Ludwig Boltzmann Institute of Osteology at the Hanusch Hospital of OEGK and AUVA Trauma Centre Meidling, 1st Medical Department, Hanusch Hospital, Vienna, Austria.
Ludwig Boltzmann Institute of Osteology at the Hanusch Hospital of OEGK and AUVA Trauma Centre Meidling, 1st Medical Department, Hanusch Hospital, Vienna, Austria.
Bone. 2022 Sep;162:116478. doi: 10.1016/j.bone.2022.116478. Epub 2022 Jun 29.
Postmenopausal osteoporosis (PMOP) therapies are frequently evaluated by bone mineral density (BMD) gains against patients receiving placebo (calcium and vitamin D supplementation, a mild bone turnover-suppressing intervention), which is not equivalent to either healthy or treatment-naive PMOP. The aim of the present observational study was to assess the effects of TPTD treatment in PMOP (20 μg, once daily) at 6 (TPTD 6m; n = 28, age 65 ± 7.3 years), and 24 (TPTD 24m; n = 32, age 67.4 ± 6.15 years) months on bone quality indices at actively forming trabecular surfaces (with fluorescent double labels). Data from the TPTD-treated PMOP patients were compared with those in healthy adult premenopausal women (HC; n = 62, age 40.5 ± 10.6 years), and PMOP receiving placebo (PMOP-PLC; n = 94, age 70.6 ± 4.5 years). Iliac crest biopsies were analyzed by Raman microspectroscopy at three distinct tissue ages: mid-distance between the second label and the bone surface, mid-distance between the two labels, and 1 μm behind the first label. Mineral to matrix ratio (MM), mineral maturity/crystallinity (MMC), tissue water (TW), glycosaminoglycan (GAGs), and pyridinoline (Pyd) content were determined. Outcomes were compared by ANCOVA with subject age and tissue age as covariates, and health status as a fixed factor, followed by Sidak's post-hoc testing (significance assigned to p < 0.05). Both TPTD groups increased MM compared to PMOP-PLC. While TPTD 6m had values similar to HC, TPTD 24m had higher values compared to either HC or TPTD 6m. Both TPTD groups had lower MMC values compared to PMOP-PLC and similar to HC. TPTD 6m patients had higher TW content compared to HC, while TPTD 24m had values similar to HC and lower than either PMOP-PLC or TPTD 6m. Both TPTD groups had lower GAG content compared to HC group, while TPTD 6m had higher values compared to PMOP-PLC. Finally, TPTD 6m patients had higher Pyd content compared to HC and lower compared to PMOP-PLC, while TPTD 24m had lower values compared to PMOP-PLC and TPTD 6m, and similar to HC group. The results of the present study indicate that effects of TPTD on forming trabecular bone quality indices depend on treatment duration. At the recommended length of 24 m, TPTD restores bone mineral and organic matrix quality indices (MMC, TW, Pyd content) to premenopausal healthy (HC) levels.
绝经后骨质疏松症 (PMOP) 治疗方案常通过骨密度 (BMD) 增加来评估,与接受安慰剂 (钙和维生素 D 补充剂,一种轻度抑制骨转换的干预措施) 的患者相比,这些治疗方案与健康人群或未经治疗的 PMOP 人群并不等效。本观察性研究的目的是评估 TPTD 治疗 PMOP (20μg,每日一次) 在 6 个月(TPTD6m; n=28,年龄 65±7.3 岁)和 24 个月(TPTD24m; n=32,年龄 67.4±6.15 岁)时对活跃形成的小梁表面骨质量指数的影响(用荧光双标记)。将 TPTD 治疗的 PMOP 患者的数据与健康成年绝经前妇女 (HC; n=62,年龄 40.5±10.6 岁)和接受安慰剂的 PMOP 患者 (PMOP-PLC; n=94,年龄 70.6±4.5 岁)进行比较。通过拉曼微光谱分析髂嵴活检标本,在三个不同的组织年龄进行分析:第二个标记和骨表面之间的中间距离、两个标记之间的中间距离和第一个标记后面 1μm 的位置。测定矿化基质比(MM)、矿化成熟度/结晶度(MMC)、组织水(TW)、糖胺聚糖(GAGs)和吡啶啉(Pyd)含量。采用协方差分析比较结果,以受试者年龄和组织年龄为协变量,健康状况为固定因素,然后进行 Sidak 事后检验(赋值显著性为 p<0.05)。与 PMOP-PLC 相比,两组 TPTD 均增加了 MM。TPTD6m 组与 HC 相似,而 TPTD24m 组与 HC 或 TPTD6m 组相比,其值更高。两组 TPTD 均降低了 MMC 值,与 PMOP-PLC 相似,与 HC 相似。TPTD6m 组 TW 含量高于 HC,而 TPTD24m 组 TW 含量与 HC 相似,低于 PMOP-PLC 或 TPTD6m 组。两组 TPTD 组的 GAG 含量均低于 HC 组,而 TPTD6m 组的 GAG 含量高于 PMOP-PLC 组。最后,TPTD6m 组 Pyd 含量高于 HC 组,低于 PMOP-PLC 组,而 TPTD24m 组 Pyd 含量低于 PMOP-PLC 组和 TPTD6m 组,与 HC 组相似。本研究结果表明,TPTD 对形成小梁骨质量指数的影响取决于治疗时间。在推荐的 24 个月治疗长度时,TPTD 将骨矿物质和有机基质质量指数 (MMC、TW、Pyd 含量) 恢复到绝经前健康 (HC) 水平。