by Dr. John Neustadt

The Rx Dilemma

More people than ever are taking prescription medications in the United States. A study from the Mayo Clinic revealed that 70% of Americans are on one prescription drug, more than 50% take two medications and 20% are on at least 5 prescriptions. Every year more than $450 billion are spent on medications in the US alone.

While medications may be necessary, they also come with risks. Many side effects are mild, such as getting a rash or nausea. But side effects can also be serious and life-threatening. There’s a long list of medications that damage bone and cause osteoporosis and fractures.

While glucocorticoids such as prednisone are most commonly associated with drug-induced osteoporosis, the use of several other medications increase the risk of significant bone loss and fracture. These medications include acid-blockers, antidepressants, anticonvulsants, medroxyprogesterone acetate (MPA), hormone deprivation therapy and chemotherapies.

Osteoporosis and osteoporosis fractures are surprisingly common. One in 3 postmenopausal women in the United States has a diagnosis of osteoporosis, and 1 in 2 women will experience an osteoporosis fracture in her lifetime. The numbers are lower for men, but the lifetime risk for an osteoporosis fracture in men is still as high as 1 in 5. Given that research shows 50% of women and 20% of men will get an osteoporosis fracture during their life, it’s important to know if your prescriptions are putting you at risk.

Medication-induced osteoporosis is called secondary osteoporosis because it’s caused by factors other than the normal aging process. When osteoporosis occurs as people get older without any other known risk factors other than aging, it’s called primary osteoporosis. In postmenopausal women diagnosed with osteoporosis, 70% have primary osteoporosis. Secondary osteoporosis is caused by another disease or from medications. About 30% of postmenopausal women with osteoporosis and 50% of men with osteoporosis have secondary osteoporosis.

Why Bones Become Fragile

To understand the causes of osteoporosis, it’s helpful to first learn a bit about healthy bone and how it changes over time. Bone is a tissue and, like all tissues in the body, it’s made up of different components. Minerals in bone, such as calcium, give bone its hardness. But another, critical part of bones is the collagen.

The collagen protein matrix provides the scaffolding on which bone minerals bind. Bone collagen is flexible, and can bend without breaking. If you were to fall, the collagen is what allows the impact of the fall to be dispersed over a larger area and gives bone the ability to deform and bend slightly to absorb the impact without breaking. If all the minerals were to dissolve out of bone it would bend without breaking, like a toy rubber chicken. But if all the collagen dissolved, you’d end up with a column of minerals that would be brittle like chalk, and break easily.

As a living tissue, bone is continually being remodeled. Old bone is broken down and new bone is created. The healthy and ongoing process of remodeling deposits new minerals into bone and also regenerates the collagen matrix.

Unfortunately, there aren’t any tests that can directly measure and quantify the amount of collage in bone. Bone minerals are detected with a bone mineral density scant, also called a DEXA scan. Bone mineral density increases throughout childhood and into adulthood until about the age of 30. It can then begin to decline. Bone density is lost fastest during the 10 years following menopause. Because of this, even the healthiest people can expect to see some decline in bone mass as a normal part of aging.

For some people, the age-related deterioration of bone is gradual enough that it never becomes osteoporosis and never leads to fractures. For others, the decline is more severe. These are the people who begin to see bone mineral density test results plummet or who begin to experience fractures. Diseases and medications can both damage bone and cause osteoporosis. Knowing if you’re at risk is important for taking steps to protect your bones.

Medications

Antidepressants

The most common medications to treat depression increase serotonin and are called selective serotonin reuptake inhibitors (SSRIs). They include Prozac, Celexa, Lexapro, Paxil and Zoloft. Serotonin is a neurotransmitter in the brain that may help improve mood, but serotonin also has actions throughout the body, so the drugs affect more than just the brain. Taking SSRI’s is associated with lower bone mineral density in children and adults. In a study of adults over the age of 50, use of SSRIs not only lowered bone mineral density but they also increased the odds of falling and doubled the risk of osteoporosis fractures.

Thyroid Hormone Replacement

Thyroid medication provides thyroid hormone when the thyroid gland isn’t producing enough. This occurs if the thyroid gland is surgically removed or chemically destroyed, which are treatments for hyperthyroid diseases. This also occurs when the thyroid gland isn’t producing enough hormone, called hypothyroidism.

Excessive thyroid hormone causes osteoporosis and fractures. This can occur when hyperthyroid disease goes untreated. The good news is that once hyperthyroid disease is treated osteoporosis risk decreases.

