Orr-Walker B, Wattie D J, Evans M C, Reid I R
Department of Medicine, University of Auckland, New Zealand.
Clin Endocrinol (Oxf). 1997 Jan;46(1):87-92. doi: 10.1046/j.1365-2265.1997.d01-1741.x.
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.
双膦酸盐已被证明在绝经后骨质疏松症的治疗中有效。然而，长期（>2年）给药的益处以及双膦酸盐治疗停药后的影响尚不清楚。
我们之前报道了一项为期2年的随机、双盲、安慰剂对照试验，该试验针对患有确诊绝经后骨质疏松症的女性进行帕米膦酸治疗（150毫克/天）。我们现在报告那些继续接受第三年积极治疗然后停药观察12个月的女性的骨密度（BMD）变化。
22名女性（平均年龄66岁）在第3年继续接受帕米膦酸治疗，其中16名研究了随后停药12个月的影响。
使用Lunar DPX-L双能X线吸收仪测量全身、腰椎和股骨近端的骨密度。
帕米膦酸治疗的第三年仅在腰椎与骨密度显著进一步增加相关（2.1±0.6%，P = 0.003），导致该部位在3年治疗期间总增加9.5±1.0%。在全身，骨密度在第3年有下降趋势（-0.6±0.3%）。帕米膦酸停药1年后，全身（-1.9±0.3%，P < 0.0001）和股骨转子（-2.7±0.9%，P = 0.01）骨密度有显著降低，而腰椎（-0.9±0.8%）、股骨颈（-0.5±1.6%）和沃德三角区（-2.9±3.7%）无显著变化。到停药1年末，仅腰椎（7.1±1.1%，P < 0.0001）和股骨转子（4.5±1.88%，P < 0.03）的骨密度高于基线。在全身，骨密度比试验开始时的值低0.3±0.7%（P = 0.7）。
这些数据表明，与双膦酸盐使用相关的骨增加速率随时间减慢，并且停用这些药物后会出现显著的骨质流失。这些发现对于这些新药在骨质疏松症治疗中的使用持续时间具有重要意义，并表明在停药后需要密切观察。
