Effects of prolonged bisphosphonate therapy and its discontinuation on bone mineral density in post-menopausal...

The bisphosphonates have proven efficacy in the management of post-menopausal osteoporosis. However, the benefits of prolonged (> 2 years) administration and the effects of discontinuation of bisphosphonate treatment are not clear.

We have previously reported a 2-year, randomized, double-blind, placebo-controlled trial of pamidronate therapy (150 mg/day) in women with established post-menopausal osteoporosis. We now report the bone mineral density (BMD) changes in those women who continued for a third year of active treatment and were then observed off therapy for a further 12 months.

Twenty-two women (mean age 66 years) continued on pamidronate in year 3, and in 16 of these the effects of subsequent discontinuation of therapy for 12 months were studied.

BMD was measured in the total body, lumbar spine and proximal femur using a Lunar DPX-L dual-energy, X-ray absorptiometer.

The third year of therapy with pamidronate was associated with a significant further gain in BMD only at the lumbar spine (2.1 +/- 0.6%, P = 0.003), resulting in a total gain of 9.5 +/- 1.0% at that site over 3 years of treatment. In the total body, BMD tended to decline (-0.6 +/- 0.3%) in year 3. One year after discontinuation of pamidronate, there were significant losses of BMD in the total body (-1.9 +/- 0.3%, P < 0.0001) and femoral trochanter (-2.7 +/- 0.9%, P = 0.01), and non-significant changes at the lumbar spine (-0.9 +/- 0.8%), femoral neck (-0.5 +/- 1.6%), and Ward's triangle (-2.9 +/- 3.7%). By the end of one year off therapy, BMD was greater than baseline only in the lumbar spine (7.1 +/- 1.1%, P < 0.0001) and femoral trochanter (4.5 +/- 1.88%, P < 0.03). In the total body, BMD was 0.3 +/- 0.7% below the values at the trial's inception (P = 0.7).

These data demonstrate that the rate of bone gain associated with bisphosphonate use slows over time, and that significant bone loss follows withdrawal of these agents. These findings have important implications for the duration of use of these novel drugs in the therapy of osteoporosis and suggest a need for close observation following their discontinuation.