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The Three Most Dangerous Drugs for Bones

Article at-a-glance:

  • Nearly half of Americans used at least one prescription drug in the last 30 days, and three-quarters of visits to the doctor include discussion and prescription of medications.
  • One serious hidden risk of a wide range of medication is osteoporosis and fractures.
  • Glucocorticoids like prednisone are the most common iatrogenic cause of osteoporosis, meaning osteoporosis caused by the treatment for a different disease.
  • Acid-blocking drugs like proton-pump inhibitors (PPIs such as Protonix, Prilosec) increase osteoporosis and fracture risk, but since 75% of all PPI prescriptions have no appropriate indication you may not even need them.
  • Antidepressants, both SSRI’s and SNRI’s, are associated with increased fractures, which is tragic since fracturing a bone can worsen depression
Caution Sign

by Dr. John Neustadt

The numbers are sobering: Americans filled over 5.8 billion prescriptions in 2018, and over two-thirds of those were for only two illnesses—diabetes and hypertension.1 According to the CDC, nearly half of Americans used at least one prescription drug in the last 30 days, and three-quarters of visits to the doctor include discussion and prescription of medications.2 While the overuse of medications is in itself shocking and well documented,3 equally concerning is that doctors too often don’t talk to their patients about common and dangerous side effects. 

All medications come with risks for side-effects, including nausea, drowsiness, dry mouth, rashes, diarrhea, and serious complications such as liver damage or heart attacks and strokes.4,5 But too many people, including physicians, are unaware of the damaging effects common medications have on bone, which includes causing dangerous drops in bone density and increasing fracture risk.6

Fractures aren’t simply painful or disruptive to quality of life, they increase the risk of disability and death. Each year over 300,000 Americans over 65 years old are hospitalized for hip fractures; of those, three-quarters are women.7

Osteoporosis is a systemic skeletal disease, defined as low bone mass and deteriorating bone tissue, which leads to increased susceptibility to fractures. Osteoporosis is a serious and widespread condition, with 53 million adults having osteoporosis or being at risk for the disease.8 A wide range of medications can lead to drug-induced osteoporosis, including steroids, acid-blocking medication, antidepressants, anticonvulsants, blood thinners such as heparin, pre-menopausal tamoxifen use, medications for diabetes and other prescription and over the counter drugs. Here, we’ll consider three of the most commonly prescribed medications: steroids, acid-blocking medications (proton-pump inhibitors), and antidepressants.

Corticosteroids (Prednisone)

Corticosteroids, also called glucocorticoids, are powerful anti-inflammatory and immune-modulating drugs. Prednisone, methylprednisolone, betamethasone, prednisolone, and dexamethasone are examples of corticosteroids. These medications are prescribed for a wide range of conditions inflammatory and autoimmune diseases, including Lupus, Crohn’s disease, ulcerative colitis, rashes, asthma, and arthritis. They’re also now being used to treat the acute phase of coronavirus infections. 

Weighing the risks and benefits of taking medications is always important, and perhaps never more so than with this category of drugs. Corticosteroids can be lifesaving and provide relief to people who are suffering. But the effects of taking these medications are often not fully understood by patients. The US FDA-approved package insert for prednisone lists more than ten serious side effects.9 These include: 

  • Increased risk for new infections and reactivation of old infections 
  • Hiding the signs and symptoms of an active infection
  • Elevated blood pressure
  • Increased risk of bowel perforation in patients with certain GI disorders
  • Behavioral and mood disturbances, including euphoria, insomnia, mood swings, personality changes, severe depression, and psychosis
  • Can affect the eyes and contribute to cataracts, infections, and glaucoma.
  • And decreased bone density

