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Are bisphosphonates safe long-term?

A Bisphosphonate drugs improve bone density and decrease fracture risk. At a tissue level they do this by decreasing bone turnover. Measurement of bone markers (chemical indicators of bone formation and resorption, which can be measured in blood or urine) indicate both bone resorption and formation are reduced by bisphosphonate therapy.

Histological studies before and after bisphosphonate treatment confirm this.

Because bone formation is reduced there are theoretical concerns that long-term use may compromise bone integrity. Furthermore, early studies with etidronate showed it can cause osteomalacia by reducing bone mineralisation, particularly with high, continuous doses and when there is concomitant vitamin D deficiency.

Fortunately there is now published long-term follow-up data on subjects who have taken cyclical etidronate or alendronate for seven years and risedronate for three years.

These have variously reviewed a combination of bone density measurements, bone bichemical marker changes, fracture reduction and histological changes.

None has found any evidence for adverse effects in bone, in fact they show the opposite ­ patients continue to gain benefit and those with the longest exposure have the lowest fracture rates.

There is no published data on people who have taken bisphosphonates for longer than seven years, although in practice there are many who seem to be doing well beyond seven years and I do not recommend routinely stopping treatment then.

Dr Theresa Allain is a

consultant geriatrician at Southmead Hospital, Bristol

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