Prolia: Osteoporosis Drug May Lead to Atypical Fractures

When the Food and Drug Administration (FDA) approved the drug denosumab (PROLIA) for treating postmenopausal osteoporosis in 2010[1], it was the first time a drug of its kind was to be used for this purpose. Despite the FDA’s ultimate approval of the drug, serious safety concerns had arisen prior to an August 2009 FDA advisory committee meeting discussing issues of safety and efficacy. These safety concerns led denosumab to be categorized as Do Not Use on WorstPills.org.

Denosumab interferes with the body’s important processes of bone metabolism and immune function. One result is that its use may lead to atypical fractures (breaks in the bone that occur spontaneously with little to no trauma, unlike breaks involving major trauma, such as a fall). In November 2012, the drug company issued the first of two warning letters to health care professionals, informing them of the risks of atypical fractures with use of the drug.

http://www.worstpills.org/member/newsletter.cfm?n_id=851

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Yes, I read in the product information that Prolia can also cause atypical femur fractures the same as Bisphosphonates. I don't know if people here realize that Prolia is not much different than a Bisphosphonate in result. It does the same thing by lowering the activity of osteoclasts there by slowing the bone break down, and slowing down bone renewal.

The only difference is the mechanism that Prolia works by. Instead of coating the osteoclasts it injects antibodies to attack them. I'm not saying anyone should not take Prolia but just that many don't seem to realize that it performs the same function as Bisphosphonates, so if one is afraid of those risks then they should realize that Prolia is much the same and do some research. Of course incidental side effects are different.

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I would have to say that 90% of the people that I've seen on this forum who are taking Prolia are fully aware of it's mechanism of action, etc. Ideally, the number would be 100%.

Heck, I researched the drug for almost 1 full year prior to having an injection.

Some people here on this forum end up NOT having the injection due to fear of having an adverse side-effect (which is low statistically, but certainly possible).

Some people here on this forum end up not having the injection due to fear of having a less serious side-effect.

The chance of having an atypical femur fracture during treatment with Prolia was publicized by Amgen late last year and is displayed on each page of the Prolia website, plus the product monograph.

Yup. Both the bisphosphonates and denosumab have the same goal in common: Reducing the activity of the osteoclasts. People such as I who have post-menopausal osteoporosis are suffering from osteoclasts that are on SPEED DIAL. LOL

That's why bisphosphonates or denosumab may be prescribed ... in order to slow down that activity. They go about it differently, but yes, they both have the same goal.

Prolia is a very powerful medication and isn't given to post-menopausal women as a first line of defence against osteoporosis.

Anyway, thanks for bring up this topic again for anyone who wasn't aware of it. Yet, please for all who read this .... remember that this type of fracture is extremely rare and hopefully will not sway someone from not taking medication (be it a bisphosphonate or denosumab).

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Little Sparrow,

It's good if so many are aware. In some of the posts I've read it has appeared that some believed Prolia was a bone builder or that it was safer than Bisphosphonates. I think Prolia is no stronger of a defense than Bisphosphonates. The only reason to select one over the other would be because of individual reactions to side effects or ease of use. In other words if one couldn't tolerate the Bisphosphonates one could try Prolia to see if that was more agreeable.

As for the rareness of femur fractures I'm not sure what they mean by rare or how they could know that fully. It's also rare that anyone would get bone cancer from Forteo but yet they prescribe that for only 2 years to guard against the rare bone cancer occurring. Do we need to be afraid of taking Forteo for more than 2 years? I also wonder if Femur bones are becoming weakened but not to the point of breaking so therefore they would not be noticed as a side effect or counted. By weaken I mean that the matrix is degraded, not that the bone density is affected. I'm just saying that because the theory of the Atypical Femur fractures is that the matrix gradually becomes weakened through lack of remodeling causing the sudden fracture about at the 5 year point. Obviously a Femur doesn't just degrade in an instant at the 5 year point. It would be a gradual and unnoticeable process until the break happens, but what if one's femur didn't actually break but was very weakened resulting in less strength. I'm just saying it's a bigger issue than what is identified currently as the atypical fractures. Also with many elderly it would not be known if the person fell and broke a femur or if they the femur broke and then they fell. So it's possible this occurrence is not really rare.

As for me my latest urine tests and blood tests show I'm not losing any bone even though I'm not on a drug, so it is possible to stop bone loss without drugs. Of course we are all different I'm not saying that's the case for everyone.

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Actually I remember the lady here who thought that Prolia worked on the osteoblasts. Hopefully, we clarified things for her. She was happy with her decision so it doesn't really matter I suppose.

Atypical femur fractures. Awful sounding thing to have to suffer from, and unfortunately even people who have never taken any sort of osteoporosis medication can still have this occur. Wouldn't that be a downer if someone didn't take a medication because they were worried about having an atypical femure fracture ..... and ended up suffering from one (or two) anyway?

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Little Sparrow,

I haven't heard of the atypical fractures happening to anyone not on a drug. I thought that they had identified this as related to the drug based on biopsies of the bone. It stands to reason that anyone with extreme OP could have a sudden fracture out of weakness. No drug would stop that any way. Once a person gets to paper thin bones nothing helps except not moving.