Glucocorticoids are the most common iatrogenic osteoporosis, which is osteoporosis caused by something being used to treat another condition. Essentially, steroids wreak havoc on your bones’ healthy metabolism and strip bones of minerals and collagen. Steroids inhibit vitamin D3 synthesis and modify vitamin D effects on osteoblasts, the cells that build bone.10 Bone loss occurs most quickly in the first 6 months after starting oral steroids, and even though inhaled steroids are less risky than oral steroids, they can also cause bone loss at higher doses.11

As many as half of patients receiving steroids develop fractures, and even at low doses (prednisone dosages of 3 to 10 milligrams) fractures of the spine and hip can occur. Fractures can be asymptomatic and occur in up to 50% of patients who chronically take corticosteroids.12,13 

Unfortunately, once someone is taking steroids, bone loss occurs almost immediately, and fracture risk increases within just a few months of taking it.14 In spite of this, doctors often don’t test bone mineral density in their patients. In one study of 15,285 adults taking glucocorticoids, only one-quarter received a bone mineral density test or osteoporosis treatment within 6 months.15

Acid-blocking medications

Stomach acid is necessary for healthy digestion; however, it can also inflame and irritate the stomach and esophagus and cause heartburn, gastroesophageal reflux disease (GERD), and stomach ulcers. Proton pump inhibitors (PPI) are the most popular medications for excess stomach acid. They include drugs like Prevacid (lansoprazole), Prilosec (omeprazole), and Nexium (esomeprazole). 

PPIs are approved by the Food and Drug Administration (FDA) for 10 days for the treatment of Helicobacter pylori (H. pylori) infections, up to two weeks for heartburn, up to eight weeks for GERD, and for two to six months for ulcers.16 For individuals who develop peptic ulcers as a result of taking NSAIDs (such as ibuprofen), an eight-week course of PPIs is recommended.17 

PPI’s are so popular that nearly 15 million prescriptions a year are written in the U.S. alone.18 Their global market value is around $13 billion, and yet they are often prescribed inappropriately. A study from New Zealand found that 40% of hospital inpatients were taking proton pump inhibitors when they did not need them. Another study of a hospital in Wales found that one out of every four patients was taking a proton pump inhibitor but in only half of those patients was the indication appropriate.19 And other researchers have concluded that up to 75% of all PPI prescriptions have no appropriate indication.20 

In 2010, the FDA issued a warning about PPIs and the risk of fracture. The agency found that although over the counter doses for two weeks or less did not present a risk, individuals taking higher doses of prescription PPIs, or using PPI’s for a year or more, had a higher risk of osteoporosis and fractures.21 Indeed, research has shown that using PPI for more than a year is correlated with an increased risk of hip and vertebral (spine) fracture.22

Since that FDA warning came out, acid-blocking medications have been associated with increased risk for dementia and gastric cancer. Their dangerous effects on bones has also been widely documented. In a 2018 meta-analysis of fifteen different studies on PPI’s, there was a significant association between the medication and increased hip fracture risk.23 Those taking PPI’s having a 26% greater risk. And in postmenopausal women, who already have an increased risk of osteoporosis and fracture, taking PPI’s long-term increased the risk of spine fractures threefold.24

In another 2016 meta-analysis in which eighteen studies containing 244,109 fracture cases were evaluated, PPI use increased the risk of fractures—not just hip and spine, but other bones as well.25

A 2006 study published in the Journal of the American Medical Association, showed that fracture risk increases the longer some take the medication.26 After one year of taking a PPI, there was a 22% increase in hip fracture risk, which climbed each year: 41% increased hip fracture risk after two years, 54% increased hip fracture risk after three years, and 59% increase hip fracture risk after four years. 

Antidepressants

Despite there being effective natural strategies for depression, antidepressants are one of the most commonly prescribed drugs in the U.S. Almost 25 million adults have been on antidepressants for over two years, and another 15 million have been on the medications for at least five years.27 The most popular—selective serotonin reuptake inhibitors (SSRIs) or serotonin and norepinephrine reuptake inhibitors (SNRIs)—are widely prescribed for everything from depression to anxiety, fibromyalgia, premenstrual syndrome, and more. SSRI drugs include fluoxetine (Prozac), citalopram (Celexa), escitalopram (Lexapro), paroxetine (Paxil, Pexeva), sertraline (Zoloft).

