Evidence in Animals and Cell Culture

Clearly Show Benefit-Contain/Reduce Bone Mets

October 2010

Monthly infusion of pamidronate 30 mg should be the recommended dose for prevention of bone disease in patients with multiple myeloma.

Lancet Oncol. 2010 Oct 1;11(10):973-982 (ABSTRACT Shown below on separate page)


As reported at the 08 annual International Scientific Assembly of the Am College of Chest Physicians' Meeting, Philadelphia, PA (October 08)

For patients who have osteoporosis, the use of bisphosphonates appears to increase the risk of serious atrial fibrillation, according to a meta-analysis.

The risk of atrial fibrillation leading to hospitalization or death was 68% greater in patients taking alendronate (Fosamax) or zoledronic acid (Reclast, Zometa) than in those taking placebo (OR 1.66, 95% CI 1.23 to 2.24), Jennifer Miranda, M.D., of the University of Miami in Florida, reported at the American College of Chest Physicians meeting here.


Data is 'preliminary' and FDA is examining this situation.

1/08 It is now completely accepted that osteonecrosis is an unwanted effect from bisphosphonates. Some have suggested that visiting a dentist and having one's teeth and gums treated PRIOR to treatment, may be one way to reduce risk.

10/06 Although we still occasionally see a paper suggesting this is an unproven connection, it seems most accept that bisphosphonates, like so many drugs, have complications.

5/31/04 The International Myeloma Foundation has issued a special advisory on this potential complication of bisphosphonate therapy.

There is not yet any conclusive evidence that bisphosphates can cause this complication. Nevertheless, there have been enough cases reported to prompt the FDA to require that it be added to the Aredia and Zometa labeling.

People taking bisphosphonates such as Aredia and Zometa should be aware of this issue and be particular attentive to any dental problems and catious about dental procedures.

See http://www.myeloma.org/myeloma/myeloma_news.jsp?type=detail&id=1228 to read the advisory.

You can find general information about bisphosphonate therapy at http://myeloma.org/myeloma/kb_index.jsp?type=detail&id=1165

8/03 HEADS UP on Possible Complications:

A woman from SHARE (NYC-based self-help group for those w/breast or ovarian cancer) told Helen S. that she developed renal problems when she was on Aredia.

Her oncologist, thinks it was caused by the interaction of Celebrex with Aredia. Apparently two other of his patients who were also taking both drugs also developed kidney problems. The woman said her kidney function is returning to normal but the doctor is worried about her developing kidney failure and does not want her to be on a bisphosphonate again. The dosage the woman was on was 800 mg a day. You might want to post this information online

From Helen S.

There is growing evidence that bisphosphonate drugs not only reduce bone pain and prevent tumor progression in cancer patients with bony metastases, but that they can reduce the size of metastatic tumors and possibly even prevent them.

But these drugs are not yet indicated for prophylactic use outside of study protocols, even though off-label use is common.

The latest data on bisphosphonates in cancer treatment were reviewed in presentations at the International Congress on Bone Metastases (ICBM), in Paris, France.

"At the moment, all the evidence is in animal models and cell line systems, but, consistently, these have shown that most of the bisphosphonates have effects on cell proliferation in breast cancer and in myeloma," said Robert E. Coleman, MD, a consultant medical oncologist in the Department of Clinical Oncology, University of Sheffield. "The more potent agents also can induce apoptosis and affect adhesion molecules in various metastatic processes."

He said these effects are seen at 10- to 100-micro-molar concentrations. These are higher than the doses indicated for treatment of osteoporosis, the original indication for bisphosphonates, but the higher drug levels are achievable close to the bone surface where metastatic destruction occurs.

"We need to wait for the ongoing clinical studies to show whether the newest bisphosphonates really do cause apoptosis, and hopefully we will have clinical evidence of this in the next six to 12 months," Dr. Coleman said.

Meanwhile, he said, bisphosphonates should only be used prophylactically in cancer patients in clinical trials, except, of course, in those who need these compounds for concomitant osteoporosis.

"Osteoporosis is a very common co-existing condition with cancer," Dr. Coleman said. For example, older women with breast cancer and older men with prostate cancer would be at risk for osteoporosis, he said. "And younger women who have had chemotherapy would have early menopause and, therefore, similar concerns about skeletal health," he added.

The osteoporosis dose of bisphosphonate tends to be lower than that used in cancer protocols, Dr. Coleman reiterated, but he added that the bisphosphonates have very mild toxicity profiles and there is little harm in giving higher doses for osteoporosis.

"One would not be doing any harm with regard to the cancer, and the hope would be that one might be doing some good," he said.

Ann's NOTE: This relatively non-toxic treatment can be given as a preventive measure. Show these articles to your doctor. Most oncologists are willing to use chemotherapy experimentally, why not these drugs? Bisphosphonates include Aredia (pamidronate) Zolodronate, clodronate (available as oral medication in Canada and Europe), also Fosomax. I have been interested in bisphosphantes since 1995.

Thanks to Doctor's Guide for this important information.

