Dr Sharon Rees @reesprescribe
Day 1: Developed in the cleaning industry in the nineteenth century to prevent calcium deposition, bisphosphonates have been in medical use since the 1960s. Recognition of affinity for hydroxyapatite crystals in bone led to medical applications and #alendronic acid was licensed by EMA in 2005
Dr Sharon Rees @reesprescribe
Day 2: Second-generation bisphosphates eg #alendronic acid are used for the prevention and treatment of osteoporosis in men and women. The optimum duration of treatment is unclear but is at least 3 years. Some are also licensed for Paget's disease such as risedronate and malignant bone diseases like pamidronate. Daily #alendronate 10 mg once daily; treatment of osteoporosis with risedronate can be 5 mg once daily or 35 mg once weekly
Dr Sharon Rees @reesprescribe
Day 3: Adequate oral bioavailability is taken before food; person must be upright 30 mins after swallowing to reduce the risk of oesophagitis. Drug taken up in bone lasts 10 years! No metabolism and unabsorbed drug rapidly excreted in urine. Renal impairment can mean accumulation in bone; avoid eGFR < 35 mL/min/1.73m2
Dr Sharon Rees @reesprescribe
Day 4: A synthetic analogue of pyrophosphate, #alendronic acid inhibits an osteoclastic enzyme (FPP) involved with isoprenoid lipid synthesis. Osteoclast function (resorption of bone) relies on small GTPases, which, in turn, rely on isoprenoid led modifications. Bisphosphonates such as #alendronic acid reduce osteoclast activity and induce apoptosis. Reducing rate of bone turnover helps bone malignancy, bone pain and hypercalcaemia. May also help prevent metastasis to bone eg breast cancer
Dr Sharon Rees @reesprescribe
Day 5: ADEs; Common include GI disturbance/pain, nausea, MSK pain, vertigo, headache, pruritis, asthenia, oesophagitis. Uncommon/serious; eye inflammation, osteonecrosis jaw, atypical femoral fracture, photosensitive rash, SJS (not exhaustive). Alopecia associated with bisphosphonates #alendronic acid may occur because of interference with the mevalonate pathway. Disruption of cholesterol homeostasis could affect the hair follicle, but the mechanism for this remains unclear
Dr Sharon Rees @reesprescribe
Day 6: Drug-drug interactions #alendronic acid are all moderate e.g relating to reduced absorption or GI irritation, except for GI bleeding risk with deferasirox (severe). NOTE there is a very useful NICE ‘patient decision aid’ to assist choice, found at https://www.nice.org.uk/guidance/ta464/resources/bisphosphonates-for-treating-osteoporosis-patient-decision-aid-pdf-6896787085
Dr Sharon Rees @reesprescribe
Day 7: Development of the nitrogen-containing bisphosphonates has led to improved biological activity, duration of action and potency. iv infusion of zoledronate is now used for hip/femoral neck fracture prevention in women with osteopenia once every 18 months as single 5mg dose (off-license)
EARN YOUR CPD CERTIFICATE
With the help of Prescribing and Therapeutics Training Ltd and the Journal of Prescribing Practice, you can earn your 1-hour CPD certificate
In addition to the tweets, read the BNF section on osteoporosis, as well as the monograph on alendronic acid, which contains a general bisphosphonate overview. The SPC for alendronic acid contains significant detail about the background and clinical application of this drug.
Complete the suggested reading and then answer the ten questions below. Please submit the answers to reesprescribe@gmail.com as a numbered list with TRUE/FALSE or the correct A, B, C, D option. If you achieve 8 or more out of ten on the questions, a CPD certificate will be emailed to you.
Further reading on #bisphosphonates and #alendronic acid
- Osteoporosis: https://bnf.nice.org.uk/treatment-summary/osteoporosis.html
- Alendronic Acid 10 mg Tablets: https://www.medicines.org.uk/emc/product/6050/smpc#gref
- Alendronic Acid: https://bnf.nice.org.uk/drug/alendronic-acid.html
The bisphosphonate drugs are used for prevention, but not treatment of osteoporosis
TRUE or FALSE?
Why should oral bisphosphonates be taken standing up for at least 30 minutes?
- To ensure the whole drug is absorbed
- To remind people that no food should be taken during this time
- To help prevent the tablet becoming lodged in the oesophagus leading to oesophagitis
- Because correct posture will help to prevent stomach electrolyte contents from binding to the drug
Risedronate, pamidronate and zoledronic acid are all licensed for use in Paget's disease of bone
TRUE or FALSE?
Bisphosphonate drugs bind so strongly to bone crystals they remain in the body for years
TRUE or FALSE
Which best describes the mechanism of action for all bisphosphonates?
- They inhibit osteoclastic action and reduce cell numbers by inducing apoptosis
- They inhibit osteoblastic action and reduce cell numbers by inducing apoptosis
- Prevent bone turnover by inducing bone marrow suppression leading to reduced osteoclast cell population
- Prevent calcium deposition on bone by preventing chloride deposition
The BNF contains ‘important safety information’ about the risk of damage to bone from these drugs, which can cause bone fracture or necrosis
TRUE or FALSE?
Which of the following is a common adverse drug event?
- Osteonecrosis of the jaw
- Oesophagitis
- Severe cutaneous adverse reactions (SCARs)
- Angioedema
Oral antacids will increase the oral absorption of bisphosphonate drugs
TRUE or FALSE?
There are a variety of dosing regimens for the bisphosphate drugs, ranging from daily administration to once every 18 months
TRUE or FALSE?
Some patients may benefit from a bisphosphonate ‘holiday’ given the long-lasting effects of this drug group
TRUE or FALSE?