Jump to content

Denosumab: Limited efficacy in fracture prevention, too many adverse effects (anon)

Recommended Posts

Prescrire Int. 2011 Jun;20(117):145-8.

Denosumab. Limited efficacy in fracture prevention, too many adverse effects.

[No authors listed]


The standard drug for postmenopausal osteoporotic women with a high risk of fracture is alendronic acid, used in conjunction with non-drug measures. There are no drugs with demonstrated efficacy on the risk of fracture in castrated men with prostate cancer. Denosumab, a monoclonal antibody that inhibits a cytokine acting mainly on bone cells and lymphocytes, has been authorised in the European Union for use in both these settings. There are no trials comparing denosumab versus alendronic acid for symptomatic fracture prevention. In two trials involving 1189 and 504 women, the incidence of clinical fractures, recorded as simple adverse effects, did not differ significantly between the groups. In a placebo-controlled trial in about 7900 elderly osteoporotic women, denosumab significantly reduced the incidence of symptomatic vertebral fractures (0.8% versus 2.6% after 3 years) and hip fractures (0.7% versus 1.2%). An indirect comparison, providing weak evidence, suggests that denosumab is less effective than alendronic acid. In a placebo-controlled trial in 1468 castrated men with prostate cancer, denosumab did not reduce the incidence of symptomatic fractures after 3 years. Only the incidence of vertebral fractures, detected on routine radiographs, showed a statistically significant decline (1.5% versus 3.5%). Denosumab has numerous adverse effects. In placebo-controlled trials, this monoclonal antibody was associated with a higher incidence of deep-seated infections such as endocarditis, cancer, and skin rash. More data are needed on the risk of pancreatitis, long-term bone disorders (atypical fractures, delayed fracture healing, osteonecrosis of the jaw), hypocalcaemia and cataracts, all of which were reported in clinical trials. In practice, denosumab is not sufficiently effective to outweigh its established and potential risks in postmenopausal osteoporotic women or in castrated men with prostate cancer.

PMID: 21678700

This extract can be found on http://PubMed.com, and is in the public domain.

On PubMed.com there will be a link to the full paper (often $30, sometimes free).

Any highlighting (except the title) is not by the author, but by Jim Marshall.

Jim is not a doctor.

Link to comment
Share on other sites


I dont know that the above article is the full story in the use of denosumab for advanced PC.

I have seen some question marks on its efficacy in some cases and the side effect risk may be greater than zometa in others but am sure I have seen journal articles claiming better results than zometa in others again.

The above article seems to emphasise fracture prevention in women rather than bone metastases resistance in men.

If the above article is the full story then why in the heck are PBS approving denosumab for subsidised usage by advanced PC patients?

Link to comment
Share on other sites


Find attached brief article on FDA approval for Denosumab – I extracted it from the ACT Support Group website.

Next email I read after yours was from ACT incl their newsletter (The Walnut) – which referred to this.

So throw it into the mix for consideration.

Certainly don’t want to oversell the benefits of treatments and any warts should be fully exposed but reading the article you posted by itself would make me run a mile from denosumab.

I suspect that may not be the full story.

Regards Tony

Click on this link for: FDA Approves Denosumab for the Treatment of Bone Loss in Patients With Prostate or Breast Cancer


Link to comment
Share on other sites


The New England Journal article seems to confirm that Denosumab did not cut the number of symptomatic fractures in 3 years.

And that significantly more non-symptomatic vertebral fractures, detectable only on scans, were found in the placebo group.

Of course, if these later progressed to symptomatic, fractures of the spine are much more significant, and potentially fatal.

A longer study would be needed to see if this progression of the vertebral fractures to symptomatic fractures is significantly different in Denosumab vs placebo.

Again we have to depend upon the experience and judgement of our doctors, balancing the risk that scan-only fractures of the spine might progress against the known, and unknown (because of newness) side effects of the drug.

Link to comment
Share on other sites


This topic is now archived and is closed to further replies.

  • Create New...