R E S E A R C H A N D R E P O R TS

A Dentist’s Perspective on the

Need for Interdisciplinary
Collaboration to Reduce
Medication-Related Osteonecrosis
of the Jaw
Alec Griffin, DDS1,2; Patrick Brain, DDS2,4; Colby Hancock, PharmD5; Sujee Jeyapalina, PhD1,3

1 George E. Wahlen Department of Veterans Affairs Medical Center, Research and Development, Salt Lake City, Utah.
2 George E. Wahlen Department of Veterans Affairs Medical Center, Dental Clinic, Salt Lake City Dental Clinic, Salt Lake City, Utah.
3 Division of Plastic and Reconstructive Surgery, Department of Surgery, University of Utah School of Medicine, Salt Lake City, Utah.
4 Lone Peak Oral and Maxillofacial Surgery, Sandy, Utah.
5 Utah Cancer Specialists, Salt Lake City, Utah.

For Correspondence: Alec Griffin, 590 Foothill Drive, Salt Lake City, UT 84113. Telephone: (801) 584-1206. Fax: (801) 584-5690.
Email: [email protected]., [email protected]

Disclosure: This case report was exempt from Institutional Review Board (IRB) approval per VA Hospital and University of Utah
IRB criteria. The authors have no conflicts of interest to disclose.

Contributions: Alec Griffin and Sujee Jeyapalina contributed to conception and design and to drafting the article. Alec Griffin,
Sujee Jeyapalina, and Patrick Brain contributed to acquisition of data. Alec Griffin and Sujee Jeyapalina contributed to analysis of
interpretation of data. Alec Griffin, Sujee Jeyapalina, Patrick Brain, and Colby Hancock contributed to critically revising the article
and to final approval of the article.

Acknowledgments: Special thanks to Greg A. Roberts, DDS for his contributions and insight in the management of our patient,
and to Associate Editor of The Senior Care Pharmacist, Demetra Antimisiaris, PharmD, BCGP, FASCP, for her knowledge and input

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during editing.

© 2022 American Society of Consultant Pharmacists, Inc. All rights reserved.

Doi:10.4140/TCP.n.2022.458.

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A DENTIST’S PERSPECTIVE ON THE NEED FOR INTERDISCIPLINARY COLLABORATION

Antiresorptive medications, including bisphosphonates stomatognathic consequences to the physician, who

and RANK-L inhibitors, are commonly used to prescribed the causative agent, and the pharmacist,
treat various skeletal pathologies. One devastating who dispensed it. Collaboration between the dentist,
complication associated with these drugs is medication- physician, and pharmacist has tremendous potential to
related osteonecrosis of the jaw (MRONJ). Patients who improve treatment strategies and, ultimately, optimize
develop MRONJ suffer immensely from oral lesions that patient care.
may persist, even with treatment, until their death. The
jawbone is known to remodel 5 to 10 times faster than KEY WORDS: Anti-resorptive medication, Bisphosphonate,

skeletal bone. Dentists are at the forefront in managing Dental, Medication-related osteonecrosis of the jaw,
the severe maxillofacial repercussions of MRONJ. Pharmacology, RANK-L inhibitor.
Because MRONJ risk is relatively low (reportedly 0.7% to
ABBREVIATIONS: AAOMS = American Association of
6.7%) it is underappreciated by many clinical specialties.
Oral and Maxillofacial Surgeons, AFF = Atypical femoral
The minimization of MRONJ is further compounded
fracture, BP = Bisphosphonate, FDA = US Food & Drug
because it may take months or years to develop. To date,
Administration, ID = Infectious Disease, IV = Intravenous,
dental treatment protocols are based more on expert
MRONJ = Medication-related osteonecrosis of the jaw,
opinion than concrete scientific evidence. This iatrogenic,
MRSA = Methicillin-resistant Staphylococcus aureus,
intractable illness is discouraging for both the patient
ONJ = Osteonecrosis of the jaw, PICC = Peripherally
and the treating dentist. To promote multidisciplinary
inserted central catheter, PRF = Platelit-rich fibrin,
understanding and cooperation, a single MRONJ case
RANK-L = Receptor activator nuclear factor-kappa B
caused by intravenous pamidronate is presented, along
ligand, T-99 = Technetium-99.
with commentary from a dentist’s perspective. The intent
is that these data will increase awareness of MRONJ’s Sr Care Pharm 2022;37:458-67.

