Nakatoh Shinichi
Department of Orthopedic Surgery, Asahi General Hospital, 477 Tomari, Asahimachi, Toyama, 939-0741, Japan.
J Bone Miner Metab. 2018 Mar;36(2):221-228. doi: 10.1007/s00774-017-0829-4. Epub 2017 Mar 14.
This study reveals the changes in bone mineral density (BMD), the turnover rate, and the balance [multiple of median formation/multiple of median resorption (MoMf/MoMr)] affected by the selection of different bone resorption inhibitors after 24-month daily teriparatide (20 µg/day) administration. The turnover rate was calculated as √(MoMf + MoMr), where MoMf = bone-specific alkaline phosphatase (BAP) value/18.6 and MoMr = tartrate-resistant acid phosphatase 5b (TRACP-5b) value/463. One hundred and twenty-one osteoporotic women (mean age 82.4 years) were randomly administered minodronate (50 mg/28 days), raloxifene (60 mg/day), or eldecalcitol (0.75 µg/day) after teriparatide discontinuation. BMD was measured at 0, 24, and 48 weeks; BAP values and TRACP-5b were measured at 0, 12, 24, 36, and 48 weeks after administration of bone resorption inhibitors. In the minodronate group, BMD increased significantly from week 0 to weeks 24 and 48. The turnover rate was significantly reduced at week 12, and remained so over the entire course in all three groups. The speed of change of turnover rate was greatest in the minodronate group. The balance in the minodronate group shifted significantly toward formation dominance at week 12 (to 0.97 from 0.87) and then again toward resorption dominance (to 0.84) at week 24. However, no further advancement in resorption dominance was observed until week 48. Conversely, the balance in the raloxifene and eldecalcitol groups shifted toward resorption dominance gradually over the entire course. In conclusion, the BMD-increasing effect was greatest with minodronate administration and depends not only on the decrease in turnover rate but also on changes in balance after teriparatide discontinuation.
本研究揭示了在每日给予特立帕肽(20μg/天)24个月后,选用不同的骨吸收抑制剂对骨密度(BMD)、骨转换率以及平衡状态[成骨中位数倍数/破骨中位数倍数(MoMf/MoMr)]的影响。骨转换率的计算方法为√(MoMf + MoMr),其中MoMf = 骨特异性碱性磷酸酶(BAP)值/18.6,MoMr = 抗酒石酸酸性磷酸酶5b(TRACP-5b)值/463。121名骨质疏松女性(平均年龄82.4岁)在停用特立帕肽后被随机给予米诺膦酸(50mg/28天)、雷洛昔芬(60mg/天)或依地骨化醇(0.75μg/天)。在第0、24和48周测量BMD;在给予骨吸收抑制剂后的第0、12、24、36和48周测量BAP值和TRACP-5b。在米诺膦酸组中,BMD从第0周显著增加至第24周和第48周。骨转换率在第12周显著降低,且在所有三组中在整个过程中均保持如此。骨转换率变化速度在米诺膦酸组中最大。米诺膦酸组的平衡状态在第12周显著向成骨优势转变(从0.87变为0.97),然后在第24周再次向破骨优势转变(变为0.84)。然而,直到第48周才观察到破骨优势的进一步发展。相反,雷洛昔芬组和依地骨化醇组的平衡状态在整个过程中逐渐向破骨优势转变。总之,米诺膦酸给药的BMD增加效果最大,且不仅取决于骨转换率的降低,还取决于停用特立帕肽后的平衡状态变化。