Biomedical subjects

M G Mullender

Publications and source records attributed to M G Mullender.

8 recordsLinked to original sources

PubMed2005

Differences in osteocyte density and bone histomorphometry between men and women and between healthy and osteoporotic subjects.

Bone defects related to osteoporosis develop with increasing age and differ between males and females. It is currently thought that the bone remodeling process is supervised by osteocytes in a strain-dependent manner. We have shown an altered response of osteocytes from osteoporotic patients to mechanical loading, and osteocyte density is reduced in osteoporotic patients, which might relate to imperfect bone remodeling, leading to lack of bone mass and strength. Hence, information on osteocyte density will contribute to a better understanding of bone biology in males and females and to the assessment of osteoporosis. Osteocyte density as well as conventional histomorphometric parameters of trabecular bone were determined in cancellous iliac crest bone of healthy postmenopausal women and men and of osteoporotic women and men. Osteocyte density was higher in healthy females than in healthy males and lower in osteoporotic females than in healthy females. Bone mass was reduced in osteoporotic patients, both male and female. In females, trabecular number was reduced, whereas in males, trabecular thickness was reduced and eroded surface was increased. There were no correlations between the parameter groups bone architecture, bone formation, bone resorption, and osteocyte density. These results are consistent with impaired osteoblast function in osteoporotic patients and with a different mechanism of bone loss between men and women, in which osteocyte density might play a role. The reduced osteocyte numbers in female osteoporotic patients might relate to imperfect bone remodeling leading to lack of bone mass and strength.

Aged↗

PubMed2005

Mechanobiology of bone tissue.

In order to obtain bones that combine a proper resistance against mechanical failure with a minimum use of material, bone mass and its architecture are continuously being adapted to the prevailing mechanical loads. It is currently believed that mechanical adaptation is governed by the osteocytes, which respond to a loading-induced flow of interstitial fluid through the lacuno-canalicular network by producing signaling molecules. An optimal bone architecture and density may thus not only be determined by the intensity and spatial distribution of mechanical stimuli, but also by the mechanoresponsiveness of osteocytes. Bone cells are highly responsive to mechanical stimuli, but the critical components in the load profile are still unclear. Whether different components such as fluid shear, tension or compression may affect cells differently is also not known. Although both tissue strain and fluid shear stress cause cell deformation, these stimuli might excite different signaling pathways related to bone growth and remodeling. In order to define new approaches for bone tissue engineering in which bioartificial organs capable of functional load bearing are created, it is important to use cells responding to the local forces within the tissue, whereby biophysical stimuli need to be optimized to ensure rapid tissue regeneration and strong tissue repair.

Animals↗

PubMed1997

Osteocytes and bone lining cells: which are the best candidates for mechano-sensors in cancellous bone?

Previously, we have investigated the possible role of osteocytes as mechano-sensors, and mediators of bone turnover. It was found that the proposed regulatory mechanism produced morphologies of trabecular bone, under particular loading conditions, which were consistent with morphogenesis and adaptation as seen in reality. The main objective of this study was to discern whether lining cells or osteoblasts could possibly play a similar role as effectively with regard to their capacity for self-optimization of the trabecular architecture, in terms of a low apparent mass to stiffness ratio. For that purpose the earlier analyses with osteocytes as mechano-sensors, distributed throughout the bone, were repeated for mechano-sensors located at bone surfaces only. Compared to the osteocyte model, the surface cell remodeling algorithm was reluctant to change its architecture, which implies that it is less sensitive to changes in the loading pattern. This resulted in less efficient bone adaptation, which was reflected by a considerably higher relative mass for a similar apparent stiffness in the loading direction. In other words, more mass is needed to obtain an equally stiff structure, at the apparent level, with respect to the externally applied loads. Furthermore, stresses and strains at the tissue level vary across a much wider range, relative to the osteocyte model, where the higher incidence of elevated strains indicates an increased failure risk. Therefore, we conclude that mechanical information at the bone surface may not be sufficient to adequately regulate functional bone adaptation.

Animals↗

PubMed1996

Osteocyte density and histomorphometric parameters in cancellous bone of the proximal femur in five mammalian species.

The species-specific relationships between trabecular morphology and osteocyte density were investigated in the femoral heads of 30 adult animals of five mammalian species (rat, rabbit, Rhesus monkey, pig, and cow). Our hypothesis is that osteocytes are mechanosensory cells and are involved in the regulation of bone remodeling. According to the predictions from a simulation model, this hypothesis implies that the influencing distance of osteocytes, together with the magnitude of the mechanical loads, determines the thickness of trabeculae and that the number of osteocytes primarily affects the rate of bone remodeling. The number of osteocytes per bone volume ranged from 93,200 mm-3 in rat to 31,900 mm-3 in bovine cancellous bone. Osteocyte density was inversely related to the size of the species. Since basal metabolic output is related to body mass, we speculate that osteocyte density may be related to metabolic rates. Trabecular thickness was larger in the cow than in the other species, but the range of variation between species was relatively small. This agrees with the hypothesis that trabecular thickness is limited by the domain that can be regulated by an osteocyte and that this domain is of similar size regardless of the species. Only in the rat was trabecular thickness considerably smaller than in the other species. This is probably due to the presence of the cartilaginous growth plate in the femoral head of the rat. The relationships with species are different for osteocyte density than for morphometric parameters. Hence, our data support our hypothesis that osteocyte density is not directly associated with the macroscopic trabecular architecture.

