Bisphosphonates

Question 1

what are the two types of bisphosphonates?

Answer 1

1. non nitrogen containing
2. nitrogen containing

Question 2

name some non-nitrogen containing and nitrogen containing bisphosphonates?

Answer 2

Question 3

describe the two classifications of bisphosphonates

Answer 3

Question 3

what are the mechanism of action for bisphosphonates

Answer 3

inhibit HMG-CoA
inhibiting osteoclasts = inhibiting bone resorption
=bind strongly onto the bone (up to 10 years)

they also inhibit formation and dissolution of hydroxyapatite crystals = potential to interfere with bone mineralisation

Question 4

compare the activity of two types of bisphosphonates?

Answer 4

Question 5

describe the PK of BP’s?

Answer 5

Poor oral absorption
* Alendronate, risedronate F= 0.7%
* Etidronate F=6%
* Oral absorption reduced
- Excreted unchanged in urine = no metabolism

Question 6

why do BP’s have a reduced oral absorption?

Answer 6

this is due to food increasing gastric emptying
particularly calcium containing products or polyvalent cations = decrease the efficacy of BP’s

Question 7

what are the clinical indications for BP’s?

Answer 7

1. Prevention and treatment of osteoporosis
2. Hypercalcaemia of malignancy
3. Bone damage due to metastatic cancer and bone pain 4. Paget’s disease

Question 8

what are the overall aims of BP’s?

Answer 8

increase bone mineral density
= reduce fracture risk
-vetebral/non-veterbral/hip fractures

Question 9

what are the conditions you must meet as a patient to take BP’s for osteoporosis?

Answer 9

1. eligible under NICE recommended guidance for osteoporosis
2. fracture score is at least 1%
   
   • determined by FRAX score/ BMD with DXA/ Fracture score

Question 10

what are symptoms of malignancy?

Answer 10

Skeletal (pain, fracture)
Neuromuscular and psychiatric (drowsiness, muscle weakness, impaired concentration/ memory) Gastrointestinal (nausea, anorexia, constipation)
Renal (renal colic, thirst)
Cardiovascular – (arrhythmia, shortened QT interval)

Question 11

how does malignancy cause hypercalcemia?

Answer 11

malignancy = increase bone turnover = increase calcium release

Question 12

what are symptoms of hypercalcemia?

Answer 12

confusion
nausea
Anorexia
impaired concentration

Question 13

what BPs are licensed to treat hypercalemia?

Answer 13

IV zoledronic
IV pamidronate
with IV fluids
effective within 24 hrs

Question 14

what monitoring is required for BPs to treat hypercalemia?

Answer 14

Check renal function (adjust dose if necessary),
- renally excreted
* Check calcium at 5 to 7 days be careful of hypocalcemia

HYPOCALCEMIA with those with amino glycoside antibiotics toxicity

Question 15

what BPs are licensed to treat osteoporosis?

Answer 15

Aledronic acid
Ibandronic acid
Risedronate
Zoledronic acid

Question 16

what is Paget disease?

Answer 16

Question 17

what are the adverse effects of BPs?

Answer 17

Osteonecrosis of the jaw (ONJ) - dentist must be aware when commencing and undergo regular check ups
Osteonecrosis of external auditory canal - v rare
Oesophageal ulceration
oesophageal risks
Atypical femoral fractures -rarely reported

Question 18

which BPs are most at risk of osteonecrosis of the jaw?

Answer 18

Risk highest for IV (zoledronate, pamidronate) use in cancer and for higher potency bisphosphonates (zoledronate)

Question 19

when must you review BP treatment?

Answer 19

after 5 years:
alendronic acid
risedronate sodium
ibandronic acid

after 3 years:
zolendronic acid

Question 20

what are the oesophageal risks associated with BPs? therefore consoling points you may consider

Answer 20

Oesophagitis
Oesophageal ulcers
Oesophageal strictures
Oesophageal erosions

minimise formulation getting stuck to the oesophagus

reinforce with 200mL of water and sit up right