2.5 Bisphosphonates in Dentistry Flashcards
Bone remodelling is the constant and coordinated turnover of mineralsied bone matrix. This is achieved through two specialised cells, what are they?
- Osteoclasts = bone resorbing
- Osteoblasts = bone forming
What are bisphosphonates?
Chemically stable analogues of pyrophosphate
Compounds characterised by two C-P bonds called geminal phosphates
What are the two classifications of bisphosphonates?
- Non-nitrogen bisphosphonates
- Nitrogen-containing bisphosphonates
What are examples of non-nitrogenous bisphosphonates?
Etidronate
Clodronate
Tiludronate
What are examples of nitrogen-containing bisphosphonates (N-BPs)?
Pamidronate
Alendronate
Ibandronate
Risedronate
Zoledronic acid
What are the two fundamental effects of bisphosphonates in vivo?
- Inhibition of calcification when given at high doses due to physiochemical mechanism (useful for treating ectopic mineralisation)
- Inhibition of resorption due to effect in cellulatr + molecular (potency varies according to structure)
Bisphosphonates inhibit bone resorption on the cellular level by targeting osteoclasts with 4 mechanisms. What are the 4 mechanisms behind inhibitoin of osteoclast activity?
- Inhibition of osteoclast recruitment
- Inhibition of osteoclastic adhesion
- Shortening the lifespan of osteoclasts via apoptosis
- Inhibition of osteoclast activity (directly engaging osteoclast)
There are 2 major distinct bisphosphonate mechanisms on the molecular level, both related to chemical properties. What are these mechanisms?
- Non-nitrogen bisphosphonates metabolically incroporate into non-hydrolysable ATP via reversal of aminoacyl-tRNA
- Nitrogen-containging bisphosponates (N-BPs) interfere wtih specific mevalonte pathways (important for cholsterol synthesis) by targeting farnesyl pyrophosphate synthase (FPPS)
Oral bisphosphonates have been in widespread use for osteoporosis and are generally well tolerated, what are the possible safety concerns for their use?
Common = GI symptoms
(nausea, dyspepsia, constipation, diarrhoea, vomiting)
Serious = esophagitis + esophageal ulcers
Intravenous bisphosphonates are also well tolerated, but what are the possible safety concerns associated with their use?
- Transient influenza-like symptoms after initial dose of any nitrogen-containing bisphosphonate
- May cause transient changes in electrolytes
- Renal toxic effects
- Osteonecrosis of the jaw
What is medication related to osteonecrosis of the jaw (MRONJ)?
Area of exposed bone in the jaw persisting for more than 8 weeks in a patient currently / previously treated with antiresorptive or antiangiogenic drug, who has NOT received radiation therapy to the cranofacial region
What are the stages of MRONJ?
0 = Pain + x-ray changes
1 = Asymptomatic + exposed bone
2 = Pain + exposed bone + adjacent inflammation / infection
3 = Pain + full bone involvement + pathological fracture + soft tissue infection
What are the frequent symptoms / signs of MRONJ?
- Pain
- Soft tissue infection
- Swelling
- Numbness
- Paraesthesia
- Exposed bone
- Delayed healing after bone-invasive dental procedure
The risk of MRONJ increases when undertaking a bone-invasive dental procedure when a patient is taking bisphosphonates. Is this the only way MRONJ can occur?
No, MRONJ can occur in patients who haven’t had a bone invasive dental procedure, but is an extremely rare condition and should not discourage patients from bisphosphonates, nor dental treatment
What treatment practices should a dentist / OHT be aware of when a patient is about to begin taking bisphosphonates?
- Ensuring optimal oral health
- All existing dental problems should be addressed before therapy begins
- If necessary, dental treatments can be completed shortly after starting therapy (within 6 months)
- Patients with a history of periodontitis should have regular dental reviews