Introduction apoptosis. BPs are then recirculated in the blood owing

to the biostable chemical structure of its phosphorus-
Osteoporosis, rheumatoid arthritis, Paget’s disease of carbon-phosphorus backbone, effectively redosing
bone, osteogenesis imperfecta, ankylosing spondylitis, the body. These pharmacokinetics are consistent
and cancers affecting bone are all applications with reports that state depending on the dose, route,
where antiresorptive therapy may be indicated.1 and frequency of BP administration, a BP can cause

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Bisphosphonates (BPs) and receptor activator nuclear irreversible changes in bone physiology.6 RANK-L
factor-kappa B ligand (RANK-L) inhibitors are used inhibitors can be excreted from the body completely if
to manage such skeletal pathologies.1 Both BPs and the drug is held, and thus, the pharmacodynamics of
RANK-L inhibitors are known to disrupt osteoclast- RANK-L inhibitors are theoretically more responsive
related resorption of bone tissue, hence their ability to a permanent or temporary cessation of the drug

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to increase bone density and prevent the spread of (termed a drug holiday),4 where osteoclasts can
bony metastasis.2 The literature explains that BPs function normally with the restoration of healthy
have antiangiogenic properties (ie, inhibit blood RANK-L/RANK receptor interactions.
vessel formation during healing—accumulate to toxic
levels in bone, and induce osteoclast apoptosis by In contrast, the risk of developing or the ability to
disrupting farnesyl pyrophosphate synthase).3-7 In treat MRONJ does not necessarily decrease when
contrast, RANK-L inhibitors are monoclonal antibodies BPs are discontinued. This information is important
that inactivate the osteoclast RANK receptor through when considering the choices for pharmacologic
competitive inhibition.2 Both medications are known antiresorptive therapy.
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causes of medication-related osteonecrosis of the

jaw (MRONJ) and share similar risks.1 However, while It seems counter-intuitive that a drug class intended
RANK-L inhibitors have a 26-day half-life, BPs have an to “strengthen bones” causes irreversible bone lesions
11-year half-life.8-10 It is known that the BPs irreversibly in the jaw while benefiting the axial skeleton. The US
adsorb to the hydroxyapatite component of bone Food & Drug Administration (FDA) has noted that
tissue, subsequently becoming part of the bony there has been a significant increase in subtrochanteric
architecture. Osteoclast activity releases embedded fractures and atypical femoral fractures (AFF) in
BPs from bone, which subsequently leads to osteoclast patients with long-term BP and RANK-L inhibitor

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A DENTIST’S PERSPECTIVE ON THE NEED FOR INTERDISCIPLINARY COLLABORATION

use. These fractures occur in the same location the intractable maxillofacial side effects, the physician
as those seen in osteopetrosis.6,11 Osteopetrosis is prescriber and pharmacist who dispensed the
caused by malfunctioning osteoclasts. Rather than medication may never be informed that MRONJ has
removing damaged bone, they continue to build more developed.17 Therefore, it is essential to include all
minerally dense, brittle bone over existing osseous concerned clinicians in candid dialogue that fosters
tissue. Moreover, studies corroborate that the use of multidisciplinary care. Because pharmacists often
bisphosphonates may weaken bone with prolonged counsel prescribers on appropriate administration
use as osteoclasts are unable to resorb old, damaged of medications, they seem to be in an ideal position
bone. Of note, the appearance of improved bone to broker communication between physicians and
density on the DEXA scan of an osteopetrosis, BP, dentists and promote best practices where BP therapy
or RANK-L inhibitor patient does not necessarily is concerned. To highlight the gravity of this condition,
represent improved bone health and function. The the authors present a case describing the diagnosis,
increased risk of osteonecrosis of the jaw (ONJ) progression, and management of the patient’s
and AFF reported in patients who have a history worsening MRONJ condition.
of significant or prolonged antiresorptive therapy
suggests a common pathogenesis and is further cause Medication-related Osteonecrosis of the
for concern when considering the duration of use Jaw Case Report
and therapeutic index.6,11 In short, long-term use of
antiresorptive medications includes the risk of serious A 64-year-old male was referred to the dental clinic
skeletal side effects.4-6,11-15 in 2016 to be evaluated for “jawbone necrosis”
after receiving 41 doses of IV pamidronate to treat
Miksad and colleagues reported that patients who ankylosing spondylitis. This patient met MRONJ
developed MRONJ had a significant reduction in diagnostic criteria, showing a non-healing socket
quality of life, which often worsened with disease where tooth #5 (maxillary right 1st premolar) had been
progression.16 General discomfort and tenderness, extracted, that persisted for longer than eight weeks.5
recurrent infections, pain when eating, ulcerations, Carious root tips were present in site #31 (mandibular
exposed necrotic bone, chronic sinus tracts, impaired right 2nd molar) and generalized chronic periodontitis
speech, disfigurement, foul taste and smell, poor diet, (gum disease) was apparent. The medical history
self-consciousness, irritability, and overall decreased included 6 500 mg infusions of IV infliximab (from
satisfaction with life are the reality for many, if not all, June 2009 to December 2011) and 41 60 mg doses
MRONJ patients. Advanced MRONJ is undoubtedly of IV pamidronate (from January 2012 to June 2015).

