Local irradiation alters bone morphology and increases bone fragility in a mouse model

Wernle, James D.; Damron, Timothy A.; Allen, Matthew J.; Mann, Kenneth A.

doi:10.1016/j.jbiomech.2010.06.017

Cited by 70 publications

(95 citation statements)

References 27 publications

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“…According to Nyaruba et al (21) and Wernle et al (22), alterations in bone strength seem to be more related to changes in the trabecular morphology than in the cortical morphology of irradiated bone. Nevertheless, the influence of ionizing radiation on the mechanical properties of bone was not yet fully clarified, as there are conflicting reports in previous studies (11,(21)(22)(23). In addition, the micro-CT images (Fig.…”

Section: Discussionmentioning

confidence: 96%

Meloxicam as a Radiation-Protective Agent on Mandibles of Irradiated Rats

et al. 2017

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This study evaluated the action of ionizing radiation and the possible radioprotective effect of the non-steroidal anti-inflammatory drug meloxicam on the bone physiology of rat mandibles by assessing the alveolar socket healing and bone strength. Forty male Wistar rats were divided in 4 groups (n=10): control (CG), irradiated (IG), meloxicam (MG), meloxicam irradiated (MIG). A dose of 0.2 mg/kg meloxicam was administered to MG and MIG. After this, IG and MIG were irradiated with 15 Gy radiation dose in the mandible. Forty days after the above procedures, the mandibular first molars were extracted and the animals were killed after 15 or 30 days (n=5). Micro-computed tomography and bending test were used to evaluate alveolar socket healing and bone strength, respectively. At 15 days, bone volume, bone volume fraction and trabecular thickness were higher in the CG and MG than in the IG and MIG; and trabecular separation was higher in the IG compared with the others. At 30 days, there was a difference only in trabecular separation, which was higher in IG than in CG and MG, and MIG did not differ from the others. Bone strength was lower in IG compared with CG and MG, and MIG did not differ from the others. In conclusion, the ionizing radiation affected the bone physiology of rat mandibles, delaying the alveolar socket healing and reducing the bone strength. Moreover, the meloxicam had a positive effect on the trabecular separation in alveolar socket healing and on the bone strength.

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Section: Discussionmentioning

confidence: 96%

Meloxicam as a Radiation-Protective Agent on Mandibles of Irradiated Rats

et al. 2017

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“…However, radiation regimens in these studies differed (eg, no high-dose radiation) from ours and those studies focused on radiation to visceral tumors in the pelvis rather than primary bone tumors. Radiation is a recognized risk factor for the development of insufficiency fractures; it decreases bone strength and the number and resiliency of trabeculae [5,19,21]. It seems plausible that higher doses of radiation would increase the risk of a fracture developing.…”

Section: Discussionmentioning

confidence: 99%

Sacral Insufficiency Fractures are Common After High-dose Radiation for Sacral Chordomas Treated With or Without Surgery

Osler

Bredella

Hess

et al. 2016

Clinical Orthopaedics &Amp; Related Research

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Background Surgery with high-dose radiation and highdose radiation alone for sacral chordomas have shown promising local control rates. However, we have noted frequent sacral insufficiency fractures and perceived this rate to be higher than previously reported. Questions/purposes We wished (1) to characterize the incidence of sacral insufficiency fractures in patients with chordomas of the sacrum who received high-dose radiation, and (2) to determine whether patients treated with surgery plus high-dose radiation or high-dose radiation alone are more likely to experience a sacral fracture, and to compare time to fracture in these groups. Methods Sixty-two patients who received high-dose radiation for sacral chordomas with (n = 44) or without surgical resection (n = 18) between 1992 and 2013 were included in this retrospective study. At our institution, sacral chordomas generally are treated by preoperative radiotherapy, followed by en bloc resection, and postoperative radiotherapy. Radiation alone, with an intent to cure, is offered to patients who otherwise are not good surgical candidates or patients who elect radiotherapy based on tumor location and the anticipated morbidity after surgery (such as sexual, bowel, or bladder dysfunction). MRI and CT scans were evaluated for evidence of sacral insufficiency fractures. Complete followup was available at a minimum of 2 years (or until fracture or death) for all 18 patients who underwent radiation alone, whereas 14% (six of 44 patients) in the surgery plus radiation group (9% [three of 33] after high sacrectomy and 27% [three of 11] after low sacrectomy) were lost to followup before 2 years. Results Sacral insufficiency fractures occurred in 29 of the 62 patients (47%). A total of 25 of 33 patients (76%)One author (SJJ) certifies that he has received, an amount less than USD 10,000 from the Anna Foundation (Oegstgeest, The Netherlands), an amount less than USD 10,000 from the De Drie Lichten Foundation (Hilversum, The Netherlands), an amount less than USD 10,000 from the KWF Kankerbestrijding (Amsterdam, The Netherlands), and an amount less than USD10,000 from the Michael van Vloten Foundation (Rotterdam, The Netherlands). One author (JHS) certifies that he or a member of his family has or may receive payments or benefits, an amount less than USD 10,000 from Stryker (Kalamazoo, MI, USA), and an amount less than USD 10,000 from Biom'up (Saint-Priest, Lyon, France). All ICMJE Conflict of Interest Forms for authors and Clinical Orthopaedics and Related Research 1 editors and board members are on file with the publication and can be viewed on request. Each author certifies that his or her institution approved or waived approval for the reporting of this investigation and that all investigations were conducted in conformity with ethical principles of research. This work was performed at Massachusetts General Hospital, Boston, MA, USA. with high sacrectomy had fractures develop compared with zero of 11 (0%) after low sacrectomy, and four of the 18 patients (22%) w...

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“…The mFEAs derived from the 12-mm isotropic voxel scan under predicted strength by 2 N, but the strength predictions were highly correlated with those from the high mesh density model (threshold ¼ 421.8 mg HA cm À 3 ). Figure 7 Of the published relationships to convert mCT-derived volumetric density to elastic modulus, this study used those derived by Wagner et al 32 , Easley et al 28 and Renders et al 35 The typical TMD range for this study is highlighted with the darker colors. A linear regression equation derived from the Wagner relationship (dashed white line) was used to calculate element-specific E t in the inhomogeneous mFEAs.…”

Section: Methodsmentioning

confidence: 99%

“…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. [31][32][33] In effect, mFEAs of rodent bones rely on assumptions of material properties and failure criteria from the many correlation studies involving cadaveric bone from larger species.…”

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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Local irradiation alters bone morphology and increases bone fragility in a mouse model

Cited by 70 publications

References 27 publications

Meloxicam as a Radiation-Protective Agent on Mandibles of Irradiated Rats

Meloxicam as a Radiation-Protective Agent on Mandibles of Irradiated Rats

Sacral Insufficiency Fractures are Common After High-dose Radiation for Sacral Chordomas Treated With or Without Surgery

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

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