Disorders of bone growth (incl osteoporosis)

Question 1

What is Osteoporosis?

Answer 1

Progressive systemic skeletal disease characterised by low bone mass and microarchitectural deterioration of bone tissue, with a consequent increase in bone fragility and susceptibility to fracture.

Question 2

Why are the number of hip fractures in the UK on the rise?

Answer 2

Due to an increase in the elderly population.

Question 3

Approximately how many people in the UK suffer from osteoporosis?

Answer 3

Approx. 3 million

Question 4

What are the symptoms of osteoporosis?

Answer 4

Fractures

without fractures, osteoporosis is asymptomatic

Question 5

What are the common fracture sites due to osteoporosis?

Answer 5

Neck of femur
Vertebral body
Distal radius
Humeral neck

Question 6

What percentage of the human skeleton is remodeled each year?

Answer 6

About 10%

Question 7

Bone undergoes a ______ remodeling cycle at distinct sites called ___________________.
This contributes to calcium homeostasis and also to _______ ________.

Answer 7

Bone undergoes a continual remodeling cycle at distinct sites called bone remodeling units.
This contributes to calcium homeostasis and also to skeletal repair.

Question 8

Which cells secrete the substance of bone?

Answer 8

Osteobalsts

Question 9

Which substance, put down by osteoblasts, is mineralised to form new bone?

Answer 9

Osteoid

unmineralised organic compound of bone

Question 10

What, in osteoporosis, leads to increased bone loss?

Answer 10

In osteoporosis, there is a relative or absolute increase in resorption over formation that leads to increased bone loss

Question 11

Which regulating factors cause bone loss?

Answer 11

Sex hormone deficiency

Body weight

Genetics

Diet

Immobility

Diseases

Drugs (e.g. glucocorticosteroids, aromatase inhibitors)

Question 12

What is the major determinant of bone loss in women after menopause?

Answer 12

Oestrogen deficiency

Question 13

Who do we target therapeutic intervention for in patients with osteoporosis?

Answer 13

Those at high risk of low impact fractures

Question 14

Name 6 NON-MODIFIABLE clinical risk factors for fragility fractures:

Answer 14

Age
Gender
Ethnicity
Previous fracture
Family history
Early menopause (45 or younger)

(co-existing disease is also a risk factor)

Question 15

Name 5 MODIFIABLE clinical risk factors for fragility fractures:

Answer 15

BMD (bone mineral density)
Alcohol
Weight
Smoking
Physical inactivity

(there are also pharmacological risk factors)

Question 16

What does the WHO fracture risk calculator do?

Answer 16

allows calculation of absolute risk by incorporating additional risk factors rather than just BMD (bone mineral density)

prediction of 10 year fracture risk of major osteoporotic fracture or hip fracture

(has some limitations)

Question 17

What does “FRAX” underestimate?

Answer 17

Underestimated vertebral fracture risk

Question 18

What is the negative side of using Qfracture?

Answer 18

Does not include BMD when available

Question 19

What does a DEXA scan measure?

Answer 19

Bone mineral density (BMD)

predicts fracture risk

Question 20

Who do you refer for DXA?

Answer 20

Anyone with a 10 year risk assessment for any OP fracture of at least 10%

Question 21

What is osteopenia?

Answer 21

Low bone mass

BMD >1 SD below the yound adult mean but less hen >2,5 below this value

Question 22

What is the BMD in osteoporosis?

Answer 22

> (or equal to) 2.5 SD below the young adult mean

worse than osteopenia

Question 23

What is severe osteoporosis?

Answer 23

BMD ≥2.5 SD below the young adult mean with fragility fracture

Question 24

Which investigations would you do for someone with ostorporosis presentation?

Answer 24

U + Es
FBC
LFTs
PV
TSH
Bone biochemistry

Question 25

Name 4 secondary causes of osteoporosis:

Answer 25

Endocrine eg hyperthyroidism, hyperparathyroidism, Cushing’s disease Gastrointestinal eg coeliac disease, IBD, chronic liver disease, chronic pancreatitis Respiratory eg CF, COPD Chronic kidney disease

Question 26

What lifestyle advice for management of osteoporosis would you give?

Answer 26

High intensity strength training Low impact weight bearing exercise (standing, one foot always on the floor) Avoidance of excess alcohol Avoidance of smoking Fall prevention Diet: RNI 700mg calcium (2-3 portions from milk and dairy foods group) Postmenopausal women aim dietary intake 1,000mg calcium per day to reduce fracture risk (3-4 portion calcium rich foods) Non-dairy sources include bread and cereals (fortified), fish with bones, nuts, green vegetables, beans

Question 27

Which drug treatments are available to treat osteoporosis?

Answer 27

Calcium & vitamin D supplementation Bisphosphonate Denosumab Teriparatide Strontium Ranelate HRT SERMS (Selective Estrogen Receptor Modulators) Testosterone

Question 28

What does the SIGN guidelines say about taking calcium supplements and bisphosphonates?

Answer 28

Calcium supplements should not be taken within 2 hours of oral Bisphosphonates

Question 29

What are bisphosphonates and what do they do?

