Over the past few years an increasing number of my patients with low to moderate fracture risk have been prescribed a bisphosphonate. To help my patients (and readers of this blog), I have prepared this blog post with my recommended bisphosphonates osteoporosis guidelines.
Bisphosphonates Osteoporosis Guidelines
I am a Physiotherapist and I treat many patients with osteoporosis. My preferred modality is safe and effective osteoporosis physiotherapy treatment for the individual. However, most of my patients have taken or are prescribed an osteoporosis medication such as a bisphosphonate, Prolia or Forteo.
I am not philosophically against the use of pharmaceutical intervention and believe it is the appropriate course for individuals who are at an elevated risk of fracture. However, I believe it is important that all health care professionals who treat this population be familiar with the issues associated with these medications and can provide informed guidance to their patients.
A bisphosphonates osteoporosis guidelines should include a comprehensive overview of many of the questions people face when they are prescribed bisphosphonates. In this bisphosphonates osteoporosis guidelines post, I will address several questions and topics related to bisphosphonate use:
- What Are Bisphosphonates
- Use of Bisphosphonates
- When to Stop Bisphosphonates • Bisphosphonate Drug Holiday
- Long Term Bisphosphonate Use
- Bisphosphonate Femur Fracture
- Alternatives to Bisphosphonates
What Are Bisphosphonates
Let’s start the bisphosphonates osteoporosis guidelines with a definition of bisphosphonates.
Bisphosphonates are a class of drugs developed to arrest the loss of bone density. They bind to the surface of bone and reduce the effects of bone loss caused by osteoclasts (cells that erode bone). Osteoblasts (cells that build bone) can be more effective when it comes to creating bone.
How do they work? An abstract on PubMed explains in more technical detail:
At the tissue level, they decrease the rate of bone resorption and turnover, increase bone mineral density, and maintain or improve structural and material properties of bone and thereby reduce the risk of fractures.
Next let’s discuss use of bisphosphonates in the bisphosphonates osteoporosis guidelines.
As I mentioned earlier in this blog, I notice that bisphosphonates are frequently prescribed to my patients with have DEXA scores that indicate a reduction in bone density but are still at a low risk of fracture. This causes me to ask the following questions:
- Are bisphosphonates prescribed to people with low bone mass (osteopenia) when they are more appropriate for people with more advanced osteoporosis?
- Are safer and more natural ways to build bone quality — such as an osteoporosis exercise program, nutrition, safe daily activities and movements, and Vitamin D — under prescribed for people with low bone mass and osteoporosis?
- Since recent developments are calling attention to the potential problems associated with extended and early use of bisphosphonates, should we take a more cautious approach to their application?
The US Federal Drug Administration initiated a review of the long term use of bisphosphonates and provided some degree of bisphosphonates osteoporosis guidelines because of the concerns associated with their use an the elevated risks of atypical femur fractures and esophageal cancer.
Why are people with low to moderate fracture risk being prescribed an osteoporosis medication with a potential for negative side effects when osteoporosis experts are recommending bisphosphonates only for people with high fracture risk?
This question has become increasingly confusing and frustrating for people with low bone density. In a recent article in the New York Times on bisphosphonates even the physicians who are quoted disagree on appropriate bisphosphonate use.
The World Health Organization has developed a tool called FRAX to assist individuals in determining their fracture risk. This is a good starting point and you should consult this tool to determine your fracture risk.
According to pharmacist Kent MacLeod, owner of Ottawa-based Nutrichem Compounding Pharmacy and Clinic, many of the patients he is seeing are not being assess with the FRAX before being prescribed bisphosphonates. Kent recommends that patients and their physicians use the online FRAX to determine fracture risk.
- In the US, bisphosphonates should be considered for an individual whose 10 hip year fracture risk is above 3% or their major fracture risk is above 20%.
- In Canada, bisphosphonates should be considered when an individual’s major fracture risk is above 20%. For individuals whose fracture risk is moderate (10 to 20%) pharmaceutical intervention may be considered dependent upon additional risk factors.
The decision has become more complicated now that studies are showing an increased risk of femoral shaft fractures for people who take bisphosphonates for an extended period of time (I will cover this in more detail later in this article).
