Bone adaptation to load: microdamage as a stimulus for bone remodelling

Lee, T. C.; Staines, Anthony; Taylor, David

doi:10.1046/j.1469-7580.2002.00123.x

Cited by 206 publications

(149 citation statements)

References 30 publications

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“…It has been known for some time that BMUs are targeted towards damage (Burr and Martin, 1993;Burr, 2002;Lee et al, 2002), i.e. the removal of bone is not a random process but is directed to places where microcracks exist.…”

Section: Introductionmentioning

confidence: 99%

Rupture of osteocyte processes across microcracks: the effect of crack length and stress

Dooley

Tisbo

Lee

et al. 2011

Biomech Model Mechanobiol

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Bone cells are connected to one another in a network, via their dendritic cellular processes. Previously, we hypothesised that these processes could be ruptured by microcracks. We proposed this as a mechanism by which osteoctyes could detect the presence of microcracks. In order for this mechanism to be effective, the number of ruptured processes would have to increase with microcrack length and also with the applied cyclic stress applied. This paper presents for the first time experimental data which shows that this is indeed the case. We examined samples of bovine, ovine and murine bone ex vivo and observed processes passing across crack faces: some were still intact whilst others had ruptured. The number of intact processes per unit crack length decreased significantly with increasing crack length, and also decreased in samples which had been tested in vitro at higher stress levels. A theoretical model which we had developed previously was able to predict the overall magnitude and general trends in the experimental data. This work has provided further support for our "scissors" model which proposes that microcracks can be detected because they disturb the osteocyte network, specifically by rupturing cellular processes where they pass across the crack faces. AbstractBone cells are connected to one another in a network, via their dendritic cellular processes. Previously, we hypothesised that these processes could be ruptured by microcracks. We proposed this as a mechanism by which osteoctyes could detect the presence of microcracks. In order for this mechanism to be effective, the number of ruptured processes would have to increase with microcrack length and also with the applied cyclic stress applied. This paper presents for the first time experimental data which shows that this is indeed the case. We examined samples of bovine, ovine and murine bone ex vivo and observed processes passing across crack faces: some were still intact whilst others had ruptured. The number of intact processes per unit crack length decreased significantly with increasing crack length, and also decreased in samples which had been tested in vitro at higher stress levels. A theoretical model which we had developed previously was able to predict the overall magnitude and general trends in the experimental data. This work has provided further support for our "scissors" model which proposes that microcracks can be detected because they disturb the osteocyte network, specifically by rupturing cellular processes where they pass across the crack faces.

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Section: Introductionmentioning

confidence: 99%

Rupture of osteocyte processes across microcracks: the effect of crack length and stress

Dooley

Tisbo

Lee

et al. 2011

Biomech Model Mechanobiol

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“…6,64,68 As in other materials experiencing prolonged and repeated use, tetrapod bones often accumulate fatigue damage in the form of microcracks. 69,70 Remodeling allows bones to replace these damaged regions within their bulk with new bone material, via coordination of the activity of osteoblasts and osteoclasts. This dynamic remodeling process is triggered by osteocytes.…”

Section: Remodeling: Evidence For and Implications In Acellular Bonementioning

confidence: 99%

The enigmas of bone without osteocytes

Shahar¹,

Dean²

2013

BoneKEy Reports

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One of the hallmarks of tetrapod bone is the presence of numerous cells (osteocytes) within the matrix. Osteocytes are vital components of tetrapod bone, orchestrating the processes of bone building, reshaping and repairing (modeling and remodeling), and probably also participating in calcium-phosphorus homeostasis via both the local process of osteocytic osteolysis, and systemic effect on the kidneys. Given these critical roles of osteocytes, it is thought-provoking that the entire skeleton of many fishes consists of bone material that does not contain osteocytes. This raises the intriguing question of how the skeleton of these animals accomplishes the various essential functions attributed to osteocytes in other vertebrates, and raises the possibility that in acellular bone some of these functions are either accomplished by non-osteocytic routes or not necessary at all. In this review, we outline evidence for and against the fact that primary functions normally ascribed to osteocytes, such as mechanosensation, regulation of osteoblast/clast activity and mineral metabolism, also occur in fish bone devoid of these cells, and therefore must be carried out through alternative and perhaps ancient pathways. To enable meaningful comparisons with mammalian bone, we suggest thorough, phylogenetic examinations of regulatory pathways, studies of structure and mechanical properties and surveys of the presence/absence of bone cells in fishes. Insights gained into the micro-/nanolevel structure and architecture of fish bone, its mechanical properties and its physiology in health and disease will contribute to the discipline of fish skeletal biology, but may also help answer questions of basic bone biology.

