Metabolic bone disorders

Question 1

Define osteoporosis

Answer 1

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.

Question 2

What is the important factor when assessing severity of osteoporosis?

Answer 2

Assessing fracture risk

Question 3

What is the name of the WHO fracture risk assessment tool? What factors does it take into account?

Answer 3

FRAX

• bone density
• age
• gender
• prior fracture
• family history
• smoking, alcohol
• use of steroids
• RA

Question 4

Give six causes of secondary osteoporosis

Answer 4

Endocrine e.g. hyperthyroid, cushings
Malabsorption e.g. coeliac, CF
Malignancy e.g. myeloma
Rheumatic e.g. RA, ankylosing spondylitis, PMR
Drugs e.g. steroids, heparin...
Amenorrhoea

Question 5

What drugs can cause / exacerbate osteoporosis?

Answer 5

Steroids
Heparin
Warfarin
Anticonvulsants
PPIs
GnRH inhibitors
Aromatase inhibitors

Question 6

List the main types of treatment for osteoporosis

Answer 6

Bisphosphonates
Hormone replacement therapy
Selective oestrogen receptor modulator e.g. raloxifene
Teriparatide (form of parathyroid hormone)
Monoclonal antibody - denosumab

Question 7

List some risk factors for osteoporosis / reduced BMD

Answer 7

Increasing age
Female sex
Low BMI ± anorexia nervosa
Parental history of hip fracture
Past history of fragility fracture
Corticosteroid therapy
Cushing's syndrome
Alcohol > 2 units/day
Smoking

Question 8

What bone mass density (on DEXA scan) constitutes osteoporosis?

Answer 8

Osteoporosis: hip BMD 2.5 SD or more below the reference mean.
Severe osteoporosis: hip BMD 2.5 SD below reference mean PLUS one of more fragility fracture.

Question 9

What is denosumab? When is it used and how does it work?

Answer 9

A monoclonal antibody
Used to treat osteoporosis
Reduces osteoclast activity, therefore reduces bone breakdown.

Question 10

Which disease(s) are caused by severe vitamin D deficiency? Describe the mechanism

Answer 10

Osteomalacia (adults)
Rickets (growing children)
–> inadequate mineralisation of bone matrix due to low calcium and phosphate

Question 11

What is the difference between osteomalacia and rickets?

Answer 11

Rickets occurs if there is a vit D / calcium deficiency before the epiphyseal lines are closed.

Question 12

How can rickets be fatal?

Answer 12

Can cause respiratory failure

Question 13

Describe the presentation of rickets

Answer 13

Bony abnormalities e.g. leg-bowing, knock knees
Poor growth
Bone/joint pain
Delayed walking or waddling gait
Dental deformities
Severe vitD deficiency can cause hypocalcaemic seizures/tetany

Question 14

Describe the presentation of mild osteomalacia

Answer 14

Widespread bone pain/tenderness
Proximal muscle weakness
Lethargy

Question 15

Describe the presentation of more severe osteomalacia

Answer 15

Fatigue, bone/joint pain
Proximal muscle weakness/paraesthesia
Waddling gait /difficulty walking, adductor spasm
Spinal curvature
Signs of hypocalcaemia e.g. tetany
Pathological fractures
Skeletal deformity e.g. vertebral bodies, skull

Question 16

Give one difference between osteoporosis and osteomalacia

Answer 16

The bone mineralisation process is normal in osteoporosis but abnormal in osteomalacia

Question 17

What is osteopenia?

Answer 17

A reduction in bone density (-1 - -2.5; osteoporosis is -2.5)

Question 18

Describe the general management for osteomalacia / rickets

Answer 18

Education: dietary advice (refer to a dietician).
Encourage exposure to sunlight.
Vitamin D supplementation.
Treatment of any underlying condition.
Treatment of pain.
Orthopaedic intervention may be required.

Question 19

What pharmacological agents can be used in the treatment of osteomalacia / rickets?

Answer 19

Calciferol (vitamin D2)

Question 20

What is Paget’s Disease of Bone?

Answer 20

A localised disorder of bone turnover. Increased bone resorption (osteoclasts) followed by increased bone formation (osteoblasts). Bone becomes disorganised and is therefore bigger, less compact, more vascular and more susceptible to deformity and fracture.

Question 21

What are the typical signs/symptoms of Paget’s disease of bone?

Answer 21

Bone pain (constant)
Bone deformity e.g. bowing of long bones.

Others: excessive heat over pagetic bone, neurological complications, hearing loss, pathological fractures.

Question 22

Give a rare but serious complication of Paget’s disease of bone

Answer 22

Osteosarcoma

Question 23

When should Paget’s disease be treated?

Answer 23

If present in skull 
If present in an area requiring surgical intervention
If symptomatic (i.e. if there is bone pain)

Question 24

What biochemical test can be used as a marker for Paget’s disease of bone?

Answer 24

Serum alkaline phosphatase (raised in Paget’s disease)

Question 25

How is Paget’s disease treated?

Answer 25

IV Bisphosphonate therapy; single IV zoledronic acid once every 5 - 10 years.

Question 26

Which disorder is colloquially known as “brittle bone disease”?

Answer 26

Osteogenesis imperfecta

Question 27

How many types of osteogenesis imperfecta are there?

Answer 27

8, but only the first 4 are remotely common:

• Type I: mildest form
• Type II: lethal form
• Type III: severely progressive (deforming)
• Type IV: moderately severe

Question 28

What causes osteogenesis imperfecta?

Answer 28

Usually due to an autosomal dominant genetic defect that causes a reduced amount/quality of type 1 collagen.
In mild OI, less collagen is produced
In severe OI, collagen chains formed are abnormal so degrade rapidly

Question 29

What is the main treatment for OI?

Answer 29

IV bisphosphonates e.g. pamidronate

Question 30

Give a characteristic feature of type I OI

Answer 30

blue sclera; caused by scleral thinness allowing the pigmented coat of the choroid to become visible

Question 31

Give some features of OI

Answer 31

Bone deformity, and bone pain.
Short stature.
Spine curves.
Low Bone Density.
Loose joints, ligament laxity and muscle weakness
Distinctive features of the skull including late closing fontanels, and head circumference greater than average.
Hearing loss
Brittle teeth
Respiratory problems including asthma; may be aggravated by chest wall deformity and/or spine deformity.
Vision problems including myopia and risk for retinal detachment
Skin hyperlaxity; easy bruising.
Cardiac issues.
Fatigue.
Basilar Invagination a serious neurological problem is seen in some people with the more severe forms of OI.
Skin, blood vessels and internal organs may be fragile.