Bisphosphonates for osteoporosis--where do we go from here?

@article{Whitaker2012BisphosphonatesFO,
  title={Bisphosphonates for osteoporosis--where do we go from here?},
  author={Marcea B Whitaker and Jia Guo and Theresa Kehoe and George Benson},
  journal={The New England journal of medicine},
  year={2012},
  volume={366 22},
  pages={
          2048-51
        }
}
In response to reports of rare but serious adverse events associated with bisphosphonates, the FDA reviewed long-term bisphosphonate efficacy. Two FDA committees recommended an update to bisphosphonate labeling but no regulatory restriction on duration of use. 
Bone diseases: Bisphosphonates in osteoporosis—beyond 5 years
TLDR
The identification of patients who will benefit from continuing therapy is of primary clinical importance and a subject of current research.
Advances in Osteoporosis Treatment: Five Things to Know
How serious is the risk of atypical femur fracture for osteoporosis patients on bisphosphonates, and when is a "drug holiday" justified? There are no definitive studies or guidelines, but here are
When Is Prolonged Bisphosphonate Treatment for Osteoporosis Appropriate
TLDR
Registration trials of bisphosphonates for preventing osteoporotic fractures have consistently shown good efficacy and safety profiles, however, the safety profiles are still vulnerable to abuse.
Drug holidays in women treated for postmenopausal osteoporosis.
In this Practice Pearl, the experience with long-term treatment of osteoporosis with bisphosphonates and denosumab will be reviewed as well as the effects of discontinuing therapy, providing the
Risk of atypical femoral fracture during and after bisphosphonate use.
This letter indicates that there is long-lasting skeletal accumulation of bisphosphonate, and ongoing use appears to be the dominant risk factor for rare fractures.
Bisphosphonate therapy and atypical fractures.
Romosozumab versus Teriparatide for the Treatment of Postmenopausal Osteoporosis: A Systematic Review and Meta‐analysis through a Grade Analysis of Evidence
To provide a systematic review about the efficacy and safety of romosozumab and teriparatide for the treatment of postmenopausal osteoporosis.
Osteoporosis Treatment: When to Discontinue and When to Re-start
TLDR
Bisphosphonate treatment, unlike hormone replacement, denosumab or teriparatide, is associated with benefits extended even after treatment discontinuation, most apparent for alendronate and zoledronate.
Bisphosphonate drug holiday: who, when and how long
TLDR
There is considerable controversy regarding the optimal duration of therapy and the length of the holiday, both of which should be based on individual assessments of risk and benefit.
...
...

References

SHOWING 1-5 OF 5 REFERENCES
The Effect of 3 Versus 6 Years of Zoledronic Acid Treatment of Osteoporosis: A Randomized Extension to the HORIZON-Pivotal Fracture Trial (PFT)
  • D. Black, I. Reid, R. Eastell
  • Medicine
    Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research
  • 2012
TLDR
Small differences in bone density and markers in those who continued versus those who stopped treatment suggest residual effects, and therefore, after 3 years of annual ZOL, many patients may discontinue therapy up to 3 years, however, vertebral fracture reductions suggest that those at high fracture risk, particularly vertebral fractures, may benefit by continued treatment.
Seven Years of Treatment with Risedronate in Women with Postmenopausal Osteoporosis
TLDR
After 7 years of continuous risedronate treatment there were significant increases in BMD and decreases in bone turnover to within premenopausal levels and there was no indication of any loss of anti-fracture efficacy.
Effects of continuing or stopping alendronate after 5 years of treatment: the Fracture Intervention Trial Long-term Extension (FLEX): a randomized trial.
TLDR
The results suggest that for many women, discontinuation of alendronate for up to 5 years does not appear to significantly increase fracture risk, however, women at very high risk of clinical vertebral fractures may benefit by continuing beyond 5 years.
Efficacy of continued alendronate for fractures in women with and without prevalent vertebral fracture: The FLEX Trial
  • A. Schwartz, D. Bauer, D. Black
  • Medicine
    Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research
  • 2010
TLDR
Continuing ALN for 10 years instead of stopping after 5 years reduces NVF risk in women without prevalent vertebral fracture but does not reduce risk of NVF in women whose T‐scores are greater than −2.5 or less.
Immigrants and health care--at the intersection of two broken systems.
  • S. Okie
  • Medicine, Political Science
    The New England journal of medicine
  • 2007
TLDR
Dr. Susan Okie writes that the remedy is not immigrant bashing but health care reform.