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ORLANDO, Fla. — Use of calcitonin gene-related peptide (CGRP) monoclonal antibodies for migraine was associated with a 19% increase in adjusted odds of fracture over 1 year.

Results of a large retrospective case-control study showed that erenumab, galcanezumab, and fremanezumab were together associated with an average 19% greater odds of fracture at 1 year.

Results of a large retrospective case-control study showed that the increased fracture risk was observed across all three CGRP monoclonal antibodies evaluated — erenumab, galcanezumab, and fremanezumab — even after accounting for baseline osteoporosis and prior fractures.

“Greater adjusted odds of fracture were consistent and significant among all three drugs evaluated, and even though individuals on CGRP monoclonal antibodies had greater comorbidities, had higher BMIs, had osteoporosis at a greater rate, and had prior fractures in the prior 18 months at a higher rate, adjustment for all these things did not alter our conclusions,” said study investigator John P. Ney, MD, MPH, assistant professor of neurology at Yale University School of Medicine, New Haven, Connecticut.

However, he cautioned that the results show only an association, “so we’re not trying to intimate that this is at all causative.”

Ney presented the results on June 5 at the American Headache Society (AHS) Annual Meeting 2026.

Bone Health Concerns

CGRP monoclonal antibodies are recommended by the AHS as first-line options for migraine prevention.

The AHS position statement identifies constipation, hypertension, and Raynaud syndrome as the principal adverse events reported in real-world studies. Potential effects on bone mineral density changes and fracture risk are not mentioned in the statement or in prescribing information for the drugs.

Ney said the current study was prompted by concerns that blocking CGRP signaling could affect bone health. Experimental data suggest CGRP promotes osteoblast activity and bone formation, providing a biologically plausible mechanism for an increased fracture risk.

Few studies have examined the association between CGRP monoclonal antibodies and bone health. A small 2024 cross-sectional study showed no link between CGRP inhibitor use and bone mineral density abnormalities.

Similarly, a small 2026 prospective study showed no adverse effects of CGRP monoclonal antibodies on bone density, structure, or turnover. Another small prospective study, published in 2023, showed the drugs were associated with increased levels of procollagen type I N-terminal propeptide, a marker of bone formation, but not C-terminal telopeptide of type I collagen, a marker of bone resorption.

Ney and colleagues analyzed data from 2019 to 2024 in 139,976 veterans with migraine enrolled in the Veteran’s Headache Cohort, maintained by the Veterans Health Administration and the VA Headache Centers of Excellence.

The 35,086 patients who were taking erenumab, galcanezumab, or fremanezumab were matched 1:3 by age, sex, race, ethnicity, and Census Bureau region with 104,890 patients not receiving CGRP monoclonal antibodies.

The study cohort had an average age of 48 years, with slightly more men (59%) than women (41%). The cohort was predominantly White (65%) but included 22% Black patients and 13% from other racial groups. Ten percent were Hispanic. Just over half (53%) had a BMI of ≥ 30, and about a third (32%) had a BMI of 25-29.9.

Chronic migraine was far more common among individuals receiving CGRP monoclonal antibodies than among those not receiving them (62% vs 13%). Although prior fractures were more common in the CGRP monoclonal antibody group (13% vs 9%), baseline rates of osteoporosis were similar between patients receiving and not receiving the drugs (1.1% vs 0.7%).

Increased Fracture Risk

The researchers compared the odds of any ICD-10-coded fracture between patients receiving and not receiving CGRP monoclonal antibodies during up to 1 year of follow-up after treatment initiation. The analysis adjusted for prior fracture, osteoporosis, BMI, and comorbidity burden.

Before accounting for the covariates, odds of fracture at 1 year were 31% greater in those taking any of the three CGRP monoclonal antibodies (odds ratio [OR], 1.31, 95% CI, 1.29-1.35).

After adjustment, the overall odds of fracture were 19% for the three drugs combined (OR, 1.19; 95% CI, 1.13-1.25), though the odds of fracture for fremanezumab were higher (OR, 1.33; 95% CI, 1.22-1.44) than for galcanezumab (OR, 1.28; 95% CI, 1.17-1.39) or erenumab (OR, 1.17; 95% CI, 1.10-1.24).

The study only tracked risk for fracture for 1 year and did not consider dosage or cumulative exposure, nor did it look at CGRP monoclonal antibodies infusions, Ney cautioned.

Risk for fracture was independently significantly higher in those with osteoporosis (OR, 1.49), a prior fracture (OR, 4.4), and comorbidities (OR, 1.17-1.5), but no association was found with BMI alone.

“One could argue that if you’re, you have more comorbid conditions, if you have a greater BMI, and you’re less mobile, you might be at greater risk for fracture rate, and the more migraine you have, the less you want to move around,” Ney told conference attendees.

Although the study population consisted exclusively of veterans, Ney told Medscape Medical News he would expect similar findings in a civilian population. He said he is currently conducting a separate study using commercial claims data to examine the same question among adults aged 18-64 years.

As with any treatment, Ney said clinicians should engage in shared decision-making with patients and discuss the potential risks of these medications.

“I think we should be informing our patients that there’s at least some data that suggests that there is an increased fracture risk associated with this,” Ney said. “Whether or not it’s causative, we don’t know, but it’s still something to consider.”

He added that further basic science research is needed to better understand the potential mechanisms underlying the association. CGRP is known to play a role in bone health, raising the possibility that inhibiting the pathway could have unintended skeletal effects.

Potential Confounders

Commenting on the findings, Lex Denysenko, MD, of Thomas Jefferson University Hospital in Philadelphia, who was not involved in the research, said it remains unclear whether the association reflects a direct effect of CGRP inhibition or other factors.

Patients with chronic migraine may be less likely to engage in behaviors that support bone health, such as spending time outdoors, participating in weight-bearing exercise, maintaining a healthy diet, and seeking regular medical care, Denysenko said.

They also may be taking other medications that increase fracture risk, making it important to determine whether the association reflects a direct effect of CGRP inhibition or other differences between treated and untreated patients.

The study was independently supported. Ney reported consulting for Cerebella, Zimmer Biomet, SpecialtyCare, and Pertrero, and he is medical director for Surgical Neuromonitoring Associates and an associate editor of Neurology Clinical Practice. Denysenko had no disclosures.