CGRP Migraine Drug Erenumab Possibly Linked to Unusual Thigh Bone Fractures | Research

The takeaway

A woman on the CGRP-blocking migraine drug erenumab developed bilateral atypical femur fractures, raising a new safety concern about long-term bone effects of CGRP peptide antagonists.

Bilateral AFFs
A migraine patient on the CGRP antagonist erenumab developed atypical fractures in both thigh bones — a fracture type previously only associated with bisphosphonate use

What the researchers found

A 56-year-old woman on erenumab (a CGRP receptor antagonist monoclonal antibody) for migraine prevention presented with bilateral atypical femur fractures (AFFs) after a mechanical fall. Imaging showed lateral cortical beaking — a hallmark of stress-related atypical fractures typically associated with bisphosphonate use. She required bilateral femoral intramedullary nailing.

The authors note that CGRP has roles in bone biology and that blocking it may affect bone formation, potentially linking CGRP antagonist therapy to atypical fracture risk. This appears to be an early report raising this safety concern.

Why it matters

Millions of migraine patients use CGRP-targeting peptide antibodies (erenumab, fremanezumab, galcanezumab), and atypical femur fractures are a serious, potentially disabling complication. CGRP is known to play a role in bone metabolism — it's not just a pain signaling molecule. If CGRP antagonism disrupts normal bone remodeling, this could represent a significant long-term safety concern for a drug class used chronically by a predominantly young female population already at risk for osteoporosis.

The numbers in context

1 patient · 56 years old · Bilateral AFFs · Lateral cortical beaking · Erenumab (CGRP antagonist) · Bilateral intramedullary nailing required

How the study worked

Single case report describing a 56-year-old woman with bilateral atypical femur fractures identified on imaging after a fall. Medical history review identified erenumab use for migraine prevention. Treatment was bilateral femoral intramedullary nailing followed by rehabilitation.

Who was studied

Single 56-year-old woman with recurrent migraines on erenumab therapy

What this study cannot tell us

Single case report (n=1) cannot establish causation between erenumab and atypical fractures. Other risk factors for AFFs (bisphosphonate use, vitamin D status, bone density) may not have been fully reported. The patient's fall was the proximate cause of fracture, though AFFs are stress fractures where the fall may simply complete an already weakened bone. No population-level data on fracture rates in CGRP antagonist users is available.

How to read the evidence

Single case report — the lowest tier of clinical evidence. It raises a safety signal but cannot establish causation or prevalence. Published in JBJS Case Connector, a reputable orthopedic journal.

When this study was published

Published in 2025, this is a very timely safety report given the rapid expansion of CGRP antagonist prescribing for migraine prevention over the past several years.

The bigger picture

CGRP-targeting drugs are the first migraine-specific preventive therapy class and are used by millions of patients, often for years. While their safety profile has been considered favorable, long-term bone effects haven't been specifically studied. CGRP plays roles in bone formation, fracture healing, and vascular supply to bone — blocking it chronically could theoretically affect bone health. This case should prompt pharmacovigilance studies examining fracture rates in CGRP antagonist users.

Questions still open

Do population-level data show increased atypical fracture rates in patients on CGRP antagonists?
Does CGRP blockade affect bone density or bone quality in long-term migraine patients?
Should bone health monitoring be recommended for patients on chronic CGRP-targeting therapy?

Common questions

What are atypical femur fractures and why are they concerning?

Atypical femur fractures (AFFs) are unusual breaks in the thigh bone that occur with minimal trauma — often during normal activities. They develop because of abnormal bone remodeling that weakens a specific area of the bone shaft. They're called 'atypical' because they differ from normal hip fractures. Previously, AFFs were mainly associated with long-term bisphosphonate osteoporosis drugs. This case suggests CGRP antagonists might also be a risk factor.

Why would blocking CGRP affect bones?

CGRP isn't just a pain molecule — it also helps regulate bone formation and blood supply to bone tissue. Studies have shown that CGRP promotes bone growth and aids fracture healing. Blocking CGRP with drugs like erenumab could theoretically disrupt these bone maintenance processes over time, potentially weakening bone structure. This is why this case report, while preliminary, raises an important question about long-term bone safety.

Read the original research

Calcitonin Gene-Related Peptide Antagonist Use and Atypical Femur Fractures: A Case Report.

JBJS case connector, 15(3)

View on PubMed ↗Publisher’s paper ↗

Citation

Choy, Kenneth; McDonald, Jason J; Geiselmann, Matthew; Daubs, Gregory. (2025). Calcitonin Gene-Related Peptide Antagonist Use and Atypical Femur Fractures: A Case Report.. JBJS case connector, 15(3). https://doi.org/10.2106/JBJS.CC.25.00148