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a debilitating condition, and it is imperative for both The patient had also been prescribed adalimumab and
patient and provider to consider the implications of eteracept. Similar medications have been implicated
living with this morbidity.7,16 as risk factors for MRONJ development because
drugs that inhibit vascular supply or wound healing
Though MRONJ is well recognized in dentistry, the (ie, antiangiogenic drugs) are believed to potentiate

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severity of the condition is not well appreciated BP toxicity.1,18 Other active medications at the initial
by many health care providers. It has been shown encounter included oxycodone, fish oil, gabapentin,
that ONJ was decreased by 50% in patients who and cholecalciferol. The initial active problem list
received a dental consultation before initiating drug included ankylosing spondylitis and methicillin-
therapy.1,4 Yamori and colleagues found that 62% of resistant Staphylococcus aureus (MRSA).
physicians did not require an oral exam prior to the
administration of bone-modifying drugs.17 Moreover, This patient was treated with the standard of care
in this survey, of the physicians who prescribed treatment recommendations by the American
bone-altering medications, 41% did not mention Association of Oral and Maxillofacial Surgeons
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MRONJ to their patients as a potential deleterious (AAOMS). These recommendations include

outcome. Furthermore, only 50% of dentists and 25% conservative, supportive, and medical management
of physicians were aware of the most recent position favored at early stages, while aggressive surgical
paper published concerning MRONJ. If these findings approaches are reserved for advanced or recurrent
are representative, then it is easy to see why no clear cases. However, it is worth noting that these
prescribing, prevention, and treatment guidelines recommendations rely more on expert opinion than
exist. As dentists (primarily oral and maxillofacial scientific evidence. Chlorhexidine 0.12% mouth rinse,
surgeons) are more often the clinicians who manage brushing and flossing teeth after eating, regular dental

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Figure 1. Cone-beam Computed Tomography Transverse Section Demonstrating the

BONY DESTRUCTION Associated With MRONJ. Arrows Indicate Loss of Bone Density in
the (A) Mandible and (B) Maxilla

cleanings, and a dental exam to monitor disease prescribed amoxicillin/clavulanic acid (Augmentin®).1
progression were prescribed. Routine restorative dental In addition, a 0.12% chlorhexidine rinse was prescribed.
care (fillings) and endodontic (root canal) therapy The orthopedic service delayed the procedure for six

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were performed. Such dental procedures can be weeks and completed the joint replacement successfully
completed without additional risk of MRONJ. Periodic after this acute dental infection had been controlled.
oral amoxicillin was prescribed, when necessary (ie,
significant purulence/swelling). Tooth #6 (maxillary During the COVID-19 pandemic, the patient’s care was
right canine) developed a significant infection that disrupted. Upon resumption of care, it was evident

