A must read for biphosphoate users ...CAUTION

RobinP · 07-02-2006, 07:50 PM

JAMA June 28th issue sites the following article, "Reports of Adverse Events From Bone Drugs Prompt Caution", reports 2000 cases of osteonecosis of the jaw as a rare adverse event from taking biphosphonates, MOSTLY but NOT ENTIRELY as a result of high dose intravenous use as opposed from oral use. And it appears that jaw injury, poor oral hygiene or jaw injury percipitated this adverse event in biphosphonate users.

Wished I had a link to this article, but I only have the magazine here at home.If anyone subscribes online, please post the link. Below is another resource article on the same topic.It just seems there is never free lunch with any of these meds for breast cancer patients, very discouraging and displeasing to say the least.

Fosamax and Osteonecrosis
http://www.adrugrecall.com/fosamax/osteonecrosis.html

June 2, 2006

For a decade, millions of patients have been taking seemingly safe bisphosphonates to treat painful and debilitating bone conditions for metasicized cancer, osteoporosis, and Paget's disease. While this class of drugs has been on the market for a decade, research is now culminating to reveal the serious risk of osteonecrosis of the jaw (ONJ) associated with drugs like Fosamax .

Doctors, dentists, drug makers, medical researchers, and patients are now scrambling for answers to questions, many of which have no clear answers.

What is the risk of osteonecrosis caused by Fosamax?

While most experts agree the incidence of osteonecrosis among bisphosphonate users is rare, it is unclear the extent of the risk. Experts estimate that one to ten percent of the 500,000 cancer patients taking Fosamax or a related bone drug will develop osteonecrosis. Patients using lower doses of bisphosphonates for osteoporosis appear to be at a lesser risk, though know one appears able to quantify this risk.

What is clear is that dozens of bisphosphonate users have developed this painful and debilitating condition.

How are experts and consumers reacting to this risk?

Drug makers and medical groups are rushing to provide some answers, but so far, most of these are based on hunches, not scientific evidence. Doctors have been besieged by concerns from their patients about Fosamax and osteonecrosis risks. Some dentists are refusing to provide treatment to patients taking these drugs for fear that dental work will trigger this jaw-rotting disease.

Consumer legal advocates, plaintiff's attorneys, are investigating claims of those who have developed osteonecrosis due to bisphosphonates. At least 16 lawsuits have been filed against the various makers of bisphosphonates. The FDA has required additional osteonecrosis warnings on all bisphosphonates.

Patients want to know if they should stop or continue to take these medications. Some are avoiding any type of invasive dental work, such as tooth extraction, for fear of osteonecrosis. Patients want to know if osteonecrosis can be treated and what the prognosis would be. Some people have chosen to stop taking these medications until more answers are available. Firm data is, so far, rare to non-existent.

The Story of Fosamax and Osteonecrosis

Evidence of the connection between Fosamax and Osteonecrosis first surfaced with a 2003 letter to The Journal of Oral Maxillofacial Surgery , in which Dr. Robert E. Marx of the University of Miami reported 36 cases of osteonecrosis in cancer patients taking Fosamax or related bisphosphonates.

While experts were still speculative about these risks, another study followed, confirming this first report. Dr. Salvatore Ruggiero of the Long Island Jewish Hospital also found numerous cases of osteonecrosis among patients taking bisphosphonates in his own clinical experience.

While the first doctor reports of Fosamax and Osteonecrosis appeared in 2003, Novartis, the maker of one bisphosphonate, got its first patient report of osteonecrosis in December of 2002. This eventually prompted Novartis to voluntarily add warning labels to their medication, as more reports of osteonecrosis trickled in.

In 2004, Dr. Ruggiero discovered that patients taking bisphosphonates for osteoporosis were also at risk. He and his team published are report of 63 patients with osteonecrosis – 56 had cancer and seven had osteoporosis.

A recent article in the Annals of Internal Medicine included reports of 388 cases of osteonecrosis in cancer patients, 15 cases in patients with osteoporosis, and 3 cases in patients with Paget's disease. The researchers, medical experts from Harvard, estimate that the risk of cancer patients developing osteonecrosis from bisphosphonate use is between six and ten percent. The researchers did not quantify the risk for osteoporosis patients.

