Osteoporosis

Question 1

What is osteoporosis?

Answer 1

Osteoporosis is a skeletal disorder where bone loss leads to reduced bone strength and an increased risk of fractures​.

As age increases, bone breakdown by osteoclasts increases and is not compensated for by osteoblasts creating new bone​.

Also characterized by changes in the composition of bone along with deterioration in the micro-architecture and geometry​.

This causes bones to become thin and porous which weakens them thereby increasing the fracture risk​.

Question 2

Who is at increased risk of osteoporosis?

Answer 2

Postmenopausal women​.

Men aged over 50​.

Patients on long term systemic corticosteroids​.

Question 3

What are the two types of cells involved in bone remodelling?

Answer 3

Osteoblasts – create bone​.

Osteoclasts – break down bone and release calcium into the blood​.

The activity of osteoblasts and osteoclasts can be regulated by:

Oestrogen.​
Vitamin D​.
Parathyroid hormone​.
Calcitonin​.

Question 4

What is the link between ageing and bone loss​?

Answer 4

As you age, you begin to experience bone loss of 0.5-1% per year starting around the age of 35​.

Peak bone mass is achieved in the third decade and depends on genetics, nutrition, levels of oestrogen and androgens and physical activity​.

Bone loss occurs as a result of increased bone breakdown by osteoclasts and decreased bone formation by osteoblasts​.

Rate accelerates by as much as 10-fold during the menopause due to decreased oestrogen levels and increased osteoclast activity​.

Rate of loss also increases in older men due to decreased testosterone​.

Question 5

What are the symptoms of osteoporosis?

Answer 5

Back pain​.
Loss of height​.
Deformity​.
Reduced pulmonary function​.
Loss of self esteem​.
Distorted body image​.
Dependence on medication​.
Sleep disturbance​.
Depression​.
Loss of independence​.

Question 6

What are the risk factors for osteoporosis?

Answer 6

Low BMI (<19kg/m2)​.
Smoking​.
Excess alcohol.​
Lack of physical activity.​
Early menopause (i.e. hormonal status).​
Family history of maternal hip fracture​.
Long term systemic corticosteroid use​.
Conditions affecting bone metabolism especially those causing prolonged immobility​.
Genetic factors can affect peak bone mass which is an important determinant of bone mass later in life​.
Poor nutrition (especially calcium and Vitamin D intake).

Question 7

What is the role of oestrogen in osteoporosis?

Answer 7

Oestrogen inhibits bone resorption by interfering with osteoblast derived factors that stimulate osteoclast activity​.

May also stimulate osteoblasts to create bone​.

Women have a lower peak bone mass than men and when oestrogen levels fall during the menopause, women lose bone mass rapidly​.

Women also tend to live longer leading to more bone loss​.

Bone mass in elderly men is also positively related to oestrogen levels​.

Question 8

What is the role of vitamin D in osteoporosis?

Answer 8

Facilitates intestinal absorption of calcium​.

Stimulates osteoclasts leading to bone resorption​.

With parathyroid hormone maintains serum calcium levels​.

Question 9

What is the role of parathyroid hormone in osteoporosis?

Answer 9

Indirectly stimulates osteoclasts leading to bone resorption and increased serum calcium​.

Has a complicated mechanism – ratio of various different receptors and ligands determines the extent of bone resorption​.

Question 10

What is the role of calcitonin in osteoporosis?

Answer 10

Calcitonin is also important in the balance of serum calcium​.

It has the opposite effects to parathyroid hormone and reduces serum calcium​.

Inhibits osteoclasts which indirectly leads to increased activity of osteoblasts​.

Was used for osteoporosis but no longer recommended for prophylaxis or treatment of osteoporosis since the benefits are outweighed by a risk of malignancy when used long term​.

Question 11

What lifestyle advice​ can be given to manage osteoporosis?

Answer 11

Stopping smoking and drinking alcohol within recommended limits reduces risk of fracture​.

Maintaining a BMI in the normal range of 20-25kg/m2​.

Exercise improves bone strength and growth and reduces the rate of falls and risk of fracture​.

Outdoor exercise and sun exposure will help to increase Vitamin D levels and promote bone growth and maintenance​.

Measure to help with falls prevention in the elderly​.

Increased education on lifestyle measures to achieve peak bone mass e.g. diet – sources of calcium, and Vitamin D, reduction in alcohol, stopping smoking​.

Question 12

What are the aims of prophylaxis treatment?

Answer 12

Aim of prophylaxis (prevention) is to reduce the risk of fractures occuring by increasing bone mineral density and correcting deficiencies in calcium and vitamin D​.

Since fractures due to osteoporosis can cause considerable morbidity and mortaility, prophylaxis is considered for individuals in high risk groups such as the elderly and housebound​.

Many different drugs can be used for prophylaxis and treatment​.

Question 13

What are bisphosphonates?

Answer 13

Main pharmacological class used for prophylaxis and treatment of osteoporosis​.

