Dr. Richard Besser on ABC News this evening revealed the results of a special medical investigation that were shocking to this female podiatrist "of a certain age" - women who have been on bisphosphanates for osteoporosis, in his report Fosamax, in particular - for over 5 years are experiencing sudden femoral fractures on slight stress.

One 48-year old female was jumping rope with children and experienced a displaced femoral fracture that resembled a fracture a person would receive in a car accident. Another woman, who had been on Fosamax for eight years, fractured both femurs, while walking down stairs. Most women had had pain in their thighs for up to a year before experiencing the breaks. Their x-rays, however, showed thick cortices.

The FDA required the pharmaceutical company to include a few words of warning in the pckage insert, warning of a potential complication. You heard me right - a few words. The FDA has not publicized the findings. Physicians from various teaching centers have begun to notice the uptick in femoral fractures though and THEY are talkiing.

Now, with all of this publicity, the FDA will have to research the issue. It owes it to the woman who take this medication and to the physicians who prescribe it.

I can just see it now!!!!....lots of attorney ads on television ......Have you been hurt by this drug? Call us at 800-BAD-DRUG!
The development of bisphosphonates was to address the medical concerns of estrogen supplementation for osteopenia. The advantages of estrogen supplementation was to delay onset of cardiovascular risks and osteopenia but may have been associated with an increase risk of breast carcinoma. The only option is to conduct a large study of non-treated patients, biphosphonate patients and estrogen supplemented patients to observe their risks for fracture, carcinoma incidence, etc. I am always leery of non-medical literature sources since other issues like smoking, alcohol intake, being overweight and inactivitiy may influence the therapeutic goals of these drugs. However, that being said, there is certainly a need for further investigation and probably should be explained to patients in that manner. The study should probably evaluate if the formation of cortical bone is at the expense of trabecular bone since these bones bear torsional vs.compressive stresses differently.

So according to Merck and Co Fosamax (alendronate sodium) is a bisphosphonate that acts as a specific inhibitor of osteoclast- mediated bone resorption. Bisphosphonates are synthetic analogs of pyrophosphate that bind to the hydroxyapatite found in bone.

Mechanism of Action
 

Animal studies have indicated the following mode of action. At the cellular level, alendronate shows preferential localization to sites of bone resorption, specifically under osteoclasts. The osteoclasts adhere normally to the bone surface but lack the ruffled border that is indicative of active resorption. Alendronate

does not interfere with osteoclast recruitment or attachment, but it does inhibit osteoclast activity. Studies in mice on the localization of radioactive [3H]alendronate in bone showed about 10-fold higher uptake on osteoclast surfaces than on osteoblast surfaces. Bones examined 6 and 49 days after [3H]alendronate administration in rats and mice, respectively, showed that normal bone was formed on top of the alendronate, which was incorporated inside the matrix. While incorporated in bone matrix, alendronate is not pharmacologically active. Thus, alendronate must be continuously administered to suppress osteoclasts on newly formed resorption surfaces. Histomorphometry in baboons and rats showed that alendronate treatment reduces bone turnover (i.e., the number of sites at which bone is remodeled). In addition, bone formation exceeds bone resorption at these remodeling sites, leading to progressive gains in bone mass.

So what this relates is that Fosamax slows down the reabsorption of bone and aids in  the "laying down" of new bone, thus increasing bone density.

ABC Living Healthy had this to say:

"We are seeing people just walking, walking down the steps, patients who are doing low-energy exercise," said Dr. Kenneth Egol, professor of orthopedic surgery at NYU Langone Medical Center. "Very unusual, the femur is one of the strongest bones in the body."

Egol said X-rays of some of his patients look more like an injury endured by a car accident than an otherwise minimal fall.

"Over the last 18 months we are seeing this more frequently," he said.

In 2008, the Food and Drug Administration reached out to the pharmaceutical company Merck about the reports of femur fractures. After 16 months, Merck added patients' reports of femur fractures to the list of possible side effects reported by patients included in the drug's package insert.

http://abcnews.go.com/GMA/OnCall/fosamax-long-term-bone-strengthening-drug-linked-fractures/story?id=10045179

And from MayoClinic.com I found interesting: 

Since 2003, there have been reports of a possible link between bisphosphonates and a rare disorder called osteonecrosis, or "death of bone," involving the jaw — a condition marked by pain, swelling, infection and exposed bone. The majority of cases of osteonecrosis of the jaw involved people with cancer who were receiving chemotherapy and had been given intravenous bisphosphonates to treat cancer that had spread (metastasized) to the bone.

http://www.mayoclinic.com/health/fosamax/AN01379

And my favorite that I found was:

Fosamax Linked to Severe Musculoskeletal Painand Osteonecrosis of the Jaw Injury - Free Lawsuit Case Review by a Fosamax Side Effects Injury Lawyer

"If you have used Fosamax and have suffered any sever muscle, joint or bone pain, or have experienced jaw injury or disease, contact Parker & Waichman, LLP to have a Fosamax lawyer review your case. Please complete the contact form on the right of this page to have your Fosamax side effects case review today. Alternatively, call 1-800-LAW-INFO (1-800-529-4636) to speak to someone immediately." 

