Download osteonecrosis of the jaw (onj)

OSTEONECROSIS OF THE JAW (ONJ)
Fosamax (Generic: Alendronate, manufactured by Merck, was approved by the FDA in
1995. Fosamax was originally prescribed to treat osteoporosis and Paget's disease.
Fosamax is a type of drug known as a bisphosphonate. Three others of interest are Aredia
(Generic: Pamidromate), Zometa (Generic: Zoledronate) and Actonel (Generic:
Risedronate).
A connection between Fosamax and other bisphosphonates with a serious bone disease
called Osteonecrosis of the Jaw (ONJ) was found. This condition is also known as Dead
Jaw. This finding was published in the Journal of Oral and Maxillofacial Surgeons. This
prompted the FDA and the manufacturer of Fosamax to issue a warning to health care
professionals on September 24, 2004.
A search of the Adverse Event Reports (AERS) database, posted March 3, 2005, found
139 cases of osteonecrosis (bone death), 47 with pamidronate, 33 with zoledronic acid
and 59 in patients receiving both drugs. Twelve cases were found in alendronate patients
and one in risedronate patients.
Bisphosphonates are commonly used in tablet form to prevent and treat osteoporosis in
post- menopausal women. Stronger forms given orally or intravenously (IV) are
commonly used in the management of advanced cancers that have metastasized to the
bone, where the disease often causes bone pain and possibly even fractures. Many
cancers can involve or metastasize to the bones including, but not limited to, lung cancer,
breast cancer, prostate cancer, multiple myeloma, and others.
When bisphosphonates are given in cancer chemotherapy, the drugs may not only be
given intravenously but for longer periods of time. There have been reports that both
modalities, tablets or IV solutions, can cause osteonecrosis of the jaw. ONJ is a condition
in which the bone tissue in the jaw fails to heal after minor or major, such as tooth
extraction, causing the bone to be exposed. This exposure can eventually lead to
infection and maybe even fracture which will require long-term antibiotic therapy or
surgery to remove the dying bone tissue. It is extremely important that prevention and
early treatment of patients using bisphosphonates be undertaken to preserve the jawbone
and other bones of the body.
Bisphosphonates are a unique class of drugs. As a family, they are characterized
pharmacologically by their ability to inhibit bone resorption, whereas,
pharmaeokinetically, they are classified by their similarity in absorption, distribution, and
elimination. Although all bisphosphonates have similar physicochemical properties, their
antiresorbing activities differ substantially. Activity is dramatically increased when the
amino group is contained in the aliphatic carbon chain. For example, alendronate, an
aminobisphosphonate, is approximately 700-fold more potent than etidronate, both in
vitro and in vivo. In general, bisphosphonates are poorly absorbed from the
gastrointestinal tract as a result of their poor lipophilicity. In vitro and in vivo studies
have shown that bisphosphonates are absorbed from the gastrointestinal tract
via paracellular transport. Systemically available bisphosphonates disappear very rapidly
from plasma, and are partly taken up by the bone and partly excreted by the kidney. The
relative contribution of these two processes to overall plasma elimination differs
significantly among bisphosphonates. To date, all bisphosphonates studied show no
evidence of metabolism. Renal excretion is the only route of elimination. Studies with
alendronate in rats indicate that the drug is actively secreted by an uncharacterized renal
transport system, and not by the anionic or cationic renal transport systems.
Bisphosphonates bind preferentially to bones which have high turnover rates, and their
distribution in bone is not homogeneous. After bone uptake, the bisphosphonates are
liberated again only when the bone in which they are deposited is resorbed. Thus, the
half-life of bisphosphonates in bone is very long, ranging among different species from 1
to 10 years, depending largely on the rate of bone turnover.
(Bone 18:75-85; 1996
Bisphosphonates cause inhibition of osteoclasts (and in some cases apoptosis). This cell
death causes a loss of the growth factors for bone vascularization and a reduction of the
factors that stimulate osteoblasts to add new bone. Other mechanisms could be involved
as well and continued research is needed.
