Metabolic and endocrine Bone Disorder

Question 1

What are the 2 aspects of bone ? What cells do you find?

Answer 1

Organic componenets (unmineralised) and Inorganic mineral component (Calcium hydroxyapatite)
The 2 cell types to remember are osteoblasts and osteoclasts (multinucleated, large)
Remodelling is a constant dynamic process

Question 2

How do osteoclasts differenciate?

Answer 2

Osteoclast precursors need to bind osteoblasts to initate Differenciation and fusion
The RANK receptor on precurosor bind RANKL on osteoblast

Question 3

What hormones receptor do osteoblasts express?

Answer 3

Responds to both PTH and calcitriol-because its the start of all dynamic bone remodelling

Question 4

What types of bone exist? where are they?

Answer 4

Exteriot cortical bone (hard, solid), interior-trabecular bone
Lamellar pattern normally-woven bone is diseased

Question 5

What are the effects of vitamin D deficiencies (concrete disease exemples)

Answer 5

Vit D def leads to inadequate mineralisation in newly formed matrix
in Children-reickets-affects growth plates-skeletal abnormality, bent bones
Adults-osteomalacia-skeletal pain and fracture risks-stress fractures (rare-waddling gait)

Question 6

How does adenoma lead to hyperparathyroidism? how does this differ from Vit D deficiency? And Chronic low plasma Ca?

Answer 6

PTH produces from PT glands -if adenoma in there, increase PTH levels, Increase Ca release from bone, Ca absorption and less loss in urine.
No negative feedback-so PTH HIGH, CA HIGH (Primary hyperparathyroidism)
In Vit D-needed to reabsorb the Ca+ ->so Ca is low/normal ->leads to increase PTH, but still can absorb -> High PTH, Normal Ca (secondary hyperparathyroidism)

Chronic low plasma Ca-often CKD related (cant make Vit D/Calcitriol)-PT glands become autonomous overtime (as grow to produce PTH)-Cant switch off, so if Ca/Vit D given-PTH high Ca high (difference from primary is kidney function)

Question 7

Why is kidney function important for Ca balance?

Answer 7

Kidneys do the reaction to make calcitriol -If not there, cant reabsorb Ca
Furthermore, cant excrete properly-PO4 cannot be exctreted (and that drops Ca too)
=>Hypocalcaemia -> Bone mineralisation down
PTH up->bone resorption down =>rare-osteitits fibrosa cystica (large cysts-brown tumours

Question 8

How do you treat Osteitis Fibrosis Cystica?

Answer 8

caused by hyperthryoidism leading to reduced bone mass
Hyperphosphateamia-Low phosphate diet + Phosphate bindinders
Cant give Vit D-give alfa calcidol (calcitriol analogue)
And in cases of tertiary hyperPT -thyroiectomy

Question 9

What is and Who gets osteoporosis? What is the cut off (clinically)? How do you measure it? Where?

Answer 9

Loss of bony trabecular , reduced bone mass-predisposed to fracture -bone just isnt as dense
Everyone loses bone mass with age (especially woment after menopause)
Use T score-bone mass of patient vs bone mass of population - and check if 2.5 SD away from population
Measure Bone Mass (BMD)-DEXA scan-check NOF and lumbar spine

Question 10

What is the difference between osteoporosis and osteomalacia?

Answer 10

malacia-Vit D deficiency-cant mineralise bone-PAINFUL-abnormal Biochemistry serum - increase fracture risk
Porosis-Mismatch between resorbpion and Formation-decrease bone MASS-biochemistry normal serum-increase fracture risk, but NOT painful (until fracture)

Question 11

What are important pre-disposing conditions for osteoporosis?

Answer 11

Post menopausal oestrogen deficiency
Age related bone homeostasis deficicency (normal)
Hypogonadism in young women/men
Endocrine condition-cushings, Hyperthryro, Primary hyperpara
Iatrogenic-prolong Glucosteroids, heparin

Question 12

what are the main treatment options of Osteoporosis?

Answer 12

Oestrogen replacement, bisphonates, Denosumab, teriparatide

Question 13

How does HRT treat osteoporosis?

Answer 13

Oestrogen prevents bone loss-but is not long term treatment option (can cause breast cancer)
And if uterus is intact-need progesteren to prevent hyperplasia
also increase thrombocytopenia, thrombisos

Question 14

How do bisphononates help treat osteoporosis? What else can they treat?

Answer 14

Bisphos bind avidly to Hydroxyapatite-when ingested by osteoclasts-impairs them and kills em
Also reduce differentiation

Main treatment for Osteoporosis
can help for malignancies-when too much bone-help reduce bone pain, and reduce hypercaclemia
Pagets disease
Severe hypercacleamic

Question 15

How is the phramacokinetics of bisphophonates?

Answer 15

Orally active but poorly absorbed-cant with meal, other tablets, reduce all other drug abosption, can be painful)
Sometimes also can be too effective-last for years and years (in young patients might not be good)

Question 16

What are the side effects of Bisphonoates?

Answer 16

Oesophagitis-sits in oesophagus and irritates
osteonecrosis of the Jaw-greatest risk in cancer patients (as you impact bone remodelling balance)
Atypical fractures-may not remodel well after

Question 17

How does Denosumab treat osteoporosis?

Answer 17

Denosumab-monoclonal AB
Binds RANKL, inhbiting osteoclast formation and activity
2nd line to bisphosphonates -only need every 6 months

Question 18

How does Teriparatide treat osteoporosis?

Answer 18

Recombinant PTH fragments

Increases formation and resobption, but formation outweights it (unsure why)-very expensive-3rd line of treatment

Question 19

What is Paget’s disease of bone? What is its cause?

Answer 19

Accelerated LOCALISED bone remodelling
Exess bone resorption followed by compensatory osteoblast formation
Usually lays down woven bone (bad)-frail
Get deformed, hypertrophy and frail bone

Cause is unsure-Family history, viral origin (?)-but mainly prevalent in UK, NA, Aus, Nz
Men women same, but usually aged - most patients asymptomatic

Question 20

What are clinical features of Pagets disease?

Answer 20

Some bones feel warm because how active
Can go deaf because skull is affected
Pain, arthiritis, fractures, frontal bossing, weird bone shapes.
Often affects the tibia, skull

Question 21

How do you diagnose pagets disease? And how do you treat it?

Answer 21

Plasma Ca normal, but usually ALKALINE PHOSPHATSE (plasma)-HIGH
Xrays-show lytic lesion, thickened, enlarged, deformed boned
(ALK PHOSPH-EITHER FOUND IN LIVER OR BONE-DIAGNOSIS TOOL TO SHOWING REMODELLING WHEN BONE VERSION)

Treat-bisphosphonates (treat pain and extra activity), analgesia