Following is a Table of Contents of this section.  If it is blue you can click on it to go directly.

Complication of ADT - a study

Side Effects - Possible 

Side Efects - A Patients Report 

Side Effects - Counter Measures

Bone Integrity during Hormonal Ablation Therapy

Osteoporosis & Men

Hormonal Therapy and Osteoporosis 

First Guidelines For Osteoporosis

OSTEONECROSIS OF THE JAW (ONJ)

Complications of ADT - A Study

Here is a study entitled "Complication of Androgen-deprivation Therapy in Men with Prostate Cancer" Bu Allne C. Chen MD and Daniel P Petrylak MD. Read the complete study by clicking on ADT Complications a PDF file.

Side Effects - Possible

To All

Here is a list of side effects of CHB (Combined Hormone Blockade)

SIDE EFFECTS OF HORMONAL THERAPY, THINGS TO READ AND COUNTER MEASURES

There are a number of papers on hormonal ablation therapy at http://www.prostate-cancer.org/eduction/eduction.html. Look for the words Anti-Androgen, Androgen Deprivation Therapy (ADT), Intermittent Hormonal Blockade (IHB or IHT), CHB, CHT or anything on advanced disease.

Possible Side Effects of Hormone-Blockade Drugs:

The side effects of hormone blockade are the same for local and advanced cancers. Some of these effects may appear early on while others may only appear after a year or more of treatment.

alcohol intolerance (with Casodex and Eulexin)

anemia

anxiety or depression

arthritic symptoms

appetite loss

blood in urine

breasts, swelling of (gynecomastia)

cholesterol and triglycerides increase

constipation

diarrhea (Eulexin)

disturbed sleep

drowsiness

dry mouth

emotional instability (esp. crying)

feet or lower legs, swelling of (peripheral edema)

flatulence

flu syndrome

hair: decrease in pubic and axillary hair; facial hair grows more slowly

headache

high blood pressure (hypertension)

hot flashes

hyperglycemia (high blood sugar )

impotence (during the period of treatment and some months after)

indigestion

itching

insomnia

liver problems

memory loss

methemoglobinemia (a crystalization in the blood)

nausea

nocturia (need to urinate frequently at night)

nervous and twitchy legs

osteoporosis

pain: abdominal, back, chest, in right side

pressure: feeling of extreme pressure in head

prickling sensation on the skin

shortness of breath

testicular atrophy (shrinking); soreness

sweating

weight gain (weight gain may continue for a while after treatment)

weight loss

The following symptoms may reflect serious problems. Contact your doctor immediately.

bluish lips, fingernails, or palms of hands

dizziness (extreme) or fainting

fatigue, weakness

pain: bone, joints, pelvic

numbness, coldness, or tingling of hands or feet

infections

rash

urinary incontinence

urinary tract infection

vomiting

weak and fast heartbeat

yellow eyes or skin

Side Efects - A Patients Report

By Lu Rudolph

In a post on July 5th to six PCa lists, I posed the question, "Are the side effects of hormone therapy really reversible?", and asked for responses from those who had been on CHT and come off. I felt it was important to get at least some anecdotal information on this because many of us (including me) have been told by docs, "Just go on hormones while deciding what to do. The side effects are reversible, so it's no big deal." Tempting if true, but is it true? I needed to know, and I've heard from a number of you that you wanted to know too.

I thank all of you who emailed me your experiences. It's a little hard to know what to do with all the anecdotal material I've accumulated. I'd really like to include extensive quotes, but that would wind up being a book, so I'll have to summarize as best I can. A place to start is with the list of acute and chronic symptoms listed in the paper by Dr. Strum (see http://prostatepointers.org/strum/ads.html ).

ACUTE (<2 mos) SYMPTOMS:

HOT FLASHES: These are apparently truly reversible, although some guys report hot flashes continuing as long as two years after stopping CHT. A few months seems more typical.

JOINT / MUSCLE PAIN: Mostly reversible, but the few who report trouble with this after coming off CHT *really* have trouble.

FATIGUE: Most guys report that this is largely reversible, but that they never quite got back to their pre-hormone level. As with many of the side effects, Herculean efforts may achieve complete reversibility (but how many Hercules are there among us?).

MEMORY DIFFICULTIES: Reversible, as far as I can tell, although a couple of guys were still having trouble up to a year later.

MOOD AND EMOTIONAL SWINGS: A goodly number of men experience a softer side of themselves on CHT which they value and hang onto afterwards. Others just return to their original "ornery" selves.

SYMPTOMATIC ANEMIA (SHORTNESS OF BREATH, CHEST PAIN, SEVERE WEAKNESS): The weakness is the one that seems to persist post CHT. Most men report that they haven't gotten back to pre-CHT levels of strength, especially upper body. This is more in the area of chronic symptoms, though.

INCREASED URINARY FREQUENCY: No mention of this, so I assume this is reversible.