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PamV, sadly it is possible to have an atypical femur fracture without having had taken osteoporosis meds (such as bisphosponates or denosumab). I think that you probably hit the nail on the head regarding this though. The thinner and thinner that our bones become, the more apt we would be to suffer from a fracture such as this. It's not an every day sort of occurance though. I think that there are far more hip fractures than these atypical femur fractures.

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Little Sparrow, I thought I had remembered reading studies that supports your statement about atypical femur fractures occurring in people who have never taken these drugs, so I researched a little and did find studies that showed this. Here is an abstract from one of these studies.

A controversy: linking atypical femoral fractures to bisphosphonate therapy.
Trotter CC, Pfister AK, Whited BA, Goldberg TH, Artz SA.
Source
West Virginia University School of Medicine, Charleston, WV, USA.
Abstract
Several cases have been reported of unusual spontaneous fractures with minimal trauma in the subtrochanteric and diaphyseal areas of the femur linked to long-term bisphosphonate use. After encountering three such patients, we conducted a review of published cases. The average age of these individuals were 68 years and approximately 25% had received concomitant glucocorticoids. Histomorphometric bone biopsy studies performed in some individuals have suggested that severe suppression of bone turnover may be the underlying cause; however, cause and effect has not been firmly established. Moreover, population studies have found this type of fracture rare and not increased in patients who have received bisphosphonate treatment. Physicians should continue to use bisphosphonate agents as a primary treatment for osteoporosis.
PMID: 21476471 [PubMed - indexed for MEDLINE]

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I am having difficulty in finding a calcium supplement that doesn't upset my stomach, any suggestions would be appreciated.I am 69 and had my gal bladder removed years ago so have stomach issues already.I am considering prolia as I have taken fosamax for years with little improvement.

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I take Citrical Petite twice a day with no problems

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Sometimes trying a pill not in a hard tablet, but a capsule filled with a powder helps. That way it doesn't sit in your stomach like a rock waiting to dissolve. I know doing this helped me!

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Thanks KMF,

I find this excerpt worth noting as well:

Notably, in the group taking denosumab, the incidence of hip fractures increased almost threefold during the third year as compared with the second (0.12 to 0.34 percent). In the group taking the placebo, the incidence of such fractures decreased about 0.1 percent during the same period (0.38 to 0.26 percent).

In terms of new vertebral fractures, the placebo group experienced a 1.6-fold increase during the third year (2.5 to 4.0 percent), while such fractures increased almost threefold in the denosumab group over the same period of time (0.48 to 1.4 percent).

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Zeta,

I love statistics. Although I'm not truly mathematically inclined, I still love reading statistics. Although these stats are quite small (except I'm not to crazy about the 2.5 to 4.0 percent stat), could you please give us the link to the reference material. Thanks. :)

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The link that I have is at the bottom of my post

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Notice, unless I am reading this wrong, the placebo group had almost 4 times the rate of vertebral fractures compared to the people taking prolia! Also hip fractures were less for the prolia group except in year 3 where hip fractures were slightly higher in the prolia group, but not statistically significant.

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What I find note worthy about the excerpt I posted above is that in the third year Denosumab is associated with a greater INCREASE in fracture than the placebo. If this trend were to continue that would be very bad news for folks taking Denosumab. Perhaps Amgen didn't study the drug long enough. This information raises serious questions about the safety of Prolia beyond the many adverse effects (especially high rates of infection) we already know about.

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I am not taking prolia now, but am watching it closely. I believe that what may be happening is that prolia is beneficial for a certain period of time, as are the bisphosphonates. Long term use becomes questionable. I guess time will tell! I certainly don't like taking any medication for an extended period.

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Here is an interesting scientific study on the atypical femur fracture issue. It still hasnt been determined to be a cause of bisphosphonates but cautions are now in place. I think this is why its so hard for some lawsuits to succeed or drugs to be pulled from the market. As stated here, these fractures occur and not only to those on medication and not to all those on the meds.

<<Whether this phenomenon represents “a new breed” of femoral fracture, the body of evidence supports the emergence, or at least recognition, of atypical fractures since 2005. However, fractures with striking similarities have been long seen in sufferers of rare genetic conditions, suggesting an underlying genetic role in the development of atypical fractures.
Until further research eventuates, it is also unclear whether bisphosphonate therapy is a prime culprit, one of several compounding causes, or merely an innocent bystander indicative of severe osteoporosis, in the development of atypical femur fractures. Whilst physicians should remain vigilant of the possibility of cortical insufficiency and atypical femur fractures in patients on long-term bisphosphonate therapy and accordingly investigate such patients who report unexplained thigh or groin pain, the established efficacy of bisphosphonates in the prevention of common fragility fractures in patients with osteoporosis should be borne in mind.>>

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3383496/ Ther Adv Musculoskelet Dis. 2011 December; 3(6): 301–314.

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Interesting article Chalk, thanks for posting. Just pointing out that one of the authors does receive funding from drug companies - see end of article.

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Thanks for the article Chalk. Hopefully, this will help prevent some people from being unnecessarily frightened to take a bisphosphonate medication because of the "fear" of acquiring an atypical femur fracture.

Even "I" went down that path recently ... worried about having an incomplete atypical femur fracture, when that was not the case.

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I keep hearing that atypical femur fractures are rare (and perhaps they are), yet I know five people in my circle of "friends and friendlies" who have experienced this dreadful experience. I wonder how many of these fractures are reported appropriately so that the statistics are accurate. Just a thought...not an accusation.

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