DEFINITIONS
Osteoporosis: a disease in which the bone loses density and become so porous that it can
break as a result of even minor trauma.
Osteonecrosis: (pronounced OSS-tee-oh-ne-KRO-sis) a disease in which a temporary or
permanent loss of blood supplies to the bone causes bone tissue to die and the bone to
collapse. This condition is also known as avascular necrosis, aseptic necrosis and
ischemic necrosis.
Osteonecrosis can happen to any bone but most commonly affects the ends
(epiphysis) of the femur, the bone extending from the knee joint to the hip joint. Other
common sites include the upper arm, these, shoulders and ankles. The disease may affect
just one bone, more than one bone at the same time, or more than one bone at different
times. The American Academy of Orthopedic Surgeons reports that 10,000 to 20,000
people develop osteonecrosis every year. The report states that most of those affected are
between the ages of 20 and 50. This report did not differentiate between male and female.
The amount of disability that results from osteonecrosis depends on what part of
the bone is affected, how large an area is involved and how the bone rebuilds itself.
Normally, bone continuously breaks down and rebuilds. Old bone is replaced with new
bone. This process, which takes place after an injury as well as during normal growth,
keeps the skeleton strong and helps to maintain a balance of minerals. In the course of
osteonecrosis, however, the healing process is usually ineffective and the bone tissues
break down faster than the body can repair them. If left untreated, the disease progresses,
the bone collapses and the surface breaks down leading to pain and in joints arthritis.
Osteonecrosis is caused by impaired blood supply to the bone, but it is not always
clear what causes this impairment. Osteonecrosis often occurs in people with certain risk
factors and medical conditions. However it also affects people with no health problems
and for no known reasons.
Osteoclasts: a large cell with many nuclei, found in growing bone. It assimilates bony
tissue and is active in the formation of canals and cavities.
Osteoblasts: a cell from which bone develops.
Apoptosis: a form of cell death necessary to make way for new cells and to remove cells
whose DNA has been damaged to the point at which cancerous change is liable to occur.
POTENTIAL CAUSES
Steroid Medications: aside from injury, one of the most common causes of osteonecrosis
process is the use of corticosteroid medications, such as prednisone. Corticosteroids are
commonly used to treat inflammatory diseases. Studies suggest that long-term use of oral
or intravenous (IV) corticosteroids is associated with nontraumatic osteonecrosis. It has
not been made clear why corticosteroids sometimes leads to osteonecrosis. There has
been speculation that the drugs may interfere with the body's ability to break down fatty
substances called lipids. The lipids then build up in and clog of blood vessels, causing
them to narrow and reduce the amount of blood that gets to the bone.
Alcohol Use: excessive alcohol use is another common cause of osteonecrosis. People
who drink alcohol in excess can develop fatty substances that may block blood vessels,
causing a decreased blood supply to the bones.
Injury: when a fracture, a dislocation, or some other joint injury occurs, the blood vessels
may be damaged. This can interfere with the blood circulation to the bone and lead to
trauma-related osteonecrosis.
Other Risk Factors: other risk factors for osteonecrosis include radiation therapy,
chemotherapy and organ transplantation. Osteonecrosis is also associated with a number
of medical conditions, including cancer.
THOSE LIKELY TO DEVELOP OSTEONECROSIS
Osteonecrosis affects both men and women. It can occur in people of any age, from
children to the elderly. However it is most common in people in their thirties, forties and
over 50. With the use of bisphosphonates in women over 50, for the prevention of
osteoporosis, this appears to be the most common sex and age. Certainly, use of
bisphosphonates is the common factor. Whether or not the likelihood is influenced by
the type of bisphosphonate, how it is administered and/or the duration of treatment is not
known yet. It does appear that the condition was much more likely in those patients who
had been having bisphosphonate treatment for 3 to 4 years than it was in patients who’d
had treatment for less than a year. In fact, no one got ONJ if they had had fewer than 13
treatments with BP. It could be concluded from this that while dental treatment is a risk
factor, the most important risk factor is the length of time you’ve had BP treatment. ONJ
was not associated with treatment for any one particular type of cancer.
