Bone and new markers

?
  • Created by: hadar
  • Created on: 12-02-18 16:50
What is the purpose of bone?
1) structural support 2) protection of vital organs 3)blood cell production via marrow 4) storage for minerals- calcium
1 of 87
What are the 3 types of bone composition?
1) cortical bone 2) trabecular bone 3) cancellous bone
2 of 87
What is the composition of bone?
1) cells--> bone forming and resorbing 2) extracellular- organic matrix (collagen) and inorganic components (hydroxyapatite and minerals such as calcium and phosphate)
3 of 87
What is cortical bone?
hard outer layer- compact bone- usually found on the outer cortex layer.
4 of 87
What is trabecular bone?
spongy inner layer- consists of multiple microscopic columns (osteon)- cortical bone covered by periosteum on its outer surface- endosteum on inner surface.
5 of 87
What is an osteoblast?
a cell that makes bone (from mesenchymal stem cell)- makes osteoid (non-mineralised organic matrix, consists of mainly Type 1 collagen)
6 of 87
What are osteoblasts a terminally differentiated product of?
Mesenchymal stem cells
7 of 87
What do osteoblast make? (3)
Make hormones (e.g. osteocalcin), matrix proteins and alkaline phosphatase
8 of 87
What are osteoclasts?
rge. Multi nucleated Ruffled-resorption border cells
9 of 87
What is the function of osteoclasts?
Break down bone – critical for repair and maintenance of bone. Produce enzymes such as tartrate resistant acid phosphatase (TRAP) and Cathepsin K - secreted to breakdown extracellular matrix. help enhance blood calcium levels
10 of 87
What are osteoclasts regulated by?
Regulated by hormones including PTH, calcitonin and IL-6
11 of 87
What help osteoclastic maturation and activity?
RANK ligand and osteoprotegrin
12 of 87
What are osteocytes?
Star shaped Trapped/buried osteoblasts Communicate with each other via cytoplasmic extensions Mechanosensory properties Involved with regulating bone matrix turnover
13 of 87
Why is bone a dynamic tissue?
Constant remodelling Highly vascular tissue Metabolically active Osteoblasts constantly producing and secreting matrix and helping with mineralisation Osteoclasts causing bone resorption
14 of 87
Describe the bone cycle
resting- lining cells --> resorption-multinuclear osteoclast with ruffled boarder, adhesion zine with resorption pit --> osteoid formation- by osteoblasts --> mineralisation --> resting -->
15 of 87
Describe bone with age
peak bone mass in males at 20-50 and females 30-50- decrease after that- female have large bone loss due to menopause
16 of 87
What happens to bone with increasing age?
bone formation decreases and bone resorption increases
17 of 87
How is bone disease investigates? (4)
1)gross structure- X-ray 2)Bone mass- DEXA 3) cellular function/ turnover- biochemistry 4) Microstructure/ cellular function- biopsy, qCT
18 of 87
What is the biochemical marker showing bone formation?(3)
1)Alkaline phosphatase (TAP, BAP) 2) Osteocalcin (OC) 3) Procollagen type I propeptides (P1NP)
19 of 87
What is the biochemical marker showing 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
20 of 87
What releases bone alkaline phosphate?
Osteoblasts- Release stimulated by increased bone remodelling Childhood / Pubertal growth spurt Fractures Hyperparathyroidism Primary Secondary Pagets Disease of the Bone
21 of 87
What is phosphatase involved in?
Bone mineralisation
22 of 87
Describe P1NP (Procollagen type 1N propeptide) as a marker
Synthesized by osteoblasts - precursor molecule of type 1 collagen Has low diurnal and intraindividual variation Serum concentrations not affected by food intake Increased with increased osteoblast activity Decreased by reduced osteoblast activity
23 of 87
Describe Collagen Cross-links (NTX, CTX) as a marker
Cross-linking molecules which are released with bone resorption, correlate highly with bone resorption Increased in periods of high bone turnover - hyperthyroidism, adolescents, menopause Have diurnal variation Do not predict bone mineral density
24 of 87
Why would you see decreased Collagen Cross-links (NTX, CTX)?
Decrease seen in anti-resorptive therapy
25 of 87
What do bone markers show?
They show whats happening with the osteoblast and osteoclasts at the time of marker But do not show the bone quality
26 of 87
Wha are bone marker results used for?
1) evaluation of bone turnover and loss 2) evaluation of treatment effect 3) evaluation of compliance with medication
27 of 87
What medications impact bone turnover?