IMPOTENCE AND LOSS OF LIBIDO: Libido seems to return in most cases. Potency is a little more ambiguous. Another one of the "80% of what I had" categories. But if hormone therapy is continued long enough, then some say that T may not return, in which case all bets are off.

CHRONIC (>6 mos) SYMPTOMS:

LOSS OF MUSCLE BULK AND STRENGTH: Mentioned above. Only a couple of guys report that they fully regained their strength and muscle bulk. This seems to be related to how long they were on CHT (as are a number of residual side effects). Again, Herculean efforts may prevail here.

WEIGHT GAIN AND FAT REDISTRIBUTION: This is apparently a really tough one. Most men I heard from had not lost the extra weight in the year or two after coming off CHT.

CHRONIC FATIGUE SYNDROME: No mention of this specifically, although getting back to previous levels of vitality is clearly a struggle.

GYNECOMASTIA: Nipple soreness goes away after a while, but breast enlargement does not for most men from the reports I've received. One of the most frequently expressed regrets is that they didn't have breast irradiation prior to going on hormones. And a couple of guys who did have the irradiation said "it helps", which suggests that irradiation isn't totally successful. Nipple soreness and breast enlargement seems to be a major side effect of PC-SPES.

OSTEOPOROSIS: One man reported osteoporosis to the point of broken bones within seven months on CHT, and a number mentioned osteoporosis post CHT. It appears that preventive action is in order here as recommended so strongly by Strum et al. How effective such action is at preventing permanent deterioration post CHT I couldn't judge from the responses I got.

ALZHEIMER'S - LIKE SYMPTOMS: No permanent after effects that I heard about.

INCREASED CHOLESTEROL AND TRIGLYCERIDE LEVELS: Quite a few guys reported wildly out-of-range swings while on hormones, and a couple were still having problems up to a year after coming off, but no long term permanent side effects were reported.

OTHER SIDE EFFECT

ATROPHY OF THE PENIS AND TESTICLES:

This seemed to be one of those "80% of what I had" cases. Use of VED, etc. while on hormones, and after, can apparently help, but not eliminate, the permanence of these side effects.

Personal comments:

First of all, let me say emphatically that this is *not* objective and unbiased information. The respondents were self-selected and thus not representative, and although I have tried to be even handed in my summary, I'm sure I haven't succeeded. But then I was only trying to test the hypothesis that "all side effects of CHT are reversible", and that is clearly not true. As one man put it, "The succinct answer is some side effects are obviously temporary, some apparently not."

Does that mean that CHT should be avoided? Certainly not. All but two of the people who responded to my request for information said they had no regrets and that they would do it again if necessary. Some did express regrets that they didn't know more before they went on CHT, and a number wished they had had their breasts irradiated, had exercised more, had eaten less, had used the pump more, etc. And a number were less than pleased with the cavalier attitude of their docs toward hormone therapy. But the consensus was that CHT is effective and was the best choice in their case. Clearly, the seriousness of the side effects both during hormone treatment and afterwards is individual and varies all over the map.

Hope this is helpful to some of you in your decision making process. It certainly has been for me. Again, thanks to all of you who were kind enough to share your experiences with me.

Best to all,

Lu Rudolph in Tucson

Side Effects - Counter Measures

Here is a list of some of the most frequent side effects and some of the counter-measures you can implement

Loss of libido may be helped to a small degree by deprenyl citrate though the effect is far from dramatic

Fatigue can be helped by Enada, Spes, Exercise, Nicotine, B12

Impotence is usually reversible with Viagra. Men who are sexually active before HB and plan to be after HB should artificially induce erections a couple of times a week (with viagra or via other means) or they risk developing penile atrophy that may not be reversible

Anemia is correctable with Epogen

Osteoporosis is reversible with Bisphosphonates such as Aredia, Fosamax, Actonel

Memory loss or concentration difficulties may be improved with Ginkgo

Hot flashes can be treated with Provera, Megace, Venalfaxine, Acupuncture, Clonidine

Increased urinary frequency responds to Detrol

Diarrhea from Flutamide usually requires a change of therapy to casodex

Minor elevations in liver function tests can be treated with Silymarin. Elevations above 100 require stopping the antiandrogen and switching to another.

Changes in blood sugar or blood pressure or cholesterol are treated the same way as in anyone else with the problem who is not on HB

Depression and emotional swings are improved with low dose prozac

^To Top Of Page^

Bone Integrity during Hormonal Ablation Therapy

BONE INTEGRITY

The bones are the structural framework of the body. Maintenance of bone integrity is therefore vital to good health. This is especially true in the case of prostate cancer since the osseous tissue or bone is a favored place for spread of PC. Bone metastases are a major part of the morbidity of advanced PC resulting in bone pain, anemia due to bone marrow involvement, fracture, and spinal cord and nerve root compression. Why does PC so frequently spread to the bone? One explanation may be related to the observation that bone marrow growth factors have been isolated. These growth factors showed preferential stimulation of PC while tumor cell lines not related to PC showed little or no growth response to the same substance.1

The bone is in a constant state of growth, with bone formation and resorption occurring throughout life. In our early years the balance is towards bone formation. At approximately age 25, we reach our peak bone mass. Depending on how high or low this peak bone mass is, we are at a lesser or greater risk for the development of osteoporosis as we lose bone during the aging process.