Although there has been an increase in osteonecrosis of the jaw in people taking
bisphosphonates, this is still only a very small percentage of people overall. Anecdotal
cases and roughly 875 reports that one of the IV drugs' maker had received by February,
2005 from among millions of users point to a small risk among users. Fewer than 7 out
of 100 people were found to be affected in a November 2005 study. While this number
may appear as small, it is still significant. It should be noted that 90 to 95 percent of the
875 cases have been in cancer patients taking the IV versions, stated Dr. John Hellstein,
clinical professor of oral and maxillofacial pathology at the University of Iowa.
But Dr. Robert Recker, director of Creighton University's Osteoporosis Research Center,
said he isn't convinced that there's a risk associated with the osteoporosis drugs.
Recker has treated several thousand patients with oral bisphosphonates in clinical trials
and in practice. He also has seen clinical trial data on the drugs as a member of scientific
advisory boards for Merck and Procter & Gamble Pharmaceuticals, the respective makers
of Fosamax and Actonel.
"I don't think there's any significant risk in patients who have osteoporosis," he said. "The
risk is in patients who are taking giant doses for cancer."
It should be emphasized that this statement should be looked at carefully since Dr.
Recker is a member of scientific advisory boards for Merck and Procter & Gamble
Pharmaceuticals.
SYMPTOMS
In the early stages of osteonecrosis, people may not have any symptoms. As the disease
progresses, however, most experience pain. Pain usually develops gradually, but may be
mild or severe. If osteonecrosis progresses and the bone surface collapses, pain may
develop or increase dramatically. The period of time between the first symptoms may be
different for each person, but it typically ranges from several months to more than a year.
Sometimes a patient may start to experience swelling and numbness or a "heavy jaw
feeling". There may even be a loosening of teeth, as in periodontal disease. There can be
bone necrosis or loss of bone which causes this. There can be sharp edges of exposed
bone, bone spurs or the breaking loose of small bone spicules around tooth sockets.
DIAGNOSIS
After performing a complete physical examination and asking about the patient's medical
history, the use of one or more bone imaging techniques can help to diagnose
osteonecrosis. As with many other diseases, early diagnosis increases the chances of
treatment success.
X-ray: a radiograph is probably one of the first tests that would be recommended.
However x-rays are not sensitive enough to detect bone changes in the early stages of the
disease. If the x-ray is normal, more tests may be ordered. In later stages of
osteonecrosis, x-rays may very well show bone damage, and once the diagnosis is made,
they ordered often used to monitor disease progression.
Magnetic Resonance Imaging (MRI): this is probably the most sensitive method for
diagnosing osteonecrosis in the early stages. Unlike x-rays, bone scans, and CT
(computed/computerized tomography) scans, MRI detects chemical changes in the bone
marrow. MRI provides a picture of the affected area and the bone rebuilding process. In
addition, MRI may show deceased areas that are not yet causing any symptoms. There
have been some cautions against aggressive treatment of osteonecrosis that has been
detected by MRI. but is not causing symptoms. One study has shown evidence that for a
select group of patients in early stages of osteonecrosis, the disease may improve
spontaneously.
Computed/Computerized Tomography (CT scan): this type of test is an imaging
technique that provides a three-dimensional picture of the bone. It also shows "slices" of
the bone, making the picture much clearer than x-rays and bone scans. There has been
disagreement about the usefulness of this test to diagnose osteonecrosis.
Bone scan: this test is not normally used for diagnosing osteonecrosis.
Biopsy: a surgical procedure in which tissue sample from the affected bone is removed
and studied. Although a biopsy can conclusively diagnose osteonecrosis, it is rarely used
because it requires surgery.
Functional Evaluation of Bone: a test to measure the pressure inside the bone may be
used when there is a strong suspicion of osteonecrosis, despite normal results of x-rays,
bone scans and MRIs. These tests are very sensitive for detecting increase pressure
within the bone, but they do require surgery.
