How rare are the bisphosphonate class of osteoporosis drugs’ devastating side effects, which ironically include bone fractures?
Side Effects of Osteoporosis Medications Like Fosamax, Boniva, and Reclast
Below is an approximation of this video’s audio content. To see any graphs, charts, graphics, images, and quotes to which Dr. Greger may be referring, watch the above video.
Potential lack of efficacy is not the only reason why most people prescribed bisphosphonate drugs for osteoporosis like Fosamax, Actonel, Boniva, or Reclast may stop taking them within a year. There are two rare but devastating side effects—osteonecrosis of the jaw and atypical femur fractures—that contributed to around a 50 percent drop in the use of this class of drugs when they came to light. The New York Times article noting the decline explained the reasoning: “Reports of the drugs causing jawbones to rot and thighbones to snap in two have shaken many osteoporosis patients so much, that they say they would rather take their chances with the disease.”
The jaw-rot syndrome that prevents many from initiating treatment for fear of “their jaw falling off” can severely impact many aspects of quality of life, but is exceedingly rare, affecting at most one in a thousand patients treated for osteoporosis. Atypical femur fractures can occur more frequently, though––as many as one in 300 users treated for three years. They are called “atypical,” because they occur not after a fall or trauma, but just during routine activities, like walking, twisting at the waist, or even just standing still. Your femur, your thigh bone, the biggest bone in your body—just breaks in half. Too cruel an irony from a drug that’s supposed to protect your bones. This is what it looks like on x-ray. Ouch.
Bisphosphonates work by inhibiting the action of a type of bone cell called osteoclasts. Your entire skeleton is constantly being remodeled, with bone added in some spots and taken away in others to conform to changing demands. The cells that are continually laying down new bone are called osteoblasts, and the ones that chisel away old bone are the osteoclasts. It makes sense, then, that curbing the ‘clasts would prevent bone loss. But by reducing the active remodeling process, bisphosphonates can “freeze” the skeleton, allowing for the accumulation of microcracks over time, resulting in stress fractures. Other osteoporosis drugs like Denosumab (sold as “Prolia”) prevent the same formation of osteoclasts in the first place, and have been plagued by the same kinds of rare but disturbing side effects.
As with anything in life, it all comes down to risks versus benefits. How many hip fractures are prevented for every femur that snaps? It depends on your race, and how long you’re on these drugs. After five years in, white women, 36 hip fractures are prevented for every atypical femur fracture. Hispanic women only get half the benefit, about 18 to 1. And for Asian women, it’s only about five hip fractures prevented for every femur fracture caused. (The study claims it failed to accrue enough data on Black women.) At ten years of drug exposure, the ratios get worse: 16:1 for white women, 5:1 for Hispanic women, and only 1.5:1 for Asian women––meaning that the devastating fractures prevented and caused in Asian women are nearly comparable.
A nationwide survey of resident physicians found that knowledge regarding osteoporosis diagnosis and treatment was poor, with a particularly striking lack of knowledge regarding the two serious drug side effects. The good news is that after stopping the drugs, the risk of femur fracture rapidly drops by 70 percent within a year, leading to the suggestion that a drug “holiday” be considered after a few years on the drug to help mediate the risk.
Please consider volunteering to help out on the site.
- Järvinen TL, Michaëlsson K, Aspenberg P, Sievänen H. Osteoporosis: the emperor has no clothes. J Intern Med. 2015;277(6):662-673.
- Black DM, Rosen CJ. Clinical Practice. Postmenopausal Osteoporosis [published correction appears in N Engl J Med. ;374(18):1797]. N Engl J Med. 2016;374(3):254-262.
- Lems WF, Raterman HG. Critical issues and current challenges in osteoporosis and fracture prevention. An overview of unmet needs. Ther Adv Musculoskelet Dis. 2017;9(12):299-316.
- Kolata G. Fearing drugs' rare side effects, millions take their chances with osteoporosis. New York Times. June 1, 2016.
- Adler RA. Update on Rare Adverse Events from Osteoporosis Therapy and Bisphosphonate Drug Holidays. Endocrinol Metab Clin North Am. 2021;50(2):193-203.
