Thursday, 12 November 2015

Bones and Bisphosphonates

Confused about when you can treat patients who are taking bisphosphonates? Here's some things I've learnt during my time at hospital about how to manage these patients.

Bisphosphonate-induced osteonecrosis of the jaw. Photo credit: Borgioli et al. Ther Clin Risk Manag. 2009; 5: 217–227.


 Why are bisphosphonates prescribed?

  1. Osteoporosis
  2. Metastatic bone cancer
  3. Paget's disease/Fibrous dysplasia/Osteogenesis Imperfecta
  4. Multiple myeloma

How do they work?


Bisphosphonates decrease hypercalcaemia and reduce bone resorption by inhibiting osteoclasts. They tend to accumulate in areas of high bone turnover such as in the jaw - reducing bone turnover and bone blood supply. 

Your skeleton is completely remodelled around every 2 years in order to adapt to mechanical stress, remove micro-fractures in bone and as a result of calcium homeostasis.  Alveolar bone is perforated by teeth which are loaded when in function which can lead to micro-fractures, this fact on top of the high turnover of bone makes the jaw a highly susceptible site for osteonecrosis. 

Which ones are the problems?


Amino bisphosphonates are the ones which mean there is an increased risk e.g. zoledronic acid  

Risk of MRONJ for IV bisphosphonates is around 2% compared to oral which is 0.1% (and that is after 5 years of use).

Co-risk factors:
  • Steroids
  • Poorly controlled diabetes
  • Smoking
  • Increased age

Osteoporosis


2 million women in the UK suffer from osteoporosis. This condition leads to a loss in density of bone which makes bone fractures much more likely. 

There is little evidence to support the long-term use of bisphosphonates i.e. for more than 5 years and the type of oral bisphosphonate tends to be ones that are less likely to cause problems e.g. alendronic acid.

Metastatic bone cancer


Most likely primary tumours that metastasise to bone: 
  • Prostate
  • Lung
  • Breast
They are used to help increase chances of survival by decreasing hypercalcaemia. This decreases pain and delays other skeletal effects of the cancer. 

Bisphosphonates that are prescribed for bone metastases are:
  • High dose treatments
  • IV
  • Duration is often for life
  • 100% bio-availability 
  • Often weekly infusions

Osteonecrosis


Previously known as BRONJ/BONJ, the more accepted term more often used is MRONJ (medically related osteonecrosis of the jaw).

Other causes of osteonecrosis include:
  • Trauma
  • Steroids
  • Radiation
  • Excess alcohol
  • Herpes
  • Cocaine
  • Bonjella
  • Lupus
The diagnosis can only be made if there is exposed bone in the jaw for more than 8 weeks which fails to heal. 




50% of MRONJ is precipitated by extractions but it can also be triggered by periodontal treatment, lingual tori, implant placement or it can even be spontaneous. 

Staging


0 - no exposed bone but painful or numb

1 - exposed bone but no infection

2 - exposed bone and infection

3 - fracture or fistula formation

Management


ORAL
  1. Chlorohexidine mouthwash
  2. Doxycycline 100/200mg OD if there is infection
  3. Remove sequestra if they are loose or traumatic
IV
  1. Minimise risk of MRONJ i.e. excellent OH, restore teeth rather than XLA if possible, adjust flanges of dentures so they are not traumatic
  2. XLA non-restorable teeth before being placed on meds if possible
  3. Stopping the meds is not useful, if MRONJ develops maintain oral comfort as much as possible i.e. CHX, antibiotics if become infected

In stage 3 disease (commonly caused more by radiation), you should consider resection and reconstruction of the diseased area. 

Some useful guidelines to follow when dealing with these patients and when you may want to refer to secondary care are the SDCEP guidelines (click here).


Do you feel confident treating these patients in practice? Let me know in the comments below!


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