TREATMENTS FOR ONJ
Appropriate treatment for osteonecrosis is necessary. Without treatment, most people
with the disease will experience severe pain and limitations within two years.
Consultation with an oral surgeon/maxillofacial surgeon or dental oncologist familiar
with osteonecrosis is recommended. It may be difficult to find someone who has
diagnosed and treated this problem. To determine the most appropriate treatment the
following is considered:
1. Age
2. Stage of the disease
3. Location and extent of affected area
4. Underlying cause
Nonsurgical Treatments: may used by itself or in combination with other types of
treatment. Usually these treatments may relieve pain or help in the short term, but for
most people they don't bring lasting improvement.
1. Nonsteroidal anti-inflammatory drugs (NSAIDs) are often prescribed to reduce
pain. People with clotting disorders may be given blood thinners to reduce clots
that block the blood supply to the bone. Cholesterol reducing medications may be
used to reduce fatty substances (lipids) that increase with corticosteroid treatment,
which is a major risk factor for osteonecrosis. There have been limited studies
that people who took cholesterol lowering medications called statins along with
corticosteroids significantly reduce the risk of developing ONJ, in the first place.
2. Electrical stimulation has been used in several centers to induce bone growth,
and in some cases has been helpful when used prior to certain types of
osteonecrosis. There is no place in the literature that shows this has been used
for ONJ.
3. Antibiotic or antimicrobial treatments are used to eliminate or reduce the
possibility of infection. Specific drugs should be selected based upon the type
of bacterial infection found.
4. Stopping the bisphosphonate therapy, when possible. This is not a proven part
of treatment due to the long half-life of bisphosphonates.
Surgical Treatment: there are a number of different surgical procedures used to treat
osteonecrosis. Most people with osteonecrosis will eventually need surgery. It has been
strongly recommended that if surgery is used, bisphosphonates therapy should be
interrupted. There is some data to suggest that cessation of taking bisphosphonates for 24 months is necessary to facilitate recovery.
1. Core decompression removes the inner cylinder of bone, which reduces
pressure within the bone. This causes and increase blood flow and allows more
blood vessels to form. This works best in people who were in the earliest stages
of osteonecrosis. This procedure sometimes reduces pain and slows the
progression.
2. Osteotomy involves shaping the bone to reduce stress on the affected area.
Recovery can be lengthy process, requiring 3 to 12 months of very limited
activities. This procedure is most effective for patients with early-stage
osteonecrosis and those with a small area of affected bone.
4. Bone graft is a transplantation of healthy bone from another part of the body.
There
were no reports in the literature that this is used in treating ONJ.
Miscellaneous Treatment: Hyperbaric oxygen does not seem to be helpful. Dental
implants and any elective oral surgery should be avoided.
OTHER CONSIDERATIONS/REPORTS
In a letter to the editor, by Dr. Robert Marx, to the Journal of Oral Maxillofacial Surgery,
in 2003, it was stated that he was seeing more patients with ONJ. All of the patients had
been taking Aredia or Zometa. 18 out of 36 of these patients had multiple myeloma. He
and others stated that there was a risk of very poor healing of the jaw after dental surgery.
The most important finding was that there was an apparent occurrence of jaw
osteonecrosis in patients taking bisphosphonates.
There are 2 reports from the New York area by Dr. Ruggiero and colleagues. They
reported 63 total patients, 28 with myeloma over a 3-year span (2001-2003) inclusive. A
group at Memorial Sloan Kettering noted 4 myeloma patients with osteonecrosis in their
review of bisphosphonate patients.
In a personal communication with Lewis W. Williams, D.D.S., M.S., a maxillofacial
surgeon in Honolulu, he states that in the past years he and his partners have seen six
patients with Osteonecrosis of the Jaw. All of them were on women over 50 years of age,
taking Fosamax. He states that he has heard of other cases by other dentists.
Many patients who had ONJ were also receiving corticosteroids and chemotherapy.
More research needs to be done to determine the role of other drugs and treatment
modalities during treatment with the bisphosphonates and the occurrence of ONJ.