Answer 29

Bisphosphonates and antiresorptive agents Prevent bone loss at all sites vulnerable to osteoporosis Reduce risk of hip and spine fracture Bisphosphonates and analogues of pyrophosphate that adsorb onto bone within the matrix Bisphosphonates are ingested by osteoclasts leading to cell death thereby inhibiting bone resorption Increases BMD e.g. Alendronate and Risedronate

Question 30

How long is it ok to be on bisphosphonate therapy?

Answer 30

Good data for benefir for 5 years (10 years if vertebral fracture) Long term concerns: Osteonecrosis of the jaw Oesophageal Ca Atypical fractures

Question 31

How is Zolendronic Acid administered?

Answer 31

IV infusion (once yearly for 3 years) 5mg in 100mls NaCl over 15 minutes

Question 32

What is the risk of acute phase reaction with first infusion of Zoledronic Acid?

Answer 32

1 in 3 acute phase reaction with 1st infusion –-> paracetamol

Question 33

What effect of fracture risk does Zoledronic Acid treatment have?

Answer 33

Approximately 70% reduction in vertebral fracture 40% reduction in hip fracture

Question 34

What is Denosumab and how does it work?

Answer 34

``` Antibody Binds to RANKL (high affinity) Inhibits RANK Inhibits osteoclast activity Decreases bone resorption Increases bone density ```

Question 35

How is Denosumab administered?

Answer 35

Subcutaneous injection 6 monthly

Question 36

What does Denosumab do?

Answer 36

Increases bone density by binding to RANKL, inhibiting RANK and therefore, inhibiting osteoclast activity, causeing increased bone density. Reduces risk of vertebral fracture by approx. 68% Reduces risk of hip fracture by 40% And reduces risk of non-vertebral fracture by approx. 20%

Question 37

What is Strontium Ranelate

Answer 37

An Antoresorptive agent 3rd line agent (fracture risk reduction lightly less than bisphosphonate) (contraindications:) Contraindicated if history of thromboembolic disease, IHD, peripheral arterial disease, uncontrolled hypertension Not recommended if there is an alternative osteoporosis treatment available

Question 38

What type of agent is strontium ranelate?

Answer 38

Antiresorptive agent

Question 39

What type of agent is Denosumab?

Answer 39

Fully Human Monoclonal Antibody

Question 40

What is Teriparatide?

Answer 40

Recombinant parathyroid hormone (1-34) Stimulates bone growth rather than reducing bone loss – anabolic agent

Question 41

What effects do corticosteroids have one bone?

Answer 41

Direct: Reduction of osteoblast activity and lifespan Suppression of replication of osteoblast precursors Reduction in calcium absorption Indirect: Inhibition of gonadal and adrenal steroid production

Question 42

What is the aim of osteoporosis therapy?

Answer 42

To provide sustained efficacy to reduce the long-term risk of fractures

Question 43

What is Paget's disease of bone?

Answer 43

Abnormal osteoclastic activity followed by increased osteoblastic activity --> Abnormal bone structure with reduced strength and increased fracture risk may be single site - monostotic or multiple sites - polyostotic

Question 44

Paget's disease of bone may be single site or multiple sites, what are the names for these?

Answer 44

Monostotic - single site Polystotic - multiple sites

Question 45

Which bones are predominantly affected by Paget's?

Answer 45

Long bones, pelvis, lumbar spine and skull.

Question 46

Does incidence of Paget's disease of bone increase or decrease with age?

Answer 46

Increases with age | rare < 40 y

Question 47

What is the typical presentation of Paget's?

Answer 47

Presents with bone pain, deformity, deafness or compression neuropathies (osteosarcoma - rare complicaion) (may be incidental finding on XR or isolated raised alkaline phosphate)

Question 48

What would test results likely show in patient with Paget's?

Answer 48

Diagnose on XR Isotope bone scan shows distribution Raised alkaline phosphotase with NORMAL LFTs

Question 49

How is Paget's treated if pain not responding to analgesia

Answer 49

Treat with bisphosphonates if pain not responding to analgesia

Question 50

What is Osteogenesis Imperfecta?

Answer 50

Rare group of genetic disorders mainly affecting bone (most secondary to mutations of type 1 collagen genes (COL1A1, COL1A2)) (most autosomal dominant inheritance)

Question 51

``` There are at least 8 types of Osteogenesis Imperfecta, of varying severity. Which types are: Mild (1) Very severe (2) Neonatal lethal (1) ```

Answer 51

Mild – type 1 Very severe - types III and IV Neonatal lethal – type II

Question 52

What other presentations may osteogenesis imperfecta be associated with?

Answer 52

Blue sclerae | Dentinogenesis Imperfecta

Question 53

Is there a cure for Osteogenesis Imperfecta?

Answer 53

No | fracture fixation, surgery to correct deformities, bisphosphonates

Question 54

When does Osteogenesis Imperfecta present?

Answer 54

More severe forms - present with fractures in childhood Mild forms - may not present til adult life