Osteonecrosis treatment and prognosis

So far, medical experts have found that cutting out decaying portions of the jaw in osteonecrosis patients only serves to make the condition worse . Patients using antibiotic rinses appear to have greater success with treatment endeavors. Many patients who have developed this condition have NOT been successful with treatment and live every day with a painful and deforming condition caused by their bone medication.

Other concerns

Many doctors indicate that they have long been concerned with the recommendation that patients take bisphosphonates for life . “The pharmaceutical industry has every desire that a patient who starts on a bisphosphonate would take it for life. The bone community, of which I am a member, has always been suspicious of that viewpoint,” contends Dr. Robert Gagel of Houston's M.D. Anderson Cancer Center.

Of additional concern is the length at which Fosamax and related drugs remain in the body after terminating treatment. Bisphosphonate drugs remain in the bone tissue for years and it is unclear what risks remain after terminating treatment. Some doctors and dentists say to stop using bisphosphonates for a few months to a year before dental surgery, though these are merely educated guesses about patient safety.

The Legal Consequences

Dozens of injured patients have pursued legal action against the makers of bisphosphonate drugs, alleging that the drug makers failed to adequately warn consumers about the potential risk of osteonecrosis. Merck, the makers of Fosamax , has been named as a defendant in 15 Fosamax lawsuits so far. Roche, who manufactures Boniva , has not reported any litigation against their company. Proctor & Gamble has been named in two lawsuits, one involving Actonel and one for Didronel . Novartis has refused to disclose information about litigation.

If you or a loved one has been injured by this medication, help may be available. You may be eligible to file a legal claim to seek compensation for your losses and suffering. If you would like to learn more, please contact us to speak with a qualified and experienced attorney who can answer your questions and determine the best way to protect your interests.

PS http://jama.ama-assn.org/cgi/content...urcetype=HWCIT

above is the link to the JAMA abstract. Note this is not the complete article.

http://www.adrugrecall.com/news/fosamax-danger.html

http://www.adrugrecall.com/fosamax/osteonecrosis.html

R.B. · 07-03-2006, 02:25 AM

More possible reasons fro balancing the omega threes and sixes.

RB

Ratio of n–6 to n–3 fatty acids and bone mineral density in older adults: the Rancho Bernardo Study1,2,3

http://www.ajcn.org/cgi/content/full/81/4/934

ABSTRACT

In this cohort, an increasing ratio of dietary n–6 to n–3 fatty acids was significantly associated with lower BMD. The most consistent association was seen with the ratio of LA, the predominant n–6 fatty acid, to ALA, the predominant n–3 fatty acid, where an increasing ratio of n–6 to n–3 fatty acids was associated with lower BMD at the hip in men and in women regardless of HT status and at the lumbar spine in women not using HT. In addition, the ratio of total n–6 to n–3 fatty acids was inversely associated with BMD at the hip in both groups of women and at the lumbar spine in women not using HT. These associations were independent of other bone-related variables, such as age, lifestyle, and medication use.................

There are a plethora of biologically plausible pathways whereby PUFAs may regulate the factors involved in bone metabolism, such as prostaglandins, cytokines, insulin-like growth factor I, and calcium. Reviewers have suggested that one or a combination of these factors may have an effect on bone (5, 6, 13, 23). For example, PGE2, the major prostaglandin involved in bone metabolism, is synthesized from n–6 fatty acids, whereas n–3 fatty acids inhibit its production (1, 13). Normal or moderate concentrations of PGE2 support bone formation, whereas greater quantities promote bone resorption (5). Fatty acids are also involved in calcium metabolism. Higher n–3 fatty acid intake enhances calcium absorption, decreases calcium loss, and increases bone calcium (13, 20,23). In addition, the inhibition of cytokine production has been implicated as a potential mechanism of the favorable effects of fatty acids on bone, with higher intakes of n–3 fatty acids inhibiting the synthesis of proinflammatory cytokines, such as interleukin 6, interleukin 1, and tumor necrosis factor {alpha} (24, 25). Kettler (6) suggested that bone loss is mediated by cytokines, and n–3 fatty acid supplementation in animals and humans reduces cytokine synthesis and increases calcium absorption............

