A patient recently asked me "How long should I stay on alendronate?" A very good question that had me struggling. A
local rheumatologist has stopped alendronate in several of my patients after five years. "A
practical guide to stopping medicines in older people" (BPJ 27, Apr 2010) mentioned alendronate as a medication that
could be considered for possible cessation in the elderly, but gave no clear guide on who and when. My limited reading
suggests that a holiday from alendronate should be considered after five years in most and ten years in the rest, as
alendronate has an ongoing effect after its cessation, the maximal bone strength is attained at three years and additional
risk of atypical fracture occur after that duration. I am unsure what to do here? This is an expensive medication and
its unnecessary use would be good to eliminate. Wonder if you can answer my questions? What is the optimal duration of
alendronate treatment, in whom should we stop it and what monitoring is required?
Treatment with a bisphosphonate, such as alendronate, has proven benefits in terms of the prevention of bone loss
and the reduction of fractures in males or post-menopausal females with osteoporosis. However, alendronate is associated
with adverse effects such as oesophagitis, oesophageal ulcers and strictures, as well as a very small increased risk
of osteonecrosis of the jaw and atypical femur fractures.1 Therefore the benefits vs. risks of alendronate
treatment must be carefully weighed up and regular review should take place.
There is currently a lack of evidence to form a consensus on the optimal length of alendronate treatment and when,
if ever, it should be stopped, and for how long. Many clinicians recommend that alendronate should be interrupted periodically.
In theory, this is to allow recovery of bone turnover, which is suppressed during treatment, but it is unknown whether
this suppression contributes to the rare adverse effects associated with alendronate.1 The beneficial effect
of alendronate remains for three to five years after ceasing treatment.
In a patient who has taken alendronate for five years and whose bone density is no longer in the osteoporotic range,
discontinuing alendronate is a reasonable approach. The patient is likely to have substantial residual anti-resorptive
activity during this period. N.B. this can be checked through the measurement of serum P1NP, with a value < 35 μg/L
indicative of significant inhibition of bone resorption, however, this test is not usually carried out in general practice.
Bone density and fracture risk can be re-evaluated (using DEXA scan) after two years off treatment, and alendronate
resumed in patients with a 10-year hip fracture risk greater than 3% (calculated using FRAX).
If patients are still at high risk after five years of alendronate treatment (bone mineral density remains low, fragility
fracture has occurred), the risk of stopping treatment is likely to exceed the risk of continuing.1
In a recent perspective article in the New England Journal of Medicine, the authors concluded the following, based
on the limited evidence about long-term alendronate use:2
- Patients with bone density T-scores of −2.5 or below at the femoral neck, after three to five years of treatment,
benefit the most from continuation
- Patients with bone density T-scores between −2.5 to −2.0 and an existing vertebral fracture, after three to five
years of treatment, may also benefit from continuation
- Patients with bone density T-scores above −2.0 at the femoral neck, after three to five years of treatment, are
unlikely to benefit from continuation
The authors also note that reduced doses may be considered if alendronate is continued beyond five years.2
Acknowledgement
Thank you to Professor Ian Reid, Professor of Medicine and Endocrinology, Faculty of Medical and
Health Sciences, University of Auckland for expert guidance in preparing this answer.
References
- Khosla S, Bilezikian J, Dempster D, et al. Benefits and risks of bisphosphonate therapy for osteoporosis. J Clin
Endocrinol Metab 2012;97:2272-82.
- Black D, Bauer D, Schwartz A, et al. Continuing bisphosphonate treatment for osteoporosis - for whom and for how
long? N Engl J Med 2012;366(22):2051-3.