For many women in midlife, menopause brings a host of unwanted physical changes, including weight gain and more abdominal fat. Increasingly, women are turning to popular GLP-1 weight-loss drugs to drop extra pounds and fat.

But the growing number of older women who are losing significant amounts of weight while also dealing with the impacts of menopause could create future bone health problems, according to Wendy Kohrt, a University of Colorado Anschutz School of Medicine expert on bone health.

“A perfect storm could be brewing right now,” Kohrt said. “Postmenopausal women are already at a time of life when they’re losing bone at an accelerated rate. They are seeking a treatment with GLP-1 drugs that will likely accelerate bone loss even more.

“As the prevalence of overweight and obesity increased in this country over the past 30 years, the incidence of hip fracture decreased. If we start to see people losing weight, osteoporotic fracture rates may rise again,” she said. “That’s part of this perfect storm.”

Kohrt is the Ludeman Center’s Nancy Anschutz Chair in Women’s Health Research and a distinguished professor in the division of geriatric medicine at the School of Medicine. She has a doctorate in exercise science and has conducted research on women’s health, exercise and bone density for more than 35 years.

Three overlapping trends that may signal trouble for women who are losing both fat and muscle mass at a vulnerable time in their lives, according to Kohrt:

• Women in menopause lose bone at an accelerated rate due to declining levels of estrogen, which supports bone health.
• Women are increasingly turning to GLP-1 medications to lose weight, especially during menopause.
• Weight loss at any age typically causes bone loss.

Why GLP-1 drugs and menopause could create a ‘perfect storm’ for bone loss

Bone loss can lead to osteoporosis, which causes bones to become porous, weaker and brittle, making them more likely to break, often in the hips, spine and wrists.

As people age, they face greater risks of becoming medically “frail.” Health problems can then spiral during the final years of a person’s life.

Kohrt advises women in midlife who want to use GLP-1 drugs to lose weight to also think carefully about how weight loss will affect their bone health. And she encourages older women to mitigate their risks.

How GLP-1 weight-loss drugs work and why they’re so popular

Researchers developed the GLP-1 drug, Ozempic, to treat Type 2 diabetes. GLP-1 stands for glucagon-like peptide-1, which is a hormone that helps slow digestion and reduce food cravings. When researchers discovered that GLP-1s also help people lose significant weight, patients quickly began using the medications. And the manufacturers of Ozempic created a weight-loss version of the same medication. It’s called Wegovy.

Competition among drugmakers has resulted in other new drugs, including Zepbound — which spurs even greater weight loss than Wegovy. And millions of people across the U.S. — and the world — have been using GLP-1s. Doctors regularly prescribe the drugs to patients who are overweight or are fighting obesity.

About 40% of adults in the U.S. are obese, with a body mass index (BMI) of 30 or higher. Obesity can cause a host of health problems, including various cancers, coronary heart disease, high blood pressure, stroke, Type 2 diabetes, sleep apnea and more.

As more and more patients have turned to GLP-1 medications to lose weight, researchers also have found that GLP-1s reduce the risk of heart attacks and strokes for some people and help with sleep apnea, substance use disorder and cancer risks.

Those benefits do not appear to extend to bone health. Emerging research on GLP-1 drugs and their impact on bone health is mixed and continues to evolve.

For women in menopause, using a GLP-1 medication requires careful evaluation of risks and benefits, Kohrt said.

Menopause and bone health: Why women lose bone as estrogen declines

Menopause refers to the stage of life when a woman no longer has menstrual cycles. This transition often brings a variety of symptoms, including hot flashes, night sweats, mood changes and more due to declining levels of the hormones estrogen and progesterone.

Researchers have thoroughly studied accelerated bone loss during menopause, Kohrt said.

As a woman’s estrogen levels decline, her body loses a key protection against bone loss. Women going through menopause typically experience a drop in bone density, increasing the risk of osteoporosis and bone fractures. Estrogen hormone therapy can help women maintain their levels of estrogen during menopause, but they’re not right for everyone. (Learn more about the pros and cons of hormone therapy during menopause.)

“Eventually, you’ll start to lose bone anyway because of other factors of aging,” Kohrt said.

Bone loss is one of the most critical and least visible effects of aging, Kohrt said. “Bone loss occurs silently,” she said. “You don’t know that you’re losing bone.”

The first sign might be a broken wrist, which is manageable. Worse is a broken hip, which can be life-altering, leading to a hospital stay and months of recovery.

Patients and doctors often overlook bone health and therefore leave bone loss untreated, she said.

Meanwhile, more perimenopausal and early menopausal women are seeking anti-obesity treatments, Kohrt said.

