scholarly journals Feeding intervention potentiates the effect of mechanical loading to induce new bone formation in mice

2020 ◽  
Author(s):  
Hasmik Jasmine Samvelyan ◽  
John Cummings Mathers ◽  
Timothy Michael Skerry

AbstractThe benefits of increased human lifespan depend upon duration of healthy, independent living; the healthspan. Bone-wasting disorders contribute significantly to loss of independence, frailty and morbidity in older people. Therefore, there is an unmet need globally for lifestyle interventions to reduce the likelihood of bone fractures with age. Although many mechanisms are involved in disorders of bone loss, there is no single regulatory pathway and, therefore, there is no single treatment available to prevent their occurrence. Our aim in these studies was to determine whether fasting/feeding interventions alter the effect of mechanical loading on bone anabolic activities and increase bone mass. In young 17-week-old mice, 16-hour fasting period followed by reintroduction of food for 2 hours increased markedly the potency of mechanical loading, that mimics the effect of exercise, to induce new cortical bone formation. Consistent with this finding, fasting and re-feeding increased the response of bone to a loading stimulus that, alone, does not stimulate new bone formation in ad-lib fed mice. Older mice (20-months) experienced no potentiation of loading-induced bone formation with the same timing of feeding interventions. Interestingly, the pre-, prandial and postprandial endocrine responses in older mice were different from those in young animals. The hormones that change in response to timing of feeding have osteogenic effects that interact with loading-mediated effects. Our findings indicate associations between timing of food ingestion and bone adaptation to loading. If translated to humans, such non-pharmacological lifestyle interventions may benefit skeletal health of humans throughout life-course and in older age.

2013 ◽  
Vol 39 (6) ◽  
pp. 671-679 ◽  
Author(s):  
Guhan Dergin ◽  
Mustafa Akta ◽  
Bahar Gürsoy ◽  
Yalçin Devecioglu ◽  
Mehmet Kürkçü ◽  
...  

In an effort to obtain a high-quality bone-implant interface, several methods involving alteration of surface morphological, physicochemical, and biochemical properties are being investigated. The aim of our study was to increase the osseointegration rate and quality and decrease the waiting period of dental implants before loading by using a microelectric implant stimulator device. It imitates microelectrical signals, which occur in bone fractures described in terms of piezoelectric theory. A single dental implant (Zimmer Dental), 3.7 mm in diameter, was inserted into the tibia of sheep bilaterally. Twenty-four dental implants were inserted into 12 sheep. Implant on the tibia of each sheep was stimulated with 7.5 μA direct current (DC), while the other side did not receive any stimulation and served as a control. Animals were sacrificed 1, 2, and 3 months after implantation. Bone segments with implants were processed with unclassified method. The determination of new bone formation and osseointegration around the dental implants was investigated by means of undecalcified method, histomorphologically. No statistically significant difference in bone-to-implant contact (BIC) ratio, osteoblastic activity, and new bone formation was found between the stimulation group and the control group at the late phase of healing (4, 8, and 12 weeks). No evidence was found that electric stimulation with implanted 7.5 μA DC is effective at late phase implant osseointegration on a sheep experimental model.


2016 ◽  
pp. 53-75
Author(s):  
Bernadette Manifold Bernie

Skeletal health indicators are often employed to measure how past populations adapted to their physical environment. The skeletons of children provide a measure of population fitness, as the ability of a community to keep their younger inhabitants alive and in general good health attest their ability to adapt to their environment. In this study, skeletal remains of non-adults from foetal to 17 years of age (n=300) from two cemetery populations in western Britain, namely the early medieval site of Llandough in south Wales (n=204) and the multi-period site of St Oswald’s Priory in Gloucester (n=96), were assessed. Non-specific indicators of physiological stress (cribra orbitalia, porotic hyperosprotosis, dental hypoplasia) and non-specific infections (periosteal new bone formation and endocranial lesions) are compared. Results suggest that the children from the English site enjoyed better health than their counterparts in Wales, where there was an increase in physiological stress during childhood.


2014 ◽  
Vol 23 (03) ◽  
pp. 202-206
Author(s):  
M. Reusch ◽  
T. Wehner ◽  
L. Dürselen ◽  
A. Ignatius ◽  
L. Claes

SummaryIt is well known that bone adapts to increased mechanical loading by the apposition of newly formed bone. The correlation between load-induced bone stress and strain with bone formation has often been investigated in cortical bone, however, little is known about this relationship in trabecular bone. In particular, nothing is known about trabecular bone adaptation in response to very high mechanical loading close to its fatigue load. Here, we investigated trabecular bone formation in a sheep osteotomy model of the femoral condyle in a region of interest close to the osteotomy, where local stresses in the range of the fatigue strength of trabecular bone occurred. After eight weeks, the trabecular bone volume and the mineral apposition rate increased two-fold and threefold, respectively, at this highly loaded location, compared to the corresponding region of interest in intact femoral condyles under physiological loading. This study demonstrated, for the first time, the remarkable capability of trabecular bone to adapt to stress and strain close to its failure load.


