Metabolic bone disease

Question 1

Which cells create new bone during bone remodelling cycles?

Answer 1

Osteoblast

Question 2

Which cells break down bone during bone remodelling cycles?

Answer 2

Osteoclasts

Question 3

Bone remodelling occurs all the time in the human skeleton but at different rates depending on what?

Answer 3

The age of the individual and their clinical circumstances (i.e co-morbidities)

Question 4

Factors that influence bone turnover

Answer 4

PTH - parathyroid hormone
Vitamin D
Interleukins - cytokines (secreted proteins and signal molecules) such as in rheumatoid arthritis
Effective steroids

Question 5

Where is vitamin D stored in the body?

Answer 5

Liver
Fat
Muscle

Question 6

What is the active form of vitamin D called and where is it metabolised?

Answer 6

Calcitriol - 1,25(OH)2 Vit D

The kidney

Question 7

What is the main function of vitamin D in the body?

Answer 7

Absorption of calcium and phosphate from the gut.

It then works with PTH to move Ca2+ in and out of tissues and to store it.

Question 8

What is the test used to measure vitamin D levels in the body?

Answer 8

25-hydroxyvitamin D

Question 9

Why might someone have low calcium levels in the body?

Answer 9

Liver or kidney disease

Darker skin (melanocytes compete for uv radiation and prevent initial chemical reaction)

Older people (less 7 DHC (dehydrocholesterol) in skin so harder for them to make vitamin D)

Geographical distribution (living away from the equator have seasoned vitamin D production – we store vitamin D throughout this time so that we can use it all year round)

Question 10

What is Paget’s disease?

Answer 10

A disease where there is interference with the body’s normal bone turnover processes.

Increased bone resorption followed by increased bone formation

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

Question 11

Who gets Paget’s disease?

Answer 11

Patients are always over 40 years old but commonly over 60.

Strong genetic component - 15-30% familial

Restricted geographic distribution: commonly found in the UK, Australia, East coast of America etc

Environmental trigger - possibility of chronic viral infection within osteoclast celsl

Question 12

Symptoms of Paget’s disease?

Answer 12

Deep seated bone pain

Occasionally presents with bone deformity

Excessive heat over the Pagetic bone (tends to be long bones but also pelvis and skull)

Neurological complications i.e nerve deafness - only occurs if there is paget’s in the skull bone

Question 13

Which investigation is good for Paget’s disease?

Answer 13

An isotope bone scan - shows the spread of Paget’s throughout the skeleton

X-ray good too

Question 14

What is the most common presentation of Paget’s?

Answer 14

An isolated elevation of alkaline phosphatase on blood test. Should not treat on this alone though.

Any condition of bone growth or an increased activity of bone cells, including Paget disease, will cause alkaline phosphatase levels to rise.

Question 15

What is a rare presentation of Paget’s?

Answer 15

Osteosarcoma in affected bone

Question 16

Treatment for Paget’s disease?

Answer 16

1st line = IV Bisphosphonate therapy - a one off infusion of zoledronic acid

Oral bisphosphonate is also suitable but not tolerated as well
NSAIDs for bone pain
Calcium and vitamin D supplementation, particularly whilst on bisphosphonates

Question 17

If a Paget’s patient is asymptomatic what would be the only reasons to treat them?

Answer 17

If their skull is affected

Or if they require surgical intervention for something i.e a hip replacement - this proves difficult in a pagetic bone as it’s very vascular and the surgery would be easier when the paget’s disease was quiet

Otherwise, these patients can be safely ignored in most cases

Question 18

What causes Rickets (in children) and Osteomalacia (in adults)?

Answer 18

Severe nutritional vitamin D or Calcium deficiency which causes insufficient mineralisation

Osteomalacia occurs when the epiphyseal lines are closed

Question 19

Symptoms associated with Rickets in children?

Answer 19

Large skull (large forehead)
Stunted growth
Bowing of the legs (odd-shaped)
Large abdomen 
Odd-shaped ribs and breast bones
Wide bones
Odd curve to spine or back

Question 20

Osteomalacia

Answer 20

Most common in elderly especially those institutionalised or house bound

symptoms - bone pain, muscle weakness, increased fall risk

Sometimes see microfractures on x-ray particularly on pelvis, ribs or long bones

Question 21

What is Osteogenesis Imperfecta?

Answer 21

A genetic disorder of connective tissue (collagen type 1)

Causes fragile bones from mild trauma and even acts of daily life

There are other non-bone clinical features as type 1 collagen is found in other tissues

Broad clinical range - from those which are prenatally fatal to those only presenting in 40s

There are 8 types - first 4 are more common though

Question 22

Other than fragile bones what are the other features of Osteogenesis Imperfecta?

Answer 22

Growth deficiency

Defective tooth formation (dentigenesis imperfecta)

Hearing loss

Blue sclera – white of the eye appears blue

Scoliosis / Barrel Chest

Ligamentous laxity - hypermobility

Easy bruising

Question 23

How is osteogenesis imperfecta managed?

