Bisphosphonates and non-bisphosphonates

The information provided here is not intended as a substitute for professional medical advice, diagnosis, or treatment. It is provided to help you communicate effectively with your oral and maxillofacial surgeon or health care provider.

(Antiresorptive or Antiangiogenic Medications)

Before having any surgery (especially dental procedures), tell your oral surgeon, dentist, or physician about this medication and all medications and supplements you are taking.

This is an area of pharmacology that is changing rapidly. Initially, medications were introduced for metastatic (bone) cancer patients. These medications were noted to be very beneficial for osteoporetic or osteopenic patients. Following this observation, prescriptions for these medications were commonly written for the osteoporetic or osteopenic patient. In the beginning these were mainly bisphosphonates (BP) drugs. Recently newer drugs have been released that are not BP but have the same therapeutic effect and complications. The new drugs are called RANK Ligand inhibitors and Antiangiogenic medications. This finding has now changed the wording of the jaw complications from Bisphosphonate Related Osteonecrosis of the Jaw (BRONJ) to Medication Related Osteonecrosis of the Jaw (MRONJ).  

What are Oral Antiresorptive Medications?

Antiresorptives are excellent medications for bone diseases and osteoporosis that help relieve bone pain and prevent fractures. However, long-term use of these medications may be associated with a small but real risk of developing osteonecrosis of the jaw.

Antiresorptive agents, such as those listed below are used to treat and prevent osteoporosis—or, bone thinning—which occurs when the bones lose calcium and other minerals that help keep them strong and compact. This condition can lead to fractures, bone pain, and shorter stature. Oral Bisphosponates also are used to treat some rare bone diseases (eg, Paget’s disease).

Some Antiresorptive Agents             

  • Actonel (Risedronate)                 
  • Boniva (Ibandronate)
  • Fosamax (Alendronate) 
  • Prolia (Denosumab)
  • Reclast (Zoledronic acid)
  • Xgeva (Denosumab)
  • Zometa (Zoledronic acid)

How do Antiresorptive Medications Work?

Your bones are constantly remodeling in a process that removes old bone cells and deposits new ones. In people with osteoporosis, the bones lose minerals faster than they can be regenerated. Antiresorptive medication help prevent your bones from losing calcium and other minerals by slowing or stopping the natural processes that dissolve bone tissue. In doing this, they help your bones remain strong and intact. If you have already developed osteoporosis, these medications are used to slow the thinning of your bones and help prevent bone fractures.

What are Antiangiogenic Medications?

Antiangiogenic medications inhibit the growth of new blood vessels (angiogenesis). By doing so, they starve the cancer cell of oxygen and nutrition. These are medications that have shown great promise as anti-cancer drugs. 

Some Antiangiogenic Medications

  • Avastin (Bevacizumab)
  • Sutent (Sunitinib) 

How Do Antiangiogenic Medications Work?

These medications interfere with the formation of new blood supply by blocking some of the chemical reactions necessary for blood vessel formation. Without a blood supply the cells cannot thrive. These medicines have demonstrated efficacy in the treatment of gastrointestinal tumors, renal cell carcinomas, neuroendocrine tumors, and others.     

What is Medication Related Osteonecrosis of the Jaw (MRONJ) or Bisphosphonate Related Osteonecrosis of the Jaw (BRONJ)? 

MRONJ  (formerly referred to as BRONJ) is an area of bone in the jaw that has lost its blood supply, died and is exposed in the mouth for more than 8 weeks in a person taking any antiresorptive or antiangiogenic medications. MRONJ can also lead to infection. Although the exact cause is unknown, MRONJ is considered to be a side effect of antiresorptive or antiangiogenic medication therapy.

MRONJ may present following an invasive surgical procedure in the jaw such as tooth removal, periodontal surgery, apicoectomy, or dental implant placement. While MRONJ is a new and potentially serious condition, it is important to know that your oral and maxillofacial surgeon is experienced and knowledgeable in the prevention and treatment of this disease.

The reason MRONJ  appears in the jaw bone in patients taking antiresorptive medications is due to the remodeling rate of bone in the jaw. The jaws undergo bone turnover/renewal at a rate 10 times faster than any other bone in the adult skeleton and are exposed to a tenfold greater effect from the antiresorptive drugs.   

Before I Start Taking Oral or IV Antiresorptive or Antiangiogenic Medications What Should I Do?

  • Patients should undergo a comprehensive dental exam that may include a panoramic radiograph to detect potential dental and periodontal infections.
  • Remove abscessed and non-restorable teeth and teeth with severe periodontal disease
  • Remove teeth with poor long-term prognosis
  • Functionally rehabilitate salvageable dentition

If you need surgery, including extractions and implants, get it done at least 3 to 4 months before starting treatment so that the bone will have time to recover.                                                                                     

What if I Have Been Taking Oral Bisphosphonates or Other Antiresorptive Medications?

Do not panic since you are already at low risk. It is important for you to maintain good oral hygiene, and for those who wear dentures, have them properly fitted. Patients should be vigilant about getting a dental exam and cleaning twice annually and to make sure they tell the dentist that they are taking these medications to ensure a gentle cleaning.

For patients who have taken an oral bisphosphonate or antiresorptive medication for less than 3 years and have no clinical or radiographic risk factors, no alteration or delay is necessary for planned surgeries common to oral and maxillofacial surgeons, and other dental providers. However, there could be risk in the event the patient continues to take an oral bisphosphonate.   

For patients who have taken an oral bisphosphonate or antiresorptive medications for less than 3 years, but have at least one medical risk factor it is advised that the prescribing physician be contacted and a recommendation made to suspend use of the oral bisphosphonate (drug holiday) for at least 3 months.  After 3 months, a serum CTX test is recommended.  CTX values of less than 150 pg/mL indicate that the surgery should be deferred and the drug holiday maintained for another 3 months.  If the serum CTX value is greater than 150 pg/mL, it is reasonable to proceed with the planned surgery.  Use of the medication should not be reinstated until 3 months of healing have passed.

For patients who have taken an oral bisphosphonate or antiresorptive medication for more than 3 years regardless of any risk factors, it is advised that the prescribing physician be contacted and a recommendation made to discontinue the medication for 3 months prior to the procedure and to refrain from reinstating use until 3 months after the procedure. It is also advisable to perform a serum CTX bone turnover marker study at the time of the initial oral consultation and immediately before performing the procedure. Regardless of the initial CTX value, any increase at the time of surgery represents a margin of reduced risk. A value of > 150 pg/mL is a minimum requirement for surgery in this group.

For patients who are taking antiangiogenic medications. Consultation will be sought with the physician prescribing the medication as to the advisability of any surgical procedures and the best way to manage your medications.