EFFECTS OF PROLONGED BISPHOSPHONATE THERAPY AND ITS DISCONTINUATION ON BONE-MINERAL DENSITY IN POSTMENOPAUSAL OSTEOPOROSIS

OBJECTIVE The bisphosphonates have proven efficacy in the management o f post-menopausal osteoporosis, However, the benefits of prolonged (> 2 years) administration and the effects of discontinuation of bisphosp honate treatment are not clear. DESIGN We have previously reported a 2 -year, randomized, double-blind, placebo-controlled trial of pamidrona te therapy (150 mg/day) in women with established post-menopausal oste oporosis. We now report the bone mineral density (BMD) changes in thos e women who continued for a third year of active treatment and were th en observed off therapy for a further 12 months, PATIENTS Twenty-two w omen (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. MEASUREMENTS BMD was measured in the total body, lumbar spine and proximal femur using a Lunar DPX-L dual-energy, X-ray absorptiometer, RESULTS The third year of therapy with pamidronate wa s 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 t ended to decline (-0.6 +/- 0.3%) in year 3. One year after discontinua tion of pamidronate, there were significant losses of BMD in the total P < 0.0001) and femoral trochanter P = 0.01), and non-significant cha nges 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 ther apy, 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 i nception (P = 0.7), CONCLUSIONS These data demonstrate that the rate o f bone gain associated with bisphosphonate use slows over time, and th at significant bone loss follows withdrawal of these agents, These fin dings have important implications for the duration of use of these nov el drugs in the therapy of osteoporosis and suggest a need for close o bservation following their discontinuation.