Metabolic Bone Disease

Question 1

with a diagram describe bone remodelling

Answer 1

see notes

Question 2

with a diagram show the factors stimulating osteoblast expression of RANK ligand

Answer 2

see notes

Question 3

what is paget’s disease of the bone?

Answer 3

Paget’s of the bone is a localised disorder of bone turnover. It results from increased bone resorption followed by an increase in bone formation.

Question 4

clinical features of paget’s disease of the bone

Answer 4

disorganised bone: bigger, less compact, more vascular and more susceptible to deformity and fracture

Question 5

what % of paget’s disease of the bone are familial?

Answer 5

15-30%

Question 6

name the important loci in paget’s disease of the bone

Answer 6

SQSTMI

Question 7

presentation of paget’s disease of the bone

Answer 7

> 40
bone pain
occasionally : bone deformity, excessive heat over the pagetic bone or by neurological complications such as nerve deafness
isolated serum ALP - most common
bone pain, local heat, bone deformity or fracture, hearing loss

Question 8

treatment of paget’s disease of the bone

Answer 8

IV bisphosphonates

Question 9

severe nutritional vitamin D or calcium deficiency causes:

Answer 9

insufficient mineralisation and thus rickets in growing child and osteomalacia in adult

Question 10

function of vitamin D

Answer 10

Vitamin D stimulates the absorption of calcium and phosphate from the gut and calcium and phosphate then become available for bone mineralisation. Muscle function is also impaired in low vitamin D states.

Question 11

symptoms of osteomalacia

Answer 11

bone pain
muscle weakness
increased falls risk

Question 12

what is osteogenesis imperfecta?

Answer 12

This is a genetic disorder of connective tissue characterised by fragile bones from mild trauma even acts of daily life. There are other non-bone clinical features to consider. There is a broad presentation ranging from prenatally fatal to those only presenting in 40s with early osteoporosis.

Question 13

where are the defects in osteogenesis imperfecta?

Answer 13

type 1 collagen

Question 14

features of the 4 most common types of osteogenesis imperfecta

Answer 14

1. Milder form – when child starts to walk and can present in adults
2. Lethal by age 1
3. Progressive deforming with sever bone dysplasia and poor growth
4. Similar to type 1 but more severe

Question 15

other features of osteogenesis imperfecta

Answer 15

• Growth deficiency
• Defective tooth formation (dentigenesis imperfecta)
• Hearing loss
• Blue sclera
• Scoliosis/barrel chest
• Ligamentous laxity
• Easy bruising

Question 16

management of osteogenesis imperfecta

Answer 16

• Surgical
o Treat fractures
• Medical
o Prevent fractures
o IV bisphosphonates
• Social
o Educational and social adaptation
• Genetic
o Counselling for parents and next generation

Question 17

define osteoporosis

Answer 17

A metabolic bone disease characterised by low bone mass and micro architectural deterioration of bone tissue, leading to enhanced bone fragility and a consequent increase in fracture risk. A result on DXA bone scanning <2.5 SDs below the young adult mean in a post-menopausal woman (T-score)

Question 18

what is the risk of fracture in osteoporosis related to?

Answer 18

age
BMD
falls
bone turnover

Question 19

describe the Q fracture tool

Answer 19

• Developed in 2009 from large primary care populations in the UK
• Applicable for those aged 30-85, men and women
• Contains multiple variables including:
o CV risk
o Falls
o TCA
• Does not have the ability to add BMD
• Some of the variables and risks cannot be altered by osteoporotic medications

Fracture risk assessment tools indicate whether someone is at risk of osteoporosis or not. If the risk is
considered significant (normally defined as a >10% risk of osteoporotic fracture over 10 years) the
individual should be referred for a DXA scan (dual energy x-ray absorptiometry). All who are on oral
steroids or suffer from a low trauma fracture should be referred for a DEXA scar regardless of their
fracture risk percentage.

Question 20

how many women will have an osteoporotic fracture before they die?

Answer 20

1 in 2

Question 21

how many men will have an osteoporotic fracture/

Answer 21

1 in 5

Question 22

causes of osteoporosis: endocrine

Answer 22

thyrotoxicosis
hyper and hypoparathyroidism
Cushing's 
hyperprolactinaemia
hypopitutarism
low sex hormone levels

Question 23

causes of osteoporosis: rheumatic

Answer 23

RA
ankylosing spondylitis
polymyalgia rheumatica

Question 24

causes of osteoporosis: GI

Answer 24

inflammatory diseases e.g. UC and Crohn’s
liver diseases: PBC, CAH, alcoholic cirrohsis, viral cirrhosis
malabsoprtion: CF, chronic pancreatitis, coeliac, whipples disease, short gut syndromes, ischaemic bowel

Question 25

causes of osteoporosis: medications

Answer 25

o Steroids
o PPI
o Enzyme inducting antiepileptic medications
o Aromatase inhibitors
o GnRH inhibitors
o Warfarin

Question 26

prevention of osteoporotic fractures

Answer 26

minimise risk factors
ensure good calcium and vit D status
falls prevention
HRT
bisphosphonates
Denosumab
teripartide

Question 27

SE of HRT

Answer 27

• Increased risk of blood clots
• Increased risk of breast cancer with extended use into late 50s/early 60s
• Increased risk of heart disease and stroke if used after large gap from menopause
• Selective oEstrogen Receptor Modulator (SERMS)
o Raloxifene
o No effect on non-vertebral fracture rates
o Hot flushes if taken close to menopause
o Increased clotting risks
o Lack of protection at hip site

Question 28

discuss bisphosphonate use in osteoporosis

Answer 28

• Main Tx option
• Oral generally first line
• Adequate renal function required
• Adequate calcium and vit D
• Good dental health and hygiene advised
o Notify dentist
o Encourage regular check-ups/well-fitting dentures
• Side effects
o Oesophagitis
o Iritis/uveitis
o Not safe when eGFR <30 mls/min
o ONJ (osteonecrosis of jaw)
o Atypical femoral shaft fractures
• Drug holiday for 1-2 years usually after 10 years use

Question 29

describe denosumab in osteoporosis

Answer 29

• Monoclonal antibody against RANKL
• Reduces osteoclastic bone resorption
• SC injection every 6 months
• Safer in patients with significant renal impairment than bisphosphonates
• Side effects
o Allergy/rash
o Symptomatic hypocalcaemia if given when vitamin D deplete
o ?ONJ
o ?atypical femoral shaft fractures

Question 30

SE of teriparatide

Answer 30

o Injection site irritation
o Rarely hypercalcaemia
o Allergy
o cost