Article

Strength of cancellous bone trabecular tissue from normal, ovariectomized and drug-treated rats over the course of ageing

Trinity Centre for Bioengineering, School of Engineering, Trinity College, Dublin, Ireland.
Bone (Impact Factor: 4.46). 09/2006; 39(2):392-400. DOI: 10.1016/j.bone.2006.02.070
Source: PubMed

ABSTRACT Hormone therapy (HT) drugs and bisphosphonates prevent osteoporosis by inhibiting osteoclastic bone resorption. However, the effects of osteoporosis and anti-resorptive drugs on the mechanical behavior of the bone tissue constituting individual trabeculae have not yet been quantified. In this study, we test the hypothesis that the mechanical properties of bone trabecular tissue will differ for normal, ovariectomized and drug-treated rat bones over the course of ageing. Microtensile testing is carried on individual trabeculae from tibial bone of ovariectomized (OVX) rats, OVX rats treated with tibolone and placebo-treated controls. The method developed minimizes errors due to misalignment and stress concentrations at the grips. The local mineralization of single trabeculae is compared using micro-CT images calibrated for bone mineral content assessment. Our results indicate that ovariectomy in rats increases the stiffness, yield strength, yield strain and ultimate stress of the mineralized tissue constituting trabecular bone relative to normal; we found significant differences (P < 0.05) at 14, 34 and 54 weeks of treatment. These increases are complemented by a significant increase in the mineral content at the tissue level, although overall bone mineral density and mass are reduced. With drug treatment, the properties remain at, or slightly below, the placebo-treated controls levels for 54 weeks. The higher bone strength in the OVX group may cause the trabecular architecture to adapt as seen during osteopenia/osteoporosis, or alternately it may compensate for loss of trabecular architecture. These findings suggest that, in addition to the effects of osteoporosis and subsequent treatment on bone architecture, there are also more subtle processes ongoing to alter bone strength at the tissue level.

