Metabolic Bone Disease

Question 1

What cell makes new bone and which destroys old bone?

Answer 1

• Osteoblasts
  
  • Builds new bone
• Osteoclasts
  
  • Destroys old bone

Question 2

What is the main thing that regulates bone remodelling cycles?

Answer 2

Many factors regulate remodelling cycles, mainly osteoblast being stimulated by a variety of things:

• TNF alpha
• IL-1
• IL-11
• Vitamin D
• Glucocorticoids
• PTH

Question 3

Describe vitamin D metabolism?

Answer 3

Question 4

What is the main storage form of vitamin D and where is it found?

Answer 4

25(OH)vit D is main storage form of vitamin D, and is found in liver, adipose tissue and muscle

Question 5

What is the main function of vitamin D?

Answer 5

Main function is to work with PTH to move calcium

Question 6

What are risk factors for vitamin D deficiency?

Answer 6

• Liver disease
• Kidney disease
• Darker skin
• Increased age
• Time of year/where we live (further away from equator)

Question 7

Describe the hormonal regulation of vitamin D?

Answer 7

• Is absorbed from gut with vitamin D
• Moved in and out of bone under action of PTH
• ECF calcium levels kept within right parameters at the expense of the calcium within bone

Question 8

ECF calcium levels are kept within tight parameters at the expense of what?

Answer 8

• ECF calcium levels kept within tight parameters at the expense of the calcium within bone

Question 9

Where are most of the bodies calcium stores found?

Answer 9

Within bone

Question 10

What is Paget’s disease?

Answer 10

• Localised disorder of bone turnover where increased bone resorption followed by increased bone formation
• Leads to disorganised bone which is
  
  • Bigger, less compact, more vascular and more susceptible to deformity and fracture

Question 11

What changes does Paget’s disease cause in bone?

Answer 11

• Leads to disorganised bone which is
  
  • Bigger, less compact, more vascular and more susceptible to deformity and fracture

Question 12

What is the aetiology for Paget’s disease?

Answer 12

• Genetics
  
  • Loci of SQSTMI
  • Geographical distribution due to genetic link
• Environmental trigger
  
  • Possible chronic viral infection within osteoblasts

Question 13

Describe the clinical presentation of Paget’s disease?

Answer 13

• Always over 40 years
• Bone pain
• Bone deformity
• Excessive heat over Pagetic bone
• Neurological complications such as nerve deafness
• Elevation of alkaline phosphatase on blood tests

Question 14

What is elevated in blood tests for Paget’s disease?

Answer 14

• Elevation of alkaline phosphatase on blood tests

Question 15

What is the treatment for Paget’s disease?

Answer 15

• No evidence treating asymptomatic pagets disease increases outcome unless in skill or area requiring surgical intervention such as hip replacement
• IV bisphosphonate therapy one off zoledronic acid infusion

Question 16

What is rickets and osteomalacia?

Answer 16

Severe nutritional vit D or calcium deficiency causing insufficient mineralisation causes rickets in growing child and osteomalacia in adult when epiphyseal plates are closed

Question 17

Does rickets and osteomalacia affect children or adults?

Answer 17

Rickets - children

Osteomalacia - adults

Question 18

What is the presentation of rickets?

Answer 18

Question 19

What are risk factors for osteomalacia?

Answer 19

• Elderly
• Darker skin

Question 20

What is the treatment for rickets?

Answer 20

• Calcium and vitamin D supplements

Question 21

What is the presentation of osteomalacia?

Answer 21

• Bone pain
• Muscles weakness
• Increased falls risk

Question 22

What investigation should be done for osteomalacia?

Answer 22

• X-ray
  
  • Can see micro fractures

Question 23

What is the treatment for osteomalacia?

Answer 23

• Vitamin D and calcium supplements

Question 24

What does OI stand for?

Answer 24

Osteogenesis imperfecta

Question 25

What is osteogenesis imperfecta (OI)?

Answer 25

Is a genetic disorder of connective tissue (type 1 collagen) characterised by fragile bones from mild trauma and even acts of daily life

Question 26

Genetic disorder of what connective tissue causes OI?

Answer 26

Type 1 collagen

Question 27

How many genetic types of OI are there?

Answer 27

28 different genetic types, 4 of which are most common: * Type 1 * Milder form, often when child starts to walk and can present in adults * Type 2 * Lethal by age 1, most severe form * Type 3 * Progressive deformity with severe bone dysplasia and poor growth * Type 4 * Similar to type 1 but more severe

Question 28

What are the 4 most common genetic types of OI?

Answer 28

* Type 1 * Milder form, often when child starts to walk and can present in adults * Type 2 * Lethal by age 1, most severe form * Type 3 * Progressive deformity with severe bone dysplasia and poor growth * Type 4 * Similar to type 1 but more severe

Question 29

What is the presentation of osteogeneis imperfecta?

