Bisphosphonate drugs are a go-to treatment for osteoporosis, but they come with a significant risk of triggering an atypical femoral fracture, especially if you use them for more than five years. Their use is controversial, particularly because bone mineral density isn’t an accurate measure of bone strength and fracture risk.
And yet, bisphosphonate drugs are the first-line therapy for the prevention and treatment of osteoporosis, with 14.7 million prescriptions written annually in the U.S.[i]
The drugs, which include alendronate (Binosto, Fosamax), ibandronate (Boniva), risedronate (Actonel, Atelvia), and zoledronic acid (Reclast, Zometa),[ii] work to inhibit bone resorption by blocking the action of osteoclasts, which are cells that degrade bone.
Osteoclasts, however, have many functions beyond bone resorption, including affecting immune responses, and their role of bone degradation serves to initiate the normal bone remodeling process. Drugs that inhibit osteoclast activity, therefore, may have “unexpected negative … effects on bone homeostasis.”[iii]
One risk that’s been widely known for at least a decade is an increased risk of atypical femoral fractures—an ironic side effect for drugs that are prescribed for “bone health.” Bisphosphonates are typically taken for three to five years,[iv] although they may be taken longer—a duration that may significantly increase your risk of suffering from a serious fracture as a result.
Risk of Serious Fracture Caused by Bone Drugs Highest After 5 Years
In a study reported at the American Society for Bone and Mineral Research (ASBMR) 2020 virtual meeting, researchers analyzed data from the Danish National Healthcare database on 1.9 million people aged 50 and over.The relative risk of atypical femoral fracture among those taking bisphosphonates was highest after five years of use. During years five to seven of taking the drugs, the relative risk of atypical femoral fracture was 35.57, which rose to 40 after seven years of use.[v]
Among the people who suffered an atypical fracture, 58 percent had used bisphosphonates, as had 19 percent of those who suffered a non-atypical fracture. For comparison, 9.9 percent of the healthy control group had used such drugs.[vi]
“Since first reported more than 10 years ago, it has become clear that atypical femoral fractures are a rare but serious complication of bisphosphonate therapy, and fear of these events discourages the use of osteoporosis medications,” Dr. Douglas Bauer of the University of California San Francisco said in a release.[vii]
The risk of atypical fracture dropped rapidly when bisphosphonate drugs were no longer used, leading the researchers to suggest that “drug holidays”—during which the drugs aren’t taken—may help lower the risk of atypical femoral fractures in some people taking the drugs.
Separate research revealed that women who took bisphosphonates for five years and then discontinued treatment had about the same risk of hip fracture as those who continued taking the drugs for another five years.[viii] This suggests taking the drugs for more than five years offers little benefit, yet may increase the risk of atypical fracture.
High Bone Mineral Density Doesn’t Equal Healthy Bones
Bisphosphonates are said to be good for bones because they increase bone mineral density, but using bone mineral density as a measure of bone health is controversial because it is not the same thing as bone quality and strength.While bone mineral density is associated with bone strength, they are not equivalent. As noted in the book “Osteoporosis in Men”:[ix]
“Bone strength is the bone’s resistance to fracture. It is difficult to quantify exactly what makes up the ’strength‘ of bone. It is related to, but not equivalent with, bone mineral density (BMD). BMD is a strong predictor of fracture, but there are also other factors, such as bone structure, bone remodeling and the newly coined term ’bone quality' to consider.”BMD is easy to measure via an x-ray device known as dual-energy x-ray absorptiometry (DXA or DEXA), but the other measures of bone strength are not so easily quantified.
What’s more, even the World Health Organization’s definitions of osteopenia and osteoporosis—which are diagnosed at 1 and 2.5 standard deviations below the average peak bone mass of a Caucasian, young adult woman—are highly suspect, as it turns the natural decrease in bone density that occurs with age into a disease that needs to be treated with drugs.
Simply put, knowing your BMD isn’t an accurate gauge of your future fracture risk and that alone shouldn’t push you into using bisphosphonate drugs with serious side effects. In fact, there are risks associated with high bone mineral density, including breast cancer.
Writing in the journal Clinical Diabetes and Endocrinology, researchers stated “skeletal biomechanics, size, shape, and ultra-structural properties are the ultimate predictors of bone strength” and detailed just some of the limitations of DXA scans and the many complexities that go into evaluating your actual bone health:[x]
- Bone size, shape, architecture, and composition are the major determinants of bone strength
- Bone composition is difficult to measure non-invasively
- Collagen crosslinking and density contribute to bone matrix strength
- The number, thickness, and connectivity of plates and rods determine trabecular bone strength
- Newly formed protein matrix and the arrangement of hydroxyapatite crystals within the matrix, along with the degree of mineralization, contribute to bone hardness and strength
- Your genetics play a role in your bone health and may determine up to 70 percent of their strength and structure
- Habitual loading, repetitive damage, diseases such as diabetes, biomechanical factors, and rate of bone turnover also influence bone health and fracture risk
- Bone size is directly related to bone strength, but DXA does not account for bone size in assessing fracture risk; bone thickness isn’t measured either
- Supplements like vitamin K and vitamin D
- Exercises such as whole-body vibration and tai chi
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References
[ii] Mayo Clinic, Osteoporosis https://www.mayoclinic.org/diseases-conditions/osteoporosis/expert-answers/osteoporosis-medications/faq-20057812
[iv] Mayo Clinic, Osteoporosis https://www.mayoclinic.org/diseases-conditions/osteoporosis/expert-answers/osteoporosis-medications/faq-20057812
[v] MedPage Today September 14, 2020 https://www.medpagetoday.com/meetingcoverage/asbmr/88606
[vi] MedPage Today September 14, 2020 https://www.medpagetoday.com/meetingcoverage/asbmr/88606
[vii] MedPage Today September 14, 2020 https://www.medpagetoday.com/meetingcoverage/asbmr/88606
[viii] JAMA Netw Open. 2020;3(12):e2025190. doi:10.1001/jamanetworkopen.2020.25190 https://jamanetwork.com/journals/jamanetworkopen/fullarticle/2773774
[ix] Osteoporosis in Men: The Effects of Gender on Skeletal Health 2010, Pages 235-241, Chapter 19 https://www.sciencedirect.com/topics/medicine-and-dentistry/bone-strength
[x] Clinical Diabetes and Endocrinology volume 4, Article number: 12 (2018) https://clindiabetesendo.biomedcentral.com/articles/10.1186/s40842-018-0062-7
