Bone and new markers Flashcards
What part of the bone is corticoid bone?
Hard, out layer
What part of the bone is the trabecular bone?
Spongy, inner layer
What do osteoblasts do?
Secrete bone
What do osteoclasts do?
absorb bone
What is the function of the trabecular bone?
Bone marrow -
-Haemopoesis
What is the extracellular part of bone composed of?
Inorganic matrix - hydroxyapatite, minerals e.g. calcium, phosphate
Organic matrix - collagen
What is bone before it is mineralised?
Osteoid
What mineralises bone?
Hydroxyapatite
calcium-phosphate, hydroxide salt
Why is bone considered a dynamic tissue?
Constantly being remodelling
High vascular
Metabolically active
Osteoblasts produce and secrete metric and help with mineralisation
Osteoclasts reabsorb (both clasts/blast actions = linked)
What do osteoblasts do?
Make osteoid (non-mineralised organic matrix - mainly collagen)
Make hormones (osteocalcin), matrix proteins and alkaline phosphatase
What are osteoblasts called when buried underneath/trapped within matrix?
Osteocytes
What enzymes do osteocytes produce?
Tartrate resistant acid phosphatase (TRAP)
Cathespin K
What main hormone is osteoclasts regulated by?
PTH
What ligands/proteins helps with osteoclast maturation and activity
RANK (produced by osteoblasts)
Osteoprotegrin
What are the function of osteocytes?
Maintain bone matrix turnover
What is the bone remodelling process?
Osteocyte -> reabsorption pit -> osteoblast -> produce osteoids -> mineralisation (hydroxyapatite) -> osteocyte
Why is reduced bone mass related to menopause?
Loss of oestrogen
What also happens as you get older (i.e. osteoclastic - osteoblastic activity)
Osteoclastic activity increases - balance tipped to bone reabsorption
What diagnostic test is used to investigate bone gross structure?
X-rays
What investigative technique is used to assess bone mass? (I.e. calcium levels)
DEXA scan
What biomarkers indicate bone formation (i.e. pro-osteoblastic activity)
Osteocalcin
Pro collagen type I phosphatase (P1NP)
Alkaline phosphatase
What markers could be used for bone reabsorption
Cross linked telopeptides of type 1 collagen (CTX/NTX)
What markers could be used for osteoclastic activity? (i.e. enzymes)
TARP (tartrate acted resistant phosphatase)
Cathespin K
What produces alkaline phosphatase?
Osteoblasts - indicator of bone remodelling
When is high levels of all pos observed?
- Fractures
- Hyperthyroidism
- Pagets disease of bone
What is pro collagen type I phosphatase an indicator of? what is it a particularly good marker?
Indicates osteoblastic activity
Good because it is a very stable marker - no diurnal variation/no affected by food intake
What does cross linked telopeptides of Type I collagen indicate? What can their use be problematic?
Indicates bone reabsorption e.g. adolescence, menopause, hyperthyroidism
However diurnal variation/affected by food intake
What are the problems with using bone markers?
Not disease specific
Not specific - type I collagen which is widely distributed in body
Intra-individual variability
What is a DEXA scan used to determine? What do the T scores indicate
Bone mass/density
T score - number of SD’s away
normal = -1+
Osteopenia = -1 - -2.5
Osteoporosis =
What are the risk factors for osteoporosis?
Age Early menopause Malnutrition Alcohol/smoking Steroids
What is osteoporosis? What is it marketed by?
Generalised loss of bone
Reduced bone mass + deranged bone architecture = failure of structural integrity (propensity to fracture)
Lighter X-ray, DEXA scan (
What is a fragility fracture?
Fracture of bone by force that would usually be insufficient to fracture a normal bone (minimal trauma)
What anti-reabsorptive drug is used to treat osteoporosis? what cell does it act on?
Bisphosponates
Anti-resorptive - osteoclasts
What anabolic drug is used to treat osteoporosis? What cell does it act on?
Terparatide
Anabolic - synthetic PTN
Where are the common places for bone metastasis occur?
Femur spine pelvis skull Humerus
What are the two types of bone metastasis? Where do they originate from usually?
Lytic - osteoclastic breakdown - lung/breat
Sclerotic - osteoblastic - deposition of new bone =- prostate, lymphoma, breast/lung
What are the symptoms of bone metastasis?
- Pain
- Fractures
- Paralysis, numbness, trouble urinating - spinal cord compression
- Hypercalcaemia - thirsty, loss of appetite, confusion, fatigue
- anaemia - disrupted bone marrow function
What are the symptoms of hypercalcaemia?
Polyuria/polydipsa Dehydration Fatigue Confusion Mood disturbance Nausea Abdo pain Vomiting Coma Dehydration Cardiac arrthymias
What are the main causes of hypercalcaemia?
- Malignancy
- Hyperparathyroidism
What regulates blood calcium? What is produced and by what cells?
Parathyroid gland
Produces PTH by chief cells
What does PTH do?
increases Ca in blood by increasing decomposition of bone, and increasing absorption from intestines and kidney
What other factors act on the parathyroid gland?
Vit D (low increase PTH) Magnesium
What is secondary hyperparathyroidism usually caused by?
Vit D deficiency (marked by normal calcium levels but too high PTH)
What is tertiary hyperparathyroidism usually caused by?
When secondary hyperparathyroidism has gone on for too long
What is primary hyperparathyroidism usually caused by?
Calcium and PTH inappropriately high
Disease of
What are the main causes of primary parathyroidism
Adenoma - chief cells producing too much PTH
Also parathyroid carcinoma - malignant - aggressive but rare
Hyperplasia of glands - sporadic or genetic (MEN1, MEN2a, familial hyperparathyroidism)
Ectopic adenomas
What are the clinical manifestations of primary hyper parathyroidism?
- Renal failure
- Hypercalcaemia
- Bone disease
- proximal muscle wasting
What is the treatment for PHPT?
Surgery
Cinacalcet - activates the CaSR receptor - results in reduced PTH secretion
What is Pagets disease? What is it marked by?
Excessive bone turnover and formation resulting in abnormal remodelling
- Marked by elevated Alkaline phosphatase
What are the clinical features of Paget’s disease?
- Bone pain
- Bone deformity
- Fractures
- Arthritis
- Risk of osteosarcoma
- Pelvis, femur, lumber vert
Whats the best treatment for pages disease?
Bisphosphonates - slow down osteoclasts
What is the osteomalacia commonly referred to as?
Rickets
What is osteomalacia usually caused by?
Lack of mineralisation of osteoid
Insufficient calcium absorption from intestine e.g. lack of dietary calcium or vit D deficiency
Excessive renal excretion of phosphate
What are the presentations of osteomalacia?
- Symmetrical bone pain
- Muscle weakness
- Bone weakness
- Low Ca, low bit D
- Secondary hyperparathyroidism
What is the biochemistry (increase/decreased Alk pos, Ca, phosphate, PTH) for the following conditions…
a) HyperPTH
b) osteomalacia
c) osteoporosis
d) Pagets
e) Bone mets
a) High alk phos, high calcium, low phosphate, high PTH
b) High alk phos, low calcium, low phosphate, high PTH
c) no change
d) high alk phos,
e) high alk phos, high calcium, low PTH
