American Association of Oral and Maxillofacial Surgeons
Position Paper on Bisphosphonate-Related Osteonecrosis of the Jaws
Approved by the Board of Trustees September 25, 2006
Introduction
Bisphosphonate-related osteonecrosis of the jaw (BRON) adversely affects the quality of life and
produces significant morbidity in afflicted patients. Oral and maxillofacial surgeons have been
responsible for counseling, managing, and treating a majority of these patients. The strategies
set forth in this position paper were developed by a Task Force appointed by the American
Association of Oral and Maxillofacial Surgeons (AAOMS). The Task Force was composed of
clinicians with extensive experience in caring for these patients, clinical epidemiologists, and
basic science researchers offering a broad range of experience and background. (See
Acknowledgements.) The strategies are based on an analysis of the existing literature and the
clinical observations of the expert Task Force members. AAOMS considers it vitally important
that this information be disseminated to other dental and medical specialties. It is understood
that the strategies and treatment algorithms outlined in this paper are starting points based on our
current understanding of BRON. As the knowledge base and experience in addressing BRON
evolves, future modifications and refinements of the current strategies will necessarily be
required.
Purpose
The purpose of this position paper is to provide:
1. perspectives on the risk of developing BRON and the risks and benefits of bisphosphonates
in order to facilitate medical decision-making of both the treating physician and the patient;
2. guidance to clinicians regarding the differential diagnosis of BRON in patients with a history
of treatment with intravenous (IV) or oral bisphosphonates; and
3. guidance to clinicians on possible BRON prevention measures and management of patients
with BRON based on the presenting stage of the disease.
Background
Benefits of bisphosphonate therapy
Intravenous bisphosphonates are primarily used and effective in the treatment and management
of cancer-related conditions. These include hypercalcemia of malignancy, skeletal-related events
associated with bone metastases in the context of solid tumors such as breast cancer, prostate
cancer, and lung cancer, and in the management of lytic lesions in the setting of multiple
myeloma. 1-12 The IV bisphosphonates are effective in preventing and reducing hypercalcemia,
stabilizing bony pathology, and preventing fractures in the context of skeletal involvement.
While they have not been shown to improve cancer-specific survival, they have had a significant
impact on the quality of life for patients with advanced cancer that involves the skeletal system.
Before 2001 pamidronate (Aredia®) was the only drug approved in the United States for
treatment of metastatic bone disease. In 2002 zoledronic acid (Zometa®) was approved for this
indication by the US Food and Drug Administration (FDA). 12
Oral bisphosphonates are approved to treat osteoporosis and are frequently used to treat
osteopenia as well. 13 They are also used for a variety of less common conditions such as Paget's
disease of bone, and osteogenesis imperfecta of childhood. 14-15 By far the most prevalent and
1
common indication, however, is osteoporosis. 16-17 Osteoporosis may arise in the context of
other diseases such as inflammatory bowel disease or primary biliary cirrhosis, as the result of
medications, most commonly steroids, or as a consequence of postmenopausal aging. 18-20
Whatever the underlying etiology of the osteoporosis, bisphosphonates may play a role, perhaps
in conjunction with calcium and vitamin D, in its management.
Risks of bisphosphonate therapy
In 2003-04, oral and maxillofacial surgeons were the first clinicians to recognize and report cases
of non-healing exposed bone in the maxillofacial region in patients treated with IV
bisphosphonates. 21-22 Since these initial reports, several case series and reviews have been
published. 23-30 In September 2004, Novartis, the manufacturer of the IV bisphosphonates
pamidronate (Aredia® ) and zoledronic acid (Zometa®), notified healthcare professionals of
additions to the labelling of these products, which provided cautionary language related to the
development of osteonecrosis of the jaws. 31 This was followed in 2005 by a broader drug class
warning of this complication for all bisphosphonates including the oral preparations. 32-33 See
Appendix 1 for list of bisphosphonate medications that are currently available in the United
States.
BRON Case Definition
To distinguish BRON from other delayed healing conditions, the following working definition of
BRON has been adopted by the AAOMS:
Patients may be considered to have BRON if all of the following three characteristics are
present:
1. Current or previous treatment with a bisphosphonate;
2. Exposed bone in the maxillofacial region that has persisted for more than eight weeks; and
3. No history of radiation therapy to the jaws.
It is important to understand that patients at risk for BRON or with established BRON can also
present with other common clinical conditions not to be confused as BRON. Commonly
misdiagnosed conditions may include, but are not limited to, alveolar osteitis, sinusitis,
gingivitis/periodontitis, caries, periapical pathology, and TMJ disorders.
