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In women with osteoporosis, denosumab, teriparatide, and some bisphosphonates reduce spinal and non-spinal fractures

Crandall CJ, Newberry SJ, Diamant A, et al. Comparative Effectiveness of Pharmacologic Treatments to Prevent Fractures: An Updated Systematic Review. Ann Intern Med. 2014;161:711-23.

Review questions

In people with osteoporosis, do drugs prevent fractures (bone breaks)? Are some drugs better than others? What are the side-effects of drugs?

Background

Osteoporosis weakens your bones and makes them more likely to fracture, often at the hip, spine, or wrist. Anyone can get osteoporosis. Drugs may prevent fractures, although they also have side-effects.

How the review was done

The researchers did a systematic review, searching for studies that were published in English up to March 2014.

They found 294 studies, including systematic reviews, randomized controlled trials, and nonrandomized studies.

The key features of the randomized trials were:

  • people had osteoporosis that was not caused by other treatments;
  • drugs were bisphosphonates (alendronate [Binosto®, Fosamax®], ibandronate [Boniva®, Bondronat®], risedronate [Actonel®, Atelvia®], or zoledronic acid [Reclast®, Zometa®]), denosumab (Prolia®, Xgeva®), teriparatide (Forteo®, Parathar®), or raloxifene (Evista®, keoxifene);
  • drugs were compared with one another or placebo; and
  • people were followed-up for at least 6 months.

What the researchers found

Compared with placebo:

  • alendronate, risedronate, zoledronic acid, denosumab, and teriparatide reduced spinal and non-spinal fractures in women;
  • ibandronate and raloxifene reduced spinal fractures in women; and
  • data in men are sparse, but zoledronic acid reduced spinal fractures in men.

There wasn’t enough information to determine if some drugs were better than others.

The drugs had different side-effects.

Conclusions

In women with osteoporosis, alendronate, risedronate, zoledronic acid, denosumab, and teriparatide reduce spinal and non-spinal fractures, and ibandronate and raloxifene reduce spinal fractures. The drugs have different side-effects. In men, zoledronic acid reduced spinal fractures.

Benefits and harms of drugs for preventing fractures in people with osteoporosis

Outcomes

Drugs

Comparison

Absolute effect of drugs

Strength of evidence*

Spinal fractures in women

Alendronate, ibandronate, risedronate, zoledronic acid, denosumab, teriparatide, raloxifene

Placebo

About 11 to 17 fewer women out of 1,000 had spinal fractures

Strong

Non-spinal fractures in women

Alendronate, risedronate, zoledronic acid, denosumab, teriparatide

Placebo

About 15 to 20 fewer women out of 1,000 had non-spinal fractures

Strong

 

Raloxifene

Placebo

No effect

Not reported

Spinal fractures in men

Zoledronic acid

Placebo

About 33 fewer men out of 1,000 had spinal fractures

Moderate – just 1 study

SIDE-EFFECTS

 

 

 

 

Mild upper-gastrointestinal symptoms

Bisphosphonates, denosumab, teriparatide

Not reported

About 72 to 956 events in 1,000 people

Strong

Atypical fracture of the thigh bone

Bisphosphonates

Not reported

About 2 to 100 events in 100,000 women

Low

Osteonecrosis (loss) of the bone of the jaw

Bisphosphonates

Not reported

Fewer than 1 to about 43 people out of 1,000 had events

Low

Influenza-like symptoms

Zoledronic acid

Not reported

About 728 to 896 events in 1,000 people

Strong

Hypocalcemia (low calcium levels in blood)

Zoledronic acid

Not reported

About 5 to 118 events in 1,000 people

Strong

Infection

Denosumab

Not reported

About 8 more people out of 1,000 had infections

Moderate

Hypercalcemia (high calcium levels in blood)

Teriparatide

Not reported

About 537 to 820 events in 1,000 people

Strong

Headache

Teriparatide

Not reported

About 511 to 679 events in 1,000 people

Strong

Hot flashes or thromboembolic events

Raloxifene

Not reported

About 24 to 35 events in 1,000 people

Strong

*Based on Agency for Healthcare Research and Quality criteria.




Glossary

Gastrointestinal
Related to the stomach and the intestines (bowels).
Placebo
A harmless, inactive, and simulated treatment.
Randomized controlled trials
Studies where people are assigned to one of the treatments purely by chance.
Systematic review
A comprehensive evaluation of the available research evidence on a particular topic.

Related Web Resources

  • Preventing Blood Clots After Hip or Knee Replacement Surgery or Surgery for a Broken Hip: A Review of the Research for Adults

    OHRI
    This patient decision aid helps adults considering or planning to have a total hip or knee replacement surgery or surgery for a broken hip decide on the best method for preventing blood clots after surgery. It facilitates the process by outlining and comparing the benefits, risks and side effects of each treatment option.
  • Healthy Bones: A Decision Aid for Women After Menopause

    OHRI
    This patient decision aid helps women who have gone through menopause and may have osteoporosis decide on methods to keep your bones healthy. It facilitates the process by outlining and comparing the choices such as medicine, menopausal hormone therapy (MHT), and exercise.
  • Osteoporosis screening: topic overview

    Health Link B.C.
    Osteoporosis Canada recommends everyone over age 65 have routine bone density tests. Start routine testing earlier if you are at increased risk for broken bones. Use the FRAX tool to predict your risk of having a fracture related to osteoporosis (link in this resource).
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