2021 ◽  
pp. 153537022199309
Author(s):  
Jeffery S Staab ◽  
Alexander L Kolb ◽  
Ryan E Tomlinson ◽  
Paola Divieti Pajevic ◽  
Ronald W Matheny ◽  
...  

There is mounting evidence suggesting that the commonly used analgesics, non-steroidal anti-inflammatory drugs (NSAIDs), may inhibit new bone formation with physical training and increase risk of stress fractures in physically active populations. Stress fractures are thought to occur when bones are subjected to repetitive mechanical loading, which can lead to a cycle of tissue microdamage, repair, and continued mechanical loading until fracture. Adaptive bone formation, particularly on the periosteal surface of long bones, is a concurrent adaptive response of bone to heightened mechanical loading that can improve the fatigue resistance of the skeletal structure, and therefore may play a critical role in offsetting the risk of stress fracture. Reports from animal studies suggest that NSAID administration may suppress this important adaptive response to mechanical loading. These observations have implications for populations such as endurance athletes and military recruits who are at risk of stress fracture and whose use of NSAIDs is widespread. However, results from human trials evaluating exercise and bone adaptation with NSAID consumption have been less conclusive. In this review, we identify knowledge gaps that must be addressed to further support NSAID-related guidelines intended for at-risk populations and individuals.


2021 ◽  
Vol 35 (10) ◽  
Author(s):  
Hasmik Jasmine Samvelyan ◽  
John Cummings Mathers ◽  
Timothy Michael Skerry

2018 ◽  
Author(s):  
Abhishek Kumar Tiwari ◽  
Jitendra Prasad

AbstractIn silico models of bone adaptation successfully simulated in vivo periosteal bone apposition, however, there are instances where these models may have limited success in predicting the new bone formation at endocortical surface. In vivo studies have highlighted that cortical bone surfaces may have differences in their modeling or remodeling responses to mechanical loading. However, the principle which the two cortical surfaces follow in bone adaptation is not very clear. This work accordingly attempts to understand how periosteal and endocortical surfaces accommodate loading-induced new bone formation. A neural network model is used to serve the purpose. A relationship is established to compute new bone thickness as a function of mechanical parameters (normal and shear strains) and non-mechanical parameters (distances from the neutral axis and the centroid) at the two surfaces. Analytical results indicate that two cortical surfaces behave opposite to each other in order to achieve optimal distribution of newly formed bone. The outcomes may be useful in establishing a unifying principle to predict site-specific new bone formation.


Author(s):  
JENNEKE KLEIN-NULEND ◽  
ROMMEL GAUD BACABAC

Bone is a dynamic tissue that is constantly renewed and adapts to its local loading environment. Mechanical loading results in adaptive changes in bone size and shape that strengthen bone structure. The mechanisms for adaptation involve a multistep process called mechanotransduction, which is the ability of resident bone cells to perceive and translate mechanical energy into a cascade of structural and biochemical changes within the cells. The transduction of a mechanical signal to a biochemical response involves pathways within the cell membrane and cytoskeleton of the osteocytes, the professional mechansensor cells of bone. During the last decade the role of mechanosensitive osteocytes in bone metabolism and turnover, and the lacuno-canalicular porosity as the structure that mediates mechanosensing, is likely to reveal a new paradigm for understanding the bone formation response to mechanical loading, and the bone resorption response to disuse. Strain-derived fluid flow of interstitial fluid through the lacuno-canalicular porosity seems to mechanically activate the osteocytes, as well as ensures transport of cell signaling molecules, nutrients and waste products. Cell-cell signaling from the osteocyte sensor cells to the effector cells (osteoblasts or osteoclasts), and the effector cell response – either bone formation or resorption, allow an explanation of local bone gain and loss as well as remodeling in response to fatigue damage as processes supervised by mechanosensitive osteocytes. The osteogenic activity of cultured bone cells has been quantitatively correlated with varying stress stimulations highlighting the importance of the rate of loading. Theoretically a possible mechanism for the stress response by osteocytes is due to strain amplification at the pericellular matrix. Single cell studies on molecular responses of osteocytes provide insight on local architectural alignment in bone during remodeling. Alignment seems to occur as a result of the osteocytes sensing different canalicular flow patterns around cutting cone and reversal zone during loading, thus determining the bone's structure. Disturbances in architecture and permeability of the 3D porous network will affect transduction of mechanical loads to the mechanosensors. Uncovering the cellular and mechanical basis of the osteocyte's response to loading represents a significant challenge to our understanding of cellular mechanotransduction and bone remodeling. In view of the importance of mechanical stress for maintaining bone strength, mechanical stimuli have great potential for providing a therapeutic approach for bone (re)generation.


