Massachusetts General Hospital Department of Medicine, Endocrine Unit, Boston, MA 02114, USA.
Bone. 2011 Apr 1;48(4):713-9. doi: 10.1016/j.bone.2010.11.012. Epub 2010 Nov 24.
Once-daily injections of teriparatide initially increase biochemical markers of bone formation and resorption, but markers peak after 6-12 months and then decline despite continued treatment. We sought to determine whether increasing teriparatide doses in a stepwise fashion could prolong skeletal responsiveness. We randomized 52 postmenopausal women with low spine and/or hip bone mineral density (BMD) to either a constant or an escalating subcutaneous teriparatide dose (30 μg daily for 18months or 20 μg daily for 6 months, then 30 μg daily for 6 months, and then 40 μg daily for 6 months). Serum procollagen I N-terminal propeptide, osteocalcin, and C-terminal telopeptide of type I collagen were assessed frequently. BMD of the spine, hip, radius, and total body was measured every 6 months. Acute changes in urinary cyclic AMP in response to teriparatide were examined in a subset of women in the constant dose group. All bone markers differed significantly between the two treatment groups. During the final six months, bone markers declined in the constant dose group but remained stable or increased in the escalating dose group (all markers, p<0.017). Nonetheless, mean area under the curve did not differ between treatments for any bone marker, and BMD increases were equivalent in both treatment groups. Acute renal response to teriparatide, as assessed by urinary cyclic AMP, did not change over 18 months of teriparatide administration. In conclusion, stepwise increases in teriparatide prevented the decline in bone turnover markers that is observed with chronic administration without altering BMD increases. The time-dependent waning of the response to teriparatide appears to be bone-specific.
特立帕肽每日一次注射最初会增加骨形成和吸收的生化标志物，但这些标志物在 6-12 个月后达到峰值，尽管继续治疗，但其水平仍会下降。我们试图确定逐步增加特立帕肽剂量是否可以延长骨骼的反应性。我们将 52 名绝经后妇女随机分为固定剂量组或递增剂量组，皮下注射特立帕肽（18 个月内每天 30μg 或 6 个月内每天 20μg，然后每天 30μg 6 个月，然后每天 40μg 6 个月）。频繁评估血清Ⅰ型前胶原 N 端前肽、骨钙素和Ⅰ型胶原 C 端肽。每 6 个月测量脊柱、髋部、桡骨和全身的骨密度。在固定剂量组的一部分妇女中，检测了特立帕肽引起的尿环磷酸腺苷的急性变化。两组间所有骨标志物均有显著差异。在固定剂量组，在最后 6 个月期间，骨标志物下降，但在递增剂量组中保持稳定或增加（所有标志物，p<0.017）。尽管如此，任何骨标志物的治疗组间平均曲线下面积均无差异，且两组的骨密度增加相当。用尿环磷酸腺苷评估的特立帕肽的急性肾反应在特立帕肽给药 18 个月内没有改变。总之，特立帕肽的逐步增加可以防止在慢性给药中观察到的骨转换标志物的下降，而不会改变骨密度的增加。对特立帕肽的反应随时间的衰减似乎是骨特异性的。