In addition, the FDA recently announced an updated warning on kidney impairment associated with the use of Reclast.
Bisphosphonates or Prolia
In a recent interview I had with one of Canada’s leading Osteoporosis Specialists, Dr. Jonathan Adachi, I asked him why many physicians are switching patients from bisphosphonate treatment to Prolia.
He indicated that a physician should make the switch when “patients have side effects to the bisphosphonate, when there are declines in bone mineral density (BMD) or when patients sustain a fracture on bisphosphonates suggesting treatment failure.”
When to Stop Bisphosphonates • Bisphosphonate Drug Holiday
A 2013 study (1) published in the Journal Therapeutic Advances in Musculoskeletal Disease by Diab and Watts, Bisphosphonate Drug Holiday, states that “it is difficult to find evidence to support the need for a drug holiday or to establish the effectiveness of treatment after restarting therapy.”
However, the authors do believe that “there is logic to support the following clinical scenarios.” The scenarios that Diab and Watts refer to in their bisphosphonate drug holiday study reflect the degree of risk of a fracture. Diab and Watts identify four risk levels and provide guidance for each risk level as it relates to the questions of when to stop bisphosphonates use.
Low Risk Fracture
Diab and Watts indicate that in this scenario that treatment with bisphosphonates is not needed and if a bisphosphonate has been prescribed it should be discontinued and treatment not resumed until the patient meets treatment guidelines.
Mild Risk of Fracture
Diab and Watts recommend that a bisphosphonate be used for a 3 to 5 year period and then stopped. The bisphosphonate drug holiday can continue until there has been a “significant loss” of bone mineral density.
Moderate Risk of Fracture
In their study, Diab and Watts recommend that a bisphosphonate be used for a 5 to 10 year period and then “offer a bisphosphonate drug holiday of 3 to 5 years or until there is significant loss of bone mineral density or the patient has a fracture, whichever comes first.”
High Risk of Fracture
Diab and Watts recommend “treat with bisphosphonate for 10 years, offer a ‘drug holiday’ of 1 to 2 years, until there is significant loss of bone mineral density or the patient has a fracture, whichever comes first.”
Long Term Bisphosphonate Use
What about long term bisphosphonate use and what about the possible implications? We cover this question next in the bisphosphonates osteoporosis guidelines.
On May 9, 2012 the U.S Food and Drug Administration (FDA) published (in the online version of The New England Journal of Medicine) an analysis it has completed on bisphosphonates longterm use in post-menopausal women.
According to the FDA, while bisphosphonate therapy has demonstrated “efficacy in preventing fractures in registration trials lasting 3 to 4 years … data on safety have raised concern regarding the optimal duration of use for achieving and maintaining protection against fractures”.
These safety concerns include increased risk of femoral shaft fractures, esophageal cancer and osteonecrosis of the jaw.
Long Term Bisphosphonate Use • Findings and Recommendation
The findings of this analysis were presented to a joint meeting of two FDA committees (the Advisory Committee for Reproductive Health Drugs and the Drug Safety and Risk Management Committee). The committees jointly decided that the data from the analysis “did not support a regulatory restriction on the duration of drug use”.
However, the joint committees did recommend that the labeling on bisphosphonate drugs be updated. Bisphophonate drugs now contain an “Important Limitation of Use” definition that states:
The optimal duration of use has not been determined. All patients on bisphosphonate therapy should have the need for continued therapy re-evaluated on a periodic basis.
What is the FDA Saying?
While this recommendation can appear to fall short in terms of specifics what you, as a patient of bisphosphonates, should be doing, it probably reflects the fact that the study data reviewed by the FDA was, at times, inconsistent and incomplete.
In addition, the behaviour of bisphosphonate is quite complex and can vary from person to person and from brand to brand. Since bisphosphonates are absorbed into the bone during the treatment phase, they can persist there for years – even after cessation of treatment. Further, there have been no long terms studies of the effects of bisphosphonates after cessation.
Basically, the FDA researchers state that more work and study has to be done and that individuals should consult, on a regular basis, with their health provider on what is right for them.
This regular evaluation should include an individual assessment of the risks and benefits of bisphosphonate therapy and patient preference. A good source for your health provider to use in evaluating your fracture risk is the online FRAX tool developed by the World Health Organization and the International Osteoporosis Foundation.
