Disorders of Bone Health

Question 1

What is osteoporosis?

Answer 1

Progressive systemic skeletal tissue disease characterised by low bone mass and microarchitecture deterioration of bone tissue

Question 2

What occurs due to osteoporosis?

Answer 2

Increased bone fragility and susceptibility to fractures

Question 3

What is the natural deterioration of bone over time?

Answer 3

20 years = strong, healthy bone
50 years = decreases in trabecular thickness which is more pronounced for non-loading horizontal trabeculae
80 years = decrease in number of connections between vertical trabeculae, decrease in trabecular strength

Question 4

Where does bone remodelling take place?

Answer 4

At distinct sites called bone remodelling units = 10% of adult skeleton is remodelled each year

Question 5

What does bone remodelling contribute to?

Answer 5

Calcium homeostasis and skeletal repair

Question 6

What role do bone cells play in remodelling?

Answer 6

Osteoclasts = activation and resorption
Osteoblasts = form bone
Osteoid = undergoes mineralisation

Question 7

What are the regulating factors of osteoporosis?

Answer 7

Peak bone mass and bone loss

Question 8

What are some contributors to peak bone mass, and when is it achieved?

Answer 8

Genetics (70-80%), body weight, sex hormones, diet, exercise, achieved by age 30

Question 9

What are some determinants of bone loss, and when does it begin?

Answer 9

Sex hormone deficiency, body weight, genetics, diet, immobility, disease, drugs (glucocorticoids), occurs from age 45

Question 10

Where are some common fracture sites in patients with osteoporosis?

Answer 10

Neck of femur, vertebral body, distal radius, humeral neck

Question 11

How is bone density assessed?

Answer 11

BMD predicts fracture risk independently of other risk factors = most commonly measured using DEXA scans

Question 12

What is the normal value for BMD?

Answer 12

Within 1SD of the young adult reference mean

Question 13

What value of BMD is suggestive of osteopenia?

Answer 13

BMD >1SD below the young adult mean but <2SD below this value

Question 14

What BMD is suggestive of osteoporosis and severe osteoporosis?

Answer 14

Osteoporosis = BMD >= 2SD below young adult mean
Severe = BMD >= 2SD below young adult mean with fragility fracture

Question 15

Which patients should be referred for a DEXA scan?

Answer 15

Patients >50 with low trauma fractures

Patients at increased risk of fracture based on risk factors

Question 16

What patients with osteoporosis should be targeted for therapeutic intervention?

Answer 16

Those at high risk of low impact fractures

Question 17

What are the SIGN 142 guidelines for osteoporosis based on?

Answer 17

Fracture risk = address risk factors for fractures (modifiable/non-modifiable), assessment of fracture risk

Question 18

What are some non-modifiable risk factors for fractures in patients with osteoporosis?

Answer 18

Age, gender, ethnicity, previous fracture, family history, menopause <=45 years old, co-existing disease

Question 19

What are some modifiable risk factors for fractures in patients with osteoporosis?

Answer 19

BMD, alcohol, weight, smoking, physical inactivity, pharmacological risk factors

Question 20

How does the WHO risk calculator for fractures assess risk?

Answer 20

Calculation of absolute risk by incorporating additional risk factors = prediction of 10 year fracture risk of major osteoporotic fracture or hip fracture

Question 21

What is used rather than BMD in patient’s under 20 with osteoporosis?

Answer 21

Z score

Question 22

What patients are suitable for risk factor assessment?

Answer 22

Anyone >50 with risk factors, anyone <50 with very strong clinical risk factors (e.g early menopause)

Question 23

When does risk assessment qualify osteoporosis patients for DEXA?

Answer 23

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

Question 24

What is investigated in patients with suspected osteoporosis?

Answer 24

U & Es, LFTs, bone biochemistry, FBC, PV, TSH

Consider protein electrophoresis/Bence Jones proteins, coeliac antibodies, testosterone, vitamin D, PTH

Question 25

What are some secondary causes of osteoporosis?

Answer 25

Hyperthyroidism, hyperparathyroidism, Cushing's disease, coeliac, IBD, chronic liver disease, chronic pancreatitis, CF, COPD, chronic kidney disease

Question 26

What is some lifestyle advice for patients with osteoporosis?

Answer 26

High intensity strength training, low impact weight-bearing exercise, avoidance of excess alcohol and smoking, fall prevention

Question 27

How much calcium should patients with osteoporosis aim to include in their diet per day?

Answer 27

700mg (2-3 portions) | Post-menopausal women aim for 1000mg to reduce fracture risk

Question 28

What are some non-dairy sources of calcium?

Answer 28

Bread, cereals (fortified), fish with bones, nuts, green vegetables, beans

Question 29

What are some drug treatments used for osteoporosis?

Answer 29

Calcium and vitamin D supplements, bisphosphonates, denosumab, teriparatide, HRT, testosterone

Question 30

When should calcium and vitamin D supplements be considered?

