Dufresne T E, Chmielewski P A, Manhart M D, Johnson T D, Borah B
Procter & Gamble Pharmaceuticals, Cincinnati, OH 45040, USA.
Calcif Tissue Int. 2003 Nov;73(5):423-32. doi: 10.1007/s00223-002-2104-4. Epub 2003 Sep 11.
Risedronate reduces the risk of vertebral fractures by up to 70% within the first year of treatment. Increases in bone mineral density or decreases in bone turnover markers explain only a portion of the anti-fracture effect, suggesting that other factors, such as changes in trabecular bone architecture, also play a role. Our objective was to determine the effects of risedronate on bone architecture by analyzing iliac crest bone biopsy specimens using three-dimensional microcomputed tomography (3-D micro CT). Biopsy specimens were obtained at baseline and after 1 year of treatment from women enrolled in a double-blind, placebo-controlled study of risedronate 5 mg daily for the prevention of early postmenopausal bone loss. Trabecular architecture deteriorated in the placebo group (n = 12), as indicated by a 20.3% decrease in bone volume (25.1% vs. 20.0%, P = 0.034), a 13.5% decrease in trabecular number (1.649 vs. 1.426 mm(-1), P = 0.052), a 13.1% increase in trabecular separation (605 vs. 684 microm, P = 0.056), and an 86.2% increase in marrow star volume (3.251 vs. 6.053 mm(3), P = 0.040) compared with baseline values. These changes in architectural parameters occurred in the presence of a concomitant decrease from baseline in lumbar spine bone mineral density (-3.3%, P = 0.002), as measured by dual energy x-ray absorptiometry. There was no statistically significant ( P < 0.05) deterioration in the risedronate-treated group (n = 14) over the 1-year treatment period. Comparing the actual changes between the two groups, the placebo group experienced decreases in bone volume (placebo, -5.1%; risedronate, +3.5%; P = 0.011), trabecular thickness (placebo, -20 microm; risedronate, +23 microm; P = 0.032), and trabecular number (placebo, -0.223 mm(-1); risedronate, +0.099 mm(-1); P = 0.010), and increases in percent plate (placebo, +2.79%; risedronate, -3.23%; P = 0.018), trabecular separation (placebo, +79 microm; risedronate, -46 microm; P = 0.010) and marrow star volume (placebo, +2.80 mm(3); risedronate, -2.08mm(3); P = 0.036), compared with the risedronate group. These data demonstrate that trabecular architecture deteriorated significantly in this cohort of early postmenopausal women, and that this deterioration was prevented by risedronate. Although there is no direct link in this study between fracture and preservation of architecture, it is reasonable to infer that the preservation of bone architecture may play a role in risedronate's anti-fracture efficacy.
利塞膦酸盐在治疗的第一年可将椎体骨折风险降低多达70%。骨矿物质密度的增加或骨转换标志物的降低仅能部分解释其抗骨折作用，这表明其他因素，如小梁骨结构的变化，也发挥了作用。我们的目的是通过使用三维显微计算机断层扫描（3-D显微CT）分析髂嵴骨活检标本，来确定利塞膦酸盐对骨结构的影响。在一项双盲、安慰剂对照研究中，对每日服用5毫克利塞膦酸盐以预防绝经后早期骨质流失的女性，在基线时和治疗1年后获取活检标本。安慰剂组（n = 12）的小梁结构恶化，与基线值相比，骨体积减少20.3%（25.1%对20.0%，P = 0.034），小梁数量减少13.5%（1.649对1.426 mm⁻¹，P = 0.052），小梁间距增加13.1%（605对684微米，P = 0.056），骨髓星体积增加86.2%（3.251对6.053 mm³，P = 0.040）。这些结构参数的变化发生在同时腰椎骨矿物质密度较基线下降的情况下（-3.3%，P = 0.002），通过双能X线吸收法测量。在1年的治疗期内，利塞膦酸盐治疗组（n = 14）没有统计学上显著的（P < 0.05）恶化。比较两组之间的实际变化，安慰剂组的骨体积减少（安慰剂，-5.1%；利塞膦酸盐，+3.5%；P = 0.011）、小梁厚度减少（安慰剂，-20微米；利塞膦酸盐，+23微米；P = 0.032）、小梁数量减少（安慰剂，-0.223 mm⁻¹；利塞膦酸盐，+0.099 mm⁻¹；P = 0.010），与利塞膦酸盐组相比，板百分比增加（安慰剂，+2.79%；利塞膦酸盐，-3.23%；P = 0.018）、小梁间距增加（安慰剂，+79微米；利塞膦酸盐，-46微米；P = 0.010）和骨髓星体积增加（安慰剂，+2.80 mm³；利塞膦酸盐，-2.08 mm³；P = 0.036）。这些数据表明，在这群绝经后早期女性中，小梁结构显著恶化，而利塞膦酸盐可预防这种恶化。尽管在本研究中骨折与结构保存之间没有直接联系，但合理推断骨结构的保存可能在利塞膦酸盐的抗骨折疗效中发挥作用。