Warms your heart, doesn't it.  Food for thought.

Karr

 

Jeff and Gino,
Your postings about the lawyers waiting not in the wings but upfront and center for the lawsuits that are bound to follow upon the unveiling of this newly reported finding brought to mind this recent, non-medical experience that my husbnd and I had when we were out for a quick fast food lunch recently.

Hungry for a legendary Texas hamburger called a Whataburger, we went in to grab one of these delicious, MI-causing burgers and fries. As we were about to leave, my husband scanned the condiment bar, among the napkins and such for a toothpick. When he couldn't find one he approached the manager behind the cash register to ask for the needed item.

"Oh, no sir, we don't provide toothpicks here at Whataburger," he replied with great seriousness. So much seriousness that my husband was compelled to ask why not?

The man answered, "It is too much of a legal liability to have toothpicks in a restaurant these days."

I'm not kidding. I mean, what were we going to do with it? Put an eye out?

What has America come to?

Interestingly, I was at a Charcot Reconstruction Symposium in Santa Fe this weekend, and the issue of Bisphosphonates came up in the management of acute charcot.  Many of the panelists at the conference were utilizing, either primarily (or secondarily through the patients PCP) this therapy to reduce the destructive osteoclastic action associated with stage I charcot.  This, in addition to appropriate offloading and stabilization has been effective in managing this challenging condition early --thus reducing the need for more aggressive reconstructive efforts in the later stages of the condition.

Can any of our online community comment on their experiences in this matter?  Unlike the duration of therapy described above which was reported to promote fragility fractures, in the management of acute charcot, the recommended bisphosphonate therapy was relatively limited....

Ryan, good point about the length of treatment and strength of dosage.

In Andrew Boulton's group in 2001, under Jude's name as the lead author,  they did a double-blind randomised controlled trial studying the effects of bisphosphonates against placebo in the Charcot population. That study that encompassed a year involved only ONE single infusion of 90 mg of pamidronate. The placebo was 90 mg of saline. 

• Bisphosphonates in the treatment of Charcot neuroarthropathy: a double-blind randomised controlled trial.
Diabetologia. 2001 Nov; 44(11):2032-7.

I can see how that ONE 90 MG DOSE is so vastly different from treatment for osteoporosis where a woman is taking a weekly dose of 70 mg of alendronate that is found in the very popular Fosamax plus D. It is a common drug that is sed to treat post-menopausal women who may require additional vitamin D supplementation.

Boulton really should be credited as one of the first people to bring the idea of bisphosphonates for the treatment of Charcot into the research arena with his 1994 article:

Diabet Med  1994 Jan-Feb;11(1):28-31. Bisphosphonates: a new treatment for diabetic Charcot neuroarthropathy?

This is an issue that is not going to go away anytime soon. The follow-up on the news today reported more cases and a response, finally, from the FDA. Basically the spokesman said "There is nothing to fear."

FDA Says No "Clear Connection" Between Bisphosphonate Use and Femur Fracture Risk

Robert Lowes

March 11, 2010 — The US Food and Drug Administration (FDA) announced yesterday that patients taking bisphosphonates should continue to do so, barring any recommendation from their physician, as the agency had no evidence to conclude that the drugs increased the risk for femur fractures just below the hip joint.

The FDA advisory came a day after ABC News cited "mounting evidence" allegedly showing that long-term use of alendronate (Fosamax, Merck), a popular bisphosphonate, or its generic versions could cause spontaneous femur fractures in some women.

"At this point, the data that FDA has reviewed have not shown a clear connection between bisphosphonate use and a risk of atypical subtrochanteric femur fractures," the FDA stated, adding that it has been working closely with outside experts to investigate the issue. The FDA began their ongoing investigation on this topic in June 2008.

The FDA notes that healthcare professionals should follow the recommendations on the drug label when prescribing bisphosphonates, and adverse events potentially associated with bisphosphonates should be reported to MedWatch, the FDA's safety information and adverse event reporting program.

 

Parker & Waichman, LLP will be so disappointed

Karr

LOL!!! Good one Jeff!