RobinP · 07-03-2006, 04:51 AM

Thanks for your contribution to this topic and again for your knowledge in the esential fatty acids.You know, when there are so many side effects from meds these days, ig biphosphonate and celebrex, amoungst others, it IS essential to use preventive diet measures and diet treatments for better health, while at the same time attempting to avoid toxic meds as much as one possibly can.

HAS ANYONE CONSIDERED STOPPING ACTONEL, FOSAMAX OR OTHER ORAL BIPHOSPONATES WITH THIS NEWS?

Barbara H. · 07-03-2006, 05:57 AM

I also want to think you for finding all these articles of about the ratio of consuming fats. I am going to order the book "Smart Fats" that you keep mentioning.
Thanks again,
Barbara H.

Becky · 07-03-2006, 08:35 AM

Since I am still getting Herceptin, I have had 2 Zometa treatments, 6 months apart since I am in the very beginning stages of osteopenia (one of the readings in the spine was slightly off). Got the bone density test 3 days after my oophorectomy (so I could take Arimidex instead of tamoxifen (which I refused to take since I am only 50% ER and PR neg)). Since I am on Herceptin until the end of Sept, there will not be another 6 month interval. At the end of November, my onc is going to want to put me on something (especially since osteoporesis and the AIs were such a hot topic this year at ASCO). I am going to have to investigate other alternatives since I have 4 more years to go on Arimidex (and it is working as I had my estradiol levels checked 2 weeks ago - I am as low as it goes so it is preventing estrogen production in me). I think if I was still on Herceptin, I would not get another Zometa in November. It makes me sick (nauseous, achey, fever) anyway. Its one thing to have side effects if you have to take it because you have bone mets and another if you are just taking it as a bone hardener (and this jaw complication could occur).

I am taking 5 extra (every 3 wk) Herceptin treatments (over the one year mark) already (to get me to two years post diagnosis - I will be at 25 months then) but that is different than this.

Have a great 4th

Kind regards

Becky

Lolly · 07-03-2006, 11:24 AM

I'm also in the early stages of osteopenia and my previous PCP started me on Fosamax early last year; a weekly oral dose of 70mg. It really made me ill and I had EXTREME muscle aches, so after a month I stopped, and we talked about maybe trying it at a later date, and at a reduced dosage of 35mg, which the studies had shown was adequate for maintaining bone density. Then, I started seeing the reports of the bisphosphonate/osteonecosis connection and will have to discuss this whole thing with my onc(who is now my PCP as I changed to his office for continuity of care after my third recurrence).

<3 Lolly

StephN · 07-03-2006, 11:35 AM

Hi everyone -
At the breast cancer symposium in December, there was more presented on this newer drug. It has been used in Europe and getting approval here. Ask about this one.

My new med onc is "the Biphosphanate Queen" - bone mets and their treatment is a special interest of hers, so I will definitely be visiting the question of continuing on Zometa and what the best alternative would be.

I have been taking Zometa for just at FOUR years now. I went into my cancer treatment 6 years ago with a healthy mouth, and have had yearly cleanings and a couple of fillings repaired since. Nothing major. Fortunately dental problems do not run in my family and even my 98-year-old grandma died with ALL of her own teeth. (The nurses at the hospital were always trying to get her to take her teeth out!)

My Zometa schedule has been lengthened over time so that for the past year I have been getting it only every 12 weeks. The information in another post about the 1/2 life being something like TEN years is interesting. I will be taking this info when I see my new med onc later in the Fall.

One thing my current med onc is sure of is that my bones are much stronger and better able to resist an onset of BC mets now. I believe bones and lung are more common than the liver invasion that happened to me. I know three women here who are having a hard time with mets to bones - they are extrememly stubborn and hard to clear up.

RobinP · 07-03-2006, 02:18 PM

Thanks for your input Steph, Lolly, RB and Becky. Becky,I agree these long term delibitating side effects concerning the jaw are just not worth the risks for simply harding the bones but as Steph pointed out IV Biphosphonates may be needed for life saving measures involving stubborn bone mets. For those with just osteopenia, like myself, there are other alternatives, vit D, calcuim, exercise, diet, and the omega3 to 6 balancing.

More from the Annals of internal medicine....

http://depts.washington.edu/pha/cpe/...753%5B1%5D.pdf

StephN · 07-03-2006, 04:00 PM

Robin -
Thanks - that article IS rather graphic with the photos and all.

