Loundagin Lindsay L, Harrison Kim D, Cooper David M L
Department of Anatomy, Physiology and Pharmacology, College of Medicine, University of Saskatchewan, 107 Wiggins Road, Saskatoon, SK, S7N 5E5, Canada.
Calcif Tissue Int. 2025 Sep 19;116(1):123. doi: 10.1007/s00223-025-01426-1.
It is well documented that the activation frequency of basic multicellular units (BMUs) is increased following menopause, but it is unclear if a negative BMU balance also contributes to osteoporosis-related bone loss or how remodeling dynamics are altered to maintain or disrupt BMU balance. Time-lapsed imaging was used to track individual BMUs in cortical bone and investigate their spatio-temporal balance in a rabbit model of osteoporosis. The distal tibiae of female New Zealand White rabbits that received ovariohysterectomy (OVH) or SHAM surgery were scanned in vivo using synchrotron radiation micro-CT and two weeks later ex vivo using desktop micro-CT. Remodeling spaces were partitioned into resorption and formation zones based on their 3D morphology. BMU balance was assessed by the maximum radius, canal radius, wall thickness, and relative resorption and formation volumes. The longitudinal erosion rate and zone lengths were used to calculate the radial rate and duration of resorption and formation. Remodeling spaces were larger in OVH vs. SHAM rabbits; however, this augmented resorption was accompanied by increased formation such that OVH and SHAM BMUs were similarly balanced. Maintaining this balance was achieved by a 50% longer formation period in OVH vs. SHAM (21.0 vs 13.2days) as the radial infill rate was equivalent (OVH = 2.1 vs SHAM = 2.0μm/day). Radial erosion rate was faster in OVH (10.3 vs 8.6 μm/day), but resorption duration (OVH = 4.2 vs SHAM = 3.5days) and longitudinal erosion rate (OVH=41.3 vs SHAM = 40.1μm/day) were not different. This novel imaging pipeline demonstrated that the spatio-temporal dynamics of cortical BMUs are altered in this rabbit model of osteoporosis, but the collective changes in resorption and formation activity work in concert to maintain BMU balance. In contrast to the common perspective in the literature, this suggests that the elevated cortical porosity in osteoporosis is predominately due to increased activation of remodeling events rather than negative BMU balance.
有充分文献记载,绝经后基本多细胞单位(BMU)的激活频率会增加,但尚不清楚BMU负平衡是否也会导致骨质疏松相关的骨质流失,或者重塑动力学是如何改变以维持或破坏BMU平衡的。采用延时成像技术在骨质疏松兔模型中追踪皮质骨中的单个BMU,并研究其时空平衡。对接受卵巢子宫切除术(OVH)或假手术的雌性新西兰白兔的胫骨远端进行体内同步辐射显微CT扫描,两周后进行体外台式显微CT扫描。根据重塑空间的三维形态将其划分为吸收区和形成区。通过最大半径、管腔半径、壁厚以及相对吸收和形成体积来评估BMU平衡。利用纵向侵蚀速率和区域长度来计算吸收和形成的径向速率及持续时间。与假手术组相比,OVH组的重塑空间更大;然而,这种吸收增加伴随着形成增加,使得OVH组和假手术组的BMU平衡相似。通过OVH组比假手术组长50%的形成期(21.0天对13.2天)来维持这种平衡,因为径向填充速率相当(OVH组=2.1μm/天对假手术组=2.0μm/天)。OVH组的径向侵蚀速率更快(10.3μm/天对8.6μm/天),但吸收持续时间(OVH组=4.2天对假手术组=3.5天)和纵向侵蚀速率(OVH组=41.3μm/天对假手术组=40.1μm/天)没有差异。这种新颖的成像方法表明,在该骨质疏松兔模型中皮质BMU的时空动力学发生了改变,但吸收和形成活动的总体变化协同作用以维持BMU平衡。与文献中的普遍观点相反,这表明骨质疏松中皮质孔隙率升高主要是由于重塑事件的激活增加,而非BMU负平衡。