Research and surveys show that:

• Women are more likely than men to use GLP-1 medications.
• About 15% of adult women in the U.S. — about 19 million women — are using a GLP-1.
• Across all age groups, GLP-1 use is highest among U.S. adults ages 50 to 64. About one in 5 women in this age group has used GLP-1 medications, the highest rate of any age group.
• Women ages 18 to 39 are the fastest-growing segment of people using GLP-1 drugs, growing from 7% to 14% among all U.S. users from 2021-2024.

Weight loss can lead to bone loss

Kohrt’s research points to one important principle: “Weight loss equals bone loss,” she said. That weight loss can include loss of fat as well as loss of muscle mass. Muscle mass is important to bone density because strong muscles can help stimulate and maintain bone health.

In her landmark 2006 research study:

• Kohrt and her team enrolled women in a six-month supervised exercise program designed to burn about 400 calories during each exercise session.
• The women each lost an average of 10 pounds. Their weight loss was fat loss, not lean muscle loss.
• The women also lost bone mass to a greater extent than those who didn’t lose weight.

“If you had asked me in advance if exercise would have protected against bone loss, my answer would have been ‘yes,’ but it didn’t,” Kohrt said. “The exercise was not protective.”

She notes that the study involved endurance (cardiovascular) exercise, which does not increase muscle mass. Resistance exercise can increase muscle mass and may be more effective than endurance exercise at protecting bone during weight loss, though it does not fully prevent bone loss.

Kohrt and her fellow researchers continued to follow the women for another year, dividing them into groups depending on how much weight they regained. Neither group regained any bone density, she said.

These findings suggest that women lose and regain weight in cycles called “yo-yo dieting.” That can cause irreversible bone loss, she said.

Some GLP-1 users experience this cycle. As many as two-thirds of people using a GLP-1 to lose weight stop taking the drug within a year, citing unpleasant side effects (diarrhea, constipation, nausea and vomiting) and the relatively high cost of the medication. Within a year, patients regain as much as two-thirds of the weight they lost.

“The magnitude of weight you lose influences how much bone you’re going to lose, but the magnitude of weight you regain, at least over a one-year period of time, does not seem to have any impact on how much bone you regain,” she said. “Yo-yo dieters have repeated losses of bone with repeated weight loss attempts, but may not recover that bone.”

But research doesn’t yet offer a clear assessment of the impact of GLP-1 drugs and bone health, and researchers have called for more studies for menopausal women in particular.

How to protect your bones during weight loss

Experts expect GLP-1 use to grow. In July, millions of people could become eligible for GLP-1 drugs that cost $50 a month under a new Medicare pilot called the Bridge program. Meanwhile, drug company researchers are working on new types of GLP-1s that come in pill form that don’t require patients to inject themselves with the medication. And Eli Lilly researchers are conducting clinical trials for the newest GLP-1 drug, called retatrutide, which could help patients lose as much as 30% of their body weight.

Kohrt acknowledges that reducing obesity and related health issues is beneficial. But weight loss is not without its risks.

For people over age 65, Kohrt and other experts recommend maintaining a healthy weight or even gaining a few pounds to help protect bone health. Fat tissue is a source of an enzyme that can convert testosterone to estrogen, which protects your skeleton, Kohrt said.

“I’ve seen a lot of people who might have benefited from losing a few pounds, but now they’ve gone to an extreme that I really worry about,” she said. “You have to weigh that against the risks of weight loss.”

Kohrt recommends that doctors and patients consider the benefits of weight loss alongside potential risks to bone health. Women, especially, should learn about their bone health and get a baseline bone mineral density test, called a DXA scan, before starting a GLP-1. These tests measure calcium and other minerals in bone. Higher levels of minerals indicate denser, and therefore stronger, bones. Kohrt notes that the U.S. Preventive Services Task Force (USPSTF) recommends that doctors screen women aged 65 and older for osteoporosis, which may be too late given current weight-loss drug trends.

Patients also should discuss risks and benefits before starting on a weight-loss drug, Kohrt said.

She warns against assuming that exercise will improve bone health. The truth is that exercise, specifically endurance exercise, may not be as beneficial for bone health as once thought. This includes cycling, treadmill use, walking and running. Weightlifting and resistance exercises may be better for building bone health, she said.

Medications approved by the U.S. Food and Drug Administration can reverse bone loss and stop the progression of osteoporosis, and they have low risks associated with them, she said. There are a variety of medications for osteoporosis for women and men.

“Exercise should not be considered a substitute for medication,” she said. “When you get to the point where you have osteoporosis, we don’t have any evidence that exercise can prevent fractures.”

Kohrt has this warning for women in midlife considering GLP-1s for weight loss.

“They’re already at a time of life when they’re losing bone at an accelerated rate,” she said. “They are seeking a treatment that is likely to accelerate that bone loss even more, which is going to increase their risk for fractures, maybe at an earlier age or with more severe consequences.”