- P1NP used to monitor compliance with teriparatide - CTX used to monitor compliance/response to anti-resorptive therapy
28 of 87
What does T-score show?
-1 and above: Bone density is considered normal. Between -1 and -2.5 = osteopenia. -2.5 and below = osteoporosis.- tells you how many SD person is form the standard of young healthy person
29 of 87
Name some risk factors of osteoporosis
steroids, early menopause, smoker, alcohol(ore 20 units a weak), UC(any inflammatory condition), age, female
30 of 87
How is osteoporosis diagnosed?
Diagnosis relies on DEXA/XRay Increasing use of bone markers in management
31 of 87
What is the definition of osteoporosis?
systemic skeletal disease characterised by low bone mass and microarchitectural deterioration of bone tissue, with consequent increase in bone fragility and susceptibility to fracture
32 of 87
What is the equation for osteoporosis?
decreased bone mass + deranged bone microarchitecture = failure of structural integrity
33 of 87
What is a fragility fracture?
A fracture caused by injury that would be insufficient to fracture a normal bone
34 of 87
What is a fragility fracture a sign of?
Sign of low bone density/ quality low bone mass
35 of 87
How do you assess fracture risk?
FRAX calculation tool
36 of 87
What does FRAX calculation tool take into account?
age, sex, weight, height, previous fracture, smoker, steroids, RA, osteoporosis, alcohol, inflammatory conditions
37 of 87
Broadly what are the 2 treatment options for prevention of osteoporotic fracture?
1) anti-resorptive treatment 2)anabolic treatment
38 of 87
What is the first line treatment for prevention of osteoporotic fracture?
First line treatment= bisphosphonates usually oral therapy
39 of 87
What are the 3 types of anti-resorptive treatments?
1)SERMS 2)Bisphosphonates 3)RANK-L inhibitor
40 of 87
Give example of SERMS
Raloxiferne
41 of 87
Give example of bisphosphonates
oral--> alendronate, risedronate, ibandronate IV--> zoledronate, ibandronate
42 of 87
Give example of RANK-L inhibitor
Denosumab
43 of 87
Give example of anabolic treatment
Teriparatide- parathyroid hormone analogue--> works on osteoblasts to try and stimulate production of new bone
44 of 87
What is the mechanism of action of bisphonsphonates?
Mimic pyrophosphate structure Taken up by skeleton Ingested by osteoclasts- inhibit osteoclast formation, migrations activity and promote apoptosis
45 of 87
What side effects can you get from bisphosphonates?
Can cause oesophageal/ upper GI problems Flu-like side effects Osteonecrosis of the jaw Atypical femur fractures
46 of 87
What are the 2 main types of bone metastases?
1) Lytic 2) Sclerotic/ osteoblastic
47 of 87
Give examples of lytic bone metastases
Breast / Lung/ Kidney/ Thyroid- destruction of normal bone (osteoclasts)
48 of 87
Give examples of sclerotic/ osteoblastic bone metastases
Prostate Lymphoma Breast/lung (15-25%)- deposition of new bone
49 of 87
What is the usual site of spread of bone metastases?
Spine, pelvis, femur, Humerus, skull
50 of 87
What are the presenting symptoms with bone metastases?
1) pain- worse at night and gets better in day 2)broken bones 3)numbness, paralysis, trouble urinating- spinal cord compression 4) loss of appetite, nausea, vomiting, thirst, confusion, fatigue 5)anaemia- disruption bone marrow
51 of 87
What blood test would you do for someone with a high calcium?
PTH- parathyroid
52 of 87
What are the mild symptoms of hypercalcaemia?
Polyuria, polydipsia Mood disturbance Anorexia Nausea Fatigue Constipation
53 of 87
What are the severe symptoms of hypercalcaemia?
Abdo pain Vomiting Coma Pancreatitis Dehydration Cardiac arrhythmias
54 of 87
What are the causes of hypercalcaemia?
non-PTH mediated--> malignancy, vitamin D intoxication, chronic granulomatous disorders, medications, immobilisation, endocrine PTH-mediated--> sporadic primary hyperparathyroidism, familial
55 of 87
What medications can cause hypercalcaemia?
Thiazide diuretics, Lithium, Teriparatide, Theophylline toxicity
56 of 87
What familial conditions caused PTH-mediated hypercalcaemia?
MEN1 and 2A Familial hypocalciuric hypercalcaemia Familial isolated hyperparathyroidism
57 of 87
Where is PTH secreted from?
Secreted by chief cells of parathyroid gland
58 of 87
What regulates PTH?
magnesium, vitamin D, calcium levels
59 of 87
Describe the levels in primary hyperparathyroidism
high calcium, inappropriate high PTH, low phosphate and high alk phosphatase
60 of 87
What are the causes of primary hyperparathyroidism?
Sporadic or familial
61 of 87
