GPs can discontinue bisphosphonate treatment in postmenopausal women after three to five years without substantially increasing their risk of a subsequent fracture, say experts after a major review of recent evidence into the drugs.
The review by the US Food and Drugs Administration found a fracture rates were ‘remarkably similar' in postmenopausal women taking bisphosphonates for over six years, and those who switched to placebo after three to five years of continuous bisphosphonate therapy.
The advice comes after a major study linked bisphosphonate treatment with an increased risk of atypical femoral fractures, compounding concerns over long-term use of the drugs to prevent osteoporosis.
The FDA pooled data from three trials involving 2,496 women who took bisphosphonates for three to five years. Some of the women continued taking the treatments for six or more years, whilst others switched to placebo.
Those who continued treatment had mean fracture rates of 9.3-10.6% whilst those for those switched to placebo had rates of 8.0-8.8%.
The analysis concluded: ‘Statistical limitations preclude inferring any meaningful association between long-term treatment and increased risk of fracture.'
In an editorial discussing the FDA's analysis, experts recommended that GPs consider discontinuing bisphosphonate treatment after three to five years in the light of concerns over atypical fractures with long-term use.
‘The emergence of safety concerns warrants consideration of new treatment algorithms for patients with osteoporosis.
‘The available data do suggest that bisphosphonates may be safely discontinued in some patients without compromising therapeutic gains, but no adequate clinical trials have yet delineated how long the drugs' benefits are maintained after cessation.'
The advice comes as a new case-control study looked at 477 patients hospitalised with a subtrochanteric or femoral fracture, and compared their bisphosphnate use with a random sample of healthy indivisuals.
They found 82% of patients treated for atypical fractures had been treated with bisphosphonates, compared with just 6.4% of patients with classic fractures. There was an increased risk of atypical fracture in those patients who had a longer duration of bisphosphonate treatment.
Dr Pam Brown, a GP in Swansea with a special interest in osteoporosis, said the FDA recommendations should encourage GPs to review all bisphosphonate patients after three years, although warned against
She said: ‘Review patients after three to five years on therapy and discontinue alendronate or zoledronate in those without previous vertebral fractures with osteopenic bone mineral density.'
But she warned: ‘Much uncertainty remains – how long to continue treatment in those who remain at high fracture risk, and what treatment to use after bisphosphonates.'
NEJM 2012, online 9 May
http://www.nejm.org/doi/full/10.1056/NEJMp1202619
|
Group |
Mean fracture rates over six years |
|
Women remaining on bisphosphonates |
9.3-10.6% |
|
Those switched to placebo |
8.0-8.8%. |
Source: NEJM 2012, online 9 May