I love that, Jeff!

It seems that lately, our nightly newscast is dominated by all of these class action lawsuit lawyers and mega-firms: the  law firms that offer booklets with "family recipes" and the ad firms crooning "Have you or your family members been affected by (enter the drug or medical device that did you wrong) are creating an environment that makes patients start to analyze their own treatments, looking for any chinks that might provide an opportunity for a lawsuit.

I'm an optimist. I still believe that there are more decent attorneys out there than there are bad who help people mavigate through the morass of legalese. Heaven knows we need experts to help us with that.

But these guys and gals, the ambulance chasers of the airways, waving the red flags before potential clients, are not the good guys. At least not in our eyes.

But back to the high femoral fractures....if the Fosamax is not the culprit, I wonder what is? Any ideas??

This source comes from Medscape Medical News from the American Association of Orthopedic Surgeons 2010 Annual Meeting:

 LONG-TERM BISPHOSPHONATE USE LINKED TO ABNORMAL BONE FORMATION by Fran Lowry

3/12/2010 (New Orleans, LA) - An unusual type of bone fracture has been reported in women who have taken bisphosphonates for osteopenia and osteoporosis for more than 4 years, according to two studies reported at the AAOS 2010 Annual Meeting.
Bisphosphonates have been shown to prevent rapid loss of bone that occurs during the first years of menopause and to reduce the incidence of fracture in postmenopausal women.
However, there have been reports of "peculiar" fractures - that is low-energy femur fractures that are typically transverse or slightly oblique, diaphyseal, or subtrochanteric, with thicken cortices and a unicortical break - in patients that have been on long-term bisphosphonate treatment. This was first published in 2005 in a "semi-obscure" journal.
In a small prospective study, Dr. Lane and his colleagues obtained bone biopsies from the lateral femurs of 21 postmenopausal women with femoral fractures. Twelve of the women had been on bisphosphonate therapy from an average time of 8.5 years, and 9 had no history of bisphosphonate use. It was found that the heterogeneities of the mineral/matrix ratio were significantly reduced in the bisphosphonate group by 28% and the crystallinity of the bone was reduced by 33%. (P<.05). Dr. Lane suggested that "this suggests to us that the suppression of bone turnover, which is what bisphosphonates do long term, result in a loss of heterogeneity of the tissue properties, and this may be the contributing factor to the risk of atypical fractures that we are starting to see."
In a second study, Rosenwasser et al. at Columbia University evaluated the bone structure of 112 postmenopausal women with primary osteoporosis, 62 of whom have been taking bisphosphonates for at least 4 years and 50 in the control group taking vitamin D and calcium supplements. The results revealed that the bisphosphonate use improved structural integrity in early course of treatment, but these gains were diminished beyond the four year mark. Dr. Rosenwasser stated "it seems there is a plateau of benefit at 4 or 5 years, after that, the benefit is negated.
Both investigator told Medscape Orthopedics that women who are being treated with bisphosphonates should take a drug holiday if they have been taking them for 5 years.

WHAT DOES THIS MEAN FOR OUR PATIENTS?

First, there is a logical argument that could be made that patients under bisphosphonate therapy may require radiographic comparisons of femoral segments on an annual basis to see if any radiographic changes in the diaphyseal/subtrochanteric (trabecular) bone weakness is compensated by cortical bone thickening as an adaptive pre-cursor to stress fracture within the trabecular bone which may be more difficult to diagnose. If the patient experiences "hip pain," an MRI T2 weighted image may indicate a region of pre-stress fracture pathology within the diaphyseal/subtrochanteric spongey bone regions.

Secondly, the findings based on these two independent studies strongly suggest a possibility that the mechanisms of bone remodeling/regeneration is compromised in those patients that take bisphosphonates beyond the 4 or 5 years. This would impact on us for those patients that undergo osteotomy procedures. One may have to give consideration that in these patient populations, there may be a higher propensity of improper "scaffolding" construct in fracture/osteotomy healing and suggest the posssibility of a longer fracture healing time to be achieved. The question which is open-ended with these two studies is that there was no time frame given or suggested for this "drug holiday" in the patient population. No doubt, our pre-surgical planning may involve cessation of bisphosphonates for those patient taking them for more than 4 or 5 years if future studies uphold these two studies presented. 

http://www.medscape.com/viewarticle/718352

As per 3/11/10 FDA, has made a recommedation that it sees no clear evidence of atypical pathologic subtrochanteric/ diaphyseal femoral fractures with biphosphonates in patients with use close to ten years. However, the FDA has left the issue open pending consultation with their consultants.