Diseases of Bone and Application of New Markers Flashcards
What are the two layers of bone and what are they like?
Cortical bone - hard outer layer, makes up 80% of bone. Forms columns that hold vessels/nerves
Trabecular bone - spongy inner layer that holds bone marrow
What separates the cortical and trabecular layers of bone?
endosteum
What are the extracellular components of bone?
collagen
hydroxyapatite
calcium, phosphate
What are osteoblasts?
outside of bone
already mineralised
makes osteroid (bone)
makes hormones, matrix proteins and alkaline phosphatase
get buried/trapped within the matrix = osteocytes
What are osteoclasts?
reabsorbs bone
critical for repair and maintenance of bone
increases blood Ca levels
regulate hormones: parathyroid hormone, calcitonin and IL-6
What are osteocytes?
buried/trapped osteocytes
regulates bone matrix turnover
What is osteoid?
Bone cell before it has been mineralised
Explain the process on normal bone remodelling
Osteoclasts dissolve the collegen and reabsorb the bone
Osteoblasts lay down osteoids
Osteoids become mineralised = osteoblasts
some osteoblasts become trapped = osteocytes
cycle repeats
What are the 2 main biochemical marker of bone formation?
Alkaline phosphatase
Procollagen type I propeptides (P1NP)
What is the biochemical marker for bone degredation products of bone collagen?
Crosslinked telopeptides of type I collagen (NTX, CTX)
What are the 2 biochemical marker that are osteoclast enzymes?
Tartrate-resistant acid phosphatase (TRACP 5b)
Cathepsin K
Alkaline phosphatase (APA) is a marker for which two organs of the body?
Bone and liver
Specific isoenxymes can be measured when there is a diagnostic doubt
What does raised APA signify and in what conditions is it raised?
increased = increased bone remodelling/repair
Growing children
Fractures
Hyperparathyroidism - primary/secondary
Pagets disease of the bone
Why is P1PN a good marker and when does it increase?
Stable levels for a long time
do not need to fast the patient
increase = increased osteoblast activity
When does NTX and CTX increase?
Increase = periods of high turnover, crosslinking molecule that correlates highly with bone resorption
Hyperthyroidism, adolescents, menopause
What is DEXA imaging used for?
look at bone mass and density
small amount of radiation used
Lumbar spine/hip mostly imaged
What is a T score and what does it signify?
Amount of bone density - not age related
-1 and above = normal
Between -1 and -2.5 = osteopenia
-2.5 and below = osteoporosis
What are the features of osteoporosis?
Inside the bone: thin cortex, plate compression, loss of trabecular network, wedge fractures, sclerosis
kyphosis
increased chest infections
bloating
ALP, P1PN normal as not sensitive enough, must be diagnosed via DEXA
What are the risk factors for osteoporosis?
female age smoker alcohol menopause lack of absorption of nutrients e.g. ulcerative colitis/colonectomy steriods Vit D deficiency
What is a fragility fracture?
fracture caused my a low force that wouldn’t normally affect bone
Common sites: spine, neck of femur, wrist
What are examples of antiresrptive treatments? i.e. reduces bone breakdown
Bisphosphonates e.g. Alendronic acid
Denosumab
What drug is an anabolic method of treating low bone density?
Terparatide - synthetic PTH
What is bisphosphonates mechanism of action?
Similar structure to pyrophosphate
Inhibiting activation of enzymes that utilize pyrophosphate
Attach to Ca and accumulate on bone
Taken up by the osteoclasts
What are the side effects of bisphosphonates?
poor absorption
difficult to take - must stay upright for a certain amount of time after taking it
oesophageal/upper GI problems
flu-like side effects
osteonecrosis of the jaw - necrosis/infection of jaw
atypical femur fracture
What are the 2 catagories of bone metastases?
Lytic - destruction of normal bone
Sclerotic/Osteoblastic - deposition of new bone
What are the features of a patient with metastatic compression of the spinal cord?
Back pain - worse at night, gets better with movement initially broken bones numbness Oliguria Vomiting loss of appetite confusion fatigue anaemia known to have cancer Ca elevated dehydrated/thirst
What is checked in anyone with a high Ca level?
PTH
What are the symptoms of hypercalcaemia?
polyuria/polydipsia mood disturbances anorexia nausea/vomiting fatigue constipation abdo pain coma pancreatitis dehydration arrhythmias
What cells in which part of the body secrete parathyroid hormone?
chief cells
parathyroid gland in neck
How is parathyroid hormone regulated?
Low Ca → parathyroid gland releases PTH → decomposition of bone, increased Ca absorption from intestines, reabsorption of Ca from urine → increased Ca → negative feedback via Vit D
What are Ca and PTH levels in primary, secondary, tertiary hyperparathyroidism?
Primary: ↑ Ca and PTH
Secondary: ↓ Ca, ↑PTH
Tertiary: ↑ Ca and PTH - happens after HPT has occurred chronically so PT forgets how to work
What diseases can cause primary hyperparathyroidism?
Adenomas - can be ectopic
Carcinomas (rare)
Glandular hyperplasia - all 4 glands enlarged, usually genetic
What are the clinical signs of primary hyperparathyroidism?
hypercalcaemia symptoms
renal disease - inc stones
Bone disease
muscle wasting
What are the treatment options for primary hyperparathyroidism?
surgery
Calcimimetics - reduced PTH secretion
What is Pagets disease of the bone and what are the signs and symptoms?
Rapid bone turnover and formation → abnormal remodelling = high ALP
arthritis
painful
fractures
Cranial nerves may be affected - hearing/vision loss
risk of osteosarcoma
What investigations are used to detect Pagets disease?
Lab assessment
plain X ray
Nuclear medicine bone scan
What is the treatment option for Pagets disease and how can it be monitored?
bisphosphonates
measure ALP and NTX
What is osteomalacia?
Lack of mineralisation of the bone due to Vit D/phosphate/Ca deficiency
usually in children
What are the clinical features of osteomalacia?
bone pain
muscle weakness
bone weakness
high ALP
What would be the ALP, Ca, P and PTH levels for HyperPTH, Osteomalacia, Osteoporosis, Pagets and Bone metastasis?
HyperPTH: ↑ ALP, ↑ Ca, ↓ P, ↑ PTH Osteomalacia: ↑ ALP, Ca, ↓ P, PTH Osteoporosis: all normal Pagets: ↑ ALP, normal Ca, P and PTH Bone Mets: ↑ ALP, ↑ Ca, normal P, ↓ PTH