People can also have too much thyroid hormone if they take thyroid medication. One study of women with osteoporosis concluded that taking a high dose of thyroid hormone (>150 micrograms/day) increased their fracture risk more than a 50%. If you take thyroid medication, making sure you’re not taking too much is crucial to protect your bones.

Glucocorticoids (Prednisone)

Glucocorticoids are steroid medications used for autoimmune and other diseases. This category of drugs includes cortisone, prednisone, hydrocortisone, dexamethasone and methylprednisolone. They are the most common cause of drug-induced osteoporosis and fractures.

The medications are such powerful bone destroyers that they cause bone loss and can lead to fractures in 30-50% of people. Fracture risk increases after just three months. Even very small doses of oral glucocorticoids (< 2.5 mg/day over approximately 6 months) are associated with a 20% to 200% increase in risk of vertebral fractures. And for every 10-mg increase in dose there’s a 62% increase in risk for bone fracture.

This risk may be necessary and acceptable to control a disease. However, if there are ways to reduce the dose or stop taking the corticosteroids all together it would be advisable to do so since the risk for fracture decreases after stopping the medication.

Contraception

Women seeking contraception may be prescribed depot medroxyprogesterone acetate (DMPA) injections. This medication is called a progesterone agonist, and it magnifies the effects of progesterone on your body. While it is effective at preventing unwanted pregnancy, an unintended side effect can be bone loss and fractures. A study published in 2017 found that women under the age of 30 who had received 10 or more DMPA injections had 3 times the risk of fracture compared to women who had never received DMPA. A second study had similar results. In addition to increasing osteoporosis and fracture risk, another alarming side effect of DMPA is that it can also increase cancer risk.

Cancer Chemotherapy

Chemically altering hormone levels is a commonly used strategy in fighting cancer. Hormones such as estrogen and testosterone can promote cancer growth, so blocking the production or activity of these hormones is an important approach in some cancers.

These hormones, however, are also important for growing healthy bones, so medications that affect hormone levels can cause bone loss and lead to cancer treatment-induced osteoporosis and fractures. Examples include gonadotropin-releasing hormone (GnRH) agonists (used to treat endometriosis and prostate cancer) and These drugs don’t just affect women. Men who receive GnRH agonists for the treatment of prostate cancer have up to a 76% increased risk of hip fracture.

Aromatase inhibitors block estrogen production. Examples include anastrazole and tamoxifen, which are used to treat breast cancer. The bone-damaging risks of these medications are different depending on whether the woman is pre- or post-menopausal. One study of 308 postmenopausal women with breast cancer taking aromatase inhibitors evaluated the outcome of bone mineral density for an average of 5.6 years. The study found that anastrazole was associated with a decrease in bone mineral density. Other researchers found that women who had taken anastrazole had a 44% increased risk of fracture over 5 years. Both studies concluded tamoxifen did not seem to harm the bones in postmenopausal women. While it seems bone-safe for posmenopausal women, the American College of Obstetricians and Gynecologists (ACOG) lists pre-menopausal use of tamoxifen an osteoporosis risk.

Acid Blockers

Acid blocking medications, such as Aciphex, Nexium, Prevacid, Protonix, Prilosec and Nexium are commonly used for heartburn. These drugs are available by prescription or over-the-counter without a prescription. Although never approved by the FDA for long-term use, people oftentimes take these drugs for years to treat the symptoms of acid reflux

These medications can increase osteoporosis and fracture risk. A large study of more than 13,000 patients concluded that hip fracture risk increases by 22% after one year of taking the medication and by 54% after 3 years. Take if for 4 years, and your risk continues to increase, shooting up to 59% increase in fracture risk. The higher the dose one takes, the greater the risk, and the risk seems to be stronger for men than women.

Other Medications

There is a long list of medications that cause osteoporosis. The ones in this article are some of the most popular drugs, and some of the most dangerous when it comes to bone health. If you’re taking medications, you may want to discuss with your healthcare provider and pharmacist of the drugs that you’re taking increase osteoporosis and fracture risk.

What You Can Do

If you’ve been diagnosed with a disease or are taking medications that cause osteoporosis, talk to your healthcare provider about what they recommend you might be able to do to protect yourself. There are many natural approaches you can also take to protecting your bones. I’ve provided tips to help you in my 6 Steps to Reduce Fracture Risk article.