Answer 23

Surgical - treat fractures

Medical - prevent fractures using IV Bisphosphonates

Social - educational and social adaptations

Genetic - counselling for parents and next generation

Question 24

How is Osteoporosis defined?

Answer 24

A metabolic bone disease characterised by low bone mass and micro architectural deterioration of bone tissue

This leads to enhanced bone fragility and a consequent increase in fracture risk => this is key

Question 25

What are 2 common calculator tools used to assess fracture risk?

Answer 25

FRAX - used worldwide

Q fracture - used in the UK

Question 26

Which scanning technique is used to assess patients with a FRAX or Q fracture score greater than 10% / those on oral steroid medication / those with a low trauma fracture?

Answer 26

DEXA scan (Dual energy X-ray Absorptiometry) - a low radiation technique

Question 27

When doing a DXA scan what does it mean by the patient’s T and Z score?

Answer 27

T score = Compares the patient to a young adult. It shows the number or standard deviations the patient is below that of the young adult range (the group of patients should be of the same sex, ethnicity and BMI – the only difference must be age). For ever SD you fall below the young adult range there is a doubling of the risk of a low trauma fraction

Z score = compares the patient with an age-matched individual and determines whether their result is expected for their age. You would hope your Z score would be 0 throughout your life.

Question 28

Who is at risk of Osteoporosis?

Answer 28

MANY PEOPLE

I in 2 women over 50 will have an osteoporotic fracture before they die

I in 5 men over 50 will suffer an osteoporotic fracture

Question 29

Endocrine causes of Osteoporosis

Answer 29

Thyrotoxicosis - clinical syndrome of excess circulating thyroid hormones, irrespective of the source

Hyper and Hypoparathyroidism

Cushings disease

Hyperprolactinaemia

Hypopituitarism

Low sex hormone levels – early menopause, use of GnRH inhibitors

Question 30

Rheumatic causes of Osteoporosis

Answer 30

Rheumatoid arthritis

Ankylosing Spondylitis - sero-negative RA

Polymyalgia Rheumatica

Question 31

GI causes of Osteoporosis

Answer 31

Inflammatory diseases: UC and crohns

Liver diseases: primary biliary cirrhosis, Alcoholic cirrhosis, Viral cirrhosis (Hep C)

Malabsorption: Cystic Fibrosis, chronic pancreatitis, coeliac disease, whipples disease, short gut syndromes and ischaemic bowel

Question 32

Medications which cause osteoporosis

Answer 32

Steroids

PPI - proton pump inhibitors - decrease intestinal absorption of calcium

Enzyme inducting anti-epileptic medications e.g carbamazepine, phenytoin - reduces amount of vitamin D in the body

Aromatase inhibitors - hormone therapy

GnRH inhibitors - Gonadal steroids drive the significant bone mineral increase that occurs at puberty. Oestrogen deprivation in women results in bone loss.

Warfarin

Question 33

How does our bone mass change during our lifetime?

Answer 33

Peak height at end of puberty

Still accrue bone mass after this but at a slower pace

Late 20s – peak bone mass

This is maintained until 40s roughly

Accelerated loss begins at menopause

Question 34

How can osteoporotic fractures be prevented?

Answer 34

Minimise risk factors - smoking, alcohol, steroid use

Ensure good calcium and vitamin D status

Falls prevention

Medications - bisphosphonates

Question 35

Which medications are used to manage osteoporosis?

Answer 35

Bisphosphonates - 1st line generally

Hormone replacement therapy (HRT) - excellent at reducing spine, hip and peripheral fractures.

Selective oEstrogen Receptor Modulator (SERM)

Denosumab

Teriparatide

Question 36

Side effects of HRT

Answer 36

Increased risks 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

Question 37

Which type of Selective estrogen receptor modulators (SERM) drug is used for osteoporosis?

Answer 37

Raloxifene - reduces risk of vertebral fractures only

Question 38

Negative effects of SERMS

Answer 38

Hot flushes if taken close to menopause

Increased clotting risks

Lack of protection at hip site - doesn’t prevent hip fractures

Question 39

What is needed first before starting a patient on Bisphosphonates for osteoporosis?

Answer 39

Adequate Renal function required

Adequate Calcium and Vitamin D status

Good Dental Health and Hygiene advised

Question 40

Side effects of Bisphosphonates

Answer 40

Heart burn

Osteonecrosis of the jaw - if jaw bone becomes exposed and infected

Oesophagitis

Iritis/uveitis

Not safe when eGFR <30mls/min

Atypical femoral shaft fractures

Question 41

What is Denosumab?

Answer 41

A RANK Ligand inhibitor that alters osteoclast differentiation and activation. In this case, it reduces osteoclastic bone resorption

Patient’s get a subcutaneous injection every 6 months - this reduces bone breakdown and helps to strengthen bones

Safer in patients with significant renal impairment than bisphosphonates

Reduces fracture risk

Question 42

What is Teriparatide?

Answer 42

A form of parathyroid hormone used to treat osteoporosis - works by increasing osteoblast activity

side effects = injection site irritation and allergy