Reclast and Fertility
Based on FDA labeling and animal studies, Reclast (zoledronic acid) may impair fertility in females of reproductive potential and should be avoided in women attempting to conceive. 1
Direct Evidence on Fertility Effects
The FDA drug label explicitly states that zoledronic acid may impair fertility in females of reproductive potential based on animal studies. 1 This is the most authoritative source for this question and takes precedence over other evidence.
Animal Study Findings
In pregnant rats given zoledronic acid during gestation at doses producing systemic exposures 2.4 to 4.8 times human exposure (based on a 4 mg IV dose), the following adverse effects occurred: 1
- Increases in pre- and post-implantation losses
- Decreases in viable fetuses
- Fetal skeletal, visceral, and external malformations including unossified bones, shortened jaw, reduced or absent liver lobes, cleft palate, and edema
Even at the lowest dose tested (systemic exposure 1.2 times human exposure), skeletal variations were observed in fetuses. 1
Clinical Implications for Reproductive-Age Women
Contraception Requirements
Females of reproductive potential must use effective contraception during and after zoledronic acid treatment. 1 This recommendation extends beyond the treatment period because zoledronic acid binds to bone long-term and may be released over periods of weeks to years. 1
Pregnancy Testing
Verify pregnancy status prior to initiating zoledronic acid in all females of reproductive potential. 1
Lactation Considerations
Women should not breastfeed during and after zoledronic acid treatment because it is unknown whether the drug is present in human milk, and there is potential for serious adverse reactions in breastfed children. 1 The long-term bone retention and gradual release of the drug makes this particularly concerning. 1
Male Fertility Considerations
Current evidence suggests zoledronic acid has not demonstrated clinically relevant impact on male fertility or offspring outcomes when used in men attempting to conceive. 2 The 2025 EULAR guidelines for antirheumatic drugs in reproduction include zoledronic acid among treatments that can be continued in male patients trying to conceive, as treatment has not shown adverse effects on birth outcomes. 2
Critical Timing Considerations
The long bone half-life of zoledronic acid creates a unique challenge—the drug remains in bone for extended periods (weeks to years) after administration, meaning fertility concerns persist well beyond the infusion date. 1 This is fundamentally different from medications that clear quickly from the body.
Common Pitfalls to Avoid
- Do not assume fertility effects are limited to the treatment period—bone retention means prolonged exposure risk 1
- Do not initiate treatment without documented negative pregnancy test in reproductive-age women 1
- Do not counsel patients that effects are reversible immediately after stopping treatment—bone release continues for extended periods 1