Materials ◽  
2021 ◽  
Vol 14 (2) ◽  
pp. 381
Author(s):  
Hyunmin Choi ◽  
Kyu-Hyung Park ◽  
Narae Jung ◽  
June-Sung Shim ◽  
Hong-Seok Moon ◽  
...  

The aim of this study was to investigate the behavior of dental-derived human mesenchymal stem cells (d-hMSCs) in response to differently surface-treated implants and to evaluate the effect of d-hMSCs on local osteogenesis around an implant in vivo. d-hMSCs derived from alveolar bone were established and cultured on machined, sandblasted and acid-etched (SLA)-treated titanium discs with and without osteogenic induction medium. Their morphological and osteogenic potential was assessed by scanning electron microscopy (SEM) and real-time polymerase chain reaction (RT-PCR) via mixing of 5 × 106 of d-hMSCs with 1 mL of Metrigel and 20 μL of gel-cell mixture, which was dispensed into the defect followed by the placement of customized mini-implants (machined, SLA-treated implants) in New Zealand white rabbits. Following healing periods of 2 weeks and 12 weeks, the obtained samples in each group were analyzed radiographically, histomorphometrically and immunohistochemically. The quantitative change in osteogenic differentiation of d-hMSCs was identified according to the type of surface treatment. Radiographic analysis revealed that an increase in new bone formation was statistically significant in the d-hMSCs group. Histomorphometric analysis was in accordance with radiographic analysis, showing the significantly increased new bone formation in the d-hMSCs group regardless of time of sacrifice. Human nuclei A was identified near the area where d-hMSCs were implanted but the level of expression was found to be decreased as time passed. Within the limitations of the present study, in this animal model, the transplantation of d-hMSCs enhanced the new bone formation around an implant and the survival and function of the stem cells was experimentally proven up to 12 weeks post-sacrifice.


2021 ◽  
Vol 22 (1) ◽  
Author(s):  
Hideki Ueyama ◽  
Yoichi Ohta ◽  
Yuuki Imai ◽  
Akinobu Suzuki ◽  
Ryo Sugama ◽  
...  

Abstract Background Bone morphogenetic proteins (BMPs) induce osteogenesis in various environments. However, when BMPs are used alone in the bone marrow environment, the maintenance of new bone formation is difficult owing to vigorous bone resorption. This is because BMPs stimulate the differentiation of not only osteoblast precursor cells but also osteoclast precursor cells. The present study aimed to induce and maintain new bone formation using the topical co-administration of recombinant human BMP-2 (rh-BMP-2) and zoledronate (ZOL) on beta-tricalcium phosphate (β-TCP) composite. Methods β-TCP columns were impregnated with both rh-BMP-2 (30 µg) and ZOL (5 µg), rh-BMP-2 alone, or ZOL alone, and implanted into the left femur canal of New Zealand white rabbits (n = 56). The implanted β-TCP columns were harvested and evaluated at 3 and 6 weeks after implantation. These harvested β-TCP columns were evaluated radiologically using plane radiograph, and histologically using haematoxylin/eosin (H&E) and Masson’s trichrome (MT) staining. In addition, micro-computed tomography (CT) was performed for qualitative analysis of bone formation in each group (n = 7). Results Tissue sections stained with H&E and MT dyes revealed that new bone formation inside the β-TCP composite was significantly greater in those impregnated with both rh-BMP-2 and ZOL than in those from the other experimental groups at 3 and 6 weeks after implantations (p < 0.05). Micro-CT data also demonstrated that the bone volume and the bone mineral density inside the β-TCP columns were significantly greater in those impregnated with both rh-BMP-2 and ZOL than in those from the other experimental groups at 3 and 6 weeks after implantations (p < 0.05). Conclusions The topical co-administration of both rh-BMP-2 and ZOL on β-TCP composite promoted and maintained newly formed bone structure in the bone marrow environment.


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