Estimated Incidence and Factors Associated with Development of BRON
IV bisphosphonates and incidence of BRON
The clinical efficacy of IV bisphosphonates for the treatment of hypercalcemia and bone
metastases is well established. 1-4 Currently available published incidence data for BRON are
limited to retrospective studies with limited sample sizes. Based on these studies, estimates of the
cumulative incidence of BRON range from 0.8%-12%. 34-42 With increased recognition,
duration of exposure, and follow-up, it is likely that the incidence will rise.
Oral bisphosphonates and incidence of BRON
The clinical efficacy of oral bisphosphonates for the treatment of osteopenia/osteoporosis is well
established and is reflected in the fact that over 190 million oral bisphosphonate prescriptions
have been dispensed worldwide. 43 The specialty's experiences have identified several BRON
cases related to oral bisphosphonates. 22, 24 Patients under treatment with oral bisphosphonate
2
therapy are at a considerably lower risk for BRON than patients treated with IV bisphosphonates.
Based on data from the manufacturer of alendronate (Merck), the incidence of BRON was
calculated to be 0.7/100,000 person years of exposure. 44 This was derived from the number of
reported (not confirmed) cases that were deemed to likely represent BRON divided by the
number of alendronate pills prescribed since approval of the drug, and converted to number of
patient years. While this is the best available data to date, there may be serious under-reporting
and, as noted above, none confirmed. Correspondence with Alastair Goss, DDSc (September,
2006), reported that the estimated incidence of BRON for patients treated weekly with
alendronate is 0.01-0.04%, based on prescription data in Australia. Following extractions, this
rate increased to 0.09-0.34%.
Based on the above cited data, the risk of BRON for patients receiving IV bisphosphonates
appears to be significantly greater than the risk for patients receiving oral bisphosphonates.
Regardless, given the large number of patients receiving oral bisphosphonates for the treatment
of osteoporosis/osteopenia it is likely that most practitioners may encounter some patients with
BRON. It is important to accurately determine the incidence of BRON in this population and to
assess the risk associated with long-term use, i.e., greater than 3 years, of oral bisphosphonates.
The effect of certain comorbidities, e.g., chronic corticosteroid use, also requires further study.
Risk factors
Risk factors for the development of BRON can be grouped as drug-related, local risk factors, and
demographic/systemic factors.
I.
Drug-related risk factors include:
A. Potency of the particular bisphosphonate: zoledronate (Zometa®) is more potent than
pamidronate (Aredia®) and pamidronate (Aredia®) is more potent than the oral
bisphosphonates; the IV route of administration results in a greater drug exposure than
the oral route. 34-35, 42, 45
B. Duration of therapy: longer duration appears to be associated with increased risk. 35, 42
II. Local risk factors include:
A. Dentoalveolar surgery, including, but not limited to 34, 42, 45
1. Extractions
2. Dental implant placement
3. Periapical surgery
4. Periodontal surgery involving osseous injury
Patients receiving IV bisphosphonates and undergoing dentoalveolar surgery are at least
7-times more likely to develop BRON than patients who are not having dentoalveolar
surgery. 42, 45
B. Local anatomy
1. Mandible
a. Lingual tori
b. Mylohyoid ridge
3
2. Maxilla
a. Palatal tori
It has been observed that lesions are found more commonly in the mandible than the
maxilla (2:1 ratio) and more commonly in areas with thin mucosa overlying bony
prominences such as tori, bony exostoses, and the mylohyoid ridge. 22, 24, 46
C. Concomitant oral disease
Patients with a history of inflammatory dental disease, e.g., periodontal and dental
abscesses, are at a seven-fold increased risk for developing BRON. 42
III. Demographic and systemic factors
A. Age: With each passing decade, there is a 9% increased risk for BRON in multiple
myeloma patients treated with IV bisphosphonates. 45
B. Race: Caucasian 45
C. Cancer diagnosis: Risk is greater for patients with multiple myeloma than for patients
with breast cancer; and those with breast cancer have a greater risk than those with other
cancers. 42
D. Osteopenia/osteoporosis diagnosis concurrent with cancer diagnosis 42
The following factors are thought to be risk factors for BRON:
1. Corticosteroid therapy
2. Diabetes
3. Smoking
4. Alcohol use
5. Poor oral hygiene
6. Chemotherapeutic drugs
Further studies are required to accurately determine if these factors are associated with BRON
risk.
