is osteoid?
Non-mineralised organic matrix, consists of mainly type 1 collagen
- prerequisite for mineralisation
What is the name for osteoblasts that are buried/trapped within the matrix?
Osteocytes
Where are osteoclasts found?
In bone pits (resorption bays)
What do osteoclasts do?
- break down bone
- produce enzymes that are secreted to break down extracellular matrix
- help enhance blood calcium levels
Which enzymes do osteoclasts produce? (secreted to break down extracellular matrix)
Tartrate resistant acid phosphatase (TRAP)
Cathepsin K
Which hormones are osteoclasts regulated by?
PTH
calcitonin
IL-6
RANK ligand and osteoprotegrin do what?
Help with osteoclastic maturation and activity
What are osteocytes?
Trapped/buried osteoblasts
Describe the appearance of osteocytes
Star-shaped
How do osteocytes communicate with each other?
Via cytoplasmic extensions
What are the functions of osteocytes?
- mechanosensory properties (know which bone is being used)
- involved with regulating bone matrix turnover
Describe bone remodelling
Normal bone is in a constant state of turnover caused by resorption by osteoclasts and formation by osteoblasts
How often is the adult skeleton completely replaced?
Every 10 years
Simply, what is osteoporosis?
When there is more bone destruction than there is formation
What are the 4 main stages in the bone cycle?
- resting - lining cells of inactive osteoblasts
- resorption - osteoclasts are signalled to reabsorb areas
- osteoid formation - osteoblasts are signalled to form osteoids (non-mineralised type 1 collagen)
- mineralisation - osteoid becomes mineralised to hard bone.
How is bone mass measured?
Total mass of skeletal calcium in grams
How does bone mass change with age?
Increases from birth until a peak at around 30-40 where it then starts declining
Where is there is an accelerated bone loss in women around 50 years of age?
Due to menopause/oestrogen levels decline
what happens with bone mass as an individual ages?
- under 25’s still acquire their peak bone mass
- From 50’s onwards men and women are gradually losing bone mass year upon year
What 4 things about bone might you want to investigate?
- gross structure
- bone mass (calcium)
- cellular function/turnover
- microstructure/cellular function
How is bone gross structure investigated?
X-ray
How is bone mass (calcium) investigated?
DEXA Dual-Energy X-ray absorptiometry
[Shine two x-ray beams through bones to give a densitometry result of the bone]
How is bone cellular function/turnover investigated?
Biochemistry
How is bone microstructure/cellular function investigated?
Biopsy (rare)
Quantitative computed tomography (QCT)
What are the biochemical markers of bone formation?
Products of active Osteoblasts:
- alkaline phosphatase (TAP, BAP)
- osteocalcin (OC)
- procollagen type 1 prepeptides (P1NP)
What are the biochemical markers of bone resorption?
Degradation products of bone collagen:
- hydroxyproline
- pyridinium crosslinks
- crosslinked telopeptides of type I collagen (NTX, CTX)
+ osteoclast enzymes:
- Tartrate-resistant acid phosphatase (TRACP 5b)
- Cathepsin K
What are the osteoclast enzymes?
- tartrate-resistant acid phosphatase (TRACP 5b)
- cathepsin K
When is alkaline phosphatase measured?
Measured by the lab in LFTs and bone profiles
In health, what are the alkaline phosphatase levels?
50% liver
50% bone
NB: elevated alkaline phosphatase can be due to the liver
What is bone alkaline phosphatase involved in?
phosphatase involved in Mineralisation
What is bone alkaline phosphatase released by?
Osteoblasts
what is release of bone alkaline phosphatase stimulated by?
stimulated by increased bone remodelling e.g.:
- growth spurt
- fractures
- hyperparathyroidism (primary/secondary)
- pagets disease
What is P1NP?
Procollagen type 1N propeptide
What is P1NP synthesised by?
Osteoblasts
P1NP is the precursor molecule of what?
Type 1 collagen
P1NP levels are affected by what?
- increased with increased osteoblast activity
- decreased by reduced osteoblast activity
- serum concentrations not affected by food intake
- has low diurnal and intraindividual variation
What are collagen cross-links (NTX, CTX)?
Cross-linking molecules which are released with bone resorption
What do collagen cross-links levels correlate with?
Correlate highly with bone resorption
When do levels of collagen cross-links change?
- increased in periods of high bone turnover (hyperthyroidism, adolescents, menopause)
- decrease with anti-resorptive therapy
- have diurnal variation (change according to the time of day)
what is a disadvantage of using collagen cross-links as a bone resorption marker?
Do not predict bone mineral density
Decrease with anti-resorptive therapy
Collagen cross-links (NTX, CTX) are increased in periods of high bone turnover. Give 3 examples of when the body will experience high bone turnover.
- hyperthyroidism
- adolescents
- menopause
Collagen-related bone markers are based primarily on what?
type 1 collagen
Are changes in bone markers disease-specific?
no
reflect alterations in skeletal metabolism
What are the uses of new bone markers?
- evaluation of bone turnover and bone loss
- evaluation of treatment effect
- evaluation of compliance with medication
what is the bone marker CTX used for?
CTX used to monitor compliance/response to anti-resorptive therapy
which bone marker us used to measure compliance with teriparatide?
P1NP
What is teriparatide?
A form of parathyroid hormone - an effective anabolic (bone growing) agent used in the treatment of some forms of osteoporosis
T scores are given when doing a DEXA scan. What do T scores indicate
The T score indicates how many standard deviations the person is
away from the mean compared to someone who’s young, healthy and of the same sex
- 1 and above = normal born density
- 1 to -2.5 = low bone mass (osteopenia)
- 2.5 and below = osteoporosis
What is osteopenia?
When the protein and mineral content of bone tissue is reduced, but less severely than in osteoporosis
Which scan gives you T scores?
DEXA
What is osteomalacia?
Softening of the bones, typically through a deficiency of vitamin D or calcium
Why is hyperparathyroidism?
An abnormally high concentration of parathyroid hormone in the blood, resulting in weakening of the bones through loss of calcium.
What is osteoporosis?
The bones become brittle and fragile from loss of tissue, typically as a result of hormonal changes, or deficiency of calcium or vitamin D
what are risk factors of osteoporosis?
[Risk factors of osteoporosis: steroids, early menopause (earlier then 45), age, female,
smoker, alcohol and inflammatory conditions e.g. ulcerative colitis]
What abnormalities are seen in routine biochemical tests in osteoporosis?
None - perhaps because they are too insensitive
Diagnosis of osteoporosis relies on what?
DEXA/X-ray
What is the actual definition of osteoporosis?
- LOW BONE MASS
- MICROARCHITECTURAL DETERIORATION of bone tissue,
- consequent increase in bone fragility and susceptibility to fracture
Where are the common sites of fracture in osteoporosis?
- spine
- neck of femur
- wrist
What is the definition of a fragility fracture?
A fracture caused by injury that would be insufficient to fracture a normal bone/ occurs as a result of minimal trauma