Answer 29

* Growth deficiency * Defective tooth formation * Hearing loss * Blue sclera * Scoliosis/barrel chest * Ligamentous laxity * Easy bruising * Hypermobility

Question 30

What score can be used to assess hypermobility?

Answer 30

Beighton score

Question 31

What is the mangement of OI?

Answer 31

* Surgical * Treat fractures * Medical * To prevent fracture, IV bisphosphonates * Social * Educational and social adaptions * Genetic * Genetic counselling for parents and next generation

Question 32

What is OI characterised by?

Answer 32

Characterised by fragile bones from mild trauma and even acts of daily life

Question 33

What is osteoporosis?

Answer 33

Is a metabolic bone disease characterised by low bone mass and micro architectural deterioration of bone tissue: * Causes enhanced bone fragility and consequent increase in fracture * Also defined as on DXA bone scan

Question 34

How is osteoporosis defined on a bone scan?

Answer 34

* Also defined as on DXA bone scan

Question 35

What is risk of fracture related to?

Answer 35

* Bone density and how thick bone is * Age * How likely to fall * Bone turnover

Question 36

How can risk of fracture be assessed?

Answer 36

Risk of fracture can be assessed using online tools such as FRAX or Q fracture

Question 37

What investigation should be done for osteoporosis?

Answer 37

* DEXA scanner (DXA scan) * Examine L1 to L4 on spine for BMD (bone density) * Better for younger people * Examine left and right hip * Better for older people * Lateral DXA scan for vertebral fractures * Look at T score which is number of SDs below matched young person (except age, so same sex and ethnicity and BMI), each 1 SD below is 2x risk * Z score compares patient to matched patient of same age as well

Question 38

What are the T and Z scores on a bone scan?

Answer 38

* Look at T score which is number of SDs below matched young person (except age, so same sex and ethnicity and BMI), each 1 SD below is 2x risk * Z score compares patient to matched patient of same age as well

Question 39

1SD below on a DEXA scan represents what?

Answer 39

2x risk

Question 40

When should patients be referred to a DEXA scan after fracture risk assessment?

Answer 40

1. Risk assessment online tool 2. If risk is \>10% of osteoporotic fracture over 10 years refer for DXA scan 1. Anyone on oral steroids should be referred regardless of score

Question 41

Does osteoporosis affect more males or females?

Answer 41

F\>M

Question 42

What are some causes of osteoporosis?

Answer 42

* Endocrine causes * Thyrotoxicosis * Hyper and hypothyroidism * Cushings * Hyperprolactinaemia * Hypopituitarism * Low sex hormone levels * Rheumatic causes * Rheumatoid arthritis * Ankylosing spondylitis * Polymyalgia rheumatic * Gastroenterological causes * Inflammatory diseases (UC and Crohn’s) * Liver disease (PBC, CAH, alcoholic cirrhosis, viral cirrhosis) * Malabsorption (CF, chronic pancreatitis, coeliac disease, whipples disease, short gut syndromes and ischaemic bowel) * Medication causes * Steroids * Proton pump inhibitors (PPI) * Enzyme inducting antiepileptic medications * Aromatase inhibitors * GnRH inhibitors * Warfarin

Question 43

Describe how bone mass changes over time?

Answer 43

Question 44

How can osteoporotic fractures be prevented?

Answer 44

* Minimise risk factors * Such as smoking, alcohol, diet * Ensure good calcium and vitamin D status * Falls prevention strategies * Medication

Question 45

What medication can be used to prevent osteoporotic fractures?

Answer 45

* Hormone replacement therapy (HRT) * Not given to everyone due to side effects * Increased risk of blood clots * Increased risk of breast cancer * Increased risk of heart disease and stroke * Selective oestrogen receptor modulator (SERMS) * Such as raloxifene * Only works on vertebral fractures, not hip and peripheral * Side effects includes hot flushes, increased clotting risks * Denosumab * Monoclonal antibody against RANKL * Reduces osteoclastic bone resorption * Safer in patients with renal problems than bisphosphonates * Side effects includes allergy/rash, systematic hypocalcaemia if given when vitamin D deficient * Teriparatide * Side effects * Injection site irritation * Allergy

Question 46

What is the main treatment option for osteoporosis?

Answer 46

* Oral bisphosphonates generally first line of treatment * Adequate renal function, calcium and vitamin D status required * Mechanism of action is binds to bone mineral, osteoclasts absorbs it and is poisoned, unable to maintain its membrane it becomes stars shaped, recognising itself as being damaged and undergoes apoptosis * Side effects * Oesophagitis * Not safe when eGFR \<30mls/min * Atypical femoral shaft fractures