Management Strategies for Patients Treated with Bisphosphonates
Prevention of BRON
Prior to treatment with an IV bisphosphonate, the patient should have a thorough oral
examination, any unsalvageable teeth should be removed, all invasive dental procedures should
be completed, and optimal periodontal health should be achieved.
Based on the experience of two Task Force members (SLR, REM) with approximately 50
patients, the risk of developing BRON associated with oral bisphosphonates, while exceedingly
small, appears to increase when the duration of therapy exceeds three years. This time frame
may be shortened in the presence of certain comorbidities, such as chronic corticosteroid use. If
systemic conditions permit, it has been proposed that discontinuation of oral bisphosphonates for
a period of three months prior to and three months following elective invasive dental surgery
may lower the risk of BRON. The risk reduction may vary depending on the duration of
bisphosphonate exposure. Modification or cessation of oral bisphosphonate therapy should be
done in consultation with the treating physician and the patient.
4
Treatment Goals
The major goals of treatment for patients at risk of developing or who have BRON are:
Prioritization and support of continued oncologic treatment in patients receiving IV
bisphosphonates.
o
Oncology patients can benefit greatly from the therapeutic effect of bisphosphonates by
controlling bone pain and reducing the incidence of other skeletal complications.
Preservation of quality of life through:
o
Patient education and reassurance
o
Control of pain
o
Control of secondary infection
o
Prevention of extension of lesion and development of new areas of necrosis
Treatment Strategies 24, 29, 47-49
A. Patients about to initiate intravenous bisphosphonate treatment
The treatment objective for this group of patients is to minimize the risk of developing
BRON. Although a small percentage of patients receiving bisphosphonates develop
osteonecrosis of the jaw spontaneously, the majority of affected patients experience this
complication following dentoalveolar surgery. 34, 42, 45 Therefore, if systemic conditions
permit, initiation of bisphosphonate therapy should be delayed until dental health is
optimized. This decision must be made in conjunction with the treating physician and
dentist and other specialists involved in the care of the patient.
Non-restorable teeth and those with a poor prognosis should be extracted. Other
necessary elective dentoalveolar surgery should also be completed at this time. Based on
experience with osteoradionecrosis, it appears advisable that bisphosphonate therapy
should be delayed, if systemic conditions permit, until the extraction site has mucosalized
(14-21 days) or until there is adequate osseous healing. Dental prophylaxis, caries
control, and conservative restorative dentistry are critical to maintaining functionally
sound teeth. This level of care must be continued indefinitely.
Patients with full or partial dentures should be examined for areas of mucosal trauma,
especially along the lingual flange region. It is critical that patients be educated as to the
importance of dental hygiene and regular dental evaluations, and specifically instructed to
report any pain, swelling, or exposed bone.
Medical oncologists should evaluate and manage patients scheduled to receive IV
bisphosphonates similarly to those patients scheduled to initiate radiation therapy to the
head and neck. The osteoradionecrosis prevention protocols are guidelines that are
familiar to most oncologists and general dentists.
B. Asymptomatic patients receiving intravenous bisphosphonates
Maintaining good oral hygiene and dental care is of paramount importance in preventing
dental disease that may require dentoalveolar surgery. Procedures that involve direct
osseous injury should be avoided. Non-restorable teeth may be treated by removal of the
5
crown and endodontic treatment of the remaining roots. 49 Placement of dental implants
should be avoided in the oncology patient who was exposed to the more potent
intravenous bisphosphonate medications (zoledronic acid and pamidronate) on a frequent
dosing schedule (4-12 times per year).
There has been limited information on IV bisphosphonate use for osteoporosis, as this
indication is an off-label use. However, the dosing schedule for osteoporosis is far less
frequent than for adjunct treatment of oncology patients. A September 16, 2006 media
release from Novartis provided information on Phase III trials of a once-yearly infusion
of zoledronic acid for the treatment of postmenopausal osteoporosis, which is currently
under review by the FDA. 50 Based on the decreased frequency/dosage for this
indication, the Task Force believes the risk of developing BRON may be equivalent to or
possibly less than that of oral therapy for osteoporosis.
