Chen Peiqi, Jerome Christopher P, Burr David B, Turner Charles H, Ma Yanfei L, Rana Asad, Sato Masahiko
Lilly Research Laboratories, Eli Lilly and Company, Indianapolis, Indiana 46285, USA.
J Bone Miner Res. 2007 Jun;22(6):841-8. doi: 10.1359/jbmr.070310.
Bone microarchitecture measured at the iliac crest at 6 mo was confirmed to be a reasonable surrogate for, and a predictor of, architecture and strength of the femoral neck and lumbar vertebra after 18 mo of teriparatide treatment. However, the data taken together showed the importance of cortical bone volume for vertebra to assess pharmacological effects on bone quality.
Improvements in bone architecture with teriparatide treatment are suggested to contribute to fracture risk reduction in osteoporotic patients. Teriparatide significantly improves microarchitecture in the iliac crest of humans by stimulating bone modeling and remodeling processes that differ dramatically from those induced by antiresorptives. The relationship between improvements of bone microarchitecture and improvements of bone strength with teriparatide treatment has not yet been fully studied.
Ovariectomized monkeys were administered vehicle (n = 20); teriparatide 1.0 microg/kg/d (n = 19); or teriparatide 5.0 microg/kg/d (n = 21) for 18 mo. Iliac crest biopsies were obtained at 6 and 15 mo after initiation of treatment. Animals were killed after 18 mo of treatment, and adjacent vertebrae or contralateral proximal femora were processed for biomechanical or histomorphometric analyses. Pearson correlation analyses were performed to assess the relationship between biomechanical and static histomorphometric parameters of lumbar vertebra, femoral neck, and iliac crest biopsies.
Static histomorphometric parameters of the 6- and 15-mo biopsies were significantly correlated with the vertebral and femoral neck parameters obtained at 18 mo of teriparatide treatment. Iliac crest biopsy parameters at 6 and 15 mo also correlated with vertebral and femoral neck strength at 18 mo. Static histomorphometry of the lumbar vertebra and femoral neck at 18 mo also significantly correlated with strength at these sites. However, cortical bone volume of the lumbar vertebrae had the strongest correlation with vertebral and femoral neck strength (r = 0.74 and 0.71, respectively).
Teriparatide dose dependently improved cortical and trabecular microarchitecture of vertebra and femoral neck, as well as trabecular microarchitecture of the iliac crest. Bone microarchitecture at all sites was significantly correlated with lumbar vertebra and femoral neck strength. Cortical bone volume of vertebra had the strongest correlation with vertebral and femoral neck strength. Therefore, structural improvement seemed to be part of the mechanism for improved strength observed with teriparatide treatment. Trabecular bone architecture of the iliac crest at 6 mo also correlated with vertebral and femoral neck strength, as did femoral neck (cortical and trabecular) histomorphometry and trabecular histomorphometry of vertebra after 18 mo of treatment. Because clinical assessment of cortical bone volume is not readily possible for vertebra noninvasively, these findings confirm the importance of iliac crest biopsies to monitor skeletal health and show that biopsies are a reasonable surrogate to assess spine and femoral neck structure and function.
在接受特立帕肽治疗18个月后，6个月时在髂嵴处测量的骨微结构被证实是股骨颈和腰椎结构及强度的合理替代指标和预测指标。然而，综合数据显示，皮质骨体积对评估药物对椎体骨质量的影响具有重要意义。
特立帕肽治疗可改善骨结构，这被认为有助于降低骨质疏松症患者的骨折风险。特立帕肽通过刺激与抗吸收药物诱导的过程截然不同的骨建模和重塑过程，显著改善人体髂嵴处的微结构。特立帕肽治疗改善骨微结构与改善骨强度之间的关系尚未得到充分研究。
对去卵巢的猴子给予赋形剂（n = 20）；1.0μg/kg/d的特立帕肽（n = 19）；或5.0μg/kg/d的特立帕肽（n = 21），持续18个月。在治疗开始后的6个月和15个月时获取髂嵴活检样本。治疗18个月后处死动物，对相邻椎体或对侧近端股骨进行生物力学或组织形态计量学分析。进行Pearson相关分析以评估腰椎、股骨颈和髂嵴活检样本的生物力学和静态组织形态计量学参数之间的关系。
6个月和15个月活检样本的静态组织形态计量学参数与特立帕肽治疗18个月时获得的椎体和股骨颈参数显著相关。6个月和15个月时的髂嵴活检参数也与18个月时的椎体和股骨颈强度相关。18个月时腰椎和股骨颈的静态组织形态计量学也与这些部位的强度显著相关。然而，腰椎的皮质骨体积与椎体和股骨颈强度的相关性最强（分别为r = 0.74和0.71）。
特立帕肽剂量依赖性地改善了椎体和股骨颈的皮质和小梁微结构，以及髂嵴的小梁微结构。所有部位的骨微结构与腰椎和股骨颈强度均显著相关。椎体的皮质骨体积与椎体和股骨颈强度的相关性最强。因此，结构改善似乎是特立帕肽治疗观察到的强度改善机制的一部分。治疗18个月后，6个月时髂嵴的小梁骨结构也与椎体和股骨颈强度相关，股骨颈（皮质和小梁）组织形态计量学以及椎体的小梁组织形态计量学也如此。由于无法通过非侵入性方法轻易对椎体的皮质骨体积进行临床评估，这些发现证实了髂嵴活检对监测骨骼健康的重要性，并表明活检是评估脊柱和股骨颈结构及功能的合理替代方法。
