Metabolic bone disorders

Question 1

There are >2 million women living with osteoporosis in UK . what is Osteoporosis?

Answer 1

1) Progressive disease caused by low bone mass and deterioration of microarchitecture of bone tissue
2) Changes in bone lead to increased fragility and susceptibility to fracture

Question 2

Osteoporosis is classified using the T-score criteria. what is the T-score?

Answer 2

1) T-score is the number of units — called standard deviations — that a patient’s bone mineral density (BMD) is from reference BMD of a 25yr adult female

Question 3

what is the T-score for the following:

1) Normal
2) Osteopoenia
3) Osteoporosis
4) Established Osteoporosis

Answer 3

1) Normal: > -1
2) Osteopoenia: -1 to -2.5
3) Osteoporosis: below -2.5
4) Established Osteoporosis:

Question 4

outline the risk factors of osteoporosis

Answer 4

1) Age
2) Gender (80% cases are women)
3) low BMI (<19kg/m2)
4) Untreated premature menopause, prolonged amenorrhoea or male hypogonadism
5) Alcohol/Smoking
6) Corticosteroid use (oral/long term)
7) Family history of maternal hip fracture
8) Conditions associated with prolonged immobility

Question 5

what advice should be given to prevent Osteoporosis?

Answer 5

Lifestyle modification:

1) Regular weight-bearing exercise (reduce risk of hip fx by 50%)
2) Stop smoking before menopause (reduce risk of hip fx by 25%)
3) Maintain adequate dietary levels of calcium/vitamin D - supplement if necessary
4) Reduce alcohol consumption
5) Maintain BMI >19 kg/m2

Question 6

why are Calcium salts used in Osteoporosis?

Answer 6

1) Daily turnover of bone minerals during remodeling involves 700 mg calcium
2) Double the recommended calcium intake reduces rate of bone loss
3) Elderly patients, esp. housebound or those living in residential or nursing homes are at increased risk of calcium (and Vitamin D) deficiency
- Should be used with another therapy (i.e bisphosphonate)

Question 7

what is the first line treatment for Osteoporosis?

Answer 7

1) Bisphosphonates are first-line therapy for treatment and prevention of osteoporosis
- alendronic acid reduces vertebral, wrist and hip fractures by approx. 50%
- Risedronate sodium

Question 8

what should be used if bisphosphonates are contraindicated in Osteoporosis?

Answer 8

1) Hormone replacement therapy (HRT) if <50 years
2) Selective Estrogen Receptor Modulator (SERM) Raloxifene
3) Strontium ranelate if >75yrs with previous Fx and low BMD
4) Calcitonin, if high risk of osteoporosis
5) Teriparatide >65yrs, extremely low BMD or low BMD with 2+ Fx and other risk factors

Question 9

what is the MOA of Bisphosphonates?

Answer 9

1) The bisphosphonates inhibit the resorption of bone by osteoclasts
2) Approx. 50% of dose accumulates at sites of bone mineralisation where they bind to bone minerals in bone matrix. They are released and ingested by osteoclasts as they resorb the bone which exposes the cells to high concentrations

Question 10

what are the side effects caused by Bisphosphonates?

Answer 10

1) All bisphosphonates cause gastrointestinal side effects

2) Alendronate and risedronate are associated with severe oesophageal reactions, including stricture

Question 11

how can the side effects caused by bisphosphonates be reduced?

Answer 11

1) Patients should not take dose at bedtime and should stay upright for at least 30 mins after taking dose
2) Should avoid food before and after dose as food impairs absorption
3) Food should be avoided for at least 30 mins (2 hours before and after for etidronate)
3) Antacids, calcium salts and iron reduce absorption

Question 12

Alendronic acid is a nitrogen-containing, second generation bisphosphonate. what is its MOA and indication?

Answer 12

1) Accumulates in bone and prevents bone resorption by inhibiting osteoclast attachment and survival
2) post-menopausal osteoporosis (10mg daily or 70mg once weekly)
- osteoporosis in men (10mg daily)

Question 13

what is the counselling for Alendronic acid?

Answer 13

1) Swallow tablets whole with plenty of water while sitting or standing.
2) Take on an empty stomach at least 30 minutes before breakfast (or another oral medicine)
3) patient should stand or sit upright for at least 30 minutes after taking tablet

Question 14

Hormone Replacement Therapy is not first-line treatment for long-term prevention of osteoporosis in women >50yrs . when is HRT be used and how does it work?