There does not seem to be any treatment that definitely cures Osteonecrosis of the Jaw.
While some are successful, the literature shows that even with continued treatment, not
all patients have a total remission. No data is available to suggest whether the
discontinuation of BPs reduces the risk of ONJ prior to dental surgery. Potent
bisphosphonates bind to bone for many months, probably 1 to 10 years.
PREVENTION OF ONJ (CONSLUSION)
There have been some reports that root canal treatments should be avoided. Others have
stated that they should be done, as well as crowns and other dental restorations. These
treatments, according to some, help to preserve the teeth and eliminate oral surgery.
Have all necessary dental treatment finished prior to starting bisphosphonates.
Dental health during cancer treatment. (Any repetitions in the following are made for
emphasis and importance to prevent ONJ)
Cancer treatments can affect your entire body, including your teeth and gums. Side
effects of treatment may include inflammation of the mucous membranes in the mouth
(mucositis), infections, taste changes, dry mouth, pain, tooth decay, gum disease, and
sores inside your mouth. Therefore, good dental health practices are especially important
for people living with cancer. Good communication is important, too. Your dentist should
know that you are being treated for cancer, and your oncologist should be aware of your
dental history. As a patient living with cancer, you should:
• Schedule a dental exam and cleaning before cancer treatment begins and
periodically during the course of your treatment.
• Discuss dental procedures, such as the pulling of teeth or insertion of dental
implants, with your oncologist before you start your cancer treatment.
• Have your dentist check and adjust removable dentures, if you have them
• Tell your physician about any bleeding of the gums, pain, or unusual feeling in
your teeth or gums, or any dental infections.
Regular dental hygiene is not that different for people with cancer than it is for people
who don’t have cancer, but because cancer treatments can affect the teeth and gums, it
can be even
more important.
If you have cancer, your routine dental hygiene should include:
• Brushing your teeth and tongue after every meal and at bedtime, using a soft
toothbrush and gentle strokes.
• Gentle flossing at least once a day to remove plaque (if your gums bleed or hurt,
the area that is sore should be avoided, but the other teeth still should be flossed)
• Keeping your mouth moist by rinsing often with water (many medicines cause
“dry mouth,” which can lead to decay and other dental problems)
• Avoiding use of mouthwash that contains alcohol.
Use a mirror to check your teeth and gums daily for any changes, such as sores or
bleeding gums. If you notice a problem or a change, or experience pain in your mouth,
teeth, or jaws, report it to
your dentist or oncologist immediately.
The scope of this problem and the impact upon current bisphosphonate use in cancer
treatment remains to be assessed. With appropriate awareness and early management
serious problems from ONJ, as well as osteonecrosis in general, can be minimized. New
drugs are always being tested and maybe a drug will be found to replace bisphosphonates.
I hope this information has helped in understanding the current situation of ONJ and
bisphosphonates. Many of the conclusions or material presented is my own interpretation
or conclusion. Any mistakes in the information provided were inadvertent. Any
information that might cause a change in treatment should be discussed with your
physician or dentist prior to making such changes.
Thanks to Dr. Paul M. Lambert for the use of his extremely educational and informative
PowerPoint presentation. You can view this presentation by putting your cursor over the
link and follow the directions. Because of the size of this presentation, it may take a few
minuets to load, even with a high speed connection. Turn on your sound to listen while it
is viewed. I promise you, it is worth the wait.
PPT]
Immediate Reconstruction of Mandibular Defects
None of this information should be construed as medical/dental advice, just
recommendations.
Laurence C. Reichel, D.D.S. Copyright © 2006. All rights reserved.
SUGGESTED FORM
The following form can be used for both your physician and dentist and is not
copyrighted.
