When Do You Start and End a Bisphosphonate Drug Holiday?
Consider a bisphosphonate drug holiday after 5 years of oral therapy or 3 years of IV therapy in patients at moderate fracture risk with stable or improved BMD and no incident fractures. High-risk patients (prior hip/vertebral fracture, hip T-score <-2.5 on therapy, glucocorticoid use) should continue. Resume therapy when a new fragility fracture occurs, hip T-score drops below -2.5, or BMD declines >5% over 1–2 years.
Evidence review
Pivotal trials, effect sizes, and the populations they studied. PubMed identifiers link directly to the source.
FLEX (alendronate extension) (2006)
PMID 171908931,099 women on alendronate 5 years, randomized to 5 more vs placebo
Continued alendronate reduced clinical vertebral fractures (5.3% vs 2.4%, RR 0.45). No difference in hip or nonvertebral fractures overall — benefit limited to those with femoral neck T ≤ -2.5.
HORIZON extension (2012)
PMID 221617281,233 on zoledronic acid 3 years, randomized to 3 more vs placebo
Continued zoledronic acid reduced new morphometric vertebral fractures 49% but no difference in clinical fractures.
Practical decision algorithm
| If | Then |
|---|---|
| 5 yr oral or 3 yr IV bisphosphonate, hip T-score >-2.5, no incident fracture | Initiate drug holiday. Repeat BMD at 2 years. |
| 5 yr oral or 3 yr IV, hip T-score ≤-2.5 or prior hip/vertebral fracture | Continue therapy up to 10 years (oral) or 6 years (IV); then reassess. |
| On drug holiday, new fragility fracture | Resume therapy. Consider denosumab or anabolic if BMD markedly low. |
| On drug holiday, BMD loss >5% at hip/spine | Resume bisphosphonate. Rule out secondary causes. |
| On drug holiday, stable BMD at 2 years | Continue holiday; reassess at 4 years. Holiday rarely extends past 5 years. |
Guideline position
Endocrine Society 2019 Clinical Practice Guideline (2020 update) on pharmacological management of osteoporosis in postmenopausal women: reassess fracture risk after 3–5 years; consider a bisphosphonate holiday (up to 5 years) in those at low-to-moderate risk. AACE/ACE 2020 postmenopausal osteoporosis update: continue therapy if prior hip/vertebral fracture, T-score ≤-2.5 on treatment, or high ongoing risk. ASBMR task-force guidance supports 5 yr oral/3 yr IV reassessment points.
Contraindications and cautions
- Prior hip or vertebral fragility fracture — do not interrupt therapy
- Hip T-score ≤-2.5 on current therapy
- Ongoing glucocorticoid therapy (≥5 mg prednisone/day)
- Denosumab — never a 'holiday'; requires continuous therapy or transition to bisphosphonate
- Severe renal impairment — different agent selection, not holiday consideration