Answer 30

To reduce risk of non-vertebral fractures in patients who are at risk of deficiency due to insufficient dietary intake or limited sunlight exposure

Question 31

What is the rule when taking calcium supplements and oral bisphosphonates?

Answer 31

Calcium supplements must not be taken within 2hrs of oral bisphosphonates

Question 32

Is calcium supplementation needed if dietary intake in adequate?

Answer 32

No = only prescribe vitamin D in this case

Question 33

What are bisphosphonates?

Answer 33

Analogues of pyrophosphate that absorb onto bone within the matrix = ingested by osteoclasts leading to cell death (inhibit bone resorption)

Question 34

How do bisphosphonates improve BMD?

Answer 34

Filling of resorption sites by new bone increases BMD by 5-8%

Question 35

What are some anti-resorptive bisphosphonates?

Answer 35

Alendronate and risedronate = reduce risk of fragility fractures by 50% in patients with post-menopausal osteoporosis

Question 36

How do bisphosphonates help in osteoporosis?

Answer 36

Prevent bone loss in all sites vulnerable to osteoporosis, reduce risk of hip and spine fracture

Question 37

What is the number needed to treat (NNT) of bisphosphonates for one year to prevent one fracture in osteoporosis patients?

Answer 37

T score less than -2.5 = 150 | Plus existing fragility fracture = 30

Question 38

What are the long term concerns of bisphosphonate use?

Answer 38

Osteonecrosis of jaw, oesophageal cancer, atypical fractures

Question 39

What is an example of an IV bisphosphonate?

Answer 39

Zoledronic acid = once yearly IV infusion for three years

Question 40

What is denosumab?

Answer 40

Fully human monoclonal antibody = targets and binds with high affinity and specificity to RANKL (receptor activator of nuclear factor-kB ligand)

Question 41

What does denosumab inhibit?

Answer 41

Prevents RANK activation = inhibits development and activity of osteoclasts which decreases done resorption and increases bone density

Question 42

How is denosumab administered?

Answer 42

Subcutaneous injection 6 monthly

Question 43

What are some adverse effects of denosumab?

Answer 43

Hypocalcaemia, eczema, cellulitis | No contraindication in severe renal impairment

Question 44

What is teriparatide?

Answer 44

Recombinant parathyroid hormone (1-34) = stimulates bone growth (anabolic agent)

Question 45

When is teriparatide used?

Answer 45

In severe osteoporosis, particularly if high risk of vertebral fracture

Question 46

When should medication be considered to treat osteoporosis?

Answer 46

Consider antiresorptive therapy when T score <= -2.5

Question 47

When should medication be started to treat osteoporosis patients with a T score < -1.5?

Answer 47

If the patient is has ongoing steroid requirement >= 7.5mg prednisolone for 3 months or more If there is prevalent vertebral fracture

Question 48

What are the direct effects of corticosteroids on bone?

Answer 48

Reduction of osteoblast activity and lifespan, suppression of replication of osteoblast precursors, reduction in calcium absorption

Question 49

What is the indirect effect that corticosteroids have on bone?

Answer 49

Inhibition of gonadal and adrenal steroid production

Question 50

How do corticosteroids impact fracture risk?

Answer 50

Individual variability to glucocorticoids, dose-dependent (but no "safe" dose), rapid loss of BMD (30% in first 6 months), partially reversible on cessation

Question 51

What occurs in Paget's disease?

Answer 51

Abnormal osteoclastic activity followed by increased osteoblastic activity = causes abnormal bone structure with reduced strength and increased fracture risk

Question 52

What are some features of Paget's disease?

Answer 52

Unknown aetiology, Rare < age 40, incidence increases with age, may be single site (monostotic) or multiple sites (polystotic)

Question 53

What bones are typically affected in Paget's disease?

Answer 53

Long bones, pelvis, lumbar spine, skull

Question 54

What are the signs and symptoms of Paget's disease?

Answer 54

Bone pain, deformity, deafness, compression neuropathies, osteosarcoma may be rare complication

Question 55

How is Paget's disease diagnosed?

Answer 55

Using x-ray = may be incidental finding | May be isolated high alkaline phosphatase

Question 56

What is the classic x-ray appearance of Paget's disease?

Answer 56

Isotope bone scan shows expanded bone with coarsened trabecular pattern

Question 57

What is osteogenesis imperfecta?

Answer 57

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

Question 58

How many types of osteogenesis imperfecta are there?

Answer 58

At least 8 types of varying severity = type 1 is mild, type 2 is neonatal (lethal), types 3 and 4 are very severe

Question 59

What may be osteogenesis imperfecta be associated with?

Answer 59

Blue sclerae and dentinogenesis imperfecta More sever forms present with fractures in childhood Mild forms may not present until adulthood

Question 60

What is the treatment options for osteogenesis imperfecta?

Answer 60

No cure = fracture fixation, surgery to correct deformities, bisphosphonates