In essence then, the bone is essentially a bank account with a balance (bone density), deposits (bone growth) and withdrawals (bone loss). The factors responsible for bone deposit or formation include the endocrine environment, exercise, ample supplies of trace elements such as calcium, boron and silica, as well as induction of osteoblastic cell growth by fluoride. Vitamin D also enhances calcium absorption and may have other effects on bone formation as well. The endocrine environment is critical to build and maintain bone. It is well-established that androgens in men are stimulants towards positive bone balance the same way that estrogens favor bone growth in women. On the opposite side of the coin, factors that deplete the bone bank balance by decreasing bone growth and increasing bone loss include: lack of exercise, decreasing hormone levels, increase in osteoclast activity, deficiency in calcium and the other trace elements, and vitamin D deficiency.

Factors affecting bone growth

Exercise, Androgens, Estrogens, Adequate building elements e.g., Calcium, Boron, Silica, Vitamin D, Osteoblast stimulants e.g. fluoride, silica, vitamin D

Factors affecting bone loss

Inadequate exercise, loss of androgens, or estrogens deficiency in calcium, boron,

It has been shown that surgical or medical castration will induce osteoporosis 2, 3 This occurs immediately at a cellular level but may take months or years to manifest itself insofar as bone density changes or clinical symptoms of bone pain or bone fracture. In our experience, it is common to hear complaints of bone pain in the feet and hands within weeks of commencing androgen deprivation therapy. The measurement of bone degradation products in the urine (DPD, Pyrilinks-D, pyridinolinium cross-links) will enable us to determine if there is increased bone catabolism indicative of a negative bone balance and on-going bone loss.

Our approach toward improving bone integrity involves a graduated exercise program (read the Anti-Oxidant Revolution by Ken Cooper for such programs), the use of bisphosphonate compounds (Fosamax, Aredia or Zoledronate in increasing order of potency) that work to inhibit osteoclast cell activity, calcium supplementation in the form of calcium citrate (1000 to 1500 mg per day), synthetic vitamin D (Rocaltrol at a starting dose of 0.5 µÿg per day) and Fluoride.

Currently, the bisphosphonates commercially available are Fosamax and Aredia. The former, Fosamax, is poorly absorbed and must be taken on an empty stomach ideally 1 hour before breakfast. Aredia (also known as Pamidronate) is given intravenously thus avoiding absorption issues. Patients on such compounds must supplement their diet with calcium citrate to facilitate bone formation. We also feel that Fluoride is a key substance that will make more bone and harder bone.

We feel that bone integrity is a critical area of PC management. In future issues of Insights we will look at bone physiology in more detail. We will delve into the importance of the family of drugs called bisphosphonates that are vital to bone integrity and discuss their function to inhibit bone breakdown by blocking cells that chew up bone (osteoclasts). We will review the literature on fluoride and show how this inexpensive product can stimulate bone growth, decrease osteoporosis and bone fractures.

References

1. Chackal-Roy M, Niemeyer C, Moore M, & Zetter BR: Stimulation of human prostatic carcinoma cell growth by factors present in human bone marrow. J. Clin. Invest. 84:43-50, 1989.

2. Clarke NW, McClure J, & George NJR: The effects of orchidectomy on skeletal metabolism in metastatic prostate cancer. Scand J Urol Nephrol 27: 475-483, 1993.

Virtually all our patients are on a bisphosphonate such as Fosamax or Aredia, calcium citrate, Rocaltrol, and often fluoride.

Osteoporosis & Men

Osteoporosis, a disease that causes the skeleton to weaken and bones to break, is a significant threat to over 2.0 million men in the United States today. It affects nearly half of all people -- women and men - over the age of 75. Before age 90, 6% of all men will suffer a hip fracture as a result of osteoporosis. It is estimated that one-fifth to one-third of all hip fractures occur in men and that symptomatic vertebral fractures occur about half as often in men as in women.

Osteoporosis develops less often in men than women because men have larger skeletons, bone loss starts later and progresses more slowly, and there is no period of rapid hormonal change and accompanying rapid bone loss. However, in the last few years, it has been recognized that the problem of osteoporosis in men represents an important public health issue, particularly in light of estimates that the number of men above the age of 70 will double between 1993 and 2050.

What causes osteoporosis? >BR> Bone is constantly changing - that is, old bone is removed and replaced by new bone. During childhood, more bone is produced than removed, so the skeleton grows in both size and strength. The amount of tissue or bone mass in the skeleton reaches its maximum amount by the mid-30s. At this point, the amount of bone in the skeleton typically begins to decline slowly as removal of old bone exceeds formation of new bone.