Answer 14

1) Might be used in women with early natural or surgically-induced menopause if other therapies are contra-indicated, are not tolerated
20 Most benefit if started early in menopause, for up to 5yrs, but bone loss will resume (accelerated) on stopping HRT
3) Oestrogens important in maintenance of bone integrity by inhibiting cytokines that recruit osteoclasts and opposing the bone resorbing Ca2+- mobilising role of Parathyroid hormone

Question 15

Raloxifene is a Selective Oestrogen Receptor Modulator (SERM) licensed for the treatment of osteoporosis. what is its MOA?

Answer 15

1) Inhibits bone resorption by preventing osteoclast recruitment without problem side effects of HRT
2) Raloxifene has selective agonist activity on bone and cardiovascular system and antagonist activity on mammary tissue and the uterus
(Increased risk of venous thromboembolism)

Question 16

Strontium ranelate is licensed for post-menopausal osteoporosis. what is its MOA?

Answer 16

1) Inhibits bone resorption and stimulates bone formation but exact mechanism is not clear
- Strontium is adsorbed onto hydroxyapatite crystals in bone, is exchanged for Ca2+ in mineralised bone

Question 17

what are the side effects of Strontium ranelate?

Answer 17

1) Side effects: Nausea, diarrhoea, venous thromoembolism, headache, dermatitis, eczema
2) Well tolerated drug with few side effects but should be used with caution in those with predisposition to thromboembolism, renal impairment or requiring Ca2+ monitoring

Question 18

strontium ranelate should be restricted to use in women with high fracture risk and if bisphosphonates are contra-indicated or have failed. what dose of Strontium ranelate is used in osteoporosis and what counselling advice is given to patients?

Answer 18

1) 2g granules in water given daily, preferably at bedtime
2) Food must be avoided for 2 hours before and after granules are taken, esp. Ca2+ containing foods
3) Antacids should also be avoided for 2hrs after taking

Question 19

list the two hormones that play a key role in the homoeostasis of calcium in the body

Answer 19

1) Parathyroid hormone (PTH) and calcitonin play key roles in maintaining calcium and phosphate homoeostasis .
- calcitonin opposes the action of parathyroid hormone
2) Several treatment options for osteoporosis target mechanisms involved in calcium homeostasis

Question 20

what is the function of Calcitonin?

Answer 20

Calcitonin inhibits osteoclast action directly and decreases plasma [Ca2+] by decreasing reabsorption of Ca2+ and phosphate in kidney.

Question 21

what is the function of Parathyroid Hormone (PTH)?

Answer 21

1) PTH and its fragments can increase osteoblast number and stimulate their activity and increase bone mass, integrity and strength. Also decrease osteoblast apoptosis.
2) parathyroid hormone regulates calcium levels in the blood, largely by increasing the levels when they are too low. It does this through its actions on the kidneys, bones and intestine- Parathyroid hormone stimulates the release of calcium from large calcium stores in the bones into the bloodstream. This increases bone destruction and decreases the formation of new bone.

• Human recombinant PTH: subcutaneous injection
• Teriparatide: is a recombinant form of parathyroid hormone

Question 22

explain how corticosteroids influence bone health?

Answer 22

1) corticosteroids encompasses both glucocorticoids (eg cortisol) and mineralocorticoids (eg aldosterone)
2) Physiological concentrations of glucocorticoids are required for osteoblast differentiation
3) Excessive pharmacological concentrations inhibit bone formation by inhibiting osteoblast differentiation and their activity and might also stimulate osteoclast action
4) Corticosteroids can induce osteoporosis

Question 23

how can the risk of corticosteroid-induced osteoporosis be reduced?

Answer 23

1) Doses of oral corticosteroids should be as low as possible & shortest course possible
- High doses of inhaled corticosteroids also can contribute to risk
2) Risk increases due to cumulative dose so even intermittent doses increase risk
3) Greatest bone loss due to corticosteroids occurs in first 6-12 months of use so early steps to prevent development of osteoporosis is required
4) Advise all patients taking oral steroids to take calcium/Vitamin D supplements

Question 24

Prophylaxis and treatment options for corticosteroid-induced osteoporosis are the same. outline the treatment

Answer 24

1) A bisphosphonate (alendronic acid, risedronate etc)
- Bisphosphonate if >65yrs and taking oral/high dose inhaled steroids for > 3 mths
- If <65yrs,refer for DEXA scan & add bisphosphonate if T score is less than -1.5
2) Calcitriol (Vitamin D3 analogue)
3) Hormone treatment (HRT in women or testosterone i

Question 25

what is a Dual Energy X-ray Absorptiometry (DEXA) scan?

