Osteoporosis in postmenopausal women

Clinical question

How effective are bisphosphonates and denosumab for preventing fractures in postmenopausal women?

Bottom line

Bisphosphonates and denosumab are similarly effective. Over 1 to 4 years, bisphosphonates or denosumab provide an absolute reduction of about 0.5% to 1.0% for hip fractures, 1.5% to 3% for nonvertebral fractures, and 3% to 6% for vertebral fractures, compared with placebo.

Evidence

Differences are statistically significant unless noted.

Bisphosphonates

• Eleven systematic reviews¹ compared alendronate, risedronate, or zoledronate with placebo.

• The systematic reviews with the best quality and reporting found that over 1 to 4 years, bisphosphonates reduced the following.

  • - Hip fracture (4-7 RCTs, 9863-11 859 patients)^2-4: 0.5% to 2.0% vs 1% to 3% with placebo (NNT = 100-200).

  • - Nonvertebral fracture (4-6 RCTs, 9625-12 397 patients)^2,3,5: about 9% vs about 11% with placebo (NNT = 35-65).

  • - Vertebral fracture (2-6 RCTs, 3139-7802 patients)^2-4: 3% to 8% vs 7% to 13% with placebo (NNT = 16-33).

• Results are consistent with other systematic reviews.¹

• Systematic reviews rarely distinguish true primary and secondary prevention.^2,3 The best data⁶ suggest similar relative benefit in primary and secondary prevention (eg, alendronate: relative risk is 0.74 vs 0.81 for nonvertebral fracture and 0.60 vs 0.53 for vertebral fracture).

Denosumab

• Five systematic reviews¹ compared denosumab with placebo; absolute event rates by fracture type not reported.

• The largest RCT⁷ (7868 postmenopausal women, T-score ≤ -2.5) compared denosumab with placebo over 3 years.

  • - Hip fracture: 0.7% vs 1.1% placebo (NNT = 230).

  • - Nonvertebral fracture: 6.1% vs 7.5% placebo (NNT = 72).

  • - Vertebral fracture: 2.3% vs 7.1% placebo (NNT = 21).

Bisphosphonates versus denosumab

• One systematic review¹ reported no difference in hip, nonvertebral, and vertebral fractures.

• Four systematic reviews¹ (4-11 RCTs, 1942-5446 patients) reported no difference in clinical fracture risk.

Context

• Overall limitations: event rates infrequently reported, variable outcome definitions, industry funding of RCTs.

• Atypical fracture risk with bisphosphonates increases with duration of therapy, particularly beyond 5 years.⁸.

  - Fractures prevented outnumber atypical fractures at about 14-100:1 with 5 years of treatment.

• Approximate drug cost (per year)⁹: $480 for risedronate and alendronate, $350 for zoledronate intravenous infusion, $800 for denosumab subcutaneous injection.

Implementation

The osteoporosis screening tool is a simplified tool that reliably predicts osteoporosis and identifies those who would benefit from bone mineral density testing.¹⁰ Before starting a bisphosphonate or denosumab, discuss fracture risk and potential risks and benefits with the patient. The Mayo Clinic’s Bone Health Choice Decision Aid provides information to support that discussion.¹¹ When prescribing, consider duration of therapy. Evidence suggests that after 5 years of treatment, discontinuation of bisphosphonates carries little to no increased future fracture risk,¹² and atypical fracture risk increases with duration of therapy beyond 5 years.⁸