While women lose bone mass rapidly in the years following menopause, by age 65 or 70, women and men lose bone mass at the same rate, and calcium absorption decreases in both sexes. When bone loss is excessive, bone can become fragile and break. Once bone is lost it cannot, as yet, be replaced. Bones that have weakened are more likely to fracture. Osteoporosis is a silent disease that progresses without symptoms until a fracture occurs. Fractures resulting from osteoporosis typically occur in the hip, spine, and wrist and can be permanently disabling.

What are the risk factors for men?

There are several risk factors that have been linked to osteoporosis in men:

Prolonged exposure to certain medications, such as steroids used to treat asthma, arthritis, or other diseases, anticonvulsants, certain cancer treatments, and aluminum-containing antacids.

Chronic diseases that affect the kidneys, lungs, stomach, and intestines or alter hormone levels.

Undiagnosed low levels of the sex hormone testosterone.

Unhealthy lifestyle habits (e.g., smoking, excessive alcohol use, low calcium intake, inadequate physical exercise).

Age: The older you are, the greater your risk.

Heredity.

Race: Caucasian men appear to be at greatest risk, but all men can develop this disease.

How is osteoporosis diagnosed?

Osteoporosis can be effectively treated if it is detected before significant bone loss has occurred.

A medical workup to diagnose osteoporosis will include a complete medical history, x-rays, and urine and blood tests. The doctor may also order a Bone Mineral Density Test (BMD) or bone mass measurement. A special type of x-ray, the BMD test is accurate, quick, painless, and noninvasive and can be used to detect low bone density, predict risk for future fractures, and diagnose osteoporosis. It is important to inform the doctor about risk factors for developing osteoporosis, loss of height or change in posture, a fracture, or sudden back pain.

What treatments are available?

If you have already been diagnosed with osteoporosis, your doctor may prescribe one of the medications approved by the Food and Drug Administration (FDA) for use in women with this disease. These include calcitonin by injection or nasal spray and alendronate. If your osteoporosis is the result of testosterone deficiency, your doctor may prescribe testosterone replacement therapy. For more information about which treatment is appropriate for you, talk to your doctor.

How can osteoporosis be prevented?

There have been fewer research studies on osteoporosis in men than in women. However, experts agree that all people should take the following steps to preserve their bone health.

Avoid smoking, reduce alcohol intake, and increase level of activity.

Ensure a daily calcium intake of 1000 mg/day to age 65 and 1500 mg/day over age 65.

Ensure an adequate vitamin D intake. Normally, enough vitamin D is made from exposure to as little as 10 minutes of sunlight a day. If exposure to sunlight in inadequate, dietary vitamin D intake should be at least 400 IU but not more than 800 IU/day, the amount that is found in one cup of fortified milk and most multivitamins.

Engage in a regular regimen of weight-bearing exercises where bones and muscles work against gravity. This includes walking, jogging, racquet sports, stair climbing, team sports, lifting weights, and using resistance machines. A doctor should evaluate the exercise program of anyone already diagnosed with osteoporosis to determine if twisting motions and impact activities, such as those used in golf, tennis, or basketball, need to be curtailed.

Discuss with the doctor the use of medications, such as steroids, that are known to cause bone loss.

Recognize and treat any underlying medical conditions that affect bone health.

Additional Resources

National Osteoporosis Foundation (1995). Men with osteoporosis: In their own words. Washington, DC: National Osteoporosis Foundation.

ORBD~NRC is supported by the National Institute of Arthritis and Musculoskeletal and Skin Diseases, National Institutes of Health

Osteoporosis and Related Bone Diseases~National Resource Center

1150 17th St., NW, Suite 500, Washington DC 20036

202-223-0344 or 800-624-BONE

TTY (202) 466-4315

E-Mail: orbdnrc@nof.org

http://www.nof.org

Hormonal Therapy and Osteoporosis

PROSTATE CANCER: NOTES FROM A WIFE

By Jan Manarite

March 15th, 2000 is a day I will not soon forget. It was the day my husband was diagnosed with prostate cancer. PSA at diagnosis was 7,096. For those of you who know what PSA is, I hope you were sitting down. For those of you who don’t know what PSA is, you should. You or someone you love is, or should be getting this blood test on some type of regular basis, at least yearly. The PSA is a simple test performed to check something called prostate specific antigen, a protein manufactured exclusively by the prostate gland. Although there are other benign conditions of the prostate, which can elevate results of this test, such as prostatitis and benign prostatic hyperplasia, the PSA is still the primary marker used by physicians to check for cancer of the prostate, or PC. A PSA higher than 4.0 is considered by most labs to be out of normal range and should prompt a doctor to order a free/total PSA, biopsy or other more extensive testing. So, as you can see, my husband’s disease was incredibly extensive. Throughout my months of research, I have discovered a myriad of important issues, which I have a strong desire to share with others. I am not a physician, but I have become very educated and have spent hours upon hours networking with other PC patients and their families, and learning from the experts, through publications, interactive internet, speeches, and even personal visits. The experts I refer to are primarily the physicians and staff of The Prostate Cancer Research Institute (PCRI) in California, including oncologists Dr Stephen Strum, Dr Mark Scholz, and Dr Israel Barken.

