Can the alendronate dosage be altered when combined with high-frequency loading in osteoporosis treatment?

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. INTRODUCTION: 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. METHODS: 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(2)) or at a reduced dosage of 1 mg/kg (ALN(1)) 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. RESULTS: 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(2) or ALN(1)] or mechanical loading regime (shWBV or WBV). However, a significant positive effect of the ALN(1) 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(2). 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. CONCLUSIONS: 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.

Mechanical competence of ovariectomy-induced compromised bone after single or combined treatment with high-frequency loading and bisphosphonates.

Osteoporosis leads to increased bone fragility, thus effective approaches enhancing bone strength are needed. Hence, this study investigated the effect of single or combined application of high-frequency (HF) loading through whole body vibration (WBV) and alendronate (ALN) on the mechanical competence of ovariectomy-induced osteoporotic bone. Thirty-four female Wistar rats were ovariectomized (OVX) or sham-operated (shOVX) and divided into five groups: shOVX, OVX-shWBV, OVX-WBV, ALN-shWBV and ALN-WBV. (Sham)WBV loading was applied for 10 min/day (130 to 150 Hz at 0.3g) for 14 days and ALN at 2 mg/kg/dose was administered 3x/week. Finite element analysis based on micro-CT was employed to assess bone biomechanical properties, relative to bone micro-structural parameters. HF loading application to OVX resulted in an enlarged cortex, but it was not able to improve the biomechanical properties. ALN prevented trabecular bone deterioration and increased bone stiffness and bone strength of OVX bone. Finally, the combination of ALN with HF resulted in an increased cortical thickness in OVX rats when compared to single treatments. Compared to HF loading, ALN treatment is preferred for improving the compromised mechanical competence of OVX bone. In addition, the association of ALN with HF loading results in an additive effect on the cortical thickness.

Micro-CT analysis of the rodent jaw bone micro-architecture: A systematic review.

INTRODUCTION: Knowledge about macro- and micro-structural characteristics may improve in vivo estimation of the quality and quantity of regenerated bone tissue. For this reason, micro-CT imaging has been applied to evaluate alveolar bone remodelling, alterations of periodontal ligament thickness and cortical and trabecular bone changes in rodent jaw bones. In this paper, we provide a systematic review on the available micro-CT literature on jaw bone micro-architecture. METHODOLOGY: A detailed search through the PubMed database was performed. Articles published up to December 2013 and related to maxilla, mandible and condyle with quantitatively analysed bone micro-architectural parameters were considered eligible for inclusion. Two reviewers assessed the search results according to inclusion criteria designed to identify animal studies quantifying the bone micro-architecture of the jaw rodent bones in physiological or drug-induced disease status, or in response to interventions such as mechanical loading, hormonal treatment and other metabolic alterations. Finally, the reporting quality of the included publications was evaluated using the tailored ARRIVE guidelines outlined by Vignoletti and Abrahamsson (2012). RESULTS: Database search, additional manual searching and assessment of the inclusion and exclusion criteria retrieved 127 potentially relevant articles. Eventually, 14 maxilla, 20 mandible and 12 condyle articles with focus on bone healing were retained, and were analysed together with 3 methodological papers. Each study was described systematically in terms of subject, experimental intervention, follow-up period, selected region of interest used in the micro-CT analysis, parameters quantified, micro-CT scanner device and software. The evidence level evaluated by the ARRIVE guidelines showed high mean scores (between 18 and 25; range: 0-25), indicating that most of the selected studies are well-reported. The major obstacles identified were related to sample size calculation, absence of adverse event descriptions, randomization or blinding procedures. CONCLUSIONS: The evaluated studies are highly heterogeneous in terms of research topic and the different regions of interest. These results illustrate the need for a standardized methodology in micro-CT analysis. While the analysed studies do well according to the ARRIVE guidelines, the micro-CT procedure is often insufficiently described. Therefore we recommend to extend the ARRIVE guidelines for micro-CT studies.

Single and combined effect of high-frequency loading and bisphosphonate treatment on the bone micro-architecture of ovariectomized rats.

UNLABELLED: Mechanical loading at high frequency affects bone. Whether this also applies to osteoporotic bone, combined or not with bisphosphonate therapy, was investigated in this animal study through imaging. An anabolic effect of high-frequency loading on osteoporotic bone, however non-synergistic with bisphosphonates, was found, thereby revealing its potential for treatment of osteoporosis. INTRODUCTION: In an effort to elucidate the effect of high-frequency (HF) loading on bone and to optimize its potential for treatment osteoporosis, this study aimed to investigate the effect of HF loading via whole body vibration (WBV), alone or in association with bisphosphonate treatment (alendronate--ALN), on the micro-architecture of ovariectomy (OVX)-induced compromised bone. METHODS: Eighty-four female Wistar rats were ovariectomized (OVX) or sham-operated (shOVX). OVX animals were treated either with ALN (3 days/week at a dose of 2 mg/kg) or with saline solution. Each group (shOVX, OVX, ALN) was further divided into subgroups relative to the loading status (sham-WBV versus WBV) and the duration of experimental period (4 days versus 14 days). (Sham)WBV loading was applied for 10 min/day using 10 consecutive steps of HF loading (130, 135, 140, 145, 150, 130, 135, 140, 145, 150 Hz). Tibial bone structural responses to WBV and/or ALN treatment were analyzed using ex vivo micro-computed tomography. RESULTS: The animal's hormonal status displayed a major impact on the trabecular and cortical bone structural parameters. Furthermore, mechanical treatment with HF WBV increased the cortical thickness and reduced the medullar area in OVX rats. However, OVX trabecular bone was not affected by HF stimuli. Finally, ALN prevented OVX-associated bone loss, but the association of ALN with WBV did not lead to a synergistic bone response in OVX bone. CONCLUSIONS: HF WBV mechanical stimulation displayed an anabolic effect on osteoporotic cortical bone, confirming its therapeutic properties for enhancing compromised bone. Additionally, its association with bisphosphonates' administration did not produce any additive effect on the bone micro-architecture in the present study.