SGLT2 Inhibitors and Bone Health: What You Need to Know About Fracture Risk

When you're managing type 2 diabetes, choosing the right medication isn't just about lowering blood sugar. It’s about balancing benefits with hidden risks - and one of the most misunderstood concerns is bone health. For years, doctors and patients have worried that SGLT2 inhibitors, a popular class of diabetes drugs, might increase the chance of broken bones. But the truth isn’t as simple as it sounds. Some of these drugs carry a real risk. Others don’t. And knowing the difference could change how you or a loved one takes your medication.

What Are SGLT2 Inhibitors?

SGLT2 inhibitors are a group of oral diabetes medications that work in the kidneys. Instead of forcing the body to make more insulin or making cells more sensitive to it, they tell the kidneys to dump extra sugar into the urine. That’s it. This simple trick lowers blood glucose without causing weight gain or low blood sugar - two common side effects of older diabetes drugs.

The first one, dapagliflozin (Farxiga), got FDA approval in 2013. Soon after, canagliflozin (Invokana) and empagliflozin (Jardiance) followed. Today, these drugs are prescribed to millions worldwide. But they’re not just for blood sugar. Large studies like EMPA-REG OUTCOME and DECLARE-TIMI 58 showed they also protect the heart and kidneys. That’s why many endocrinologists now consider them first-line for patients with heart failure, chronic kidney disease, or a history of heart attacks.

The Fracture Risk That Started It All

The trouble began in 2015. Data from the CANVAS trial - a major study testing canagliflozin - showed a 26% higher risk of fractures compared to placebo. That wasn’t a small blip. It was statistically significant. The FDA took notice. By May 2016, they added a formal warning to canagliflozin’s label: “Fractures occurred as early as 12 weeks after starting treatment.” Most were from minor falls, like tripping off a curb or slipping in the shower.

What made this worse? The fractures weren’t random. They happened mostly in the arms, hands, and feet - areas that don’t usually break unless there’s a direct impact. And they happened more often in women and older adults. The numbers weren’t huge - about 15 fractures per 1,000 people per year on canagliflozin versus 12 on placebo - but for someone already at risk for osteoporosis, even a small increase matters.

Not All SGLT2 Inhibitors Are the Same

This is where things get critical. The fracture risk isn’t a class-wide problem. It’s specific to canagliflozin - and even then, mostly at the 300 mg dose.

Empagliflozin (Jardiance) and dapagliflozin (Farxiga) didn’t show the same signal in their own major trials. EMPA-REG OUTCOME tracked over 7,000 people for more than three years. DECLARE-TIMI 58 followed nearly 17,000 for five years. Neither found a meaningful increase in fractures. A 2023 meta-analysis of 27 clinical trials involving over 20,000 patients found no overall link between SGLT2 inhibitors and fractures - but when researchers pulled out canagliflozin, the risk popped back up.

Here’s what the data says:

That’s not a typo. Empagliflozin and dapagliflozin actually had slightly lower fracture rates than placebo. Canagliflozin is the outlier.

Why Does Canagliflozin Affect Bones?

It’s not one thing - it’s a mix. Researchers have found several possible reasons:

• Weight loss: SGLT2 inhibitors cause modest weight loss - around 2-4 kg on average. That sounds good, but losing weight can also mean losing bone mass. However, studies show weight loss only explains about 3% of the bone density drop.
• Phosphate shifts: These drugs cause more phosphate to be reabsorbed by the kidneys. That tricks the body into releasing parathyroid hormone and FGF23, both of which can pull calcium out of bones.
• Hormone changes: In women, canagliflozin 300 mg lowered estradiol levels by 9.2%. Estradiol protects bone density. A drop like that could matter, especially in postmenopausal women.
• Low blood pressure: SGLT2 inhibitors can cause dizziness or fainting due to low blood pressure when standing up. That increases fall risk - and falls cause fractures.
• Bone density loss: In a two-year FDA-mandated trial, patients on canagliflozin lost 0.92% of bone density at the hip and 1.04% at the spine. Placebo users lost less than half that. That’s a measurable difference.