One of the most urgent issues at hand today concerns PC and osteoporosis. As we all know, osteoporosis occurs in women as a result of menopause, or the loss of her bone-building hormones, namely estrogen and progesterone. These hormones build and maintain a woman’s bone mineral density or BMD. Similarly, a man needs his testosterone (T) to ensure his BMD. Prostate cancer, when it moves outside of the prostate (or metastasizes), moves most often to bone. These cancer cells can actually cause bone resorption, or bone breakdown, which is the road to osteoporosis. In addition, if PC is diagnosed as being metastatic, or having traveled outside the prostate, the standard form of treatment is hormone therapy or hormone blockade, which I will refer to as androgen deprivation therapy (ADT). This usually consists of a monthly or 3-month shot (Zoladex or Lupron) and a daily pill (Casodex, Flutamide, or Nilandron). This treatment is designed to eliminate a man’s testosterone, which is what the PC cell feeds on, and the few other male hormones called androgens. Once again, T is a man’s bone-building hormone and without it, there is little that can be done to actually maintain BMD other than weight bearing or resistance exercise or prescription medication.

In terms of maintaining BMD, you might say that ADT is like adding insult to injury. Excessive bone resorption can cause bone pain and lead to serious fractures, too often in critical places such as the hips and compression fractures of the spine. One of the most disturbing things I have found in the course of my husband’s PC care is the lack of knowledge and understanding about the importance of maintaining a man’s BMD while on ADT. This reality jolted my heart recently when my son’s pediatrician, a well-respected doctor in our community, told me of his father-in-law who was struggling with PC. ”He just leaned on the wall one day and broke his arm!“

I am not a physician. I am the wife of a PC patient who has been fortunate enough to be able to educate herself and her family, through a series of what I consider to be miracles. But there is extensive literature and research to back up this fact and I feel compelled to write about it in the attempt to educate others who may be struggling with this same unwanted disease and this potentially serious side effect. Dr H. Logan Holtgrewe, the Health Policy Council Chairman for the American Urologic Association, had this to say about osteoporosis and ADT, “ It’s not a matter of if, but when. It takes longer to present itself in men [than women], but once it does, it really takes off. It [ADT] is a wonderful therapy that can prolong survival, but that should not come at the price of suffering the ravages of osteoporosis.“ The article goes on to say ”All men on hormone-suppressing therapies for advanced prostate cancer will eventually develop osteoporosis.“ This article was posted on 3/8/2000 and can be found on the website, www.oncology.com.

PRESCRIPTION MEDICATION FOR OSTEOPOROSIS

As mentioned above, there is little that can be done to fight bone resorption (bone breakdown) other than weight-bearing exercise and medication that needs to be administered by your doctor. Calcium supplements alone do little to fight resorption, maybe 20% according to Dr Strum of PCRI. The medications most often used are called bisphosphonates (Bpn’s). These include Aredia (given by IV), Fosomax (pill), and Actonel (pill). In a review article from the Journal of Oncology, March 1998, the following was written in conclusion, ”Eighteen randomized trials were identified……There is…evidence for their use (Bpn’s) as a part of a pain management program for bone metastases from carcinoma of the breast, lung, and prostate, and for symptomatic myleoma. The bisphosphonates appear to be well tolerated.“ In a 1997 publication, ”Cancer“, Dr Silvano Adami reports the following, ”The majority of patients with advanced prostate carcinoma [PC] have painful skeletal metastases, which are responsible for significant skeletal morbidity and disability….This provides the rationale for using bisphosphonates, which are powerful inhibitors of osteoclastic bone resorption.“ This article was endorsed by the American Cancer Society. Simply put, Aredia, Fosomax, and Actonel can help fight bone pain and osteoporosis caused by PC. The Prostate Cancer Research Institute has been using these drugs routinely and aggressively for PC patients for almost 10 years with incredible results. To support this claim even further, Dr Charles E. (”Snuffy“) Myers of the University of Virginia Cancer Center is a nationally recognized PC expert and spends much time both writing and speaking about the disease. Unfortunately, he was recently diagnosed with PC himself. When asked at the annual PCRI conference in Oct. 2000, what he was taking for his bone integrity, he responded that he gave himself 80mg of Fosomax daily for 9 months (8 times the normal dosage), and then used 10mg daily as maintenance. Perhaps one of the major obstacles preventing PC patients from receiving these necessary drugs is that they are not FDA approved for PC specifically.

