Department of Oral Health Sciences & Dental Clinic, BIOMAT & Prosthetic Dentistry, KU Leuven & University Hospitals Leuven, Kapucijnenvoer 7, 3000, Leuven, Belgium.
Department of Prosthodontics and Periodontology, Piracicaba Dental School, University of Campinas, Piracicaba, São Paulo, Brazil.
Osteoporos Int. 2017 Apr;28(4):1287-1293. doi: 10.1007/s00198-016-3859-1. Epub 2016 Dec 5.
Alendronate therapy has been associated with serious side effects. Altering the alendronate concentration and combining with high-frequency loading as mechanical intervention was explored in this animal study as a treatment for osteoporosis. The bone anabolic potency of high-frequency loading was overruled by the different alendronate dosages applied in the present study. Further exploration of reduced hormonal therapy associated with mechanical interventions in osteoporosis treatment should be sought.
The aim of the present study was to investigate the effect of alendronate (ALN) administration at two different dosages, associated or not with high-frequency (HF) loading, on the bone microstructural response.
Sixty-four female Wistar rats were used, of which 48 were ovariectomized (OVX) and 16 were sham-operated (shOVX). The OVX animals were divided into three groups: two groups were treated with alendronate, at a dosage of 2 mg/kg (ALN()) or at a reduced dosage of 1 mg/kg (ALN()) three times per week. A third OVX group did not receive pharmaceutical treatment. All four groups were mechanically stimulated via whole body vibration (WBV) at HF (up to 150 Hz) or left untreated (shWBV). ALN and HF were administered for 6 weeks, starting at 10-week post-(sh)OVX. Tibia bone structural parameters were analyzed using ex vivo microcomputed tomography.
Trabecular bone loss and structural deterioration resulting from ovariectomy were partially restored by ALN administration, demonstrated by the improvement of trabecular patter factor (Tb.Pf), trabecular separation (Tb.Sp), and structure model index (SMI) of the ALN groups compared to that of the OVX group, regardless of the applied dosage [ALN() or ALN()] or mechanical loading regime (shWBV or WBV). However, a significant positive effect of the ALN() administration on trabecular (decrease of Tb.Sp and SMI) and cortical bone (increase of cortical thickness) microarchitecture compared to that of the OVX status group was observed for both loading regimes was not seen for ALN(). Furthermore, HF loading resulted in cortical bone changes, with an increased trabeculary area and endocortical perimeter. Finally, the benefits of a combined therapy of ALN with HF loading could not be discerned in the present experimental conditions.
The bone anabolic potency of HF loading was overruled by the ALN dosages applied in the present study. Further altering the ALN dosage combined with robust mechanical stimuli needs to be considered in osteoporosis research and eventually therapy.
本研究旨在探讨两种不同剂量的阿仑膦酸钠（ALN）联合或不联合高频（HF）加载对骨微结构反应的影响。
使用 64 只雌性 Wistar 大鼠，其中 48 只进行卵巢切除术（OVX），16 只进行假手术（shOVX）。OVX 动物分为三组：两组给予阿仑膦酸钠，剂量为 2mg/kg（ALN()）或每周三次给予低剂量 1mg/kg（ALN()）。第三组 OVX 动物未接受药物治疗。所有四组均通过全身振动（WBV）进行高频（高达 150Hz）机械刺激或不进行处理（shWBV）。ALN 和 HF 治疗于 10 周 OVX 后开始，持续 6 周。使用离体 microCT 分析胫骨骨结构参数。
与 OVX 组相比，ALN 给药部分恢复了卵巢切除术引起的小梁骨丢失和结构恶化，表现为小梁模式因子（Tb.Pf）、小梁分离（Tb.Sp）和结构模型指数（SMI）的改善，而与给药剂量[ALN()或 ALN()]或机械加载方式（shWBV 或 WBV）无关。然而，与 OVX 状态组相比，ALN()给药对小梁（Tb.Sp 和 SMI 减少）和皮质骨（皮质厚度增加）微结构有显著的积极影响，但在两种加载方式下均未观察到 ALN()的影响。此外，HF 加载导致皮质骨变化，表现为骨小梁面积增加和内皮质周长增加。最后，在本实验条件下，无法发现 ALN 与 HF 加载联合治疗的益处。
本研究中应用的 ALN 剂量否定了 HF 加载的骨合成作用。在骨质疏松症研究和最终治疗中，需要进一步改变 ALN 剂量并结合强有力的机械刺激。