Animals↗

PubMed1996

Osteocyte density changes in aging and osteoporosis.

Recently, it was suggested that osteocytes are involved in the regulation of bone remodeling. We have examined human trabecular bone of the iliac crest of fracture patients and control subjects to determine if osteoporosis is associated with changes in osteocyte density or osteocyte death. The relationships of these parameters with age was also investigated. It was found that osteocyte death was not related to age, nor was it increased in osteoporosis compared with the controls. In healthy adults ranging from 30 to 91 years, lacunar number per bone area decreases with advancing age, from about 210/mm(2) to 150/mm(2). Significantly higher lacunar and osteocyte numbers per bone tissue volume were found in osteoporotics than in controls (17,100 lacunae/mm(3) and 13,300 osteocytes/mm(3) vs. 12,900 lacunae/mm(3) and 10,500 osteocytes/mm(3), respectively), whereas lacunar area was significantly reduced in osteoporotics (from 44.1 mu m(3) to 39.1 mu m(2)). These findings are compatible with the hypothesis that, in osteoporosis, osteoblasts produce less bone per cell. This can in turn explain the reduced wall thickness, which has previously been described as characteristic for osteoporosis.

Adult↗

PubMed1995

Proposal for the regulatory mechanism of Wolff's law.

It is currently believed that the trabecular structure in bone is the result of a dynamic remodeling process controlled by mechanical loads. We propose a regulatory mechanism based on the hypothesis that osteocytes located within the bone sense mechanical signals and that these cells mediate osteoclasts and osteoblasts in their vicinity to adapt bone mass. A computer-simulation model based on these assumptions was used to investigate if the adaptation of bone, in the sense of Wolff's law, and remodeling phenomena, as observed in reality, can be explained by such a local control process. The model produced structures resembling actual trabecular architectures. The architecture transformed after the external loads were changed, aligning the trabeculae with the actual principal stress orientation, in accordance with Wolff's trajectorial hypothesis. As in reality, the relative apparent density of the structure depended on the magnitude of the applied stresses. Osteocyte density influenced the remodeling rate, which also is consistent with experimental findings. Furthermore, the results indicated that the domain of influence of the osteocytes affects the refinement of the structure as represented by separation and thickness of the struts. We concluded that the trabecular adaptation to mechanical load, as described by Wolff, can be explained by a relatively simple regulatory model. The model is useful for investigating the effects of physiological parameters on the development, maintenance, and adaptation of bone.

Adaptation, Physiological↗

PubMed1994

A physiological approach to the simulation of bone remodeling as a self-organizational control process.

Although the capacity of bone to adapt to functional mechanical requirements has been known for more than a century, it is still unclear how the bone adaptation processes are regulated. We hypothesize that osteocytes are sensitive to mechanical loading and control the regulation of bone mass in their environment. Recently, simulation models of such a process were developed, using the finite element method. It was discovered that these models produce discontinuous structures, not unlike trabecular bone. However, it was also found that severe discontinuities violate the continuum assumption underlying the finite element method and that the solutions were element mesh dependent. We have developed a simulation model (which is physiologically and mechanically more consistent) which maintains the self-organizational characteristics but does not produce these discontinuities. This was accomplished by separating the sensor density and range of action from the mesh. The results clearly show that predicted trabecular morphology, i.e. sizes and branching of struts, depend on the actual relationship between local load, sensor density and range of influence. We believe that the model is suitable to study the relationship between trabecular morphology and load and can also explain adaptation of morphology, in the sense of 'Wolff's law'.

Adaptation, Physiological↗

PubMed1990

Electromechanical delay in the vastus lateralis muscle during dynamic isometric contractions.

Electromechanical delay (EMD) values were obtained using a cross-correlation technique for a series of 14 repetitive submaximal dynamic isometric contractions of the vastus lateralis performed by five subjects. To avoid a phase lag, which is introduced with one-way filtering, the EMG was processed with a bi-directional application of a second-order Butterworth filter. A mean EMD value of 86 ms (SD = 5.1 ms) was found. Moreover, contraction and relaxation delays were computed and compared. There was a significant difference between the contraction and relaxation delays (P less than 0.005). The mean contraction delay was 81.9 ms and the mean relaxation delay was 88.8 ms. Despite this significant difference, the computed contraction and relaxation delay values lie in the same range as the total phase lag, calculated with the cross-correlation technique. The magnitude of EMD values found supports the need to account for this delay when interpreting temporal aspects of patterns of intermuscular coordination.

Adult↗