Does Fosamax (alendronate) cause cancer?

Does Fosamax (Alendronate) Cause Cancer?

No, Fosamax (alendronate) does not cause cancer in humans based on current clinical evidence, though animal studies showed increased adenomas at high doses that are not considered clinically relevant. 1

Evidence from FDA Drug Labeling

The FDA label for alendronate provides critical context from animal carcinogenicity studies 1:

• Harderian gland adenomas (a gland not present in humans) increased in high-dose female mice at doses equivalent to 0.1 to 1 times the maximum human dose of 40 mg based on body surface area
• Thyroid parafollicular cell adenomas increased in high-dose male rats at doses equivalent to 0.3 to 1 times the 40 mg human dose
• The FDA explicitly states: "The relevance of this finding to humans is unknown" 1
• Alendronate was not genotoxic in multiple mutagenesis assays 1

Human Clinical Evidence

Esophageal Cancer

The most extensively studied concern has been esophageal cancer, given alendronate's mechanism of direct esophageal contact:

• A 2013 meta-analysis of observational studies found no clear association between bisphosphonate treatment and esophageal cancer risk (pooled RR 1.23,95% CI 0.79-1.92 in cohort studies; pooled OR 1.24,95% CI 0.98-1.57 in case-control studies) 2
• A Danish nationwide cohort study (103,562 bisphosphonate users) showed an apparent excess risk of esophageal cancer with alendronate, but critically, there was no dose-response relationship and the risk was highest at low doses and short duration, suggesting the association was not causal 3

Other Cancers

Conflicting evidence exists for other cancer types, but methodological concerns limit interpretation:

• A 2015 meta-analysis suggested alendronate may increase lung cancer risk (HR 1.23,95% CI 1.03-1.47), but this association disappeared when individual studies were excluded, indicating instability of the finding 4
• The same analysis found no significant association with colorectal cancer using random effects models, though a protective effect appeared with fixed models 4
• A single Taiwanese study reported increased overall cancer risk at doses ≥1.0 g/year (HR 1.69,95% CI 1.39-2.04), including liver, lung, and prostate cancers 5, but this finding has not been replicated in other populations

Potential Protective Effects

Emerging evidence suggests alendronate may actually reduce cancer risk in specific contexts:

• In osteoporotic women with early breast cancer, prior alendronate exposure was associated with a dramatically lower risk of bone metastases (HR 0.04,95% CI 0.004-0.403) 6
• This suggests potential anti-tumor effects rather than carcinogenic properties 6

Clinical Context from Guidelines

Major cancer care guidelines extensively recommend bisphosphonates, including alendronate, for cancer treatment-induced bone loss without expressing concern about carcinogenicity 7:

• The NCCN recommends alendronate 70 mg weekly for men on androgen deprivation therapy 7
• ESMO guidelines describe bisphosphonates as standard bone-targeted agents in cancer care 7
• If alendronate caused cancer, these guidelines would not recommend its use in cancer patients

Common Pitfalls to Avoid

• Do not confuse animal toxicology findings with human risk – the FDA label clearly states the relevance to humans is unknown 1
• Do not interpret observational associations as causal – the lack of dose-response relationships in human studies suggests confounding rather than true carcinogenicity 3
• Do not overlook indication bias – patients prescribed alendronate may have underlying conditions or risk factors that independently increase cancer risk

Bottom Line for Clinical Practice

Alendronate should not be avoided due to cancer concerns. The established benefits for fracture prevention far outweigh any theoretical cancer risk that has not been substantiated in human studies. Standard precautions remain appropriate (esophageal disorders, renal function, dental health) 7, 8, 9, but cancer risk is not a contraindication to alendronate therapy.