C. Asymptomatic patients receiving oral bisphosphonate therapy
Patients receiving oral bisphosphonates are also at risk for developing BRON, but to a
much lesser degree than those treated with intravenous bisphosphonates. 22, 24-25, 46
BRON can develop spontaneously or after minor trauma. In general, these patients seem
to have less severe manifestations of necrosis and respond more readily to stage specific
treatment regimens. (See Table 1.) Elective dentoalveolar surgery does not appear to be
contraindicated in this group. It is recommended that patients be adequately informed of
the small risk of compromised bone healing. The risk of BRON may be associated with
increased duration of treatment with oral bisphosphonates, i.e., > three years, based on
experience with 50 such patients by two Task Force members (SLR, REM). The risk of
long-term oral bisphosphonate therapy clearly requires further analysis and research.
Management Strategies
Sound recommendations for patients taking oral bisphosphonates that are based on strong
clinical research designs are lacking. The Task Force strategies outlined below are based
on clinical experience of clinicians involved in caring for these patients, in which it
appears that the risk of developing BRON associated with oral bisphosphonates increased
when duration of therapy exceeded three years. As more data become available, these
strategies will be updated and modified as necessary.
For individuals who have taken an oral bisphosphonate for less than three years and
have no clinical risk factors, no alteration or delay in the planned surgery is necessary.
This includes any and all surgeries common to oral and maxillofacial surgeons,
periodontists, and other dental providers.
However, it is suggested that if dental implants are placed, informed consent should be
provided related to possible future implant failure and possible osteonecrosis of the jaws
if the patient continues to take an oral bisphosphonate. Such patients should be placed on
a regular recall schedule. It is also advisable to contact the provider who originally
prescribed the oral bisphosphonate and suggest monitoring such patients and considering
either alternate dosing of the bisphosphonate, drug holidays, or an alternative to the
bisphosphonate therapy.
6
For those patients who have taken an oral bisphosphonate for less than three years and
have also taken corticosteroids concomitantly, the prescribing provider should be
contacted to consider discontinuation of the oral bisphosphonate (drug holiday) for at
least three months prior to oral surgery, if systemic conditions permit. The
bisphosphonate should not be restarted until osseous healing has occurred. These
strategies are based on the hypothesis that concomitant treatment with corticosteroids
may increase the risk of developing BRON and that a "drug holiday" may mitigate this
risk.
For those patients who have taken an oral bisphosphonate for more than three years with
or without any concomitant prednisone or other steroid medication, the prescribing
provider should be contacted to consider discontinuation of the oral bisphosphonate for
three months prior to oral surgery, if systemic conditions permit. The bisphosphonate
should not be restarted until osseous healing has occurred. These strategies are based on
the experience of two Task Force members (SLR, REM) managing 50 BRON patients
who had a history of oral bisphosphonate therapy for three or more years, and the
hypothesis that a "drug holiday" may mitigate this risk
D. Patients with an established diagnosis of BRON
The treatment objectives for patients with an established diagnosis of BRON are to
eliminate pain, control infection of the soft and hard tissue, and minimize the progression
or occurrence of bone necrosis.
These patients respond less predictably to the established surgical treatment algorithms
for osteomyelitis or osteoradionecrosis. Surgical debridement has been variably effective
in eradicating the necrotic bone. 22-24, 29 It may be difficult to obtain a surgical margin
with viable bleeding bone as the entire jawbone has been exposed to the pharmacologic
influence of the bisphosphonate. Therefore, surgical treatment should be delayed if
possible. Areas of necrotic bone that are a constant source of soft tissue irritation should
be removed or recontoured without exposure of additional bone. Based on the experience
of the Task Force members and case reports, loose segments of bony sequestrum should
be removed without exposing uninvolved bone. 51 The extraction of symptomatic teeth
within exposed, necrotic bone should be considered since it is unlikely that the extraction
will exacerbate the established necrotic process.
Patients with established BRON should avoid elective dentoalveolar surgical procedures,
since these surgical sites may result in additional areas of exposed necrotic bone.
Symptomatic patients with pathologic mandibular fractures may require segmental
resection and immediate reconstruction with a reconstruction plate. The potential for
failure of the reconstruction plate because of the generalized effects of the
bisphosphonate exposure needs to be recognized by the clinician and patient. Immediate
reconstruction of these patients with non-vascularized or vascularized bone may be
problematic as necrotic bone may develop at the recipient site.
