Elsevier

Bone

Volume 42, Issue 4, April 2008, Pages 758-764
Bone

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

https://doi.org/10.1016/j.bone.2007.12.223Get rights and content

Abstract

Non-unions and delayed healing are still prevalent complications in fracture and bone defect healing. Both mechanical stability and age are known to influence this process. However, it remains unclear which factor dominates and how they interact. Within this study, we sought a link between both factors.

In 36 female Sprague–Dawley rats, the left femur was osteotomized, distracted to an osteotomy gap of 1.5 mm and externally fixated. Variation of age (12 vs. 52 weeks — biologically challenging) and fixator stiffness (mechanically challenging) resulted in 4 groups (each 9 animals): YS: young semi-rigid, OS: old semi-rigid, YR: young rigid and OR: old rigid. Qualitative and quantitative radiographical analyses were performed at weeks 2, 4 and 6 after surgery. Six weeks post-op, rats were sacrificed and femora were harvested for biomechanical testing (torsional stiffness (TS) and maximum torque at failure (MTF)).

Six weeks after surgery, TS showed a significant interaction between age and fixation stiffness (p < 0.0001). TS in YR was significantly higher than that in the other groups (YS: p < 0.001; OR: p < 0.001; OS: p < 0.001). Additionally, YS showed a significantly higher TS compared to the OS (p = 0.006) and OR (p = 0.046). Testing of MTF showed a significant interaction of both variables (p = 0.0002) and led to significant differences between OR and YS (p < 0.001), OS (p = 0.046) and YR (p < 0.001). The YR showed a higher MTF compared to YS (p = 0.012) and OS (p = 0.001), whereas OR's MTF was inferior compared to OS. At 2-week follow-up, YR (p = 0.006), and at 6-week follow-up, YS and YR (p = 0.032) showed significantly higher radiographic scores. At 2-week follow-up, YS's callus was larger than that of the old groups (OS: p = 0.025; OR: p = 0.003). In YR a significantly smaller callus was observed compared to YS at time points 4 and 6 weeks (p = 0.002 for both) and compared to OS at 6-week follow-up (p = 0.03).

The effect of age seems to invert the effect of mechanical properties of the callus, which was not correlated to callus size. Optimization of mechanics alone seems to be not sufficient. The underlying mechanisms and causes of the age-related influences and their clinical counterparts need to be further investigated.

Introduction

Despite the current standards in osteosynthesis of human fractures, a pseudoarthrosis rate of up to 20% leads to prolonged morbidity, resulting in high costs for the health care system [1], [2], [3]. Both systemic biological factors and mechanical stability affect the outcome and course of bone defect healing [4], [5], [6], [7], [8].

In addition to perfusion, systemic metabolism and the influence of medication, age plays an important role as a biological factor. Animal experiments in rats as well as clinical studies in humans show a delayed course of bone healing with increasing age [9], [10]. As reasons for this, a reduced number of osteogenic stem cells, their reduced proliferation and differentiation potential, and reduced systemic or local blood flow have been discussed [11], [12], [13], [14]. Whereas in transcriptional analyses in rats the generation of cartilaginous matrix seemed to be less influenced by age, clear differences could be found in genes responsible for bone matrix generation, although possible posttranslational modifications were not considered [8], [15]. Histological examinations in mice show a delay in all phases of healing with increasing age [16].

An optimal local mechanical environment is crucial for successful healing [5], [6], [7], [17]. The mechanical environment is determined in turn by the fixation stability [7], [17]. Initial instability can lead to decelerated healing or pseudoarthrosis, due to rupturing of the bridging tissue including the nutrimental vessels [4], [6], [8], [18]. In contrast to this, mechanical stimuli in an optimal biological environment result in cell proliferation and differentiation, healing and remodelling [19], [20]. Healing will also be delayed if mechanical stimuli are completely absent [4], [21].

As described, the separate influences of age and mechanical fixation stability on bone healing are well known. However, in clinical reality both age and mechanical stability affect bone defect healing simultaneously. Since previous animal studies did not take account of this situation, a need arises for searching a possible link between both factors. The synergistic or independent effects resulting from this may lead to therapeutic consequences regarding an adaptation of the mechanical environment to the biologically unfavourable situation of advanced age.

The aim of this study was to find biomechanical and radiological differences between old and young rats under the influence of variable fixation stability in sub-critical bone defect healing. The biomechanical superiority of bone defect healing in young rats compared to that in old rats served as hypothesis of this work. Secondly we hypothesized a better healing outcome for rigidly fixated defects within both age groups.

Section snippets

Animals and groups

All experiments were carried out according to the policies and principles established by the Animal Welfare Act, the NIH Guide for Care and Use of Laboratory Animals and the National Animal Welfare Guidelines and were approved by the local legal representative (Landesamt für Arbeitsschutz, Gesundheitsschutz und technische Sicherheit, Berlin, Reg. no.: G 0190/05).

36 adult female Sprague–Dawley-rats were divided into four groups with nine animals each group. Groups YS (young semi-rigid) and YR

Clinical results

One animal in group YR showed infection and one in group OS, the break-out of a Kirschner-wire. Both animals were sacrificed before the end of the study and excluded from analysis. Other complications like breaking of the wires or loosening of the crossbar or screws were not observed.

Radiological results

In all groups, a progression of consolidation could be observed in radiographical scores over time (Table 1). Significant differences were detected between groups at 2-week follow-up (p = 0.006), showing a higher

Discussion

The present work shows a dependence of bone healing on the age of the individuals as well as on the mechanical environment. For the first time, we were able to show that a superior configuration for young mammals led to worse results in bone defect healing in a group of old mammals. Whereas the hypothesis of better healing with more stable fixation could be confirmed in young animals, the mechanical results were inhomogeneous. Surprisingly, the effect of age seemed to invert the effect of

Acknowledgments

This study was funded in part by the German Research Foundation (SFB760) and the BMBF (Berlin-Brandenburg Center for Regenerative Therapies — BCRT).

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