Consultation Form
Dentist’s Name: ______________________ Phone No:___________
Oncologist’s/Physician’s Name: ___________________ Phone No:___________
About My Cancer Treatment
Diagnosis (Disease & Stage): ________________________________
__________________________________________________________
Date of Diagnosis: _________________________
Past and Planned Treatments (Date): _________________________
__________________________________________________________
__________________________________________________________
❑ Surgery (Site:___________________________________________)
❑ Radiation Therapy (Site:_________________________________)
❑ Chemotherapy
Drugs:
❑ Immunotherapy or Other Biological Therapy
(Treatments:____________________________________________)
❑ Steroids ❑ Bisphosphonates
❑ Other Cancer Treatments (Please List)
__________________________________________________________
__________________________________________________________
__________________________________________________________
About My Dental Procedures
Date of Last Complete Dental Exam: _________________________
Current and Planned Treatments (Date):
__________________________________________________________
__________________________________________________________
❑ Wisdom Teeth Extraction or Other Dental Surgery
❑ Periodontics or Other Gum Surgery
❑ Braces or Other Orthodontics
❑ Root Canal Therapy ❑ Sealants
❑ Dental Implants ❑ Fillings
❑ Dentures ❑ Bridges
❑ Caps, Bonding, Veneers ❑ Tooth Contouring or Shaping
❑ Crowns ❑ Bleaching
❑ Other Dental Procedures (Please List)
_______________________________________________________
_______________________________________________________
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ADDENDUM
The following is the newest information received.
My thanks to Lewis Williams, D.D.S., M.S. (Oral & Maxillofacial Surgery Assoc., Inc.,
Honolulu, HI), for forwarding the following information to me.
The newest nomenclature in the literature for Osteonecrosis of the Jaw is
Bisphosphonate-Associated Osteonecrosis (BON).
The material was taken from an article in the Journal of the American Dental
Association: Managing the care of patients with bisphosphonate-associated
osteonecrosis, An American Academy of Oral Medicine position.
The most important item reported in this article was the statement that the
recommendations are based on expert opinion because at this time, there are no available
randomized controlled trials that support any effect on patient management and outcomes.
The oral lesions associated with bisphosphonates are similar in appearance to those of
radiation-induced osteonecrosis. Clinically, they appear as ragged oral mucosal
ulcerations that expose underlying bone and often are extremely painful. The lesions are
persistent and do not respond to conventional treatment modalities such as debridement,
antibiotic therapy or hyperbaric oxygen therapy. The presence of these lesions
complicates the oncological, nutritional and oral management of affected patients.
Bisphosphonates clear rapidly from the circulation, bind to bone mineral and concentrate
selectively in bone. If not incorporated into the bone’s mineral matrix, bisphosphonate
are eliminated in urine.
This article stated that bisphosphonates are potent inhibitors of osteoclastic activity.
During bone resorption, bisphosphonates are released from the bone and may be either
incorporated into newly formed bone or phagocytized by osteoclasts. The latter process
results in loss of the osteoclasts' ability to resorb bone and promote apoptosis or
programmed cell death. Osteoblast-induced osteoclastic bone resorption is another
important action that may be affected by bisphosphonates. Therefore, physiological bone
deposition and remodeling are severely compromised in patients receiving
bisphosphonate therapy. There is thought that bisphosphonates have antiangiogenic
properties and may be directly tumoricidal, making them and important agent in cancer
therapy.
In laymen’s terms this means that bisphosphonates are inhibitors of osteoclasts, the cells
that remove bone. Bisphosphonates are released from the bone and then may either be
incorporated into newly formed bone or are destroyed by the osteoclasts. This latter
process results in the loss of the osteoclasts' ability to resorb bone and promote cell death.
At the same time osteoblasts, those cells that make new bone, may be affected by
bisphosphonates. This shows us that the normal bone deposition and remodeling are
severely compromised in patients receiving bisphosphonate therapy. The last statement
in the paragraph above, is where I have drawn some of my conclusions regarding blood
supply loss. It states that bisphosphonates might have properties that decreases the blood
supply. With a decrease in blood supply it could be assumed that the tumor would now
die, making bisphosphonates an important agent in cancer therapy. This is a dichotomy
when we talk about treatment therapy for the prevention of osteonecrosis of the jaw.