7
The effectiveness of hyperbaric oxygen therapy is undetermined. 52 A communication to
AAOMS from J. Freiberger, MD, MPH on May 17, 2006, reported that a clinical trial has
been funded to establish the efficacy of hyperbaric oxygen therapy in treating patients
with BRON, and began enrolling patients in August 2006 (August 31, 2006 e-mail).
Staging and Treatment Strategies (See Table 1)
Staging
In order to direct rational treatment guidelines and collect data to assess the prognosis in
patients who have used either IV or oral bisphosphonates, the AAOMS proposes use of the
following staging categories:
1. Patients at risk: No apparent exposed/necrotic bone in patients who have been treated
with either IV or oral bisphosphonates.
2. Patients with BRON
Stage 1: Exposed/necrotic bone in patients who are asymptomatic and have no evidence
of infection.
Stage 2: Exposed/necrotic bone in patients with pain and clinical evidence of infection.
Stage 3: Exposed/necrotic bone in patients with pain, infection, and one or more of the
following: pathologic fracture, extra-oral fistula, or osteolysis extending to the
inferior border
Treatment strategies
At risk - Patients who are at risk of developing BRON by virtue of the fact that they have
been exposed to a bisphosphonate do not require any treatment. However, these patients
should be informed of the risks of developing BRON, as well as the signs and symptoms of
this disease process.
Stage 1 These patients benefit from the use of oral antimicrobial rinses, such as
chlorhexidine 0.12%. No surgical treatment is indicated. Patients who present with Stage 1
disease have done well with this type of conservative treatment.
Stage 2 These patients benefit from the use of oral antimicrobial rinses in combination with
antibiotic therapy. It is hypothesized that the pathogenesis of BRON may be related to
factors adversely influencing bone remodeling. Additionally, BRON is not due to a primary
infectious etiology. Most of the isolated microbes have been sensitive to the penicillin group
of antibiotics. Quinolones, metronidazole, clindamycin, doxycycline, and erythromycin have
been used with success in those patients who are allergic to penicillin. Microbial cultures
should also be analyzed for the presence of actinomyces species of bacteria. If this microbe is
isolated, then the antibiotic regimen should be adjusted accordingly. In some refractory
cases however, patients may require combination antibiotic therapy, long-term antibiotic
maintenance, or a course of intravenous antibiotic therapy.
Stage 3 These patients typically have pain that impacts the quality of life. Surgical
debridement/resection in combination with antibiotic therapy may offer long-term palliation
with resolution of acute infection and pain.
8
Regardless of the disease stage, mobile segments of bony sequestrum should be removed without
exposing uninvolved bone. The extraction of symptomatic teeth within exposed, necrotic bone
should be considered since it is unlikely that the extraction will exacerbate the established
necrotic process.
Discontinuation of bisphosphonate therapy
IV Bisphosphonates
Oncology patients benefit greatly from the therapeutic effects of bisphosphonates by
controlling bone pain and the incidence of pathologic fractures. Discontinuation of IV
bisphosphonates offers no short-term benefit. However, if systemic conditions permit, long-
term discontinuation may be beneficial in stabilizing established sites of BRON, reducing the
risk of new site development, and reducing clinical symptoms. The risks and benefits of
continuing bisphosphonate therapy should be made only by the treating oncologist in
consultation with the OMS and the patient.
Oral bisphosphonates
Discontinuation of oral bisphosphonate therapy in patients with BRON has been associated
with gradual improvement in clinical disease. Based on the experience of two Task Force
members (SLR, REM) managing 50 BRON patients who were treated with oral
bisphosphonates, discontinuation of oral bisphosphonates for 6-12 months may result in
either spontaneous sequestration or resolution following debridement surgery. If systemic
conditions permit, modification or cessation of oral bisphosphonate therapy should be done
in consultation with the treating physician and the patient.