- Murphy J, Mannion CJ. Medication-related osteonecrosis of the jaws and quality of life: review and structured analysis. Br J Oral Maxillofac Surg. 2020;58(6):619-624.
- Abbasi J. Amid Osteoporosis Treatment Crisis, Experts Suggest Addressing Patients' Bisphosphonate Concerns. JAMA. 2018;319(24):2464-2466.
- Sedgwick P. Ecological studies: advantages and disadvantages. BMJ. 2014;348:g2979.
- Gupta T, Das N, Imran S. The Prevention and Therapy of Osteoporosis: A Review on Emerging Trends from Hormonal Therapy to Synthetic Drugs to Plant-Based Bioactives. J Diet Suppl. 2019;16(6):699-713.
- Black DM, Geiger EJ, Eastell R, et al. Atypical Femur Fracture Risk versus Fragility Fracture Prevention with Bisphosphonates. N Engl J Med. 2020;383(8):743-753.
- Crandall CJ, Chen LY, Rodriguez TD, et al. Knowledge and Needs of Resident Physicians Regarding Osteoporosis: A Nationwide Survey of Residents. JBMR Plus. 2021;5(8):e10524.
- Schilcher J, Michaëlsson K, Aspenberg P. Bisphosphonate use and atypical fractures of the femoral shaft [published correction appears in N Engl J Med. 2011 Oct 20;365(16):1551] [published correction appears in N Engl J Med. 2012 Aug 9;367(6):582]. N Engl J Med. 2011;364(18):1728-1737.
- Onafowokan OO. Atypical bilateral femoral fractures: a rare adverse effect of long-term bisphosphonate use. BMJ Case Rep. 2021;14(9):e246156.
Motion graphics by Avo Media
Below is an approximation of this video’s audio content. To see any graphs, charts, graphics, images, and quotes to which Dr. Greger may be referring, watch the above video.
Potential lack of efficacy is not the only reason why most people prescribed bisphosphonate drugs for osteoporosis like Fosamax, Actonel, Boniva, or Reclast may stop taking them within a year. There are two rare but devastating side effects—osteonecrosis of the jaw and atypical femur fractures—that contributed to around a 50 percent drop in the use of this class of drugs when they came to light. The New York Times article noting the decline explained the reasoning: “Reports of the drugs causing jawbones to rot and thighbones to snap in two have shaken many osteoporosis patients so much, that they say they would rather take their chances with the disease.”
The jaw-rot syndrome that prevents many from initiating treatment for fear of “their jaw falling off” can severely impact many aspects of quality of life, but is exceedingly rare, affecting at most one in a thousand patients treated for osteoporosis. Atypical femur fractures can occur more frequently, though––as many as one in 300 users treated for three years. They are called “atypical,” because they occur not after a fall or trauma, but just during routine activities, like walking, twisting at the waist, or even just standing still. Your femur, your thigh bone, the biggest bone in your body—just breaks in half. Too cruel an irony from a drug that’s supposed to protect your bones. This is what it looks like on x-ray. Ouch.
Bisphosphonates work by inhibiting the action of a type of bone cell called osteoclasts. Your entire skeleton is constantly being remodeled, with bone added in some spots and taken away in others to conform to changing demands. The cells that are continually laying down new bone are called osteoblasts, and the ones that chisel away old bone are the osteoclasts. It makes sense, then, that curbing the ‘clasts would prevent bone loss. But by reducing the active remodeling process, bisphosphonates can “freeze” the skeleton, allowing for the accumulation of microcracks over time, resulting in stress fractures. Other osteoporosis drugs like Denosumab (sold as “Prolia”) prevent the same formation of osteoclasts in the first place, and have been plagued by the same kinds of rare but disturbing side effects.
As with anything in life, it all comes down to risks versus benefits. How many hip fractures are prevented for every femur that snaps? It depends on your race, and how long you’re on these drugs. After five years in, white women, 36 hip fractures are prevented for every atypical femur fracture. Hispanic women only get half the benefit, about 18 to 1. And for Asian women, it’s only about five hip fractures prevented for every femur fracture caused. (The study claims it failed to accrue enough data on Black women.) At ten years of drug exposure, the ratios get worse: 16:1 for white women, 5:1 for Hispanic women, and only 1.5:1 for Asian women––meaning that the devastating fractures prevented and caused in Asian women are nearly comparable.
