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Many osteoporosis medications prevent fractures, but none is proven best

Many medications reduce the risk of bone fractures in people with osteoporosis, but the most commonly used drugs—bisphosphonates—have not been proven more effective than alternatives, according to a new report funded by the Agency for Healthcare Research and Quality (AHRQ).

The AHRQ report compared the effectiveness and risks of six bisphosphonates: alendronate (sold as Fosamax), etidronate (Didronel), ibandronate (Boniva), pamidronate (Aredia), risedronate (Actonel), and zoledronic acid (Zometa). The report also looked at estrogen, calcitonin (a man-made hormone), calcium, vitamin D, testosterone, parathyroid hormone, and selective estrogen receptor modulators (SERMs).

Not enough scientific evidence exists to establish whether bisphosphonates are better at preventing fractures than estrogen, calcitonin, or raloxifene, according to the report. Some agents, however, such as estrogen and raloxifene (a SERM), can have serious side effects such as strokes, blood clots in the lungs, or bleeding in the uterus. The effectiveness of calcium and vitamin D, meanwhile, may vary according to dosing, how often they are taken, and whether the patient taking them is at high risk for a fracture. There is limited evidence to compare the supplements with other therapies for preventing fractures.

The report also found that many osteoporosis patients stop taking their medications as prescribed. Some stop because they experience no osteoporosis symptoms. Others stop because of medication side effects or because dosing is too frequent. This finding was also true for supplements such as calcium. Not taking medications as prescribed increases the chances of bone fractures. Patients who take bisphosphonates in weekly formulations, rather than daily, are more likely to follow prescriptions.

Osteoporosis is a skeletal disease that affects about 44 million Americans, especially women who have finished menopause. It occurs when deteriorating tissue reduces bone density in the spine, hip, and other areas. Some people with the disease fracture bones, become disabled, or experience chronic pain. Overall, about half of women aged 50 and older will suffer an osteoporosis-related bone break in their lifetime. About one-fourth of those who fracture a hip will die within a year.

Bisphosphonates, the most commonly used medications for osteoporosis, are nonhormonal drugs that bind to bone to protect against tissue breakdown. AHRQ's analysis found that five bisphosphonates—alendronate, etidronate, ibandronate, risedronate, and zoledronic acid—plus calcitonin, parathyroid hormone, estrogen, and raloxifene prevent spinal fractures.

Evidence also showed that alendronate, risedronate, and zoledronic acid, as well as estrogen and parathyroid hormone, prevent hip and other nonspinal fractures. Direct comparisons, however, have not shown bisphosphonates to be superior to other therapies in preventing bone fractures. No single bisphosphonate has been proven most effective in that class.

The AHRQ report, Comparative Effectiveness of Treatments To Prevent Fractures in Men and Women With Low Bone Density or Osteoporosis, summarized the scientific evidence in 101 published articles. It was authored by the Southern California Evidence-Based Practice Center at the RAND Corporation in Santa Monica, CA.

Among the conclusions:

  • Among post-menopausal women with osteoporosis, alendronate, etidronate, ibandronate, risedronate, calcitonin, teriparatide, and raloxifene reduce fracture risks.
  • Not enough evidence exists to determine how exercise or taking testosterone compares with medications in preventing osteoporosis-related fractures.
  • Calcitonin, risedronate, and teriparatide reduce fracture risks among men.
  • For people at increased risk of falling, such as those with partial paralysis or Parkinson's disease, fracture risks are reduced if they are treated with alendronate, risedronate, or vitamin D.
  • Patients who take raloxifene face increased risk of blood clots in the lungs and other areas as well as mild cardiac problems such as chest pains or palpitations.

The report on osteoporosis medications is the newest analysis from AHRQ's Effective Health Care program. That program represents an important Federal effort to compare alternative treatments for significant health conditions and make the findings public. The program is intended to help patients, doctors, nurses, and others choose the most effective treatments.

Information on the Effective Health Care program, including full reports, can be found at

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