Do Antidepressants Increase Risk of Bone Loss?

As many as one in three women over the age of 50 will have osteoporosis, and most will suffer a fracture during their lifetime. Fractures cause pain, decreased mobility and function, and are associated with decreased quality of life and increased mortality.

Some studies suggest that depression and treatments for depression, such as selective serotonin reuptake inhibitors (SSRIs), may weaken our bones, and further increase the risk of osteoporotic fractures. Whether this occurs, and if so, why, has not been clearly established.

“The relationship between depression and antidepressants and bone loss is an understudied problem, but one that is important to clarify to improve bone health screening and treatment for older women,” said David Hellerstein, MD, professor of clinical psychiatry and director of Columbia University’s Depression Evaluation Service.

To answer these questions, Dr. Hellerstein has teamed up with Columbia endocrinologist Marcella Walker, MD, professor of medicine, to conduct a study, funded by the National Institutes of Health, to assess bone health in postmenopausal women being treated for depression.

Columbia Psychiatry News spoke with Drs. Hellerstein and Walker about the risks of osteoporosis, the link between antidepressants and bone health, and their ongoing study. 

What is osteoporosis, and why is it a major public health problem?

Osteoporosis or “porous bone” disease is a silent medical condition, common in women after menopause, which causes bone loss and weakening of the bone’s structure. It increases the risk for fractures or broken bones. Because the condition has no symptoms, people may not know they are at risk unless their bone mineral density is measured by DXA (dual-energy X-ray absorptiometry). DXA is similar to an X-ray and measures the amount of radiation passing through the bones. 

While many fractures tend to be painful and may cause a temporary reduction in normal activities, the consequences of some types of fractures may be more lasting. Hip fractures can permanently reduce independence. For example, some people who sustain hip fractures remain dependent on assisted walking devices like canes or walkers. Hip fractures sometimes even shorten one’s life due to complications that arise after fractures, such as blood clots or pneumonia. Spine fractures can cause a permanent bending of the spine or a “dowager’s hump.” If an individual has already had a fracture related to osteoporosis, their risk of future fracture is high.

How might depression and its treatment be linked to bone health?

A number of studies have found a link between depression and bone health. Some indicate reduced bone mineral density, accelerated bone loss or an increased risk of fractures among those who are depressed compared to those who are not. The mechanisms that underlie this relationship are still not known. Two neurotransmitters, serotonin and norepinephrine, are thought to contribute to regulating bone mass under normal circumstances.

With depression, these transmitters may become dysregulated and accelerate bone loss. Also, depression and psychological stress may increase cortisol (the body’s stress hormone), which can lead to bone loss. Beyond that, depression may cause weight loss, reduced physical activity, or other behaviors detrimental to bone health. Some studies indicate an increased risk for falls among those with depression. It is also possible that individuals with depression are more likely to have other medical conditions or take medications that negatively impact bone health compared to those who are not depressed. Finally, some types of antidepressants may increase the risk of bone loss—the subject of our study.

 Why is it important to study antidepressants?

Antidepressants are one of the most commonly prescribed type of drugs. Recent estimates suggest that more than 1 in 8 adults in the United States take antidepressants, a number which has increased during the pandemic. Selective serotonin reuptake inhibitors (SSRIs) are the most frequently prescribed antidepressants because they are safe and effective. Some studies have linked SSRIs to accelerated bone loss and greater risk of fracture. How this may happen is unclear. Changes in serotonin signaling that normally regulates skeletal health may occur when SSRIs are used. We hypothesize that with chronic use, SSRIs may reduce bone formation, leading to an imbalance between bone breakdown and bone build up. Some other types of antidepressants may have similar effects. There is not enough evidence in humans, however, to know if this is the case. It is important to understand the adverse effects of any treatments we prescribe so that we can adequately counsel patients about risks and benefits. Ultimately, with bone health we want to reduce risk of fracture by initiating lifestyle or pharmacologic therapies before the first fracture occurs.

What should I do if I have depression and am concerned about my bone health?

It is important for individuals being treated for depression to continue their depression treatment as prescribed by their health care provider. We do not recommend that individuals stop antidepressants due to concerns about skeletal health. If you are worried, talk to your physician who may recommend a DXA scan to evaluate your bone health and gauge your risk of fracture. DXA is a painless and non-invasive test similar to an x-ray. There are effective medications to prevent and treat osteoporosis. Depending on your results and risk, you may be a candidate. A change in lifestyle habits can help slow bone loss. To reduce your risk of osteoporosis, do regular weight-bearing exercise; eat foods that are good for bone health, such as fruits and vegetables; ensure adequate dietary calcium and vitamin D; and avoid smoking and excess alcohol use.

Tell us a about the study. Who is eligible for the trial and how can women enroll?

This is a study of post-menopausal women who have decided under the care of a clinician to take anti-depressants or receive counseling/psychotherapy for depression, low mood, or depressive symptoms. We will be accepting participants through 2026, and those who enroll will be evaluated at Columbia University Irving Medical Center four times over the course of 18 months, with DXA scans to measure bone mineral density and determine risk of fracture. Participants also receive repeat spine imaging; high resolution peripheral quantitative computed tomography (HRpQCT) scanning to assess bone microstructure; and tests of muscle function and other non-invasive testing of skeletal health. Participants will receive tests at no cost and will get results of their bone testing as well as compensation. There is no treatment for depression in this study, and participants will continue to follow their treatment course for depression as specified by their provider. 

We hope that results from this study will provide important information needed to better inform screening and treatment recommendations for assessing bone health in women with depression.  Click here to learn more.