Clearly, the FDA and researchers are grappling with this complex issue. As someone with low bone density or osteoporosis, you want clear and easy to follow guidance on one question: Should I take a bisphosphonate?
Bisphosphonates Osteoporosis Guidelines • FDA
The New England Journal of Medicine published another article to accompany the FDA review. This article was written by a group of physicians at a number of medical institutes across the United States.
In the article, the physicians review the data and shed more light on the results. They state the following:
- Vertebral Fractures (i.e., fractures of the spine): Although evidence is limited regarding the risk of fracture with the continuation of bisphosphonate therapy beyond 3 to 5 years, data from randomized controlled trials generally suggest that the risk of vertebral fracture is reduced.
- Nonvertebral Fractures (i.e., fractures of the wrist, ribs, hip, etc): The consistent evidence of a statistically significant reduction in nonvertebral fractures with the continuation of bisphosphonates is lacking.
Further, this team provides the following guidance regarding continued use of bisphosphonates – with the caveat that these recommendations could change as more research is published.
- Patients with low bone mineral density at the femoral neck (T score below −2.5) after 3 to 5 years of treatment are at the highest risk for vertebral fractures and therefore appear to benefit most from continuation of bisphosphonates.
- Patients with an existing vertebral fracture who have a somewhat higher (although not higher than −2.0) T score for bone mineral density may also benefit from continued therapy.
- Patients with a femoral neck T score above −2.0 have a low risk of vertebral fracture and are unlikely to benefit from continued treatment.
As you can see, these physicians recommend that patients with osteoporosis and a high fracture risk should continue bisphosphonate therapy. Those with low or moderate risk of fracture will probably not see material benefit from continued use of this therapy.
Long Term Bisphosphonate Use • Recommendation
Since each individual’s medical profile is unique, I strongly encourage you to discuss this issue with your physician. Hopefully, articles like this one make you a more informed patient.
As a general rule, if you are at a high risk of fracture, continued use of bisphosphonates is probably the prudent path.
If you are at low or moderate risk of fracture, you need to weigh the risks associated with long term use of this drug (as defined earlier in this article) and the research that is showing that there is no evidence that bisphoshonates cause a significant reduction in nonvertebral fractures.
And, of course, a well designed osteoporosis exercise program is something that everyone should be following.
Expect to hear more about this debate in the coming years as researchers spend more resources examining the long term effects of this drug. Clearly, people within the FDA and researchers in the field have concerns with the continued long term use of this drug and its effectiveness when it comes to reducing fracture risk. The problem today is that there is not enough data to provide definitive guidance or change the FDA’s regulatory position with regard to this drug.
FDA Review in More Detail
The FDA article goes into a lot of detail as to what the study involved. For those of you not interested in reviewing the article but still interested in the mechanics of the study, here is a brief summary.
The FDA examined the long term effects of three bisphosphonates: Fosamax, Reclast and Actonel. One study group took the bisphosphonate and the other took a placebo. The FDA studied the effect of the various bisphosphonates on changes in the bone density in the femoral neck and the lumbar spine. They also looked the effect on vertebral fractures.
The FDA found that continued use of bisphosphonate therapy beyond five years lead to “maintenance of bone mineral density in the femoral neck and further increases in bone mineral density at the lumbar spine”.
However, the FDA review found that the “data raise[s] the question of whether continued bisphosphonate therapy imparts additional fracture-prevention benefit, relative to cessation of therapy after 5 years.” It was this finding that caused the FDA to issue the label change mentioned above.
Bisphosphonate Femur Fracture
Can you experience a femur fracture as a result of bisphosphonate treatment? We cover this question next in the bisphosphonates osteoporosis guidelines.
A study was just recently released in the Journal of the American Medical Association (JAMA) on prolonged bisphosphonate therapy and the increased risk of femoral shaft fractures in older women. Treatment for five years or longer was associated with an increased risk of femoral shaft fracture.
Atypical Fracture Bisphosphonate
Today, I’d like to talk about a recent study that was published in JAMA, the Journal of the American Medical Association. In these bisphosphonates osteoporosis guidelines they spoke about unusual fractures related to bisphosphonate use.