The FDA requires large studies of certain lengths of time and with certain criteria. If these criteria are not met, the pharmaceutical companies cannot submit an application for approval. When Novartis Pharmaceuticals did its trials for Aredia, the main focus was on breast cancer, paget’s disease, and multiple myleoma. Prostate cancer studies lagged behind for some reason. Novartis is now studying the effects of their newest bisphophonate, Zometa, on patients with prostate cancer. FDA approval as far as Zometa and PC are concerned is still a few years away. However, and this is striking, Dr Strum states routinely that Medicare will pay for Aredia for a PC patient who has bone mets and bone pain. Although you may not have Medicare, other insurance companies tend to follow their lead. Our insurance company, Provident, has paid for Aredia for my husband since May, 2000. The cost is high, around $900 a month, and they have paid every red cent. If these issues concern you or someone you love, check with your insurance company to see what their particular policy is. Provident simply required a letter of ”medical necessity“ from our doctor. Again, check with your medical insurance company directly. Do not take anything for granted. Secondly, concerning Medicare, a bill was proposed in Washington last year by Representatives Connie Morella (R-Md.) and Shelley Berkley (D-Nev.) that would expand Medicare coverage of osteoporosis screening to men with advanced prostate cancer. I, personally, do no think Medicare has a reputation for forking out a lot of money for health care. One has to ask themselves why, then, would they be willing to pay for an expensive drug not FDA approved for PC specifically and why would Congress be proposing a bill to require Medicare to pay for osteoporosis screening for men with PC? The answer has to be that men with advanced PC are at high risk for osteoporosis.

If you or someone you love is on hormone therapy for PC, ask your oncologist about Aredia. If you have a problem affording or obtaining Aredia, ask about Fosomax. If your stomach cannot tolerate Fosomax (5-10% of people have difficulty), ask your doctor about Actonel. The last drug I would like to mention is a nasal spray, which is not a Bpn but has great results building bone. It is called Miacalcin and is also recommended by the PCRI. If you cannot seem to obtain a Bpn for some reason, ask about Miacalcin. All of these drugs need to be complemented with calcium. PCRI recommends calcium CITRATE, not calcium CARBONATE since it is better absorbed by the body. Dr Strum prescribes 500mg at dinner and 500mg at bedtime since all your bone building is done at night while you sleep. Other bone building supplements such as magnesium, boron, silica, and vitamin D should be considered by you and your doctor. For reliable information on all these issues, go to the PCRI website, www.prostate-cancer.org where you can download their Jan. 1999 issue of PCRInsights for free which addresses bone integrity in depth. Or you can call them at (310)743-2110 and ask to have a free copy mailed to you. PCRI also has staff available to answer any PC questions you may have. A third way to educate yourself on bone integrity is to call Pacific Audio Recording at 1-888-373-8273, where you can order a cassette tape of the 1999 PCRI Conference entitled ”Bone Integrity“. This tape and other conference tapes are inexpensive and sometimes better forms of communication than written material. I often listen to them while driving.

TESTING FOR OSTEOPOROSIS

The first test you should discuss with your doctor if you believe you are at risk for osteoporosis is probably a Bone Mineral Density test, again BMD test. However, there are a couple of problems with this test for men with PC. First of all, the DEXA scan is the most widely used BMD test in most, but not all, areas. My husband and I live in southwest Florida. I called everywhere from Tampa to Naples to Miami and could find nothing other than a DEXA scan. The problem with the DEXA scan is that it can sometimes show a false positive for men with PC. If you are trying to convince your oncologist that you have bone resorption due to ADT, this obviously could be a problem. In a November, 2000 ”Patient to Physician“ post, Dr Strum said it this way, ” My choice of qCT over DEXA is based on the finding of significant arthritis in the population of patients being studied (men with PC) and the incidence of calcifications in blood vessels within the aorta and femoral arteries. These changes, when present, confound the DEXA scan by giving results far better regarding bone density than really exist. I have had patients with normal T scores with DEXA have T scores showing flagrant osteoporosis with qCT.“ The qCT which he refers to, is a Quantitative Computed Tomography. Although the qCT gives a higher dosage of radiation to the patient than DEXA, the results are much more accurate. You may want to call facilities in your area and find out who, if anyone, offers a BMD test done with a qCT or other new technology other than an DEXA scan. Also, ask your doctor about the different doses of radiation and if they would be harmful to you in any way.

The second problem with a false positive is, and I have not heard of this specifically with anyone, that I fear your insurance company might not pay for an expensive drug such as Aredia if your BMD test is within normal range. I’m sure no one will argue with me if I say that insurance companies are not anxious to shell out large amounts of money for anything they don’t have to.

For this reason, my husband never did get a BMD test. Instead, we opted to use a urine test, which measures bone resorption, not BMD. There are two such tests that I know of. The first one I will refer to is a PyrilinksD or Dpd. This test is routinely used by Dr Strum and has been very informative for us about the condition of my husband’s bones. It is a first or second morning urine test (I always use first morning urine) and is done by Quest Diagnostics, the largest Lab Company in the US. We have 3 such labs in the Ft Myers area alone. I am told by our lab that the cost is $55. Check with your local lab, as the cost may be different in other areas of the country.

