Effects of risedronate on trabecular microstructure and biomechanical properties in ovariectomized rat tibia

Ito, Masako; Nishida, Akifumi; Aoyagi, Kiyoshi; Uetani, Masataka; Hayashi, Kuniaki; Kawase, Masahiro

doi:10.1007/s00198-004-1802-3

Cited by 49 publications

(40 citation statements)

References 19 publications

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“…Previous studies have reported that plate perforations without loss of trabecular elements tend to artificially increase connectivity (Borah et al, 2004), and this may explain why the connectivity density for the control bone tended to be higher than the suppressed bone in this study. The trends in architectural changes due to suppressed bone turnover are also consistent with previous clinical (Borah et al, 2004) and pre-clinical (Ito et al, 2005;Muller et al, 2004) studies which have shown that antiresorptive treatment preserves the trabecular architecture.…”

Section: Discussionsupporting

confidence: 89%

“…While the effects of suppressed bone turnover on the mineralization and the organic component of the trabecular tissue, and trabecular microarchitecture have been investigated through a number of clinical (Boivin et al, 2000;Borah et al, 2004;Borah et al, 2005;Roschger et al, 2001) and pre-clinical studies (Allen et al, 2006a;Allen et al, 2006b;Day et al, 2004;Ding et al, 2003;Ito et al, 2005;Mashiba et al, 2001;Muller et al, 2004), the independent contribution of suppression-induced microarchitectural changes alone to the improved mechanical properties remain unclear. Analysis of simulated microarchitectural changes have shown that inhibition of trabecular perforation (Guo and Kim, 2002;Riggs and Melton, 2002) and filling in of the remodeling space Parfitt, 2002) may have a disproportionate effect on trabecular bone strength compared to the accompanying changes in bone volume fraction, particularly for low-density bone.…”

Section: Introductionmentioning

confidence: 99%

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A computational assessment of the independent contribution of changes in canine trabecular bone volume fraction and microarchitecture to increased bone strength with suppression of bone turnover

Eswaran

Allen

Burr

et al. 2007

Journal of Biomechanics

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This study addressed the effects of changes in trabecular microarchitecture induced by suppressed bone turnover -including changes to the remodeling space -on the trabecular bone strengthvolume fraction characteristics independent of changes in tissue material properties. Twenty female beagle dogs, aged 1-2 years, were treated daily with either oral saline (n=10 control) or high doses of oral risedronate (0.5 mg/kg/day, n=10 suppressed) for a period of one year, the latter designed (and confirmed) to substantially suppress bone turnover. High-resolution micro-CT based finite element models (18-micron voxel size) of canine trabecular bone cores (n=2 per vertebral body) extracted from the T-10 vertebrae were analyzed in both compressive and torsional loading cases. The same tissue-level material properties were used in all models, thus providing measures of tissuenormalized strength due only to changes in the microarchitecture. Suppressed bone turnover resulted in more plate-like architecture with a thicker and more dense trabecular structure, but the relationship between the microarchitectural parameters and volume fraction was unaltered (p>0.05). Though the suppressed group had greater tissue-normalized strength as compared to the control group (p<0.001) for both compressive and torsional loading, the relationship between tissue-normalized strength and volume fraction was not significantly altered for compression (p>0.13) or torsion (p>0.09). In this high-density, non-osteoporotic animal model, the increases in tissue-normalized strength seen with suppression of bone turnover were entirely commensurate with increases in bone volume fraction and thus, no evidence of microarchitecture-related or "stress-riser" effects which may disproportionately affect strength were found.

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Section: Discussionsupporting

confidence: 89%

Section: Introductionmentioning

confidence: 99%

A computational assessment of the independent contribution of changes in canine trabecular bone volume fraction and microarchitecture to increased bone strength with suppression of bone turnover

Eswaran

Allen

Burr

et al. 2007

Journal of Biomechanics

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“…Oral dose rates of 0.5 and 2.5 mg/kg risedronate prevented bone loss in an ovariectomy model in rats while 0.1 mg/kg had no effect. 27 Reported results of pre-clinical testing for risedronate suggest that the dose rate needed in a rat to be equivalent to the standard 35 mg/kg/week human dose is 0.5 mg/kg. a Bone resorption along the stress fracture line was clearly depressed by treatment with risedronate.…”