5-Year Prevention Study Results

JCO, January 2001

Identifying Breast Cancer Patients at High Risk for Bone Mets
Intentional/Unintentional Weight Loss=Bone Loss
Osteonecrosis of the Jaws-Bisphophonate Use

J Oral Maxillofac Surg, 5/04

Avascular Necrosis of the Jaws: Risk Factor in Ca Mets
Package Insert re Osteonecrosis & Bisphosphonates
Risk of Ostenecrosis in Cancer Pts
Summary of FDA Hearing (ODAC), March 4, 2005
Ltr to Editor: The Oncologist - From an Advocate
'Reduced' Schedule to Reduce Osteonecrosis
Personal Story of Recovery from Osteonecrosis of the Jaw
#2986 Chemo Causes Loss of Bone Mineral Density

Every patient had loss, UNLESS they used Tamoxifen or bisphosphonates at the same time as chemo

Chemo Causes Rapid Bone Loss in Premenopausal Women
Essential Fatty Acids & Post-Meno Bone Loss
High Isoflavone Intake Increases BMD-Postmeno
CMF and Significant Loss in Clavicle-Pre-menopausal
Safety & Efficacy of Bisphosphonates

JCO, 7/01

Nursing Guidelines for Bisphosphonates
Osteonecrosis of the Jaws-Bisphophonate Use
Bone Size Matters as Much as Density

Study from Sweden, 7/03

Int'l Bone & Mineral Soc/Euro Calci Tissue Soc

Nutrition/Skeletal Health A Review

Older Adults and Dietary Issues
Oligosaccharides & Calcium Absorption/ Bone Resorption
Postmeno Women Ca/Potassium Inhibits Bone Resorption
Dietary Calcium Deficiency Promotes Breast Ca Tumor Growth in Bone
Gentle Vibration Improves Bone Growth

Nature, 8/8/01 via WebMD Medical News

Low Electrical Field Mat to Treat Osteoporosis
Research on Vibrating 'Gym' Equipment
Low-level, High-frequency Mechanical Signals Enhance...
Surgical Treatment for Skeletal Mets from Bca

Cancer, July 2001

FDA Approves Zoledronic Acid


Zometa Reduces Bone Complications in Multiple Myeloma & Bca
Aredia Cuts Hormone Thpy Bone Loss-Prostate

NEJM, 9/01

Bone Mass & Vit D Deficiency

Leukemia, 12/01

BMD, then Vit D Therapy
Stop High-Caffeine Foods, Add Exercise
Fruit /Veg intake is Assoc w/Increased Bone Mass
Pamidronate & 1,24(S)-dihydroxyvitamin D-2 inhibited growth of cancer cells
Laser-Induced Thermotherapy & Mets

Radiological Soc of NA

FDA Okays Radio Frequency Ablation for Bone Pain
Cryosurgery & Bone Metastases

Doctor's Guide (oral presentation) 12/01

BMT:20 yrs later Immunity Almost Normal

Blood, 212/01

Profound/Long-Lasting Negative Effects on Bone Marrow
Osteopathic Effect of Bca Chemo

Breast Cancer Res & Treatment, 6/02 Density of clavicle reduced in pre-meno pts

Clodronate & Primary Operable Bca


Adj Clodronate Improves Overall Survival: BCa w/Micro-mets
Back Exercises & Spine Fractures

J Bone,6/02

Aquatic & Land Exercises Improve Balance/Function
Site of Bone Mets & Prognosis:Prostate Ca

J Urol, 10/02

Treatment for Male Osteoporosis

Ego Seeman, MD, Australia Medscape 'Ask the Expert', 2/03

Against Teriparatide for Osteoporosis
Zinc Intake Useful in Osteoporosis: MEN
Phyto-estrogens & Osteoporosis: Safe Dose?

Br J Nutr, 6/03

Nutritional Considerations in Osteoporosis:Review

Curr Opin Rheumatol, 7/03

One-Time RTx Eases Bone Pain (NOT TWO WEEKS)

Am Soc Thera Rad & Onc, 10/03

Osteoplasty: Injecting Medical-grade Bone Cement into Tumors
Single 8 gray Treatment RTX Palliative for Bone Mets
Osteoarthritis and Glucosamine Res Ctr

LINK to latest research, information, tips to manage pain

Olive Oil & Phenols Prevent Inflammation (Ovariectomised Rats)

Br J Nutri, 7/04

Dietary Calcium vs Supplements

Am J Clin Nutr. May 2007

Magnesium & Zinc Spplmnttn - Beneficial Effects on Bone Density
Dietary Calcium to Prevent Bone Mets
Nutritional Zinc in the prevention of osteoporosis
Tea drinking  associated w/benefits on bone density in older women

Am J Clin Nutr, 2007; 86(4): 1243-7 September (?) 2007

Restore Bone - Fructooligosaccharide and Dried Plum

Journal of Medicinal Food, February 2010

30 mg Pamidronate= LESS Osteonecrosis in Multiple Myeloma

Lancet Onocol October 2010

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