Osteoporosis and Metabolic Bone Disease

Question 1

What is 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 fracture risk related to?

Answer 2

Age
Bone mineral density
Falls
Bone turnover

Question 3

What is referral for DXA scanning based on?

Answer 3

FRAX or Q Fracture score of > 10% fracture risk at any site over next 10 years, according to 2003 SIGN guidelines

Question 4

What is the treatment threshold in terms of fracture risk?

Answer 4

Fracture risk around 20% 10 year risk would be the treatment threshold

Question 5

What are the features of Q Fracture?

Answer 5

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

Question 6

What are the endocrine causes of secondary osteoporosis?

Answer 6

Hyperthyroid
Hyperparathyroid 
Hypoparathyroid
GH deficiency 
Hyperprolactinaemia 
Cushing's

Question 7

What are the malabsorption causes of secondary osteoporosis?

Answer 7

Coeliac disease

CF

Question 8

What malignancy causes secondary osteoporosis?

Answer 8

Myeloma

Question 9

What are the rheumatic causes of secondary osteoporosis?

Answer 9

RA
Ankylosing spondylitis
PMR

Question 10

What are the drugs that cause secondary osteoporosis?

Answer 10

Steroids
Heparin
Warfarin
Anticonvulsants
PPIs
GnRH inhibitors

Question 11

What are the causes of amenorrhoea, which can result in secondary osteoporosis?

Answer 11

Anorexia nervosa
Early menopause
Primary ovarian failure

Question 12

What is involved in osteoporotic fracture prevention?

Answer 12

Minimise risk factors
Ensure good calcium and vitamin D status
Fall prevention strategies
Medications

Question 13

What are the investigations used to confirm the diagnosis of osteoporosis?

Answer 13

Measure BMD via DXA hip and spine
If result is normal (T score above -1) then reassure and give lifestyle advice
If result indicates osteopenia (T score -1 to -2.5 then give lifestyle advice or treat if there has been a previous fracture
If result indicates osteoporosis (T score below -2.5) then give lifestyle advice and offer treatment

Question 14

What are the types of drugs used in prevention and treatment of osteoporosis?

Answer 14

HRT
Selective Oestrogen Receptor Modulators 
Bisphosphonates
Teriparatide
Denosumab

Question 15

What are the risks of HRT treatment?

Answer 15

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 a large gap from menopause

Question 16

What are the disadvantages of selective oestrogen receptor modulator treatment?

Answer 16

Hot flushes if taken close to menopause
Increased clotting risks
Lack of protection at hip site

Question 17

What is the main treatment option for osteoporosis?

Answer 17

Bisphosphonates - oral bisphosphonates generally the first line of treatment

Question 18

What is required for bisphosphonate treatment?

Answer 18

Adequate renal function
Adequate calcium and vitamin D status
Good dental health and hygiene advised

Question 19

What bisphosphonates inhibit osteoclasts?

Answer 19

Nitrogen containing bisphosphonates

Question 20

What are the potential side effects of bisphosphonates?

Answer 20

Oesophagitis
Iritis/uveitis
Atypical femoral shaft fractures

Question 21

What is teriparatide?

Answer 21

Recombinant form of parathyroid hormone

Question 22

What are the side effects/disadvantages of teriparatide?

Answer 22

Injection site irritation
Hypercalcaemia (rarely)
Allergy
Cost

Question 23

What is denosumab?

Answer 23

Monoclonal antibody against RANKL

Reduces osteoclastic bone resorption

Question 24

How is denosumab administered?

Answer 24

Subcutaneous injection every 6 months

Question 25

In what patients is denosumab safer than bisphosphonates?

Answer 25

Patients with significant renal impairment

Question 26

What are the side effects of denosumab?

Answer 26

Allergy Rash Symptomatic hypocalcaemia if given when vitamin D deplete Possible ONJ Possible atypical femoral shaft fractures

Question 27

What does severe nutritional vitamin D or calcium deficiency cause?

Answer 27

Insufficient mineralisation and rickets in a growing child, osteomalacia in an adult (where the epiphyseal lines are closed

Question 28

What does vitamin D stimulate?

Answer 28

Absorption of calcium and phosphate from the gut, so calcium and phosphate become available for bone mineralisation

Question 29

What happens to muscle function in low vitamin D states?

Answer 29

Muscle function is impaired

Question 30

What is Paget's disease? What happens in this disease?

Answer 30

Localised disorder of bone turnover Increased bone resorption followed by increased bone formation Leads to disorganised bone - bigger, less compact, more vascular and more susceptible to fracture

Question 31

What percentage of cases of Paget's disease are familial?

Answer 31

15-30%

Question 32

Mutations in what loci have been associated with Paget's disease?

Answer 32

Loci of SQSTM1

Question 33

What are the symptoms of Paget's disease?

Answer 33

Patients > 40 years Bone pain Occasionally presents with bone deformity, excessive heat over the Pagetic bone, or by neurological complications

Question 34

What is the presentation of Paget's disease?

Answer 34

Isolated elevation of serum alkaline phosphatase - commonest presentation Bone pain and local heat Bone deformity or fracture Hearing loss Rare - development of osteosarcoma in affected bone

Question 35

What is the treatment of Paget's disease?

Answer 35

No evidence to support treatment of asymptomatic disease, unless in the skull or in an area requiring surgical intervention Should not be treated based on raised alkaline phosphatase alone IV bisphosphonate therapy, one off IV xoledronic acid

Question 36

What is osteogenesis imperfecta?

Answer 36

Genetic disorder of connective tissue characterised by fragile bones from mild trauma and acts of daily life

Question 37

What is the clinical range of osteogenesis imperfecta?

Answer 37

Broad - from those that are prenatally fatal to those presenting in 40s with early osteoporosis

Question 38

What defect results in osteogenesis imperfecta?

Answer 38

Defects in type 1 collagen - 8 different types but the first 4 are the most common

Question 39

What are the features of type 1 osteogenesis imperfecta?

Answer 39

Milder form, presents when child starts to walk, but can present in adults

Question 40

What are the features of type 2 osteogenesis imperfecta?

Answer 40

Lethal by age 1

Question 41

What are the features of type 3 osteogenesis imperfecta?

Answer 41

Progressive deforming with severe bone dysplasia and poor growth

Question 42

What are the features of type 4 osteogenesis imperfecta?

Answer 42

Similar to type 1 but more severe

Question 43

What are the signs and symptoms of osteogenesis imperfecta?

Answer 43

``` Growth deficiency Defective tooth formation (dentigenesis imperfecta) Hearing loss Blue sclera Scoliosis Barrel chest Ligamentous laxity Easy bruising ```

Question 44

What is the management of osteogenesis imperfecta?

Answer 44

Surgical - to treat fractures Medical - fracture prevention, IV bisphosphonates Social - educational and social adaptations Genetic - genetic counselling for parents and next generation