Relationship of early changes in bone resorption to the reduction in fracture risk with risedronate
Relationship of early changes in bone resorption to the reduction in fracture risk with risedronate
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DOI：
10.1359/jbmr.2003.18.6.1051
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发表时间：
2003-06-01
影响因子：
6.2
通讯作者：
Delmas, PD
中科院分区：
文献类型：
--
作者：
Eastell, R;Barton, I;Delmas, PD
研究人员检查了利塞膦酸盐治疗骨质疏松症时骨吸收生化标志物水平的变化，作为骨折风险降低的替代指标。骨吸收标志物的减少幅度越大，椎骨（和非椎骨）骨折的减少幅度越大。抗骨吸收疗法的抗骨折功效只能部分由骨矿物质密度的增加来解释。骨吸收的早期减少也可能起到一定作用。我们通过在利塞膦酸盐椎体骨折试验中测量骨质疏松患者的两种骨吸收标志物，即 I 型胶原蛋白的 C 端肽 (CTX) 和 I 型胶原蛋白的 N 端肽 (NTX)，来检验这一假设。我们研究了 693 名至少患有一种椎骨畸形的女性（平均年龄 69 +/- 7 岁），她们接受钙（如果需要，还可以补充维生素 D）和安慰剂或每天 5 毫克利塞膦酸盐，为期 3 年。利塞膦酸钠治疗 3-6 个月时尿 CTX（中位数为 60%）和 NTX（51%）的降低与椎骨骨折风险的降低显着相关（p < 0.05）（1 年内降低 75%，3 年内降低 50%）。与安慰剂相比，CTX 和 NTX 的变化约占利塞膦酸钠第一年降低椎骨骨折风险效果的一半（CTX，55%；NTX，49%），约三分之二（CTX，67%；NTX，66%）超过 3 年。与安慰剂相比，CTX 和 NTX 的变化分别占利塞膦酸盐 3 年内降低非椎骨骨折风险效果的 77% 和 54%。椎骨骨折风险与 CTX 和 NTX 相对基线变化之间的关系不是线性的 (p < 0.05)。 CTX 降低 55-60%，NTX 降低 35-40%，骨折获益几乎没有进一步改善。服用利塞膦酸盐的患者骨吸收的减少在骨折风险的降低中占很大比例。骨吸收可能会降低到一定程度，低于该水平则不会对骨折产生进一步的益处。
Changes in the level of biochemical markers of bone resorption with risedronate treatment for osteoporosis were examined as a surrogate for the decrease in fracture risk. Greater decreases in bone resorption markers were associated with greater decreases in vertebral (and nonvertebral) fractures.Antifracture efficacy of antiresorptive therapies is only partially explained by increases in bone mineral density. Early decreases in bone resorption may also play a role. We tested this hypothesis by measuring two bone resorption markers, the C-telopeptide of type I collagen (CTX) and the N-telopeptide of type I collagen (NTX), in osteoporotic patients in risedronate vertebral fracture trials. We studied 693 women with at least one vertebral deformity (mean age, 69 +/- 7 years) who received calcium (and vitamin D if required) and placebo or risedronate 5 mg daily for 3 years. The reductions in urinary CTX (median, 60%) and NTX (51%) at 3-6 months with risedronate therapy were significantly associated (p < 0.05) with the reduction in vertebral fracture risk (75% over 1 year and 50% over 3 years). The changes in both CTX and NTX accounted for approximately one-half (CTX, 55%; NTX, 49%) of risedronate's effect in reducing the risk of vertebral fractures in the first year and approximately two-thirds (CTX, 67%; NTX, 66%) over 3 years compared with placebo. The changes in CTX and NTX accounted for 77% and 54%, respectively, of risedronate's effect in reducing the risk of nonvertebral fractures over 3 years compared with placebo. The relationships between vertebral fracture risk and changes from baseline in CTX and NTX were not linear (p < 0.05). There was little further improvement in fracture benefit below a decrease of 55-60% for CTX and 35-40% for NTX. The decrease in bone resorption in patients taking risedronate accounts for a large proportion of the reduction in fracture risk. There may be a level of bone resorption reduction below which there is no further fracture benefit.