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“…Fluorochrome dyes and their administration schedule were chosen based on similar studies from the literature. 19,[22][23][24][25][26] The animals' body mass was also measured at each time point. Starting 2 weeks prior to the end point of the experiment, a blood sample was collected every 2 days from each animal.…”

Section: Animal Model and Experimental Proceduresmentioning

confidence: 99%

Effects of ovariectomy on bone turnover, porosity, and biomechanical properties in ovine compact bone 12 months postsurgery

Kennedy

Brennan

Rackard

et al. 2009

Journal Orthopaedic Research

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Compact bone makes up approximately 80% of the human skeleton by mass; but there are little data available on the effects of increased bone turnover on compact bone mechanical and material properties. This study addresses this question by measuring intracortical remodeling, resorption cavity number, and porosity in an ovariectomized (OVX) sheep model, and measures changes in biomechanical properties. Thirty-eight sheep were divided into two groups. Group 1 were controls (n ¼ 19), and Group 2 were ovariectomized (OVX; n ¼ 19). Fluorochrome dyes were administered intravenously to both groups at five time points over 12 months post-OVX to label sites of bone turnover. At 12 months post-OVX all animals were euthanized. Samples were harvested from the left metatarsal and were analyzed for intracortical bone turnover at five time points, the number of resorption cavities, and the level of intracortical porosity. The effects of these parameters on bone biomechanical properties were then measured. Bone turnover was increased in the OVX group at 6, 9, and 12 months (p < 0.05). Resorption was also higher in the OVX group at 12 months (p < 0.05). Furthermore, porosity was significantly increased in the OVX group at 12 months (p < 0.05). Stiffness and yield strength were reduced in the OVX group compared to controls (p ¼ 0.05). Ultimate compressive strength and work to fracture did not differ between groups. These findings provide new insights into the mechanisms and effects of increased bone turnover on bone material and microstructural properties. Keywords: bone turnover; porosity; ovariectomy; ovine animal model Bone turnover is an important determinant of the structural integrity of bone. It is a crucial process of tissue renewal that normally occurs at an optimal physiological rate for maximum bone strength in a healthy individual. 1 Any change to the optimal bone turnover rate, such as the increase that occurs following ovariectomy (OVX) or menopause, has the potential to dramatically change the bone at microstructural and material levels. High bone turnover can have the effect of increasing remodeling spaces, accelerating bone loss, increasing stress concentrations, and increasing cortical porosity, each of which can undermine bone mechanical properties. A precise definition of bone quality remains elusive, however; bone turnover and microarchitecture are considered to be two important contributors to this phenomenon along with mineralization, microdamage, and collagen content. Thus, these parameters are important considerations in the pathophysiology of skeletal diseases such as osteoporosis and the mechanisms that underlie fracture. 2 Previous studies have shown that bone turnover has a direct influence on fracture risk. 3 It is thought that compact bone is affected by accelerated turnover in two ways. First, more mineralized bone is removed and replaced with younger, less mineralized bone, which reduces the material's local stiffness. Second, the presence of more resorption cavities creates stress concen...

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Bone adaptation to load: microdamage as a stimulus for bone remodelling

Cited by 206 publications

References 30 publications

Rupture of osteocyte processes across microcracks: the effect of crack length and stress

Rupture of osteocyte processes across microcracks: the effect of crack length and stress

The enigmas of bone without osteocytes

Effects of ovariectomy on bone turnover, porosity, and biomechanical properties in ovine compact bone 12 months postsurgery

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