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communicated with the open wound at site #5. Had both clinically and radiographically that his MRONJ
root canal therapy been a viable option, it would have had progressed significantly, showing increased bone
been the preferred treatment to avoid further surgical loss and active infection. He complained of a foul taste,
trauma. Because an active dental infection is also a risk constant putrid intra-oral drainage, stomach upset,
factor for MRONJ, tooth #6 and the diseased retained severe stress and anxiety, and a steadily diminishing
root tips at site #31 were removed. quality of life. The cone-beam computed tomography
image that was taken demonstrated significant
In 2018, the dental service was consulted regarding destruction of the right body of the mandible
clearance for a knee replacement. During this period, (Figure 1 [A]). Perforation of the mandibular lingual
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the maxillary sinus tract had not resolved. In addition, cortex (jawbone adjacent to teeth closest to the
site #31 (mandibular right second molar) developed tongue) was also evident. A large periapical lesion
a purulent oral fistula, persistent for greater than around tooth #7 (decrease in bone density caused by
eight weeks. Both the maxillary and mandibular infection at the end of a root) as well as perforation of
lesions probed to bone. This patient’s condition did the right maxillary sinus and nasal floor (Figure 1 [B]).
not yet meet the criteria for more aggressive surgical It was apparent from the radiographs (Figure 2) and
intervention outlined in the AAOMS position paper clinical exam that conservative treatment had failed.
by Ruggiero and colleagues.1 Then the patient was At that juncture, the patient was prescribed 400 mg

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A DENTIST’S PERSPECTIVE ON THE NEED FOR INTERDISCIPLINARY COLLABORATION

Figure 2. Cone-beam Computed Tomography 3-D pentoxifylline and 400 units (180 mg)
Rendering tocopherol (vitamin E) twice daily in an
attempt to increase blood flow, reduce
free radical damage, and ultimately
improve bone healing.19

The patient was sedated and a crestal

incision with vertical release exposed
large amounts of necrotic bone (Figure
3 [A and B]), which enveloped teeth #7
and #8 (maxillary right lateral and central
incisors) and extended into the right
maxillary sinus and nasal floor (Figure
3 [C]). Two aggregates of soft, necrotic
bone measuring 1.5 x 0.5 x 0.4 cm and
2.0 x 1.7 x 0.4 cm were collected, placed
in formalin, and submitted to pathology.
The site was swabbed and submitted
for both aerobic and anaerobic culture
and sensitivity. Blood was drawn from
the patient and centrifuged to collect
bioactive growth factors (ie, platelet-
derived growth factors, transforming
growth factors, etc) in the form of
chemical messenger-rich “slugs” called
platelet-rich fibrin (PRF) (Figure 3
[D]).20,21 The PRF was then packed into
Legend: Arrows indicate MRONJ loci. Diseased bone extended beyond these areas
the bony defect (Figure 3 [E]). Because
as did the need for debridement to establish clean, bleeding, surgical margins.
MRONJ in the mandible can be more
difficult to resolve, only the maxilla was

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Figure 3. Serial Photos of the Maxillary Medication-related Osteonecrosis of the Jaw Site

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Legend: (A) Surgically exposed necrotic bone. The diseased bone had the soft consistency of oatmeal. (B) Debridement. (C) Clean surgical margins
with communication to the maxillary sinus and nasal floor. Note the severe attrition of the maxillary teeth. With such significant wear, these teeth
should have been extracted prior to BP therapy. (D)—Newly harvested PRF. (E)—PRF placed in maxillary defect.

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A DENTIST’S PERSPECTIVE ON THE NEED FOR INTERDISCIPLINARY COLLABORATION

Table 1. Antibiotic Sensitivity Results

Antibiotic Escherichia coli MRSA

Ampicillin-Sulbactam Resistant
Ampicillin Resistant
Cefazolin Susceptible
Cefepime Susceptible
Ceftazidime Susceptible
Ceftriaxone Susceptible
Ciprofloxacin Susceptible
Clindamycin Susceptible
Daptomycin Susceptible
Erythromycin Resistant
Gentamicin Susceptible Susceptible
Levofloxacin Susceptible Resistant
Linezolid Susceptible
Meropenem Susceptible
Oxacillin Resistant
Penicillin Resistant
Piperacillin/Tazobactam Susceptible
Rifampin Susceptible
Tetracycline Susceptible
Tobramycin Susceptible
Trimethoprim-Sulfamethoxazole Susceptible Susceptible
Vancomycin Susceptible