A nationwide survey of resident physicians found that knowledge regarding osteoporosis diagnosis and treatment was poor, with a particularly striking lack of knowledge regarding the two serious drug side effects. The good news is that after stopping the drugs, the risk of femur fracture rapidly drops by 70 percent within a year, leading to the suggestion that a drug “holiday” be considered after a few years on the drug to help mediate the risk.
Please consider volunteering to help out on the site.
- Järvinen TL, Michaëlsson K, Aspenberg P, Sievänen H. Osteoporosis: the emperor has no clothes. J Intern Med. 2015;277(6):662-673.
- Black DM, Rosen CJ. Clinical Practice. Postmenopausal Osteoporosis [published correction appears in N Engl J Med. ;374(18):1797]. N Engl J Med. 2016;374(3):254-262.
- Lems WF, Raterman HG. Critical issues and current challenges in osteoporosis and fracture prevention. An overview of unmet needs. Ther Adv Musculoskelet Dis. 2017;9(12):299-316.
- Kolata G. Fearing drugs' rare side effects, millions take their chances with osteoporosis. New York Times. June 1, 2016.
- Adler RA. Update on Rare Adverse Events from Osteoporosis Therapy and Bisphosphonate Drug Holidays. Endocrinol Metab Clin North Am. 2021;50(2):193-203.
- Murphy J, Mannion CJ. Medication-related osteonecrosis of the jaws and quality of life: review and structured analysis. Br J Oral Maxillofac Surg. 2020;58(6):619-624.
- Abbasi J. Amid Osteoporosis Treatment Crisis, Experts Suggest Addressing Patients' Bisphosphonate Concerns. JAMA. 2018;319(24):2464-2466.
- Sedgwick P. Ecological studies: advantages and disadvantages. BMJ. 2014;348:g2979.
- Gupta T, Das N, Imran S. The Prevention and Therapy of Osteoporosis: A Review on Emerging Trends from Hormonal Therapy to Synthetic Drugs to Plant-Based Bioactives. J Diet Suppl. 2019;16(6):699-713.
- Black DM, Geiger EJ, Eastell R, et al. Atypical Femur Fracture Risk versus Fragility Fracture Prevention with Bisphosphonates. N Engl J Med. 2020;383(8):743-753.
- Crandall CJ, Chen LY, Rodriguez TD, et al. Knowledge and Needs of Resident Physicians Regarding Osteoporosis: A Nationwide Survey of Residents. JBMR Plus. 2021;5(8):e10524.
- Schilcher J, Michaëlsson K, Aspenberg P. Bisphosphonate use and atypical fractures of the femoral shaft [published correction appears in N Engl J Med. 2011 Oct 20;365(16):1551] [published correction appears in N Engl J Med. 2012 Aug 9;367(6):582]. N Engl J Med. 2011;364(18):1728-1737.
- Onafowokan OO. Atypical bilateral femoral fractures: a rare adverse effect of long-term bisphosphonate use. BMJ Case Rep. 2021;14(9):e246156.
Motion graphics by Avo Media
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Side Effects of Osteoporosis Medications Like Fosamax, Boniva, and Reclast
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Content URLDoctor's Note
If the drugs work, might the benefits outweigh the risks? See How Well Do Medicines Like Fosamax Work to Treat Osteoporosis?.
This video was originally part of my webinar all about osteoporosis. You can watch that full recording, which includes a great Q&A.
These stand-alone videos are already live on our site: Fall Prevention Is the Most Important Thing for Preventing Osteoporosis Bone Fractures and Acid Reflux Medicine May Cause Osteoporosis.
What about calcium supplements for bone health? See Are Calcium Supplements Safe? and Are Calcium Supplements Effective?.
And milk? See Is Milk Good for Our Bones?.
What are Three Reasons Fruits and Vegetables May Reduce Osteoporosis Risk? What about onions and tomatoes for osteoporosis? Check out the videos.
What is The Best Exercise Type and Frequency for Bone Density? Check out the video.
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