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Bisphosphonates, BRONJ/BON, ARONJ, MRONJ

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What does the hygienist need to know about the nomenclature of bisphosphonate‐related osteonecrosis of the jaw (BRONJ), medication‐related osteonecrosis of the jaw (MRONJ)? Patients who are immunosuppressed or are taking anticoagulants, steroids, or bisphosphonates medications can be contraindicated for implant therapy. These patients can be at risk for osteonecrosis of the jaw (37).

The American Dental Association Council on Scientific Affairs wrote an executive summary published in 2011 outlining recommendation and listing the current antiresorptive agents with current dosages and indications (38). The report based on the literature and expertise of the scientific panel states; “the risk of developing antiresorptive agent induced osteonecrosis of the jaw (ARONJ) in a patient who does not have cancer appears to be low”. The research available to date shows that the benefits of antiresorptive therapy outweigh the low risk of developing osteonecrosis of the jaw (38).

Dental Professionals do need to be aware of the latest research on MRONJ. Any medical condition or medication which inhibits cell mitosis or metabolism could affect the success of implants. The hygienist needs to be aware of patients taking antiresorptive therapy for not only the risk for implant therapy, but also tooth extractions or other dental surgical invasive bone procedures. Bisphosphonates are most common medication related to complications with osteonecrosis of the jaw and localized death of bone tissue, abbreviated BON or BRONJ. Also referred to as antiresorptive agent induced osteonecrosis of the jaw (ARONJ) Bisphosphonate are given in two forms; oral mainly for osteopenia and osteoporosis and IV mainly for cancer‐related conditions.

BON diagnoses are 94% associated with intravenous (IV) administration of bisphosphonates and only 6% of cases from taking bisphosphonates orally (37). Cases of osteoporosis in the United States in 2020, increased to 14 million and over 47 million cases of low bone mass in the over 50 years old population. One in two Americans over the age of 50 is expected to have or develop osteoporosis of the hip and other sites in the skeleton according to the bone health and osteoporosis report by the surgeon general (39).

Since 2004, oral and maxillofacial surgeons and manufactures are aware of the link of bisphosphonates IV and oral preparations to nonhealing exposed bone or BON. For practical knowledge, a MRONJ patient is a patient who is currently or have previously taken antiresorptive or antiangiogenic agents. They have exposed bone in the maxillofacial region that persists for more than 8 weeks and no history of radiation therapy to be considered to have MRONJ (40).

Doctors prescribe bisphosphonates in oral or IV form for osteoporosis (low or decreasing bone mass patient at risk for bone fractures) and cancers that are associated with the bone. Bisphosphonates in IV form are mainly prescribed for cancer patients to decrease pain, bone fractures, and in some cases to decrease spread of cancers to the bone.

What this means for hygienists is that you should assist the dentist to identify these patients. Patients need to be informed that BON is a risk associated with implant surgery for patients who have taken or are currently taking bisphosphonates. Make sure that questions on anticoagulants, steroids, and/or bisphosphonates are included on your medical history form. “Have you taken or are you taking anticoagulants? Steroids?” “Are you presently taking or have you in the past taken bisphosphonate drugs? Oral or IV?” These are critical questions to have answered before a patient has oral, periodontal, periapical (endodontic) surgery, and/or implants placed (40). Take good record notes on what your patient explains about how long and which form of bisphosphonates they are currently taking or have taken, note in the patient record.

Bisphosphonates are a class of drugs used to treat osteoporosis and some tumors associated with cancer. They are prescribed for women after menopause, men with thinning bone (Paget’s disease) caused by steroid treatment, and other bone problems associated with cancer. Bisphosphonates work by inhibiting osteoclast (bone cells) activity that removes bone tissue and induces bone cells to die. Therefore, if bisphosphonates inhibit the death of bone cells, osteoclasts will be able to continue to increase or maintain bone mass. Bone mass is maintained by a balance between bone cell destruction and bone cell generation, referred to as osteoblast activity. The jaw, with a greater blood supply than other bones, is more susceptible to high concentrations of bisphosphonates. In some patients, taking bisphosphonates can cause an abnormal imbalance of osteoblast activity that can result in infection and/or in osteonecrosis of the jaw (necrosis of the jaw).

The American Association of Oral and Maxillofacial Surgeons set the following criteria to diagnose BRONJ/BON in their updated 2009 BRONJ position paper (see Table 2.2). They concluded that “both the potency of and the length of exposure to bisphosphonates are linked to the risk of developing bisphosphonate‐associated osteonecrosis of the jaw” (41). Patients receiving intravenous bisphosphonate therapy are more likely to develop BON than are those receiving oral therapy. Also, prolonged use of over 2 years and combined with smoking or diabetes, puts a patient at an increased risk of BON.

Table 2.2 Criteria to diagnose bisphosphonate‐related osteonecrosis of the jaw.

Patient presents with an area of exposed, necrotic bone in the jaw that persists for 8 weeks or longer.Patient has had no radiation therapy to the head or neck.Patient must be taking or have taken bisphosphonate oral or IV medication.

To assess risk level for patients to develop BON (osteonecrosis) before the patient has an implant placed, the dentist/implant surgeon can prescribe a serum CTx (C‐telopeptides) blood test. It evaluates CTx levels based on the C‐telopeptides, fragments of collagen that are released during bone remodeling and turnover (see Table 2.3) (42).

The American Dental Association also put together a panel of experts on BON to make recommendations for treatment of patients taking or have taken oral bisphosphonates. A significant study, with over 700,000 cases, was completed and published in the 2008 Journal of Oral Maxillary Surgeons, titled “Bisphosphonate Use and the Risk of Adverse Jaw Outcomes.” It concluded that patients taking or who have taken oral bisphosphonatescan be a candidate for implant therapy”, but need to be evaluated on an individual basis (43). Patients taking or who have taken intravenous bisphosphonates can be contraindicated for implant placement. It is recommended that patients complete any oral surgery (i.e., tooth extraction), implant placement, periapical surgery, or periodontal surgery prior to starting bisphosphonate therapy, if possible.

Prior to starting any surgical treatment, a comprehensive exam including a very thorough medication history is essential. The patient also needs to be informed of any risks verbally and through written instruction, including risk of BON, and should sign a witness informed consent form.

Table 2.3 Risk assessment for osteonecrosis.

CTx Level (pg/mL) Risk Level
300–600 (normal)150–299101–149<100 NoneNone to MinimalModerateHigh
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