While the fact that antidepressants reduce sex drive, inhibit orgasm, cause weight gain, headaches, dry mouth and insomnia is bad enough, most people don’t realize that they also cause osteoporosis and increase fracture risk. SSRIs harm bone in many different ways, but the damage is so unique that the increase in fracture risk can occur even without declines in bone mineral density. While the mechanisms of how serotonin harms bone are still incompletely understood, there are fifteen different types of serotonin receptors in the body. Both osteoblasts (which build bone) and osteoclasts (which break down bone) have serotonin receptors and serotonin damages the natural, healthy activities of these cells.28  

But what is clear is that these drugs are dangerous for bones. In one ten-year study of 6,645 Canadians, of whom 192 were using either SSRIs or SNRIs, the medications were was associated with an increased risk of fracture linked to fragile bones.29 In a 2020 review of 37 studies, SSRIs were significantly associated with increased fracture risk. This risk was not related to geographical location, study design, risk factors, a daily dose of medication, site of the fracture, depression, physical activity, gender, or age group.30

In a separate review of 23 studies, the researchers confirmed these conclusions. Their analysis determined that people taking SSRI medications have a 67% increased risk of fractures, regardless of the age of the person taking the medication.31 Like with PPI and corticosteroid medications, the longer someone takes the medication, the greater their risk. After just one year of taking these medications, one person will sustain a fracture for every 85 people taking the drug. After five years on the medication, for every 19 patients taking them, one will break a bone. 

In the elderly, SSRIs can also increase the risk of falls that result in hip fractures, for reasons not completely clear, but possibly involving sedation, low blood pressure, or confusion.32

What You Can Do

One of the best things you could do is talk to your doctor and see if you can reduce or stop the medications. If you’re taking medications and it’s not one of the ones discussed in this blog, ask your pharmacist if your medication puts you at risk or check out the Osteoporosis Canada website for a more comprehensive list of medications. 

If you’re at risk for osteoporosis, the US National Institutes of Health (NIH) recommends people:33

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References

1 Brooks M. US prescriptions hit new high in 2018, but opioid scripts dip. Medscape Medical News May 2019. [Report]

CDC. Therapeutic Drug Use. April, 2020. [Report]

Safer DJ. Overprescribed Medications for US Adults: Four Major Examples. J Clin Med Res. 2019;11(9):617-622. [Article]

4WebMD. Drug Side Effects Explained. 2020 [Report]

Laino C. Celebrex: Use less to lessen heart risk? WebMD 2008. [Report]

6 Panday K, Gona A, Humphrey MB. Medication-induced osteoporosis: screening and treatment strategies. Ther Adv Musculoskelet Dis. 2014 Oct;6(5):185-202. [Article]

Centers for Disease Control. Hip Fractures Among Older Adults. September 2016. [Report]

8 Wright NC, Looker AC, Saag KG, et al. The recent prevalence of osteoporosis and low bone mass in the United States based on bone mineral density at the femoral neck or lumbar spine. J Bone Miner Res. 2014;29(11):2520-2526. [Article]

9 Prednisone Label. Accessed October 2020. [Label]

10 Jehle P. Steroid-induced osteoporosis: how can it be avoided? Nephrology Dialysis Transplantation, 2003, 18(5): 861–864. [Article]

11New York State Department of Health. What You Should Know About Steroids and Osteoporosis. June 2020 [Report]

12 Canalis E, Mazziotti G, Giustina A et al. J. (2007) Glucocorticoid-induced osteoporosis: pathophysiology and therapy. Osteoporos Int 18:1319–1328 [Article]

13Vestergaard P, Rejnmark L, Mosekilde L. Fracture risk associated with different types of oral corticosteroids and effect of termination of corticosteroids on the risk of fractures. Calcif Tissue Int 2008; 82: 249–257 [Article]

