Influence of age and mechanical stability on bone defect healing: Age reverses mechanical effects

Strube, Patrick; Sentuerk, Ufuk; Riha, T.; Kaspar, K.; Mueller, Christoph; Kasper, Grit; Matziolis, Georg; Duda, Georg N.; Perka, Carsten

doi:10.1016/j.bone.2007.12.223

Cited by 79 publications

(73 citation statements)

References 33 publications

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“…In groups MS and FS, a semirigid configuration of the fixator was chosen, whereas in groups MR and FR, a rigid fixator was used as previously reported [23]. Recently published (maximum torque at failure [MTF], torsional stiffness [TS], qualitative radiographic score, Jz, cross-sectional area [CsAr]) results of the female aged groups of our first study [24] and of the semirigidly fixated aged male group of the second study [22] served as historical controls for comparison (all data published earlier are marked within the tables and figures). All experiments were carried out according to the policies and principles established by the Animal Welfare Act, the National Institutes of Health Guide for Care and Use of Laboratory Animals, and the National Animal Welfare Guidelines and were approved by the local legal representative (Landesamt für Gesundheit und Soziales Berlin: G 0190/05 and G 0071/07).…”

Section: Methodsmentioning

confidence: 99%

“…Operations were performed by one surgeon (PS) under aseptic conditions on a heating plate (37°C) under general anesthesia according to previously published protocols [9,24], which are briefly summarized here. The midshaft left femur was prepared using an anterolateral approach between hamstring muscles and M. quadriceps femoris.…”

Section: Methodsmentioning

confidence: 99%

“…Callus formation (3) is illustrated by change of relative callus cross-sectional area (dCSA). Superscript letters (a) [22] and (b) [24] indicate methods, in which historical controls of recently published parameters were used for statistical comparison.…”

Section: Methodsmentioning

confidence: 99%

“…We recently reported that the healing outcome using different fixation stabilities is dependent on the individual's age [24]. Rigid external fixation led to improved mechanical properties of the callus and to higher bridging in a group of young compared with middle-aged mature female rats.…”

Section: Introductionmentioning

confidence: 99%

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Influence of Gender and Fixation Stability on Bone Defect Healing in Middle-aged Rats: A Pilot Study

Mehta

Duda

Perka

et al. 2011

Clinical Orthopaedics &Amp; Related Research

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Background Gender and stability of fixation independently influence bone regeneration but their combined effects are unclear. Questions/purposes In a pilot study we determined the combined influence of gender and fixation stability on the callus of middle-aged rats regarding (1) biomechanical properties; (2) bridging over time; (3) callus formation; and (4) callus size, geometry, mineralization, and microstructure. Methods We osteotomized the left femur of 32 SpragueDawley rats (12 months old). Femurs were externally fixed with a gap of 1.5 mm in four groups of eight animals each: female semirigid, male semirigid, female rigid, and male rigid. Qualitative and quantitative in vivo radiographic analyses were performed twice weekly. Six weeks postoperatively, harvested femora were evaluated using micro-CT and biomechanical testing. Results Torsional stiffness and maximum torque at failure were higher in male and in semirigidly fixed fractures. Radiographic analysis revealed earlier bridging and callus formation in both male groups. Micro-CT analysis showed a larger callus size, altered geometry, and microstructure in males and semirigidly fixed animals, whereas mineralization was similar in all animals. Conclusion Our data suggest female gender represents an independent risk factor for bone healing in middle-aged rats. Although healing in females was delayed compared with males, they exhibited a similar response (superior callus properties) to a more semirigid fixation. Clinical Relevance While female gender appears to reflect a risk for impaired bone healing in middle-aged female rats, clinical studies would be required to confirm the finding in humans.

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Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Influence of Gender and Fixation Stability on Bone Defect Healing in Middle-aged Rats: A Pilot Study

Mehta

Duda

Perka

et al. 2011

Clinical Orthopaedics &Amp; Related Research

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“…In the case of bone, it is intriguing that mechanical signals, which are important regulators of tissue homeostasis as well as regeneration, are also transduced via the cytoskeleton [44]. This is particularly interesting when considering that in vivo age seems to affect mechanical requirements [45]. Hence, we would postulate that aged MSCs are less responsive to environmental cues (both biological and mechanical), due to their lower actin dynamic, and that this has negative effects on their regenerative potential.…”

Section: Cytoskeleton Dynamicsmentioning

confidence: 99%

Insights into Mesenchymal Stem Cell Aging: Involvement of Antioxidant Defense and Actin Cytoskeleton

et al. 2009

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Progenitor cells such as mesenchymal stem cells (MSCs) have elicited great hopes for therapeutic augmentation of physiological regeneration processes, e.g., for bone fracture healing. However, regeneration potential decreases with age, which raises questions about the efficiency of autologous approaches in elderly patients. To elucidate the mechanisms and cellular consequences of aging, the functional and proteomic changes in MSCs derived from young and old Sprague-Dawley rats were studied concurrently. We demonstrate not only that MSC concentration in bone marrow declines with age but also that their function is altered, especially their migratory capacity and susceptibility toward senescence. High-resolution two-dimensional electrophoresis of the MSC proteome, under conditions of in vitro self-renewal as well as osteogenic stimulation, identified several agedependent proteins, including members of the calponin protein family as well as galectin-3. Functional annotation clustering revealed that age-affected molecular functions are associated with cytoskeleton organization and antioxidant defense. These proteome screening results are supported by lower actin turnover and diminished antioxidant power in aged MSCs, respectively. Thus, we postulate two main reasons for the compromised cellular function of aged MSCs: (a) declined responsiveness to biological and mechanical signals due to a less dynamic actin cytoskeleton and (b) increased oxidative stress exposure favoring macromolecular damage and senescence. These results, along with the observed similar differentiation potentials, imply that MSC-based therapeutic approaches for the elderly should focus on attracting the cells to the site of injury and oxidative stress protection, rather than merely stimulating differentiation.

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Multiscale Biomechanics

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Influence of age and mechanical stability on bone defect healing: Age reverses mechanical effects

Cited by 79 publications

References 33 publications

Influence of Gender and Fixation Stability on Bone Defect Healing in Middle-aged Rats: A Pilot Study

Influence of Gender and Fixation Stability on Bone Defect Healing in Middle-aged Rats: A Pilot Study

Insights into Mesenchymal Stem Cell Aging: Involvement of Antioxidant Defense and Actin Cytoskeleton

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