Bind to hydroxyapatite crystals on the bone surface and rapidly inhibit the resorption of bone during remodeling.

Mainly act by promoting apoptosis of osteoclasts. ​

Also indirectly stimulate osteoblast activity​.

They therefore lead to an increase in bone strength​.

All bisphosphonates decrease risk of vertebral fractures​.

Alendronic acid and risedronate sodium also decrease the risk of non-vertebral (e.g. hip) fractures​.

Question 14

What are some examples of bisphosphonates?

Answer 14

Alendronic acid​:

Prophylaxis (women) and treatment (men and women)​.
Daily (10mg) or weekly (70mg) administration​.

Ibandronic acid​:

Treatment of postmenopausal osteoporosis​.
Once a month (p.o) or once every three months (IV)​.

Risedronate sodium​:

Prophylaxis (women) and treatment (men and women)​.
Daily or weekly​.

Question 15

What are the adverse events associated with bisphosphonates​?

Answer 15

Gastrointestinal issues including constipation, dyspepsia, pain and diarrhoea are a significant barrier to adherence and are common in the first month​.

Risk of GI side effects can be reduced by ensuring proper drug administration including appropriate quantities of water and post dose postural positioning (remaining sitting or standing)​.

Rare but serious side effects include atypical femoral fractures and osteonecrosis of the jaw and external auditory canal​.

Can lead to hypocalcaemia due to inhibition of bone resorption therefore may require supplementary calcium and vitamin D and hypocalcaemia must be corrected before starting treatment​.

Atypical femoral fractures​:

Patients should be advised to report any thigh, hip or groin pain during treatment with a bisphosphonate​.

Osteonecrosis of the jaw​:

Risk is greater for patients receiving IV treatment in cancer as opposed to oral treatment for osteoporosis​.

Patients with a poor dental status should have a review and any required treatment should be completed before initiation of a bisphosphonate​.

Patients should maintain good oral hygiene, attend regular dental check ups and report oral symptoms including pain, swelling and dental mobility. ​

Question 16

Why are calcium supplements given for osteoporosis?

Answer 16

Calcium supplements have been shown to reduce bone loss in post-menopausal women​.

But there is no evidence that calcium alone reduces the incidence of fractures​.

If calcium is needed, a dose of 1000mg or more per day is required​.

Calcium should be used with caution if there is a history of renal stone formation​.

Question 17

Why are women at greater risk of osteoporosis than men?

Answer 17

Women have a lower peak bone mass​.

Women undergo profound loss of bone at and after the menopause​.

Question 18

Why is hormone replacement therapy (HRT) given for osteoporosis?

Answer 18

HRT is not considered a first line choice for prophylaxis in women over 50 due to the associated risks of long term use and a poor risk-benefit balance for osteoporosis in older women​.

It can be used in younger women especially those who have experienced premature menopause and who are at high risk of fracture, early in the menopause for up to 5 years if they have vasomotor menopausal symptoms​.

HRT is effective at preventing vertebral fractures whilst treatment continues but bone loss will resume when treatment is stopped​.

HRT would therefore need to be continued lifelong to maintain the beneficial effect which is not possible due to the increased cardiovascular and cancer risks associated with longer term use of HRT in older women​.

Question 19

What is raloxifene?

Answer 19

Raloxifene is a selective oestrogen receptor modulator (SERM)​.

It has oestrogen like effects and increases osteoblast activity and reduces osteoclast activity thereby decreasing bone resorption​.

Licensed for treatment and prevention of post menopausal osteoporosis and shown to decrease risk of vertebral fractures​.

Recommended for secondary prevention if alendronic acid and risedronate are not tolerated or contraindicated and patient meets other criteria including T score, age and clinical risk factors​.

Must be avoided in breast cancer and is associated with a VTE risk similar to that of HRT especially in first few months of treatment​.

Has oestrogen antagonist effects in breast and endometrial tissues and can lead to hot flushes which can be unacceptable for some women​.

Question 20

What is teriparatide?

Answer 20

Active fragment of human parathyroid hormone​.

Stimulates the formation of new bone since intermittent exposure will actually increase the number and activity of osteoblasts​.

Licensed for treatment of osteoporosis in men and post menopausal women at very high risk, and reduces risk of vertebral and non vertebral fractures but not hip fractures​.

Daily s/c injection for up to 24 months​.

Restricted to maximum of 2 years use due to risk of osteosarcoma​.

Very expensive therefore only used under specialist care and reserved for patients with severe osteoporosis who are unable to tolerate or seem to be unresponsive to other treatments​.

Question 21

What is denosumab?

Answer 21

Human monoclonal antibody​.

Inhibits osteoclast formation and activity via targeting a protein (RANKL) that stimulates osteoclast differentiation and therefore decreases bone resorption​.

Licensed for men and postmenopausal women​.

Given s/c every 6 months​.

Requires supplementary calcium and Vitamin D​.

Expensive​.

Associated with bisphosphonate like side effects including atypical femoral fracture, osteonecrosis of the jaw and hypocalcaemia​.