Describe the levels in secondary hyperparathyroidism
normal/low calcium, appropriately high PTH, phosphate high if due to kidney disease
62 of 87
What are the causes of secondary hyperparathyroidism?
CKD or vitamin D deficiency
63 of 87
Describe the levels in tertiary hyperparathyroidism
high calcium, inappropriately high PTH, phosphate can be high/low
64 of 87
What are the causes of tertiary hyperparathyroidism?
After prolonged secondary HPT, usually in CKD
65 of 87
How does primary hyperparathyroidism present?
Previously- severe hypercalcaemia, symptomatic renal and skeletal disease Now earlier in disease course- usually asymptomatic Majority >45 years of age Women X2 likely-Inappropriately elevated PTH in the presence of high calcium suggests PHPT
66 of 87
What adenomas seen in primary hyperparathyroidism?
bening adenomas, glandular hyperplasia, ectopic adenomas, parathyroid carcinoma
67 of 87
What are the clinical manifestations of primary hyperparathyroidism?
Symptoms related to hypercalcaemia(as described) Renal disease (nephrolithiasis, chronic kidney disease) Bone disease (osteoporosis, osteitis fibrosa cystica) Proximal muscle wasting
68 of 87
What is the treatment for symptomatic hypercalcaemia?
surgery
69 of 87
What the treatment for asymptomatic patients with primary hyperparathyroidism?
medical--> Calcimimetics (Cinacalcet)
70 of 87
What is the mechanism of action of Calcimimetics (Cinacalcet)?
Activates CaSR in the parathyroid gland Therefore leads to reduced PTH secretion Use to normalise calcium in symptomatic patients, or those who are not fit for or unwilling to have surgery Does not seem to alter bone disease
71 of 87
What is Pagets disease of bone?
Rapid bone turnover and formation Leading to abnormal bone remodelling
72 of 87
What is seen in Pagets disease of bone?
Elevated alkaline phosphatase reflecting increased bone turnover
73 of 87
What does imagine of Pagets disease of bone show?
Cotton wool appearance of excessive bone formation
74 of 87
What is the epidemiology of Pagets disease of bone?
Mainly over 50 years old Higher prevalence in men Probable genetic and environmental triggers FH in 10-15% of cases Polyostotic or monostotic
75 of 87
What are the clinical features of Pagets disease of bone?
Bone pain Bone deformity Fractures Arthritis Cranial nerve defects if skull affected Hearing and vision loss Risk of osteosarcoma Most commonly affects pelvis, femur and lower lumbar vertebrae
76 of 87
How is Pagets disease of bone investigated?
Lab assessment Plain X-rays Nuclear medicine bone scan
77 of 87
How do you monitor disease activity of Pagets disease of bone?
Monitor disease activity with a blood test looking at the osteoclast markers- ALKALINE PHOSPHATASE
78 of 87
What treatment for Pagets disease of bone?
Bisphophonates are used since they are anti-osteoclastic activity
79 of 87
What is osteomalacia?
Lack of mineralisation of bone Adult form - widened osteoid seams with lack of mineralisation Classic childhood rickets - widened epiphyses & poor skeletal growth
80 of 87
What are the causes of osteomalacia?
Insufficient calcium absorption from intestine Due to lack of dietary calcium or Vit D deficiency/resistance Excessive renal phosphate excretion Rare genetic forms (e.g. hereditary hypophosphataemic rickets)
81 of 87
What are the clinical features of osteomalacia?
Diffuse bone pains Usually symmetrical Muscle weakness Bone weakness High alk phos, low Vit D, possibly low Calcium and high PTH (secondary hyperparathyroidism)
82 of 87
What is the biochemistry of hyperparathyroidism?
Increase alk phos, calcium, PTh decreased phosphate
83 of 87
What is the biochemistry of osteomalacia?
Increased alk phos, PTH Decreased calcium, phosphate
84 of 87
What is the biochemistry of osteoporosis?
normal biochemistry
85 of 87
What is the biochemistry of Pagets disease?
normal biochemistry only increased alk phos
86 of 87
What is the biochemistry of bone mets?
Increased alk phos, calcium Decreased PTH and normal phosphate
87 of 87

Other cards in this set

Card 2

Front

What are the 3 types of bone composition?

Back

1) cortical bone 2) trabecular bone 3) cancellous bone

Card 3

Front

What is the composition of bone?

Back

Preview of the front of card 3

Card 4

Front

What is cortical bone?

Back

Preview of the front of card 4

Card 5

Front

What is trabecular bone?

Back

Preview of the front of card 5
View more cards

Comments

No comments have yet been made

Similar Medicine resources:

See all Medicine resources »See all Medicine resources »