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    • "A marked increase in bone turnover rates occurs (Balena et al., 1993) and leads to low bone mass and strength, depleted bone architecture and increased fracture risk (Cummings and Melton, 2002). Previous studies quantifying trabecular bone mineralization have found increases (Boyde et al., 1998; Busse et al., 2009; McNamara et al., 2006), decreases (Gadeleta et al., 2000; Yao et al., 2007), whilst others present no or only slight alterations in mineral content (Brennan et al., 2011; Ciarelli et al., 2003) as a consequence of estrogen deficiency. These discrepancies may be explained by the duration of estrogen depletion under investigation, as it has been shown that after the onset of estrogen deficiency, biological and structural alterations occur immediately, but these responses wane over time (Binkley et al., 1998; Smith et al., 2003). "
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    ABSTRACT: The quantity and distribution of bone tissue mineral are key determinants of bone strength. Recent research revealed altered mineral distribution within sheep femora following estrogen deficiency. Rapid increases in bone remodeling occur at the onset of estrogen deficiency and abate over time. Therefore, altered tissue mineralization might be a transient characteristic of osteoporosis. Bisphosphonates reduce fracture incidence by 40–60% but increases in bone mineral density are insufficient to explain such changes. In this study the hypotheses that bone tissue mineralization is altered over prolonged estrogen depletion and bisphosphonate treatment were tested. Quantitative backscattered imaging (qBEI) was used to quantify bone mineral density distribution (BMDD) parameters (mean, FWHM) in trabeculae from the proximal femora of an ovariectomized sheep model that underwent estrogen deficiency for 31 months, an ovariectomized group administered with Zoledronic acid and age-matched controls. To assess the effects of normal ageing and prolonged estrogen deficiency, data were compared to BMDD data from sheep that were estrogen deficient for 12 months and age-matched controls. This study reports that normal ageing increases mean mineralization and mineral heterogeneity at a trabecular level. In contrast, prolonged estrogen deficiency leads to significantly decreased mean mineralization and further exacerbates increases in mineral heterogeneity. Interestingly, ZOL treatment of OVX sheep significantly reduced tissue mineral variability, both at a trabecular level and between femoral regions. Together, these findings indicate that ZOL treatment acts to reverse the increased mineral heterogeneity occurring during estrogen deficiency, which may contribute to its capacity to reduce osteoporotic fractures.
    Journal of the Mechanical Behavior of Biomedical Materials 01/2014; 29:161–170. · 3.42 Impact Factor
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    • "A marked increase in bone turnover rates occurs (Balena et al., 1993) and leads to low bone mass and strength, depleted bone architecture and increased fracture risk (Cummings and Melton, 2002). Previous studies quantifying trabecular bone mineralization have found increases (Boyde et al., 1998; Busse et al., 2009; McNamara et al., 2006), decreases (Gadeleta et al., 2000; Yao et al., 2007), whilst others present no or only slight alterations in mineral content (Brennan et al., 2011; Ciarelli et al., 2003) as a consequence of estrogen deficiency. These discrepancies may be explained by the duration of estrogen depletion under investigation, as it has been shown that after the onset of estrogen deficiency, biological and structural alterations occur immediately, but these responses wane over time (Binkley et al., 1998; Smith et al., 2003). "
    [Show abstract] [Hide abstract]
    ABSTRACT: The quantity and distribution of bone tissue mineral are key determinants of bone strength. Recent research revealed altered mineral distribution within sheep femora following estrogen deficiency. Rapid increases in bone remodeling occur at the onset of estrogen deficiency and abate over time. Therefore, altered tissue mineralization might be a transient characteristic of osteoporosis. Bisphosphonates reduce fracture incidence by 40-60% but increases in bone mineral density are insufficient to explain such changes. In this study the hypotheses that bone tissue mineralization is altered over prolonged estrogen depletion and bisphosphonate treatment were tested. Quantitative backscattered imaging (qBEI) was used to quantify bone mineral density distribution (BMDD) parameters (mean, FWHM) in trabeculae from the proximal femora of an ovariectomized sheep model that underwent estrogen deficiency for 31 months, an ovariectomized group administered with Zoledronic acid and age-matched controls. To assess the effects of normal ageing and prolonged estrogen deficiency, data were compared to BMDD data from sheep that were estrogen deficient for 12 months and age-matched controls. This study reports that normal ageing increases mean mineralization and mineral heterogeneity at a trabecular level. In contrast, prolonged estrogen deficiency leads to significantly decreased mean mineralization and further exacerbates increases in mineral heterogeneity. Interestingly, ZOL treatment of OVX sheep significantly reduced tissue mineral variability, both at a trabecular level and between femoral regions. Together, these findings indicate that ZOL treatment acts to reverse the increased mineral heterogeneity occurring during estrogen deficiency, which may contribute to its capacity to reduce osteoporotic fractures.
    09/2013; 29C:161-170. DOI:10.1016/j.jmbbm.2013.08.029
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    • "In addition, most damage models applied in FE studies for trabecular bone samples were developed empirically and adjusted through calibration with mechanical tests (McNamara et al., 2006a, 2006b). Hence, a more suitable step toward the development of physically based damage laws of bone would be to incorporate explicit damage results obtained from experiments to test their predictive power. "
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    ABSTRACT: There is growing evidence that information on trabecular microarchitecture can improve the assessment of fracture risk. One current strategy is to exploit finite element (FE) analysis applied to experimental data of mechanically loaded single trabecular bone tissue obtained from non-invasive imaging techniques for the investigation of the damage initiation and growth of bone tissue. FE analysis of this type of bone has mainly focused on linear and non-linear analysis to evaluate the bone's failure properties. However, there is a lack of experimentally validated FE damage models at trabecular bone tissue level allowing for the simulation of the progressive damage process (initiation and growth) till complete fracture. Such models are needed to perform enhanced prediction of the apparent failure mechanical properties needed to assess the fracture risk of bone organs. In the current study, we develop a FE model based on a continuum damage mechanics (CDM) approach to simulate the damage initiation and propagation of a single trabecula till complete facture in quasi-static regime. Three-point bending experiments were performed on single bovine trabeculae and compared to FE results. In order to validate the proposed FE mode, (i) the force displacement curve was compared to the experimental one and (ii) the damage distribution was correlated to the measured one obtained by digital image correlation based on stress whitening in bone, reported to be correlated to microdamage. A very good agreement was obtained between the FE and experimental results, indicating that the proposed damage investigation protocol based on FE analysis and testing is reliable to assess the damage behavior of bone tissue and that the current damage model is able to accurately simulate the damaging and fracturing process of single trabeculae under quasi static load.
    07/2013; 27. DOI:10.1016/j.jmbbm.2013.07.005
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