Section: Discussionmentioning

confidence: 99%

Bisphosphonate treatment delays stress fracture remodeling in the rat ulna

Kidd

Cowling

et al. 2011

Journal Orthopaedic Research

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Because bisphosphonates (BPs) are potent inhibitors of bone resorption, we hypothesized that they would retard direct remodeling of stress fractures. The aim of this study was to determine the effect of risedronate on direct remodeling and woven bone callus formation following stress fracture formation in the rat ulna. In 135 adult female Wistar rats, cyclic loading of the ulna created stress fractures. Rats were treated daily with oral saline, or risedronate at 0.1 or 1.0 mg/kg. From each bone, histomorphometry was performed on sections stained with toluidine blue at a standard level along the fracture. The high dose of risedronate caused a significant decrease in the percentage of repaired stress fracture and bone resorption along the stress fracture line at 6 and 10 weeks after loading (p < 0.05). At this dose, intracortical resorption was significantly reduced at 10 weeks after loading and intracortical new bone area was significantly reduced at 6 and 10 weeks. Woven bone formation and consolidation phases of stress fracture repair were not affected by low or high doses of risedronate. In conclusion, high dose bisphosphonate treatment impaired healing of a large stress fracture line by reducing the volume of bone resorbed and replaced during remodeling. We also confirmed that periosteal callus formation was not adversely affected by risedronate treatment. ß

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“…24 Moreover, mFEA of excised bones is non-destructive allowing for subsequent histological analysis. Although a number of studies involving rodents have used mFEA to determine the effect of drug treatment on bone strength, [25][26][27][28][29][30] there is little evidence in the literature establishing that mFEA can accurately predict the mechanical properties of rodent bone, and especially murine bones. Of the few studies comparing FEA predictions to experimental measurements of strength in rodent tissues, long bones were tested with limited examination of material definitions.…”

Section: Introductionmentioning

confidence: 99%

Predicting mouse vertebra strength with micro-computed tomography-derived finite element analysis

Nyman¹,

Uppuganti²,

Makowski³

et al. 2015

BoneKEy Reports

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As in clinical studies, finite element analysis (FEA) developed from computed tomography (CT) images of bones are useful in pre-clinical rodent studies assessing treatment effects on vertebral body (VB) strength. Since strength predictions from microCT-derived FEAs (mFEA) have not been validated against experimental measurements of mouse VB strength, a parametric analysis exploring material and failure definitions was performed to determine whether elastic mFEAs with linear failure criteria could reasonably assess VB strength in two studies, treatment and genetic, with differences in bone volume fraction between the control and the experimental groups. VBs were scanned with a 12-mm voxel size, and voxels were directly converted to 8-node, hexahedral elements. The coefficient of determination or R 2 between predicted VB strength and experimental VB strength, as determined from compression tests, was 62.3% for the treatment study and 85.3% for the genetic study when using a homogenous tissue modulus (E t ) of 18 GPa for all elements, a failure volume of 2%, and an equivalent failure strain of 0.007. The difference between prediction and measurement (that is, error) increased when lowering the failure volume to 0.1% or increasing it to 4%. Using inhomogeneous tissue density-specific moduli improved the R 2 between predicted and experimental strength when compared with uniform E t ¼ 18 GPa. Also, the optimum failure volume is higher for the inhomogeneous than for the homogeneous material definition. Regardless of model assumptions, mFEA can assess differences in murine VB strength between experimental groups when the expected difference in strength is at least 20%.

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Effects of risedronate on trabecular microstructure and biomechanical properties in ovariectomized rat tibia

Cited by 49 publications

References 19 publications

A computational assessment of the independent contribution of changes in canine trabecular bone volume fraction and microarchitecture to increased bone strength with suppression of bone turnover

A computational assessment of the independent contribution of changes in canine trabecular bone volume fraction and microarchitecture to increased bone strength with suppression of bone turnover

Bisphosphonate treatment delays stress fracture remodeling in the rat ulna

Predicting mouse vertebra strength with micro-computed tomography-derived finite element analysis

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