Other SGLT2 inhibitors don’t show these same effects to the same degree. That’s why the FDA only warns about canagliflozin.

Who Should Avoid Canagliflozin?

If you’re at high risk for fractures, canagliflozin isn’t the best choice. That includes:

• People with osteoporosis (T-score ≤ -2.5)
• Those with a prior fracture, especially after age 50
• Women over 65 with low estrogen
• Anyone with poor balance, vision problems, or who takes sedatives
• People on long-term steroids or with rheumatoid arthritis

The American Association of Clinical Endocrinologists and the American Geriatrics Society’s Beers Criteria both recommend avoiding canagliflozin in these groups. Other SGLT2 inhibitors like empagliflozin and dapagliflozin are still considered safe.

Doctors now use tools like FRAX (Fracture Risk Assessment Tool) to estimate risk. The 2023 American Diabetes Association guidelines add 0.5 points to your FRAX score - but only if you’re taking canagliflozin. That small bump can push someone from “low” to “moderate” risk, which changes treatment decisions.

What About Bone Density Tests?

Should you get a DXA scan before starting an SGLT2 inhibitor?

For canagliflozin - yes, if you have any risk factors. The American College of Endocrinology recommends a bone density scan if you’re over 65, have had a fracture, have low body weight, or are on long-term steroids. If your T-score is below -2.0, they advise choosing a different drug.

For empagliflozin or dapagliflozin? Routine scans aren’t needed unless you already have osteoporosis or other risk factors. The risk isn’t there.

And don’t forget: diabetes itself harms bone health. High blood sugar weakens bone structure over time. So even if you’re on a safe SGLT2 inhibitor, your overall fracture risk might still be higher than someone without diabetes.

What Do Real Doctors Think?

A 2022 survey of 347 endocrinologists showed that 68% adjust their prescriptions based on fracture risk. But here’s the split:

• 82% avoid canagliflozin in patients with osteoporosis
• Only 34% avoid dapagliflozin for the same reason

Some doctors still worry. Dr. Robert Heaney, a leading bone expert, says the number of fractures in trials was too low to be sure. He believes longer studies are needed.

But others, like Dr. Mary Buettner and Dr. Thomas Addison, reviewed real-world data from tens of thousands of patients and found no connection between SGLT2 inhibitors and fractures - except for canagliflozin. Their conclusion: “Concerns have been largely overstated.”

And here’s something surprising: a 2023 study in JAMA Network Open found that SGLT2 inhibitors had lower fracture rates than GLP-1 receptor agonists (like semaglutide) and DPP-4 inhibitors (like sitagliptin) in high-risk patients. That’s right - some older diabetes drugs might be riskier than the newer ones.

What Should You Do?

If you’re currently taking canagliflozin and you’re healthy, with no history of fractures or osteoporosis - you’re probably fine. Don’t stop your medication without talking to your doctor.

If you’re starting a new diabetes drug and you’re over 65, have had a fracture, or have low bone density - ask your doctor:

1. Is canagliflozin the best choice for me?
2. Have I had a bone density scan?
3. Would empagliflozin or dapagliflozin be safer for my bones?
4. Should I take calcium and vitamin D?
5. Do I need physical therapy or balance training?

Don’t let fear stop you from using a drug that protects your heart and kidneys. But do make sure you’re on the right one for your body.

The Bottom Line

SGLT2 inhibitors are powerful tools for diabetes. But they’re not all the same. Canagliflozin carries a small but real fracture risk - especially in older adults and those with weak bones. Empagliflozin and dapagliflozin do not. The evidence is clear: canagliflozin is the only one you need to worry about.

For most people, the benefits of these drugs - heart protection, kidney protection, weight loss - far outweigh the risks. But if you’re at high risk for fractures, talk to your doctor. There’s a better option out there.