9
Table 1 Staging and Treatment Strategies
BRON Staging
Treatment Strategies
At risk category No apparent
·
No treatment indicated
exposed/necrotic bone in patients who have
·
Patient education
been treated with either oral or IV
bisphosphonates
Stage 1 Exposed/necrotic bone in patients
·
Antibacterial mouth rinse
who are asymptomatic and have no evidence
·
Clinical follow-up on a quarterly basis
of infection
·
Patient education and review of indications
for continued bisphosphonate therapy
Stage 2 Exposed/necrotic bone associated
·
Symptomatic treatment with broad-spectrum
with infection as evidenced by pain and
oral antibiotics, e.g. penicillin, cephalexin,
erythema in the region of the exposed bone
clindamycin, or 1st generation
with or without purulent drainage
fluoroquinolone
·
Oral antibacterial mouth rinse
·
Pain control
·
Only superficial debridements to relieve soft
tissue irritation
Stage 3 Exposed/necrotic bone in patients
·
Antibacterial mouth rinse
with pain, infection, and one or more of the
·
Antibiotic therapy and pain control
following: pathologic fracture, extra-oral
·
Surgical debridement/resection for longer
fistula, or osteolysis extending to the inferior
term palliation of infection and pain
border
Exposed bone in the maxillofacial region without resolution in 8-12 weeks in persons treated
with a bisphosphonate who have not received radiation therapy to the jaws.
Regardless of the disease stage, mobile segments of bony sequestrum should be removed
without exposing uninvolved bone. The extraction of symptomatic teeth within exposed, necrotic
bone should be considered since it is unlikely that the extraction will exacerbate the established
necrotic process.
Discontinuation of the IV bisphosphonates shows no short-term benefit. However, if systemic
conditions permit, long-term discontinuation may be beneficial in stabilizing established sites of
BRON, reducing the risk of new site development, and reducing clinical symptoms. The risks and
benefits of continuing bisphosphonate therapy should be made only by the treating oncologist in
consultation with the OMS and the patient.
Discontinuation of oral bisphosphonate therapy in patients with BRON has been associated with
gradual improvement in clinical disease. Based on the experience of two Task Force members
(SLR, REM) managing 50 BRON patients who were treated with oral bisphosphonates,
discontinuation of oral bisphosphonates for 6-12 months may result in either spontaneous
sequestration or resolution following debridement surgery. If systemic conditions permit,
modification or cessation of oral bisphosphonate therapy should be done in consultation with the
treating physician and the patient.
10
Future Research
On July 31, 2006, the National Institutes of Health announced funding opportunities for
research on the pathophysiology of bisphosphonate-associated osteonecrosis of the jaw.
53 At least one grant has been awarded for a project titled "Bisphosphonates and Oral
Complications of Cancer Chemotherapy: A Pilot Study," with Dr. Regina Landesberg as
the principal investigator. 54 Prospective clinical trials are required so that the present
staging system can evolve into a more comprehensive staging system, which would
enable clinicians to make accurate judgements about risk, prognosis, treatment selection,
and outcome for patients with BRON.
Acknowledgements: The AAOMS expresses appreciation to the Advisory Task Force on
Bisphosphonate-Related Osteonecrosis of the Jaws for their work in the development of
this position paper. The Task Force was comprised of: Salvatore L. Ruggiero, DMD,
MD, Chair; Daniel J. Daley, DDS, MS, AAOMS Board Liaison; Thomas B. Dodson,
DMD, MPH; Regina Landesberg, DMD, PhD; Robert E. Marx, DDS; Alfred I Neugut,
MD, PhD, Professor of Medicine and Epidemiology, Columbia University; and W. Mark
Tucker, DDS, Consultant to the Task Force.
11
Appendix I Bisphosphonate Preparations Currently Available in the US *
Primary
Nitrogen
Dose
Route
Relative
Indication
Containing
Potency**
Etidronate
Paget's
No
300 -750
Oral
1
(Didronel)
Disease
mg daily for
6 months
Tiludronate
Paget's
No
400 mg
Oral
50
(Skelid)
Disease
daily for 3
months
Alendronate
Osteoporosis
Yes
10 mg/day
Oral
1,000
(Fosamax)
70 mg/week
Risedronate
Osteoporosis
Yes
5 mg/day
Oral
1,000
(Actonel)
35 mg/week
Ibandronate
Osteoporosis
Yes
2.5 mg/day
Oral
1,000
(Boniva)
150
mg/month
Pamidronate
Bone
Yes
90 mg/3
IV
1,000
(Aredia)
Metastases
weeks
5,000
Zoledronate
Bone
Yes
4 mg/3
IV
10,000 +
(Zometa)
Metastases
weeks
*A once-yearly infusion of zoledronic acid for the treatment of postmenopausal
osteoporosis is under FDA review. 50
**Relative to etidronate
12
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