Krege J H, Lane N E, Harris J M, Miller P D
Lilly USA, Indianapolis, IN, USA.
Osteoporos Int. 2014 Sep;25(9):2159-71. doi: 10.1007/s00198-014-2646-0. Epub 2014 Mar 6.
Postmenopausal women with severe osteoporosis may require treatment with the bone anabolic drug teriparatide. While changes in bone mineral density (BMD) are one measure of response, BMD changes often require a minimum of one year to observe measureable changes. Biochemical markers of bone turnover change within 1 to 3 months of initiating osteoporosis therapy. Monitoring with a marker such as procollagen type I N propeptide (PINP), an osteoblast-derived protein, during teriparatide treatment may provide clinically useful information for managing patients with osteoporosis. Clinical trials have shown consistent increases in PINP within 3 months of initiating teriparatide, increases that are significantly greater than placebo and significantly different from baseline. Increases in PINP concentrations during teriparatide treatment correlate well with increases in skeletal activity assessed by radioisotope bone scans and quantitative bone histomorphometry parameters. Individuals treated with teriparatide in clinical trials usually experienced an increase in PINP > 10 mcg/L from baseline, while those given placebo usually did not. In the clinical setting, patients experiencing a significant increase in PINP > 10 mcg/L after initiating teriparatide therapy may receive an earlier confirmation of anabolic effect, while those who do not may be assessed for adherence, proper injection technique, or undetected secondary conditions that might mitigate an anabolic response. PINP monitoring may provide information supplemental to BMD monitoring and be a useful aid in managing patients receiving anabolic osteoporosis treatment in the same way that biochemical markers of bone resorption are useful in monitoring antiresorptive therapy. This review examines PINP as a biological response marker during teriparatide treatment for osteoporosis.
患有严重骨质疏松症的绝经后女性可能需要使用骨合成代谢药物特立帕肽进行治疗。虽然骨矿物质密度(BMD)的变化是反应的一种衡量指标,但BMD变化通常至少需要一年时间才能观察到可测量的变化。骨转换的生化标志物在开始骨质疏松症治疗后的1至3个月内会发生变化。在特立帕肽治疗期间,使用诸如I型前胶原N端前肽(PINP)这种成骨细胞衍生蛋白作为标志物进行监测,可能为管理骨质疏松症患者提供临床有用信息。临床试验表明,开始使用特立帕肽后3个月内PINP持续升高,升高幅度显著大于安慰剂组,且与基线水平有显著差异。特立帕肽治疗期间PINP浓度的升高与通过放射性核素骨扫描和定量骨组织形态计量学参数评估的骨骼活性增加密切相关。在临床试验中接受特立帕肽治疗的个体,PINP通常会从基线水平升高>10 mcg/L,而给予安慰剂的个体通常不会。在临床环境中,开始特立帕肽治疗后PINP显著升高>10 mcg/L的患者可能会更早得到合成代谢效应的确认,而未出现这种情况的患者可能需要评估其依从性、正确的注射技术或未被检测到的可能减轻合成代谢反应的继发疾病。PINP监测可能提供补充BMD监测的信息,并且在管理接受合成代谢性骨质疏松症治疗的患者方面是一种有用的辅助手段,就像骨吸收的生化标志物在监测抗吸收治疗中有用一样。本综述探讨了PINP作为特立帕肽治疗骨质疏松症期间的生物学反应标志物的情况。