As a person with osteoporosis, or low bone density, if you’re on a bisphosphonate, you might be a little bit concerned about this study, so I thought I’d bring up a couple of points.
First of all, I’d like to take you into the anatomy of where these fractures are occurring.
Anatomy of Fracture
We’re going to zoom right in to the bones of the lower leg, specifically the thighbone. The thighbone is also referred to as the femur.
In individuals that have osteoporosis, most typical fractures that occur, and thousands and thousands unfortunately occur a year, most of them occur in either the neck of the femur, which is this region here.
What’s called the intertrochanteric area, which is between the two trochanters that you see, this region right there. So those are typical fractures that we see. People get admitted to hospitals all the time because of this very severe fracture.
Typical Osteoporotic Fracture
That’s a typical osteoporotic fracture, and that occurs in that part of the femur because that’s the part of the femur that has more trabecular bone, the higher proportion of trabecular bone. What the study showed when they looked at over 700 women who had actually had these unusual fractures, these unusual fractures were actually in the region of the femur below the intertrochanteric area, or also referred to as the shaft of the femur.
What’s concerning is that the shaft of the femur has a lot more cortical bone, which is usually known as really good, hard bone.
Obviously, people that are on bisphosphonates for over five years, the bisphosphonates have an effect not just on the trabecular bone, but also on the cortical bone.
Effect of Bisphosphonates
What should you do with that information? One thing is that if you are at all concerned, you should definitely talk to your doctor before you discontinue your medication.
If you are already at a high fracture risk, and you haven’t been taking a bisphosphonate for five years, chances are you might be recommended to continue your bisphosphonate. If you are at a moderate fracture risk or a low-moderate fracture risk, you should definitely have a discussion with your doctor as to whether or not a bisphosphonate is the best approach for you.
Whether you are at a low, moderate, or high fracture risk, obviously I’m coming from the arena of exercise is the best prescription, and we know that it helps build quality of bone.
But exercise is going to help you recover from a fracture as well, so you really should consider starting an exercise program, regardless of your fracture risk. I hope that this allows you to have a little more clarity on the study and on the fracture sites, and thank you for tuning in.
Now onto the next topic in the bisphosphonates osteoporosis guidelines.
Alternatives to Bisphosphonates
What are the alternatives to bisphosphonates? We cover this in the bisphosphonates osteoporosis guidelines.
Are these women receiving osteoporosis medications prescriptions because the manufacturers of bisphosphonates (pharmaceutical companies such as Merck and Novartis and others) have been promoting bisphosphonates to prevent osteoporosis?
Actonel (manufactured by Warner Chilcott) advises you and your physician to “Act Early with Actonel”. Reclast (manufactured by Novartis) states that it is “FDA approved to treat osteopenia so that it does not become osteoporosis”.
Exercise, Safe Daily Activities, Nutrition and Vitamin D
The choice to take a bisphosphonate prescription (or any other osteoporosis medication) is yours. However, you should always follow a prescribed exercise program for osteoporosis.
All individuals, regardless of fracture risk, should:
- Follow a prescribed osteoporosis exercise plan that not only includes weight bearing for bone building but also includes balance, posture, strength and flexibility exercises that reduce the chance of a fall.
- Practice perfect posture and modify how they do their household chores (known as their activities of daily living), exercise routine, yoga practice, and pilates moves that can increase their risk of fracture.
You should also determine whether you are getting adequate Vitamin D and are following a proper nutrition program for your bone health.
As I mentioned earlier in this bisphosphonates osteoporosis guidelines post, Dr Adachi indicated that many physicians are shifting their patients from bisphosphonates to Prolia. However, Prolia is not without its challenges as discussed in my post, How Long Can You Take Prolia.
The following references were used in this bisphosphonates osteoporosis guidelines post:
(1) Diab, Dima and Watts, Nelson, Bisphosphonate Drug Holiday, Therapeutic Advances in Musculoskeletal Disease, 2013 Jun.
These bisphosphonates osteoporosis guidelines have covered a wide range of questions my clients have about bisphosphonate use including when to stop bisphosphonates, the implications of long term bisphosphonate use, bisphosphonate fenmur fracture and alternatives to bisphosphonates.
For more information, check out my Osteoporosis Guidelines.