However, for a stage IV BC patient, I think we have a greater percentage of chance to have disease progression than we have of getting the jaw necrosis.

In my own case, after having round after round of hard chemos for adjuvent treatment and then mets, my bone desity was quite a bit lower than the average for my age at that time. It was felt this put me at risk for further mets as well as other problems with my bones down the line.

I have not mentioned that I also took Fosamax during the 6 months of hard chemos for mets. And, even after THAT, I had the lowered bone density. Plus I did take Calcimate and try to eat dairy and other calcium rich foods.

It seems it is really hard to compensate for the bone loss that continued chemo treatment will cause. The quandry is clear, but each of us has to find out about the status of their bones, and monitor carefully to prevent too high a degree of ostopenia.

Lani · 07-05-2006, 01:51 AM

had found a couple of articles on the prevention and possible etiology of osteonecrosis of the jaw which occurs w Zometa. Studies have found that Bisphosphonates seem to have a protective effect against recurrence/growth of breast cancer (in general again, not specifically for her2 from what I remember) as well as an antiosteoclastic (discourages cells responsible for the breakdown of bone) effect, some of you may be on bisphonates for several reasons.

I am lousy with links but the first is an article in Medical Oncology 2006 Volume 23 (1), pp. 51-6 On Jaw complications associated with bisphosphonate use in patients with plasma cell dyscrasias by a group of authors from the Cleveland Clinic.

Annals of Oncology had a letter to the editor published March 8, 2006 discussing “Could the long-term persistence of law serum calcium levels and high serum parathyroid hormone levels duriing bisphosphonate treatment prediscpose metastatic breast cancer patients to undergo osteonecrosis of the jaw?” Which contains some suggestions for prevention.

I haven’t researched the topic for several month. Should I come up with more I will post.

Knowledge is ammunition.

DeborahNC · 07-05-2006, 10:01 AM

I have sent this to several friends who are on these drugs. Two have already suffered jaw breaks during dental implants, but neither reported their dentists warning them beforehand.

I'm am so very thankful my bone density results were close to perfect for a 53 y.o.; no signs of any osteo-anything!

sarah · 08-16-2006, 01:33 AM

Interesting thread. Difficult decisions.
sarah

Steph,
Since I'm in France, I've just been given Chlodronate.

heblaj01 · 08-16-2006, 06:01 PM

Clodronate has been used for over 20 years in Europe & was approved in Canada at least 5 years ago.
It is a less powerfull drug than more recent bisphosphonates such as Pamidronate,Zometa or Ibandronate for maintaining or increasing bone density in patients treated with anticancer drugs which weaken bones such as anti estrogens.
Based on personal experience with a relative treated with Femara for recurrent ER+ primary breast cancer after lumpectomy, the 6 monthly Clodronate I.V.'s (given after 2 years of Femara stopped due to bone damage) resulted in these observations:

1. Bone resorption as monitored by urine N-Telopeptide testing indicated stable condition (meaning probably: no more bone loss but no gain in bone density).
2. Monthly CEA blood marker tests started to show decreases after 3 I.V.'s.
in the absence of any anticancer treatment.

Compared to Zometa given subsequently to the same relative, there was a reduction in N-telopeptide after the first infusion indicating a probable bone density gain confirmed several months later by bone density test & CT scan showing healing of microfractures. Four monthly Zometa I.V's dropped the CEA to the same lowest level previously achieved by 6 months of Femara.
During the 18 months on Zometa alone there was no cancer progression.
Zometa was stopped (against my will) due to new regulations limiting its applcation to hypercalcemia or metastatic bone lesions.

Clodronate has been the subject of many studies in Europe in particular in Finland where some showed a long term risk reduction of remote visceral metastases.

sarah · 08-17-2006, 03:26 AM

Hebla,
Interesting info sounds like Zometa really helped. I take Clodronate as 2 pills twice a day (not an infusion) - the most difficult thing for me is that I was told to take them apart from food or taking other pills, milk just about anything but water I think so I try to take them at 10Am and between 4 and 5PM but I sometimes forget because this is often when I am away from home. I guess the habit will catch on eventually!!!
sarah