Year 2: Metabolic bone disorders Flashcards by Jule Hoelscher

What are the two components of bone?

Osteoid: unmineralised bone (organic component)
- 35%
- Mainly Type I collagen fibres
Inorganic minergal component
- 65%
- Calcium hydroxyapatite crystals (that fill the space between the collagen fibres)

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What is the function of the osteoblasts?

They built boneby synthesising collagen fibres and help in osteoid mineralisation

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What is the function of osteoclasts?

They resorb bone and thereby free calcium and phosphate via the release of lysomal enzymes

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How do osteoclasts get activated?

They differentiatiate in response to RANKL-Receptor stimmulation of surface

The RANKL is expressed on osteoblasts surfaces–> osteoclasts get activated by osteoblasts!

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How to osteoblasts get activated?

Resond to PTH & calcitriol (1,25 (OH)2 vit D)

–> regulate bone formation and absorbtion

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What is the cortical part of the bone?

The hard shell of the bone

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What is the Trabecular part of bone?

spongy, inner part of bone

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What is meant by the term “woven” bone

disorganised collagen fibrils, weaker

–> loss of lamellar sturcture

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How do you call a bone that is weaker due to unoranised collagen fibres?

Woven bone

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What is the normal structure of a bone called?

Lamellar pattern of bone :

collagen fibrils laid down in alternating orientations that makes it mechanically strong

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What are the direct effects of Vitamine D deficiency on bone?

Inadequate mineralisation of newly formed bone matrix (osteoid)

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How does Vitamin D deficiency present in children?

Rickets

skeletal abnormalities and pain, growth retardation, increased fracture risk
also affects cartilage and epiphysal growth

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What does Vit D deficiency cause in adults?

OSTEOMALACIA

affects the bone (not the epiphysal)
skeletal pain, increased fracture risk, proxmyopathy

–> might lead to wabbeling gait and looser zones (in severe deficiency)

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What is a looser zone in bone?

Fractures from inadequadly mineralised bone due to normal weight

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Explain primary, secondary and tertiary Hyperparathyroidism

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How does renal failure lead to vascular calcification?

Because there is reduced excretion of PO4 3-, therefore highter phosphate levels that form insoluble Calcium phosphate plaques

What does renal failure in terms of bone health lead to?

It leads to

more bone resorbtion (to kepp calcium levels because of VitD deficiency, no Ca2+ can be absorbed)
Leading to osteitis fibrosa cystica –> hyperparathyroid bone disease

What is osteitis fibrosa cystica?

Hyperparathyroid bone disease

leading to “Brown tumors”– >radiolucent bone lesions due to hight osteoclast activity stimmulated by high PTH to get Ca2+ up

rare now

How do you treat osteitis fibrosa cystica?

Two main issues

High Phosphate levels
- low phosphate diet
- Phosphate binders – reduce GI phosphate absorption
Alphacalcitriol
- to restore Vit D levels, decrease bone resorbiton due to low Ca2+
Parathyroidectomy in 3. hyperparathyroidism
- in hypercalcaemia + hyperparathyroid bone disease

What exactly is osteoporosis?

Loss of bony trabeculae and reduced bone mass leading to weaker bone –> increase risk of fractures

What is BMD?

What does it tell you?

BMD= Bone mineral density

Can be diagnostic of osteoporosis (T-score) if it is = 2.5 below average –>

How is bone mineral density normally measured?

Via and DEXA (Dual Energy X-ray Absorptiometry ) of the femoral neck and lumbar spine

It measures the bone calcium content–> rthe more calcium, the higher the bone mineral density

What are the factors that predispone you to osteoporosis?

Post-menopausal hormone deficiency (oestrogen is protective)
Age-related changes in bone homeostasis (osteoclast senescence)
Hypogonadism in young women and in men
Different endocrine conditons
Latrogenic
- heparin
- prolonged glucosteriods

What are latrogenic conditions?

Diseases that are caused by medical care

Which endocrine disorders can cause Osteoporosis?

oCushing’s syndrome oHyperthyroidism oPrimary hyperparathyroidism

What are the possible treatments for osteoporosis?

1. •Oestrogen/Selective Oestrogen Receptor Modulators 2. •Bisphosphonates 3. •Denosumab (antibody) 4. •Teriparatide

Explain the use of oestrogen in osteoporosis

1. Post menopausal * replace E2 to reduce bone resorbtion * also give progesterone if uterus is intact --\> to cause period and prevent endometrial CA 2. Main Risks are * Breast Cancer * Venous thromboembolism

What is the MOA of Bisphosphonates?

They impair the osteoclasts and induce apoptosis --\> redue bone reabsorbtion Happens by Bind avidly to hydroxyapatite (that is digested by osteoclasts --\> leads to disruption of intracellular enzymatic activity in osteoclast)

What is the clinical use of bisphosphonates?

It is used in 1. Osteoporosis --\> reduce bone turnover 2. Malgnancy * Associated hypercalcaemia * Reduce bone pain from metastases 3. Paget’s disease – reduce bony pain 4. After rehydration in severe hypercalcaemia emergency

What are the main side effects of bisphospobates?

Unpleasent to take, need to take on empty stomach * Oesophagitis * may require switch from oral to iv preparatåion * Osteonecrosis of the jaw * greatest risk in cancer patients receiving iv bisphosphonates * Atypical fractures * may reflect over-suppression of bone remodelling in prolonged bisphosphonate use

What is Denosumab? When and how is it used?

It is a human antibody binding to RANKL --\> inhibits osteoclast activation --\> reduces bone resporbtion * SC injection 6/12ly * 2nd line to bisphosphonates

What is Teriparatide? What and how is is used for?

•Recombinant PTH fragment * Increases bone formation and bone resorption, but formation outweighs resorption * 3rd line treatment for osteoporosis * Daily s.c. injection * £££

What would be your fist, secound and third line treatment in OSteoporosis?

1. Bisphosphonates 2. Denosumab (RANKL antibody) 3. Teriparatide (PTH fragement stimmulating bone formation)

What is pagets disease of bone? | (Cause and consequence)

•Accelerated, localised but disorganised bone remodelling --\> leading to WOVEN bone MOA: Excessive bone resorption (osteoclastic overactivity) followed by a compensatory increase in bone formation (osteoblasts) Leading to * hypertrophy with increased fragility and deformity * **Characterised by abnormal, large osteoclasts – excessive in number**

What is the cause of pagets disease of bone?

It is not knonw * Genetic cause? * viral origin? * But most commonly seen in * Highest in UK, N America, Australia and NZ, Lowest in Asian and Scandinavia * No sex difference * appears over age of 50

What are the clinical features of someone with pagets diseae?

* Skull, thoracolumbar spine, pelvis, femur and tibia most commonly affected * Arthritis * Fracture * Pain * Bone deformity * Increased vascularity (warmth over affected bone) * Deafness – cochlear involvement * Radiculopathy – due to nerve compression

How would you diagnose someonw with pagets disease of bone?

Normal Plasma **Ca2+** Increased plasma **alkaline phosphatase** Plain X-Rays: * Lytic lesions (early), thickened, enlarged, deformed bones (later) * Radionuclide bone scan demonstrates extent of skeletal involvement

How would you treat pagets disease of bone?

* Bisphosphonates – very helpful for reducing bony pain and disease activity * Simple analgesia