RISK FACTORS ASSOCIATED WITH BISPHOSPHONATE-ASSOCIATED
OSTEONECROSIS
Extent of risk factor, systemic: Intravenous use of bisphosphonates; multiple myeloma;
cancer metastatic to bone such as breast, lung and prostate.
Extent of risk factor, local: Dental extractions; surgical bone manipulation; trauma from
dentures: presence of oral infection; poor oral health. (While these possibly participate in
the process, the mechanisms by which they might do so have not yet been completely
identified).
The most common clinical history associated with the process of osteonecrosis of the jaw
or (BON) is absent or delayed hardened tissue and soft tissue healing after dental
extractions.
Conclusion: prevention of bisphosphonate-associated osteonecrosis is the best approach
to management of this complication. This involves having excellent oral health prior to
using BPs. Existing protocols to manage the care of patients who will receive radiation
therapy or chemotherapy may be used until specific guidelines for BON are developed.
Cesar Migliorati, D.D.S., M.S., Ph.D.;Jeffrey Casiglia, D.M.D.; Joes Epstein,
D.M.D., M.S.D., F.R.C.D. (C.); Peter L. Jacobsen, Ph.D., Sook-Bin Woo, D.M.D.
JADA, Vol. 136, December 2005, p. 1658.
The following information was submitted by Ludwick Papaurelis.
Oral bisphosphonates fail to prevent bone loss from androgen deprivation
therapy in men with prostate cancer. 2006 ASCO Annual Meeting
Abstract No: 14643
Citation: Journal of Clinical Oncology, 2006 ASCO Annual Meeting Proceedings
Part I. Vol 24, No. 18S (June 20 Supplement), 2006: 14643
Author(s): R. Y. Lam, M. Scholz, B. Guess, T. Trilling
Abstract: Background: Androgen deprivation therapy (ADT) is a widely
administered treatment for prostate cancer. However, ADT is associated with
accelerated bone loss, osteoporosis, and fractures (Shahinian, NEJM 2005;
352:154). According to Smith et al, annual bone loss on ADT approaches 9%
(Smith, NEJM 2001;345:948), using QCT densitometry, a highly sensitive test
for the detection of osteoporosis in men. Intravenous bisphosphonates
(pamidronate, zolendronate) have been shown to prevent ADT-related bone loss
in randomized phase III trials. We performed a retrospective analysis to
determine if oral bisphosphonates effectively prevent bone loss in men
receiving ADT.
Methods: Twenty two men, ages 60-80, were placed on alendronate or
risendronate at the initiation of ADT. Baseline and follow-up bone mineral
densitometry (BMD) studies were performed with QCT densitometry. Repeat BMD
was performed 12- 27 months (mean = 17mo) after the baseline BMD. Percentage
change in bone density was annualized. Within each treatment group, the
hypothesis of no mean change from baseline was analyzed using a paired t
test.
Results: Mean baseline bone density was 122.6mg/cc. Mean follow-up bone
density was 112.7mg/cc. For the whole group, the annualized mean change in
BMD was negative 7.77%/yr (p = 0.0003). Of note, 9/22 men maintained or
gained bone density (-1.26% to +5.95%). 13/22 men lost at least 6.03%
(-6.03% to -23.2%). There was no unexpected toxicity or fractures.
Conclusions: In this retrospective study, prophylactic oral bisphosphonates
do not protect against accelerated ADT-induced bone loss in men with
prostate cancer.
This shows the apparent lack of real good scientific evidence for some of the
treatment that is being prescribed. 22 patients does not mean the data is valid or
invalid. It is a place to start new thinking, but not to throw out all of the old
thoughts.
Again we go back to how should treatment be prescribed by the physicians and
accepted by the patients. In regards to Osteonecrosis of the Jaw, I do not believe
there is a basis from which one can make an absolute decision. Physicians and
patients will have to use their best judgments in light of the scientific data. In
laymen’s terms, we just don’t know!
All of this article may be reprinted without my specific knowledge as long as there is
no financial gain to the individual(s).
Laurence C. Reichel, D.D.S. Copyright © 2006. All rights reserved.