Centre for Biomedical Research, Northern General Hospital, Herries Road, Sheffield, South Yorkshire, S5 7AU, UK.
Bone. 2012 May;50(5):1135-40. doi: 10.1016/j.bone.2012.02.004. Epub 2012 Feb 12.
The aims of this study were to describe the changes in bone turnover markers (BTMs) in response to lasofoxifene therapy; to describe the changes in BTMs in the individual; and to examine the relationships between BTM levels on treatment and treatment outcomes. Women (n=1126) aged 59-80years with femoral neck or spine bone mineral density T-scores ≤-2.5 were randomized to lasofoxifene 0.25mg/d, 0.5mg/d, or placebo for 5years. We measured serum C-telopeptide of type I collagen (CTX) and serum procollagen I N-propeptide (PINP), osteocalcin, and bone alkaline phosphatase (ALP) at baseline and at 1, 3, 6, 12, 24, and 36months. Lasofoxifene therapy resulted in a decrease in the concentrations of bone resorption and bone formation markers compared with placebo; the decrease was maximal between 6 and 24months. The effect of lasofoxifene 0.5mg/d was similar to that of lasofoxifene 0.25mg/d. The decrease in bone ALP was less than the decreases in CTX, osteocalcin, and PINP. Lasofoxifene therapy 0.5mg/d resulted in BTM-defined response rates for CTX (decrease in concentration from baseline >60%), PINP (>50%), and bone ALP (>30%) of 35%, 45%, and 43% of women at month 12, respectively, compared with placebo responses of 4%, 4%, and 7%. In contrast, the increase in BMD took longer (50% responded after 36months of lasofoxifene 0.5mg/d) and was not as specific (15% of placebo group responded). Bone density change was weakly inversely correlated with change in the concentrations of BTMs. BTMs may prove useful in the monitoring of the response to lasofoxifene treatment for women with postmenopausal osteoporosis early in the course of treatment.
本研究的目的是描述拉索昔芬治疗后骨转换标志物 (BTM) 的变化；描述个体中 BTM 的变化；并检查治疗过程中 BTM 水平与治疗结果之间的关系。年龄在 59-80 岁之间、股骨颈或脊柱骨密度 T 评分≤-2.5 的女性患者被随机分为拉索昔芬 0.25mg/d、0.5mg/d 或安慰剂组，治疗 5 年。我们在基线和治疗后第 1、3、6、12、24 和 36 个月时测量了血清 I 型胶原 C 端肽（CTX）和血清 I 型前胶原 N 端肽（PINP）、骨钙素和骨碱性磷酸酶（ALP）。与安慰剂相比，拉索昔芬治疗导致骨吸收和骨形成标志物浓度降低；这种降低在 6-24 个月之间最大。拉索昔芬 0.5mg/d 的作用与拉索昔芬 0.25mg/d 相似。骨 ALP 的降低小于 CTX、骨钙素和 PINP 的降低。拉索昔芬 0.5mg/d 治疗 12 个月时，CTX（与基线相比浓度降低>60%）、PINP（>50%）和骨 ALP（>30%）的 BTM 定义反应率分别为 35%、45%和 43%，而安慰剂组的反应率分别为 4%、4%和 7%。相比之下，BMD 的增加需要更长的时间（拉索昔芬 0.5mg/d 治疗 36 个月后有 50%的患者出现反应），并且不那么具有特异性（安慰剂组有 15%的患者出现反应）。骨密度的变化与 BTM 浓度的变化呈弱负相关。BTM 可能在监测绝经后骨质疏松症妇女接受拉索昔芬治疗的早期反应方面具有一定价值。
