Alendronate for preventing fractures caused by osteoporosis in postmenopausal women

This summary of a Cochrane review presents what we know from research about the effect of alendronate for preventing fractures (broken bones) caused by osteoporosis.

In women who have already been diagnosed with low bone density, putting them at risk for a fracture, or have already had a fracture in the bones of their spine, alendronate:

- may prevent fractures in the spine, hip or wrist, or in bones other than the spine.

In women whose bone density is closer to normal, or who may not yet have had a fracture in the bones of their spine, alendronate:

- probably prevents fractures in the spine

- probably leads to no difference in fractures of the hip, wrist or bones other than the spine.

We often do not have precise information about side effects and complications. This is particularly true for rare but serious side effects. Possible side effects may include digestive problems such as injury to the throat, esophagus and stomach and, less commonly, reduced blood supply to the jaw bone, which causes the bone tissue to break down.

What is osteoporosis and what is alendronate?
Bone is a living, growing part of your body. Throughout your lifetime, new bone cells grow and old bone cells break down to make room for the new, stronger bone. When you have osteoporosis, the old bone breaks down faster than the new bone can replace it. As this happens, the bones lose minerals (such as calcium). This makes bones weaker and more likely to break even after a minor injury, like a little bump or fall. Women are more likely to get osteoporosis after menopause.

Alendronate belongs to the class of drugs called bisphosphonates. It is a type of medication that slows down the cells that break down the old bone.

The best estimate of what happens to women that have already been diagnosed with low bone density or have already had a fracture in the bones of their spine:

Fracture of the spine

              - 12 out of 100 women had a fracture when taking a placebo

              - 6 out of 100 women had a fracture when taking alendronate

Fracture in the hip or wrist

               - 2 out of 100 women had a fracture when taking a placebo

               - 1 out of 100 women had a fracture when taking alendronate

Fractures in bones other than the spine

               - 9 out of 100 women had a fracture when taking a placebo

               - 7 out of 100 women had a fracture when taking alendronate

The best estimate of what happens to women whose bone density is closer to normal or who may not yet have had a fracture in the bones of their spine:

Fracture of the spine

                - 3 out of 100 women had a fracture when taking a placebo

                - 1 out of 100 women had a fracture when taking alendronate

 Fractures in bones other than the spine:

                 - 1 out of 100 women had a hip fracture when taking a placebo

                 - 1 out of 100 women had a hip fracture when taking alendronate

               - 3 out of 100 women had a wrist fracture when taking a placebo

                 - 4 out of 100 women had a wrist fracture when taking alendronate

 

                - 13 out of 100 women had a fracture somewhere other than the spine when taking a placebo

                 - 12 out of 100 women had a fracture somewhere other than the spine when taking alendronate

Authors' conclusions: 

At 10 mg per day, both clinically important and statistically significant reductions in vertebral, non-vertebral, hip and wrist fractures were observed for secondary prevention ('gold' level evidence, www.cochranemsk.org). We found no statistically significant results for primary prevention, with the exception of vertebral fractures, for which the reduction was clinically important ('gold' level evidence).

Read the full abstract...
Background: 

Osteoporosis is an abnormal reduction in bone mass and bone deterioration leading to increased fracture risk. Alendronate belongs to the bisphosphonate class of drugs, which act to inhibit bone resorption by interfering with the activity of osteoclasts.

Objectives: 

To assess the efficacy of alendronate in the primary and secondary prevention of osteoporotic fractures in postmenopausal women.

Search strategy: 

We searched CENTRAL, MEDLINE and EMBASE for relevant randomized controlled trials published between 1966 to 2007.

Selection criteria: 

Women receiving at least one year of alendronate, for postmenopausal osteoporosis, were compared to those receiving placebo and/or concurrent calcium/vitamin D. The outcome was fracture incidence.

Data collection and analysis: 

We undertook study selection and data abstraction in duplicate. We performed meta-analysis of fracture outcomes using relative risks and a > 15% relative change was considered clinically important. We assessed study quality through reporting of allocation concealment, blinding and withdrawals.

Main results: 

Eleven trials representing 12,068 women were included in the review.

Relative (RRR) and absolute (ARR) risk reductions for the 10 mg dose were as follows. For vertebral fractures, a significant 45% RRR was found (RR 0.55, 95% CI 0.45 to 0.67). This was significant for both primary prevention, with 45% RRR (RR 0.55, 95% CI 0.38 to 0.80) and 2% ARR, and secondary prevention with 45% RRR (RR 0.55, 95% CI 0.43 to 0.69) and 6% ARR. For non-vertebral fractures, a significant 16% RRR was found (RR 0.84, 95% CI 0.74 to 0.94). This was significant for secondary prevention, with 23% RRR (RR 0.77, 95% CI 0.64 to 0.92) and 2% ARR, but not for primary prevention (RR 0.89, 95% CI 0.76 to 1.04). There was a significant 40% RRR in hip fractures (RR 0.60, 95% CI 0.40 to 0.92), but only secondary prevention was significant with 53% RRR (RR 0.47, 95% CI 0.26 to 0.85) and 1% ARR. The only significance found for wrist was in secondary prevention, with a 50% RRR (RR 0.50 95% CI 0.34 to 0.73) and 2% ARR.

For adverse events, we found no statistically significant differences in any included study. However, observational data raise concerns regarding potential risk for upper gastrointestinal injury and, less commonly, osteonecrosis of the jaw.