14Briot K, Roux C. Glucocorticoid-induced osteoporosis. RMD Open. 2015;1(1):e000014. [Article]

15 Majumdar SR, Lix LM, Morin M et al. The disconnect between better quality of glucocorticoid-induced osteoporosis preventive care and better outcomes: a population-based cohort study. J. Rheumatol. 2013; 40(10), 1736–1741 [Article]

16 Prilosec (Omeprazole) Label. Acceessed 10/20. [Label]

17 National Institute for Health and Care Excellence. Gastrooesophageal reflux disease and dyspepsia in adults: investigation and management. NICE, London. 2010 [Report]

18Aitken M, Kleinrock M. Declining medicine use and costs: for better or worse? A review of the use of medicines in the United States. IMS Health Web. 2013. [Report]

19 Forgacs I, Loganayagam A. Overprescribing proton pump inhibitors. BMJ 2008: 336(7634):2–3 [Article]

20 Jaynes M, Kumar AB. The risks of long-term use of proton pump inhibitors: a critical review. Ther Adv Drug Saf. 2019;10:2042098618809927. [Article]

21 U.S. Food and Drug Administration. FDA Drug Safety Communication: Possible increased risk of fractures of the hip, wrist, and spine with the use of proton pump inhibitors. Update 2011. [Report].

22 Lau Y, Ahmed N. Fracture risk and bone mineral density reduction associated with proton pump inhibitors. Pharmacotherapy, 2012: 32, 67–79. [Article]

23 Hussain S, Siddiqui AN, Habib A et al. Proton pump inhibitors’ use and risk of hip fracture: a systematic review and meta-analysis. Rheumatol Int. 2018 Nov;38(11):1999-2014. [Article]

24 Roux C, Briot K, Gossec L, et al. Increase in vertebral fracture risk in postmenopausal women using omeprazole. Calcif Tissue Int 2009: 84:13–19 [Article]

25 Zhou B, Huang Y, Li H et al. Proton-pump inhibitors and risk of fractures: an update meta-analysis. Osteoporos Int. 2016 Jan;27(1):339-47. [Article]

26 Yang YX, Lewis JD, Epstein S, Metz DC. Long-term proton pump inhibitor therapy and risk of hip fracture. JAMA. 2006;296(24):2947-2953. [Article]

27 APHA. Many people taking antidepressants discover they cannot quit. April 2018. [Report]

28 Wu Q, Bencaz A, Hentz J et al. Selective serotonin reuptake inhibitor treatment and risk of fractures: a meta-analysis of cohort and case-control studies. Osteoporos Int 2012: 23:365–375. [Article]

29 Moura C, Bernatsky S, Abrahamowicz M et al. Antidepressant use and 10-year incident fracture risk: the population-based Canadian Multicentre Osteoporosis Study (CaMoS). Osteoporos Int. 2014 May;25(5):1473-81. [Article]

30 Kumar M, Bajpai R, Shaik AR et al. Alliance between selective serotonin reuptake inhibitors and fracture risk: an updated systematic review and meta-analysis. Eur J Clin Pharmacol. 2020 Oct;76(10):1373-1392. [Article]

31 Khanassov V, Hu J, Reeves D, van Marwijk H. Selective serotonin reuptake inhibitor and selective serotonin and norepinephrine reuptake inhibitor use and risk of fractures in adults: A systematic review and meta-analysis. Int J Geriatr Psychiatry. 2018;33(12):1688-1708. [Article]

32 Pacher P, Ungvari Z. Selective serotonin-reuptake inhibitor antidepressants increase the risk of falls and hip fractures in elderly people by inhibiting cardiovascular ion channels. Med Hypotheses. 2001 Oct;57(4):469-71. [Article]

33 National Institute on Aging. Osteoporosis. Accessed October 2020. [Web page]

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