Wednesday, May 23, 2007

Clinial Innovation - A Once A Year Drug to Treat Postmenopausal Osteoporosis

Why Not A Yearly Drug for Other Diseases Too?

Another Occasional Clinical Blog

“A once-yearly infusion of zoledronic acid during a 3-year period significantly reduced the risk of verterbral, hip, and other fractures.”

Dennis M. Black, PhD, and 20 co-authors, “Once-Yearly Zoledronic Acid for Treatment of Postmenopausal Osteoporosis, New England Journal of Medicine, volume 356, pages 1809-1822, 2007.

Sometimes asking “Why not?” is the essence of innovation. If the answer is ‘yes” and has elegant simplicity, it may even be a revolutionary step forward.

Such may be the case with using zoledronic acid as an annual single intravenous intravenous infusion to treat postmenopausal osteoporosis.

I don’t know who first asked “why not” about zoledronic acid as a once year dose to treat osteoporosis, but I do know:

• 21 authors in an international study found zoledronic acid reduced vertebral fractures 70%, hip fractures 41%, and non-vertebral, clinical fractures, and other fractures by 45%.
• 50% of postmenopausal women develop osteoporosis, the progression of which can now be prevented or minimized in many as one half to thirds of affected women.
• 50% of patients taking oral drugs for osteoporosis stop taking them within a year.
• Costs of medical care for osteoporosis are $18 billion yearly, the cost of which may due to failure to take oral drugs.

A Neighborly Chat

I was musing about these numbers when chatting with an 80 year widow in our town. I was telling her of the once-yearly infusion study and its astonishingly positive results. I thought she might be fascinated. She has suffered multiple vertebral fractures, has lost 6 inches in height, and wears a back support brace to prevent further fractures.

Her response surprised me, “ I don’t care what the doctors say. They just want to hand out, inject, or infuse another drug. I won’t do another damn thing until I research it on the Internet. Besides, I want to know what the drug costs. My doctor probably doesn’t know. ”

So much for baby boomers as the only demanding U.S. demographic group.

Three Concluding Thoughts

Her response led me to three thoughts.

1. An article in the April 23-30 American Medical News, “Costs vs. Compliance: Patients Often Fall to Follow Doctors’Orders Because They Can’t Afford The Medication. Talking With Patients about Money is One Step towards Changing That.” The author, Kevin O’Reilly, cited an article in the Archives of Internal Medicine, which stated 85% of patients are sometimes noncompliant, 50% skip drugs to save money, 35% didn’t discuss their noncompliance, 32% of patients suffer declining health because of noncompliance.
2. Doctors can decrease cost, in decreasing order of doctor preference, with 5.0 being top choice by:
• switching from brand –name to generic drug 4.34,
• giving drug sample 4.16,
• discontinuing drugs 4.03,
• switching to less expensive brand-name drug 3.96,
• prescribing higher dose and telling patient to split tablet 3.58,
• referring patient to drug assistance program 3.57,
• recommending over the counter substitute 3.21,
• referring patient to public aid or social worker 3.15,
• encouraging patient to see another doctor 1.86,
• doing nothing 1.47.

3. Wondering if once yearly intravenous drug infusions might be adapted to other treatments of other diseases. This is sheer speculation on my part and may be folly since I’m not acquainted with the potential pharmacologies or disease dynamics involved.

Nonetheless innocent and ignorant questions sometimes leads to stimulating more informed persons to pursuing research outside the usual mental framework to reach for answers in the sky where others have yet to venture. I’m reminded of these lyrics of a popular 2007 song by Hillary Duff.

Why not
Take a star from the sky
Why not
Spread your wings and fly
It might take a little
And it might take a lot
But…why not
Why not.


1. D. M. Black and others, Once-Yearly Zoldronic Acid for Treatment of Postmenopausal Osteoporosis, New England Journal of Medicine, volume 356, pages 1809-1822, May 3, 2007

2. J. Compston, Treatments for Osteoporosis – beyond the HORIZON . New England Journal of Medicine, volume 356. pages 1878-1879, May 3, 2007

3. Kevin O’Reilly, Costs vs Compliance, American Medical News, pages 7-8, April 23-30, 2007

4. Archives of Internal Medicine, September 25, 2006, and March 25, 2005.


Anonymous said...

Bisphosphonate drugs for Osteoporosis, like Fosamax and Actonel, are taken up by osteoclasts with resulting loss of osteoclast activity and inhibition of bone resorption, and bone remodeling.

Although DEXA scanning confirms increased bone density and studies such as the FIT suggest reduced fracture rate, Susan Ott, MD raises questions about the long term safety of bisphosphonates. Although the bisphosphonates appear to have short term benefits, she speculates that after 5 years of use, there is severe suppression of bone formation with negative effects such as microdamage and brittleness.

Spontaneous Fractures of the Mid-Femur

Jennifer P. Schneider, MD, PhD reports a 59-year old previously healthy woman on long-term alendronate. While on a subway train in New York City one morning, the train jolted, and the woman shifted all her weight to one leg, felt a bone snap, and fell to the floor, suffering a spontaneous mid -femur fracture. This is not an isolated report.

Avacular Necrosis of the Jaw

Dimitrakopoulos reports on 11 patients presenting with necrosis of the jaw, claiming this to be a new complication of bisphosphonate therapy administration, i.e. osteonecrosis of jaws. He advised clinicians to reconsider the merits of the rampant use of bisphosphonates. Osteonecrosis of the jaw is a common finding in pycnodysostosis. The bisphosphonates recreate the same clinical profile of spontaneous mid femur fractures, failure of bone healing and jaw necrosis which tormented the famous Frnch artist, Toulouse Lautrec.

For links to references and more information see my newsletter:

Fosamax, Actonel, Osteoporosis and Toulouse Lautrec's Disease

Jeffrey Dach MD

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