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addressed in the initial operation to see how well the The patient was discharged with amoxicillin PO
patient responded to surgical management. The biggest but switched to clindamycin PO when his culture
question when attempting these procedures is, “will returned MRSA-positive. The Infectious Disease (ID)

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this work or make it worse?” The microscopic exam and service was consulted to manage antimicrobial therapy.
diagnosis were consistent with chronic osteomyelitis ID staff placed a peripherally inserted central catheter
and MRONJ. After the maxillary debridement, the (PICC) line. Intravenous vancomycin (2 g loading dose),
patient returned for a follow-up. The site demonstrated and intravenous piperacillin/tazobactam (3.37 g) was
improved healing, but a small (2 x 3 mm) oral-antral to be continued, tentatively, for six weeks. Vancomycin
fistula persisted. (1.5 g q/12 hours) antibiotics were continued, but
piperacillin/tazobactam was later exchanged with
Clinical Management of Infection ertapenem (1 g q/24 hours). Bloodwork, including a
comprehensive metabolic panel, complete blood count,
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Microbiology reported a polymicrobial infection erythrocyte sedimentation rate, and c-reactive protein,
(2+ gram-positive and negative rods), validated with was monitored regularly.
the presence of polymorphonuclear leukocytes.
Escherichia coli (4+) and MRSA (2+) were also At the one-month follow-up appointment, a
identified. Full antibiotic sensitivity results are collaborative decision (between ID and dental) was
presented in Table 1. made that the mandibular lesion should be addressed
while the patient was receiving IV antibiotics. The
patient was again sedated and mandibular extractions

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A DENTIST’S PERSPECTIVE ON THE NEED FOR INTERDISCIPLINARY COLLABORATION

(Figure 4 [A]), with marginal mandibular resection and improved. The FDA has stated that there is no true
debridement, were completed (Figure 4 [B]). benefit of bisphosphonates for the first 18 months, a
benefit that supersedes the placebo between 18 to 36
After the mandibular surgery, the patient reported months and no clear benefit beyond 36 months with
improved quality of life, though his healing was oral bisphosphonates used to treat osteoporosis.22
incomplete. The maxillary fistula remained unchanged. Furthermore, the FDA recommended that patients
The PICC line was removed, and intravenous (IV) take bisphosphonates for three years and be
antibiotics (of 8-weeks' duration) were discontinued. re-evaluated.22 The patient may continue BP therapy
After finalizing IV therapy, the patient was started on for up to but not exceeding two more years (five years
oral sulfamethoxazole 800 mg/trimethoprim 160 mg. total). This recommendation is corroborated by Black
The foul odor, purulent drainage, congestion, upset and colleagues in a 2006 study which found that five
stomach, and significant stress prior to the operation years after BP discontinuation patients had no higher
had completely resolved. Despite the discomfort from fracture risk, other than for clinical vertebral fractures,
exposed mandibular bone (Figure 4 [C]), persistent compared with those who continued BP use. In other
maxillary fistula, and the size of the resection, the words, there was no higher risk of hip or large bone
patient said he felt much happier and healthier than fracture.13 It is important that the duration and overall
he had for several years. Unfortunately, since the dose given to patients who take these medications be
submission of this paper, the authors’ beloved patient monitored carefully by the prescriber and pharmacist
has had several recurrences of MRONJ and infection to reduce the risk of MRONJ.1,5,6,15
in the mandible, requiring both conservative and
surgical therapy. The authors continue to work The fact that this patient has been living with a
toward resolution. chronically infected, progressively disintegrating
maxilla and mandible has been a constant source
Discussion of physical and emotional distress. Retrospectively
analyzing his disease progression, this patient would
This case demonstrates how debilitating MRONJ can have benefitted greatly from a dental clearance
be and how difficult it is to manage the associated exam prior to BP therapy. The short-term success
maxillofacial sequelae. Though antiresorptive of the artificial joint replacement further illustrates
medications fulfill an important niche, it is imperative that MRONJ may appear to have spared the axial
to question whether current guidelines could be skeleton in the presence of an active oral lesion. This
can promote a false sense of security for

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some physicians, even as it ravages the
rapidly remodeling maxilla and mandible.
Additionally, as the body of literature
Figure 4. Serial Photos of the Mandibular linking antiresorptive medications with
Medication-related Osteonecrosis of the Jaw Site atypical femoral and subtrochanteric

