Bone Drugs: Are they worthwhile?

Conflicting advice on bone drugs — what does the evidence say?

It’s no secret that I’m no fan of bone drugs in general. I’ve found the arguments for their use deeply unconvincing for decades. And now, European researchers looking at the accumulated evidence about the various drugs’ long-term effects are starting to come to the same conclusion:

Except in extreme cases, bone drugs don’t offer enough benefit in reducing the risk of fractures to be worth the price paid in terms of both short- and long-term side effects.

A European/Canadian research group reviewed the evidence on bisphosphonates like:

  • alendronate (Fosamax),
  • ibandronate (Boniva) and zoledronic acid (Zometa or Reclast)
  • teriparatide (Forteo)
  • denosumab (Prolia)
  • two treatments not used in the U.S.: calcitonins and strontium ranelate

Their findings struck me as good general “lessons” for all of us to learn.

‘Denser’ bones are not always stronger bones

The review found that the majority of osteoporotic fractures happened in those who did not have “osteoporotic bone density.” This helps confirm: Bone density alone cannot predict fracture risk.

Other recent studies show a large percentage of people who fracture have only osteopenia or even normal bone density. Many people with an osteoporotic bone density never fracture.

Not all fractures are created equal

When it comes to assessing bone drugs’ effects, a painless vertebral fracture or a toe fracture (painful, but not life-altering) shouldn’t be considered as clinically important as a hip fracture, which is life-changing.

Yet many drug trials either focus on vertebral fractures or on “non-vertebral” fractures as an endpoint. The stubbed toe becomes equivalent to a hip fracture in determining how effective the drugs are in fracture prevention.

Not surprisingly, when hip fractures are looked at specifically as the endpoint of choice, the researchers discover something different. They found that the data on less serious fractures of toes, wrists and so forth obscure the fact that the drugs don’t do much to prevent the most serious and dangerous osteoporotic fractures.

Bone drugs’ benefits remain inconclusive

The benefits of taking a bone drug must outweigh the costs for it to be worth recommending. And even in high-risk older adults, such benefits have not been shown conclusively.

In weighing the risk-benefits of bone drugs, researchers took a hard line on the importance of evaluating all costs. “Clinical trials evaluating harm-benefit balance in osteoporosis or fracture prevention should be well-powered long-term studies that include hard endpoints,” they note. “Total mortality, total serious adverse events, hip fractures, and functional status are essential outcomes.”

New U.S. osteoporosis guidelines miss the mark

What’s frustrating to me is that experts in the U.S. still focus uncritically on the flawed studies that the review critiques. They glibly parrot the ideas that bone density is the same thing as fracture risk and that drugs offer protection from fractures.

Case in point: The American College of Physicians’ latest osteoporosis guidelines, which were published virtually simultaneously with the European review. They make a “strong recommendation” for the use of bisphosphonate drugs “to reduce the risk of hip and vertebral fractures.” Most galling to me, they openly equate bone mineral density with fracture risk: “most women with normal DXA scores” it notes, “do not progress to osteoporosis within 15 years.”

To which I respond with the European review’s first lesson: Denser bones ≠ stronger bones.

References:
Erviti J, Gorricho J, Saiz LC, Perry T, Wright JA. Rethinking the Appraisal and Approval of Drugs for Fracture Prevention. Front Pharmacol. 15 May 2017 | https://doi.org/10.3389/fphar.2017.00265

Qaseem A, Forciea MA, McLean RM, Denberg TD, for the Clinical Guidelines Committee of the American College of Physicians. Treatment of Low Bone Density or Osteoporosis to Prevent Fractures in Men and Women: A Clinical Practice Guideline Update From the American College of Physicians. Ann Intern Med. 2017;166:818–839.


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