Answer 25

1) A DEXA scan is a special type of X-ray that measures bone mineral density (BMD).
2) the gold standard technique for diagnosis of osteoporosis

Question 26

what is Paget’s disease and who is commonly affected?

Answer 26

1) Chronic bone disorder where areas of bone undergo accelerated bone remodeling due to hyperactivity of osteoblasts and osteoclasts
2) Affects 1 in 10 elderly (3:1 male:female) but only minority are symptomatic

Question 27

which bones are commonly affected by Paget’s disease?

Answer 27

1) commonly pelvis, femur, skull, tibia, vertebrae, clavicle or humerus
2) enlarge, become structurally abnormal and weaker than normal

Question 28

summarise the symptoms of Paget’s disease

Answer 28

1) Bone pain: - deep aching pain, often worse by weight bearing that remains at rest/night
2) Bone enlargement: If skull affected, might result in hearing loss and dizziness. If spine affected, loss of height etc
3) Deformity: Changes in adjacent joint structure might lead to osteoarthritis (wear and tear)
4) Hypercalcaemia (might lead to hypertension, kidney stones etc)
5) Increased blood flow through bone might lead to heart failure
6) Increased incidence of cancer in affected bone

Question 29

what is the treatment for Paget’s disease?

Answer 29

1) Bisphosphonates slow progression of disease
2) Calcitonin
3) NSAIDS for pain

Question 30

1) what causes Osteomalacia and Rickets?

2) why does this disease lead to softening/weakening of bone?

Answer 30

1) Rickets (children) or osteomalacia (adults) is caused by a vitamin D deficiency
- Lack of sunlight exposure
- Lack of vitamin D in diet
2) Deficiency of vitamin D leads decreased plasma calcium and phosphate levels, which impacts on bone
3) To increase plasma [Ca2+] levels caused by vitamin D deficiency, PTH levels increase, which leads to depletion of calcium stores in bone (de-mineralisation), which leads to their softening/weakening.

Question 31

outline the role of vitimin D in the body

Answer 31

1) maintenance of plasma [Ca2+] by increasing its absorption in intestine and kidney, mobilising it from bone (increases osteoclast maturation and activity) and decreasing its renal excretion. Also decreases osteoblast synthesis of collagen
2) treatment with vitamin D restores bone mineralisation in bone diseases resulting from vitamin D deficiency (rickets)
- Calcitriol (active metabolite of vitamin D ) stimulates osteocalcin, Ca2+ binding protein in bone matrix.

Question 32

list the two sources of vitamin D

Answer 32

1) Vitamin D2 (calcifediol) from diet

2) Vitamin D3 (cholecalcifediol) from sunlight

Question 33

explain how Vitamin D deficiency leads to depletion of calcium stores in bone

Answer 33

1) Vitamin D deficiency results in a decrease in plasma Ca2+ levels
2) low Ca2+ levels Stimulates PTH secretion
3) PTH acts on kidney, large intestine, bone to increase blood Ca2+.
4) Increased Blood Ca2+ leads to depletion of calcium stores in bone (de-mineralisation), which leads to their softening/weakening

Question 34

what are the symptoms of Osteomalacia and Rickets?

Answer 34

1) Bone Pain/tenderness
2) Skeletal deformity (bow legs, pigeon chest)
3) Pathological fractures
4) Dental deformities
5) Muscular problems
6) Impaired growth

Question 35

what are the main causes Osteomalacia/Rickets?

Answer 35

1) Dietary deficiency: Particularly children with dark-skin living in northern climes
2) Age-related deficiency: Vitamin D metabolism decreases with age and many patients >80yrs are deficient
3) Secondary Rickets/osteomalacia: due to another condition (i.e.liver disease, renal failure)
4) Vitamin D dependent rickets: lack of enzyme requires for metabolism of Vitamin D
5) Hypophosphataemic rickets (Vitamin D resistant rickets)

Question 36

what is the treatment for Osteomalacia/Rickets?

Answer 36

Calcium and Vitamin D supplements (except hypophosphataemic rickets which is treated with phosphate replacement and calcitriol)