The procedure I follow is this: First, I get a prescription slip from my husband’s doctor, which reads ”PyrilinksD“ and a urine cup from his office lab. Next, I refrigerate the urine sample until I can drive it to the lab later that day. I am told by our local lab that it can be refrigerated for up to 12 hours, but again, check with your lab on details such as these as they may be different. Since the lab is 20 minutes away, I bring it in a cooler. The test results are faxed back to my doctor within 3 to 7 days. Normal Dpd range for a man is 5.4 or lower, according to Dr Strum. My husband’s Dpd went from 17.8 in June, 2000 to less than 2.1 in November, 2000. Since the only treatment he took for his bones was the Aredia and calcium as prescribed by Dr Strum and PCRI, I have to believe that the bisphosphonate treatment was essential for him and this is proof that the Aredia worked. The other urine test which checks bone resorption is called an Osteomark and is done by Quest also. I am told by my lab that the cost is $45, slightly cheaper than the Dpd. Our lab accidentally ran the Osteomark alongside the Dpd on 2 occasions and I can tell you from our experience that both test results were equally elevated at the same time. I also know of other PC patients who use the Osteomark to monitor their bone resorption, and unless proven otherwise, I would say that they both appear to be credible. Again, ask your doctor or lab about accuracy of these tests.

In conclusion I would like to tell you that my husband’s PSA fell to 0.65 in November of 2000 and his bone pain has gone from unbearable to almost nothing. He still does have bad days occasionally, but is very functional, including working around the house, taking out fishing charters as that is his occupation, steel sculpting in his workshop and doing what he likes best, playing catch with our 10 year old son. We thank God every day for the hundreds of people who have helped us, especially the Prostate Cancer Research Institute. We are now reluctant but willing participants in the humanity of PC, receiving help and reaching out with the desire to help others.

First Guidelines For Osteoporosis

PRESS RELEASE

FOR IMMEDIATE RELEASE

FIRST GUIDELINES FOR OSTEOPOROSIS ISSUED BY NATIONAL OSTEOPOROSIS FOUNDATION IN COLLABORATION WITH MULTIDISCIPLINARY PHYSICIAN ORGANIZATIONS

Recommendations Urge Bone Density Tests for Certain Postmenopausal Women; Women 65+

NEW YORK (November 5, 1998) - Responding to a critical need for early intervention and clear practice guidelines for physicians, the National Osteoporosis Foundation (NOF) today issued specific and aggressive recommendations for managing and preventing osteoporosis, including specific guidelines on the use of bone mineral density (BMD) tests, the single most reliable tool for assessing bone strength and osteoporosis risk. The Physician's Guide to Prevention and Treatment of Osteoporosis was developed by NOF in collaboration with ten multidisciplinary medical organizations. The guide gives specific recommendations for Caucasian women, the population at highest risk for the disease, and about whom most of the data exists.

Key Recommendations

The recommendations specify that the following people should have a BMD test: women who are 65 and older, regardless of other risk factors1; postmenopausal women who have one or more risk factors for osteoporotic fracture (besides menopause); and all postmenopausal women who have a fracture. All postmenopausal women who present with vertebral or hip fractures, two of the most common osteoporosis fracture sites, should be considered candidates for osteoporosis treatment.

"Osteoporosis is a 'silent' risk factor for fracture, just as hypertension is for stroke. Prevention, detection and treatment of osteoporosis should be a mandate of primary care, and a routine part of physicals," says NOF president Robert Lindsay, M.D., Ph.D. "Bone density tests are now widely available and should be offered to these high risk women to detect low bone density before their bones weaken and fractures occur."

Treatment Recommendations

Once patients have a BMD test, a quick, painless test, physicians should use the results to initiate therapy to reduce fracture risk and prevent further bone loss, if bone mass is low. BMD tests provide physicians with a T score expressed in standard deviations; the more negative the number, the greater the risk of fracture. Each standard deviation represents a 10-12% bone loss and a T score of -2.5 indicates osteoporosis. Women with no risk factors should begin therapy if their T score is -2 or below; and women with risk factors should begin therapy if their T score is -1.5 or below.

"Early diagnosis is important because bone loss is progressive, and by the time fractures occur the disease is advanced and the likelihood of further hip, spine or other fractures is great," explains C. Conrad Johnston Jr., M.D., chair of the Physician's Guide Development Committee and vice president of the National Osteoporosis Foundation. "Hip fractures are not only disabling, but can be life-threatening. Twenty percent of people die in the year following a hip fracture."

Universal Recommendations

All adults should: obtain adequate amount of calcium (1200 mg/day) and vitamin D (400 to 800 IU/day), engage in regular weight-bearing exercise, and avoid tobacco smoking or alcohol abuse. These universal recommendations are important to help prevent osteoporosis, and also are important for people on osteoporosis prevention or treatment therapy.