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fractures increases,6,11 it is important
to be aware of other sites that may be
affected by BP toxicity. It is also prudent
to remember that these sequelae do not
occur immediately but are generally of
insidious onset. Such bony pathology
may develop after a significant amount of
time has passed.
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It is worth noting that technetium-99

(T-99) methylene diphosphate scans,
used in nuclear medicine imaging, have
demonstrated increased bone turnover
Legend: (A) Exposed, necrotic mandibular bone after teeth #29, #30, and #32
in the maxilla and mandible relative to
had been extracted. (B) Clean, bleeding bone margins. Note the large defect that
was created. (C) One-month post-op of right mandible. Mirrored view of 4 x 6 mm the axial skeleton.6 Alveolar bone (bone
exposed bone. Such lesions are characteristic of the incomplete healing seen when housing teeth) turns over 5 times faster
treating MRONJ and may persist indefinitely. Patients must be monitored for the than the inferior border of the mandible
development of refractory or new lesions.

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A DENTIST’S PERSPECTIVE ON THE NEED FOR INTERDISCIPLINARY COLLABORATION

and 10 times faster than the tibia. Turnover rates stomatognathic condition.1,7 It is concerning that this
correlate with areas that endure significant stresses notice was not provided to all those who prescribe and
and require frequent repair (ie, jawbone). It is believed dispense the medication.1,7 Moreover, pharmaceutical-
that BPs have greater affinity for sites with higher bone sponsored studies have reported incidence of MRONJ as
turnover because, as with T-99 uptake, higher doses of 0.8% to 2.4%, while independent studies have reported
BP more readily reach actively remodeling bone. After it to be 8% to 12%, with some outliers as high as 18%.5
drug delivery, frequently traumatized areas no longer AAOMS estimates the risk of MRONJ to be 0.7% to
remodel normally, and damaged tissue is not repaired. 6.7% among cancer patients exposed to zolendronate
The bone may then become necrotic and, with only when including available level 1 literature. Hopefully, the
a few millimeters of epithelial protection, exposed to discrepancy in these percentages will be resolved with
the oral microbiota. Though three-fourths of MRONJ the discovery of more sound, impartial data. Though
cases are precipitated by dentoalveolar trauma, such almost 20 years have passed since Marx and Ruggiero
as an alveoplasty (surgical smoothing of the jawbone) first described MRONJ, there remains a need to develop
or dental extraction, the remaining one-fourth of standard, evidence-based treatment protocols .1,5,6
cases occur spontaneously.5,6,15,23 The risk of MRONJ
increases significantly after the fourth IV BP dose, and Such future protocols should stipulate that any patient
in patients who have taken oral BPs for eight years or to be prescribed IV BPs must be treated with the
more6 (Ruggiero and colleagues reports 47% increased same considerations and clearances as if they were
risk with four years of oral bisphosphonates).2 Taken receiving radiation to the head and neck (which may
together, the aforementioned deleterious properties yield osteoradionecrosis of the jaw). This means the
coupled with a high dose and long duration of BPs patient should have a dental clearance exam and all
will increase the risk of MRONJ. ONJ is less common maxillofacial surgical procedures completed, allowing
and more easily treated in patients who have taken four to six weeks for healing, prior to initiating BP
oral BPs than those who have received IV BPs. This is therapy.23 The dose and duration of oral and IV BPs
because only 0.64% of the oral BP is absorbed while need to be better defined to achieve maximum
an impressive 70% of IV BPs are absorbed.5 Lower results and minimize the risk of developing ONJ. It
BP doses are less toxic and cause less osteoclastic is important to re-evaluate BP prescribing practices
suppression. This is significant when considering for cancer patients and how that may differ from
that many patients remain on BPs well after the those implemented to treat osteoporosis and other
recommended duration. MRONJ could be avoided in bone pathologies. This patient was much healthier
many cases if the source(s), duration, and dose of BP than many who are similarly dosed with IV BPs. His

SEPTEMBER 2022
therapy were more closely monitored.5 healing reflected his general health when compared
with the capability of recovery in cancer patients.
The difficulty of managing MRONJ is compounded not Furthermore, the shorter half-life of RANK-L inhibitors
only by conflicting evidence in the literature, but also makes these drugs more attractive when considering
by a prevalence of questionable data. Marx has called MRONJ management and outcome. Drug holidays are

