Bisphosphonates - clinical applications in osteoporosis

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Editor, – At last some common sense seems to be finding its way into medical thinking. Professor John Marley assures us of what we have all known at the back of our minds: that efficacy is not the same as effectiveness (Aust Prescr 2000;23:114-5). We have heard so much about evidence-based medicine and Cochrane reviews that we have barely escaped the conclusion that evidence-based, statistically sanctified, Cochrane-metanalysed* medicine is the only proper kind for us to practise. In the real world we are not free, as trial-makers are, to exclude patients because of age or concurrently taken drugs or comorbidities, so we have to use a little of that ancient virtue intuition when grappling with many problems.

Another improvement is that we are being given absolute risks along with 'risk reduction ratios'. The latter, of course, are the selling ploys of the drug companies - they seem so persuasive! Without the corresponding absolute risks they are virtually meaningless, and no basis for clinical decisions. The derivative parameter 'number needed to treat' (NNT), admirably set out in the article on bisphosphonates (Aust Prescr 2000;23:133-6), is much more useful. However, there are grave ambiguities: is the NNT based on the number of people to whom the doctor says 'I intend to treat you with a daily dose of Bonehardna for five years', or the number who actually comply with the treatment regimen? And is it the lifetime NNT or does it apply to a time-span such as a year? These points need to be stated.

Lastly, I have struggled to find meaning in the sentence: 'Increases were 4.3% greater than placebo in the lumbar spine, 2.8% in the femoral neck ...' (p.134, col. 2). 4.3% of what? If the placebo produced 100 units of improvement, did the risedronate produce 104.3? This is what the words seem to mean (and again, in how much time?), but it is hardly a strong recommendation, since the placebo is likely to have produced a negative benefit. Or does it mean something else? If it does, why not say so?

Alasdair Livingston
Mitcham, SA

* I decline to use the horrible word 'meta-analysis'. The Greeks had no qualms about eliding two or more prefixes together, and if we borrow their language, nor should we.

Associate Professor Peter Ebeling, author of 'Bisphosphonates - clinical applications in osteoporosis', comments:

I would like to thank Dr Livingston for his comments on 'Bisphosphonates - clinical applications in osteoporosis'. I agree with Dr Livingston that the absolute risk of an outcome is more important than the relative risk reduction, particularly when considering an individual patient's treatment. The duration of treatment required to calculate the number needed to treat appears in the tables and is for five years' and three years' treatment with alendronate and risedronate, respectively, in women with postmenopausal osteoporosis and at least one baseline vertebral fracture. For osteoporotic women without vertebral fractures, the number needed to treat was calculated for only four years of treatment with alendronate - as the data for the risedronate hip fracture study1 had not been published at the time of preparation of the manuscript.

Regarding the changes in bone density in the risedronate fracture study, the differences between the treatment and placebo groups represent changes from baseline at three years, expressed as a percentage. In the placebo group small significant increases or decreases in bone density from baseline were seen depending on the skeletal site measured. Thus, treatment with calcium 1000 mg per day +/- vitamin D in the placebo group for three years resulted in a 1.1% increase in spinal bone density, but did not prevent bone loss from femoral sites in postmenopausal women with osteoporosis.


  1. Hip Intervention Program Study Group. Effect of risedronateon the risk of hip fracture in elderly women. N Engl J Med 2001;344:333-40.