Physician's Guide Addresses Critical Need for Information

The National Osteoporosis Foundation recognizes that osteoporosis is under-diagnosed among postmenopausal women, and that many women are developing osteoporosis without the disease being recognized or treated. Based on a household survey including 1.1 million women receiving medication for osteoporosis, it is estimated that only 14 percent of American women with osteoporosis receive treatment.2 The survey also estimated that only 29 percent of women with osteoporosis are diagnosed, yet osteoporosis is the underlying cause of at least 90 percent of all hip and spine fractures in older Caucasian women.3 In another study of 100 patients well over age 60 and currently in the hospital rehabilitation unit, none had been diagnosed with osteoporosis. However, when screened for osteoporosis, 78 percent of all females and 27 percent of all males were at significant risk for fracture.4

"With the rapid advances in diagnostic technology and osteoporosis therapies, we feel there is a gap between the science and current clinical practice. This guide will help physicians assess whether symptomless women are developing this disease," explains Lindsay. Only recently has enough data accumulated for the National Osteoporosis Foundation to provide physicians with clear recommendations for using the new technologies and therapies.

"When cholesterol tests first came out, it wasn't clear what the "normal" range was considered to be on the test, or at what number you should begin treatment to prevent heart disease -- the same has been true for bone density tests," explains Lindsay. "But now we have the data, and have written a guide that specifically addresses the interpretation of bone density tests, how to apply the results in clinical practice, and when to use these tests, which can detect the disease in its earliest stages, before osteoporosis develops. If detected early, therapies can be started to prevent the disease."

"It is also important to realize that until very recently there was not much that physicians could do. They lacked treatment options for this disease and bone density tests were not widely available," says Yank Coble Jr., M.D., a trustee of the National Osteoporosis Foundation and American Medical Association representative on NOF's Interspecialty Medical Council.

The Physician's Guide to Prevention and Treatment of Osteoporosis is designed to serve as a basic reference tool for physicians. It is chiefly based on evidence from randomized, controlled clinical trials. Due to the dearth of research data on men and non-Caucasian women, the guide does not provide specific recommendations for populations other than Caucasian women. However, risk factors identified for Caucasian women can be applied to other populations on an individual basis, to aid in making therapeutic decisions. "The release of the physician's guide is an important step forward, however greatly increased funding for medical research through the National Institutes of Health is needed, especially for research on men and non-Caucasian women, so that we can make specific recommendations for everyone," says Sandra C. Raymond, executive director of the National Osteoporosis Foundation.

Collaborative Effort

NOF scientists created a core scientific team of major physician groups, the Interspecialty Medical Council, to join NOF in developing a guide with specific recommendations to help all physicians in their everyday practice. "Many different kinds of physicians and health professionals see people at risk for osteoporosis," says Dr. Francis J. Bonner Jr., M.D., chair of NOF's Interspecialty Medical Council. "In creating this physician's guide, all of these specialty groups came together for the first time to agree upon recommendations that will help physicians determine who is considered to be high risk, when to use diagnostic tests, and what actions to take based on the results." The guide was developed by NOF in collaboration with the American Academy of Physical Medicine and Rehabilitation; the American Association of Clinical Endocrinologists; the American Academy of Orthopaedic Surgeons; the American College of Obstetricians and Gynecologists; the American College of Radiology; the American College of Rheumatology; the American Geriatrics Society; the American Medical Association; the American Society for Bone and Mineral Research; and The Endocrine Society.

Osteoporosis -- a disease that gradually weakens bones and often leads to painful and debilitating fractures -- is a major public health threat for 28 million Americans, 80 percent of whom are women. Osteoporosis causes 1.5 million fractures annually and costs this country nearly $14 billion each year.

With more than 200,000 members, the National Osteoporosis Foundation is the only nonprofit, voluntary health organization dedicated to reducing the widespread prevalence of osteoporosis through programs of research, education, and advocacy.

1. Risk factors for osteoporotic fracture include: personal history of fracture as an adult; history of fracture in a first-degree relative; Caucasian race; advanced age; female sex; dementia; poor health/frailty; cigarette smoking; low body weight; estrogen deficiency (past menopause, early menopause or bilateral ovariectomy, prolonged (>1 yr.) amenorrhea); low calcium intake (lifelong); alcoholism; impaired eyesight despite adequate correction; recurrent falls; and inadequate physical activity.

2. The 1997 Migliara/Kaplan Health Conditions Study.

3. Melton LJIII, et al. Fractures Attributable to Osteoporosis: Report from the National Osteoporosis Foundation. Bone Min Res, Vol. 12, No. 1, 1997.

4. Fitzsimmons, Amy et al. Failure To Diagnose Osteoporosis. Am. J. Phys. Med. Rehab. Vol. 47, No. 3, May/June 1995.

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 2-4 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)

_____________________________________________________

_____________________________________________________

REFERENCES

1. For the dental patient: oral care for cancer patients. Am Dent Assoc. 2002 133(7):1014.

2. National Cancer Institute. Oral complications of chemotherapy and head/neck radiation

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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.