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attention to the confounding of study results.15 In the theoretically more effective with RANK-L inhibitors
recent past, pharmaceutical companies have provided when compared with BPs. For this reason, it is
much-needed funding for both university and private advisable to determine under what circumstances it
research enterprises, which has allowed parties with would be safe and efficacious to substitute a BP with
conflicting interests to influence study design and a RANK-L inhibitor.24
reported outcome. In the case of BP research, Marx
has described how both Merck and Novartis sponsored Dentists advocate for higher-level evidence as well as a
significantly flawed studies that published misleading more careful, multidisciplinary approach and standard
information, maximized drug benefits, and minimized guidelines for improved management of antiresorptive
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side effects, including under-reporting ONJ.5 In agents (Table 2). The FDA has yet to place black box
September 2004, the manufacturer of IV pamidronate warnings for ONJ on BP and RANK-L inhibitor package
and zolendronic acid, Novartis International AG, inserts. Because of the severe nature of MRONJ, this
distributed warning letters to maxillofacial surgeons and warning may be one way to enhance awareness for
oncologists explaining changes to package inserts after prescribers, clinical pharmacists, and patients. It is
600 cases of ONJ were reported.1,7 In May 2005, the essential that the patient and clinician understand the
FDA prompted Novartis to send a similar warning to all risks prior to initiating treatment. The patient has a
dental professionals concerning the newly discovered right to be informed. It is much easier to have a candid

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Table 2.
RECOMMENDATIONS FOR THE PHARMACIST
Recommendations for the Pharmacist b. Routine dental treatments do not pose a risk for
1. Be familiar with AAOMS MRONJ position paper and MRONJ development
updates i. Dental cleanings, routine fillings, and root canals
2. Identify patients who are high risk for MRONJ do not cause MRONJ
development 5. Educate colleagues and patients to be aware of MRONJ
a. High-risk patients include: a. Both physicians and dentists benefit from the
i. Cancer patients (higher/more frequent doses) pharmacists’ expertise
ii. Intravenous route (higher percent absorption) 6. Monitor anti resorptive patients’ care
iii. ≥ 8 years oral bisphosphonate therapy a. Ensure drugs are not continued longer than
3. Develop a relationship with a competent dentist recommended duration
4. Ensure patients have dental clearance exam prior to b. Ensure patients don’t receive anti resorptive drugs
initiation of anti resorptive therapy from multiple providers/sources
a. Dental surgeries are a MAJOR risk factor for MRONJ 7. Encourage impeccable oral hygiene practices
development a. Routine dental care (cleanings, exams)
i. Dental surgeries (ie, extractions) should be b. Brush and floss after eating
completed prior to treatment c. Mentally or physically disabled patients must have
1. This may include removal of some or all help with daily oral hygiene
remaining teeth
ii. When possible, 4-6 weeks healing should be
allowed prior to initiating therapy to allow
complete healing

Abbreviations: AAOMS = American Association of Oral and Maxillofacial Surgeons, MRONJ = Medication-related osteonecrosis of the jaw.

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discussion of risk when such information is offered Conclusion
prior to an adverse event, rather than after the fact.
This strategy results in less patient-provider conflict. Dental professionals often witness the severe
Pharmacists can help physicians relay pertinent maxillofacial repercussions of MRONJ while

THE SENIOR CARE PHARMACIST

information to patients, regularly evaluate the pharmacists and physicians are privy to the medical
medications patients take, the potential interactions, side effects and the many benefits of BP therapy.
and whether the medication is still necessary. A closer collaboration between these specialties is
necessary to improve treatment strategies and long-
term patient outcomes. “Errare humanum est. Sed
perseverare diabolicum,” that is to say, “it is human
to err; however, to persevere in the same mistake is
diabolical.”25 More non-biased, reliable research is
essential to replace anecdotal guidelines with refined,
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evidence-based recommendations.

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REFERENCES

1. Ruggiero SL, Dodson TB, Fantasia J, et al. American 13. Black DM, Schwartz AV, Ensrud KE, et al. Effects of
Association of Oral and Maxillofacial Surgeons position paper continuing or stopping alendronate after 5 years of treatment—
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