CP9-4 bone and new markers Flashcards
What is the purpose of bone?
Facilitates movement
Provides scaffolding for whole body
Protects organs
Source of important hormones and chemicals
Production of blood cells e.g. bone marrow
What is the composition of bone?
Formed of cortical bone = hard outer layer
And trabecular bone = spongy inner layer
How much of bone in the skeleton is cortical and trabecular?
Cortical = 80%
Trabecular = 20%
What cells are found in bone?
Bone forming
Bone resorbing
Bone co-ordinating
What is the extracellular composition of bone?
30% organic matrix mainly formed of osteoid collegan
70% inorganic components e.g. calcium and phosphate and minerals like Mg, Na and K
Why is bone in a constant state of turnover?
As it is dynamic with an extracellular matrix which causes mineralisation and leads to bone remodelling
What are oestoblasts?
Bone forming cells which:
Become osteocytes
Make osteoid
Mineralise organic matter
Communicate with other bone cells
Produce hormones
What are osteoclasts?
Resorbing cells which breakdown bone which are regulated by PTH (parathyroid hormone), calcitonin and IL-6
What are osteocytes?
Bone cell originating from osteoblasts which co-ordinates the osteoblasts and osteoclasts
How often is the whole skeleton replaced?
Every 10 years
What stimulates osteoclasts?
RANK
RANKL
What inhibits osteoclasts?
OPG
Denosumab
Which gender has a lower peak bone mass?
Females
What causes females to have a more rapid/accelerated loss of bone mass?
The menopause
What disease is more common in women due to lowered peak bone mass and accelerated bone loss?
Osteoporosis
How does bone formation and resorption change with age?
As age increases, bone formation decreases and resorption increases (more breakdown than production of bone so bones become weaker)
How is bone disease investigated?
With imaging - X ray, MRI and CT
Calculate bone mineral density/mass with DEXA to look at calcium
Biochemistry/ bloods to look at cellular turnover
Biopsy and qCT to assess microstructure of bone (rare)
What are examples of biochemical markers of bone formation/osteoblasts?
Products of active osteoblasts:
- alkaline phosphatase/ALP (TAP and BAP have to be specifically requested)
- osteocalcin
- procollagen type 1 pro peptides aka P1NP
What are examples of biochemical markers of bone re absorption/osteoclasts?
Segregation products of bone collagen:
- hydroxyproline
- puridinium crosslinks
- CTX aka cross linked telopeptides type 1 collagen
Osteoclast enzymes:
- TRACP 5b
- cathepsin K
Why do specific isoenzymes need to be measured when diagnostic doubt over raised ALP levels?
Don’t know if bone or liver increasing ALP so helps to distinguish when diagnostic doubt
What is bone alkaline phosphatase?
Phosphate involved in mineralisation. Released by osteoblasts when stiumlated by increases bone remodelling e.g. in fractures, growth spurts, Paget’s, hyperparathyroidism ,
What is P1NP?
What are collagen cross links (NTX and CTX)?
Cross linking molecules which are released with bone resorption. They increase in periods of high bone turnover, have diurnal variation but do not predict bone mineral density.
What does CTX represent?
Osteoclastic activity
What treatment can decrease CTX levels?
Anti-resorptive therapy
What are bone markers?
collagen related markers based primarily on type 1 collagen and reflect changes in skeletal metabolism. Some have significant intraindividual variability.
What are tests for bone markers used for?
Treatment efficacy
Evaluate bone turnover and loss
Evaluate adherence to medication
What medication can P1PN be tested to check adherence for?
Teriparatide
What does DEXA measure?
Bone density and compares between bones
How are DEXA images scored?
With T-scores where -1 and above means normal bone density, between -1 and -2.5 is classed as osteopenia and -2.5 and below is classed as osteoporosis
What T- score is a cut off for osteoporosis?
-2.5 and below
What T-score suggests a patient has too high bone formation?
+3.5
What are 5 examples of bone disorders?
Metastatic disease
Hyperparathyroidism
Osteomalacia/rickets
Osteoporosis
Paget’s disease
What is osteoporosis?
Decreased bone mass with deterioration of bone micro architecture causing failure of structural integrity increasing bone fragility and susceptibility to fracture
What are common risk factors for osteoporosis?
Aging
Glucocorticoids
How is osteoporosis diagnosed?
With DEXA scan or an x-ray
What is the epidemiology of osteoporosis?
1 in 2 some
1 in 5 men
500,000 incidences of fragility fractures a year in UK
2-3x increased risk of another fragility fracture after 1st within 2 years
What is a fragility fracture?
A fracture caused by an injury insufficient to fracture a normal, healthy bone e.g. a fracture as a result of a fall from standing height it less or no identifiable trauma
What are risk factors for fragility fractures?
Age
Sex
Recent fragility fracture
Family history
Inflammatory conditions
Type 1 diabetes
BMI - high is protective, prolonged low BMI increases risk
Malabsorption e.g. due to coeliac disease
Smoking
Alcohol
Drugs
What are some secondary causes of osteoporosis?
Endocrine e.g. early menopause, Cushing’s, hyperthyroidism and hyperparathyroidism
GI e.g. coeliac disease, IBD, chronic liver disease, malabsorption
Rheumatological e.g. rheumatoid arthritis
Haematological e.g. myeloma
Respiratory e.g. COPD and CF
Metabolic e.g. Homocystinuria
Drugs e.g. glucocorticoids like predinsolone
What is used to calculate risk of fragility fractures?
FRAX calculation tool - over 5% requires treatment
What investigations are done into the secondary causes of osteoporosis?
How are osteroporotic fractures treated?
With anti responsive treatment:
- SERMS e.g. raloxifene
- bisphosphonates e.g. alendronate orally or zoledronate IV
- RANK-L inhibitors e.g. denosumab
With anabolic treatment:
- PTH/PTHrP analogue e.g. teriparatide
What is the mechanism of action of bisphosphonates?
What is the mechanism of action of Denosumab?
What are complications of osteoporosis treatment?
How do bone metastases affect bone?
What bones are common sites for metastases?
Spine
Pelvis
Femur
Humerus
Skull
How do patients with bone metastases present?
bone pain - worse at night initially then becomes constant
pathological fractures of bones e.g. femur, humerus and vertebrae
numbness, paralysis and trouble urinating (if spinal cord compression from metastases)
Loss of appetite + nausea, thirst, confusion and fatigue
anaemia (due to disruption in bone marrow)
How do patients with hypercalcaemia present?
What should be tested for if hypercalcaemia is suspected?
PTH
What causes non-PTH mediated hypercalcaemia?
What causes PTH-mediated hypercalcaemia?
What is parathyroid hormone? What is its role?
a polypeptide secreted by chief cells in the parathyroid gland using vit D and magnesium when blood calcium is low. It stimulates osteoblast activity to decompose bone to release calcium, increases calcium absorption from food in the intestines and increases reabsorption of calcium from urine in the kidneys.
What is primary hyperparathyroidism present?
What is secondary hyperparathyroidism present?
What is tertiary hyperparathyroidism present?
What causes primary hyperparathyroidism?
Adenomas
- benign or ectopic
Glandular hyperplasia
Parathyroid carcinoma
How is primary hyperparathyroidism manifest?
What scan is used to look for ectopic parathyroid tissue?
CT SPECT
How is primary hyperparathyroidism treated?
What is Paget’s disease?
Rapid bone turnover and formation causing abnormal bone remodelling.
What are characteristics of Paget’s disease?
How does Paget’s disease present?
What is osteomalacia?
What causes osteomalacia?
How do patients with osteomalacia present?
