Re: Bisphosphonates in the treatment of osteoporosis

3 September 2012

Dr Loukota refers to an “exponential increase” in the incidence of osteonecrosis of the jaw (ONJ) associated with bisphosphonate use. We are unaware of any evidence for this in patients treated with bisphosphonates for osteoporosis, either in the review quoted by Dr Loukota or in the published literature. The precautions set out in our paper are fully in line with those recommended by the Medicine and Healthcare Regulatory Authority (MHRA). 1 In particular, the MHRA recommends routine dental examination prior to starting bisphosphonates only in cancer patients, in whom the risk of ONJ is substantially greater.

Musini et al question the risk/benefit balance of bisphosphonates when used for the prevention of fractures, based on two brief systematic reviews available on-line as “Therapeutic letters”. Surprisingly, their assessment of efficacy, which is restricted to etidronate, alendronate and risedronate, excludes as an outcome the most common osteoporotic fracture, namely vertebral fracture. The fact that the majority of vertebral fractures do not come to medical attention does not mean that they are asymptomatic and there is robust evidence that morphometric spine fractures have significant effects on quality of life and, importantly, independently increase the risk of further fractures. 2,3 The studies on which their review of adverse effects is based also appears to be highly selective; for example, their conclusion that bisphosphonate use is associated with increased risk of oesophageal cancer is based on only one study from the General Practice Research Database (GPRD), and ignores other published reports (including another from the GPRD) that reached different conclusions. 4

When used in high-risk patients, bisphosphonates have well documented efficacy in reducing the risk of fracture. Serious side-effects, such as ONJ and atypical fractures are rare and significantly outnumbered by the number of osteoporotic fractures prevented with appropriate use of bisphosphonate therapy.

References

1. http://www.mhra.gov.uk/Safetyinformation/DrugSafetyUpdate/CON087832

2. Pluijm SM, Tromp AM, Smit JH, Deeg DJ, Lips P. Consequences of vertebral deformities in older men and women. J Bone Miner Res 2000;15:1564-72.

3. Wustrack R, Seeman E, Bucci-Rechtweg C, Burch S, Palermo L, Black DM. Predictors of new and severe vertebral fractures: results from the HORIZON Pivotal Fracture Trial. Osteoporos Int 2012;23:53-8.

4. Cardwell CR, Abnet CC, Cantwell MM, Murray LJ. Exposure to oral bisphosphonates and risk of esophageal cancer. JAMA 2010;304:657-63.

Competing interests: As stated in article

Juliet E Compston, Professor of Bone Medicine

Ken Poole

University of Cambridge School of Clinical Medicine, Hills Road, Cambridge CB2 0QQ

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