Loading and Skeletal Development and Maintenance

Bergmann, Pierre; Body, Jean‐Jacques; Boonen, Steven; Boutsen, Yves; Devogelaer, J.-P.; Goemaere, Stefan; Kaufman, Jean‐Marc; Reginster, Jean‐Yves; Rozenberg, Serge

doi:10.4061/2011/786752

Cited by 59 publications

(59 citation statements)

References 196 publications

(203 reference statements)

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“…Bone is an inherently dynamic tissue capable of recognizing and adapting to external forces to meet its functional demands. It responds to the external mechanical forces in the environment by dynamic remodeling of its mass and architecture via bone resorption, synthesis, and apposition (8,38). The importance of mechanical load is further underscored by the observations that reduced physical demands or disuse of bones leads to rapid bone loss and skeletal fragility and osteopenia generally observed in aging, spinal cord injuries, prolonged bed rest, and microgravity (9,84,86,89,120,122).…”

Section: Introductionmentioning

confidence: 99%

Mechanosignaling in Bone Health, Trauma and Inflammation

Knapik

Perera

Nam

et al. 2014

Antioxidants & Redox Signaling

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Significance: Mechanosignaling is vital for maintaining the structural integrity of bone under physiologic conditions. These signals activate and suppress multiple signaling cascades regulating bone formation and resorption. Understanding these pathways is of prime importance to exploit their therapeutic potential in disorders associated with bone loss due to disuse, trauma, or disruption of homeostatic mechanisms. Recent Advances: In the case of cells of the bone, an impressive amount of data has been generated that provides evidence of a complex mechanism by which mechanical signals can maintain or disrupt cellular homeostasis by driving transcriptional regulation of growth factors, matrix proteins and inflammatory mediators in health and inflammation. Mechanical signals act on cells in a magnitude dependent manner to induce bone deposition or resorption. During health, physiological levels of these signals are essential for maintaining bone strength and architecture, whereas during inflammation, similar signals can curb inflammation by suppressing the nuclear factor kappa B (NF-jB) signaling cascade, while upregulating matrix synthesis via mothers against decapentaplegic homolog and/or Wnt signaling cascades. Contrarily, excessive mechanical forces can induce inflammation via activation of the NF-jB signaling cascade. Critical Issues: Given the osteogenic potential of mechanical signals, it is imperative to exploit their therapeutic efficacy for the treatment of bone disorders. Here we review select signaling pathways and mediators stimulated by mechanical signals to modulate the strength and integrity of the bone. Future Directions: Understanding the mechanisms of mechanotransduction and its effects on bone lay the groundwork for development of nonpharmacologic mechanostimulatory approaches for osteodegenerative diseases and optimal bone health. Antioxid. Redox Signal. 20,[970][971][972][973][974][975][976][977][978][979][980][981][982][983][984][985]

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Section: Introductionmentioning

confidence: 99%

Mechanosignaling in Bone Health, Trauma and Inflammation

Knapik

Perera

Nam

et al. 2014

Antioxidants & Redox Signaling

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“…The respective authors were not concerned with local enthesial sites but the diaphysis as a whole. Additionally, our understanding of both mechanical and systemic influences in regional and global skeletal remodeling is much better understood since the pioneering days of these early implementers of ''Wolff 's law'' (see Frost, 2003;Bergmann et al, 2011).…”

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confidence: 99%

Understanding Entheses: Bridging the Gap Between Clinical and Anthropological Perspectives

Schlecht

2012

The Anatomical Record

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An enthesis is the interface where tendon meets bone, providing both muscle anchorage and stress dissipation. Previous anthropological research suggests size and complexity of entheses observable in osteological material, are indicative of the strain magnitude resulting from repetitive muscle contractions during the performance of daily routines. These proposed ''musculoskeletal stress markers'' are routinely incorporated into bioarcheological studies as evidence of general activity patterns past human populations participated in. However, much of how this complex osteotendinous interface develops and responds to mechanical strains is poorly understood. The following review seeks to shed light on this structural enigma by synthesizing current findings in both the clinical and anthropological literature, in the interest of generating new conversations in how entheses respond to contractual forces and the systemic influences (i.e., genetics, hormones), that surround their morphological development. Only once we truly understand the etiology of tendon insertion sites, will the value of enthesial research in reconstructing human behavior be determined. Anat Rec, 295:1239Rec, 295: -1251Rec, 295: , 2012. V C 2012 Wiley Periodicals, Inc. Keywords: musculoskeletal stress markers (MSM); fibrocartilaginous; tendon anatomy; tendon insertion; bone morphology Anthropologists regularly implement bone remodeling principles in response to mechanical loads to infer a causal relationship between muscle tendon insertions and activity levels. Previous research suggests size and complexity of tendon insertions are indicative of strain magnitude resulting from habitual physical activity (Lane, 1887;Kennedy, 1989;Hawkey and Merbs, 1995;Churchill and Morris, 1998;Hawkey, 1998;Steen and Lane, 1998;Stirland, 1998;Wilczak and Kennedy, 1998;Capasso et al., 1999;Weiss, 2003Weiss, , 2004Weiss, , 2007 alOumaoui et al., 2004;Molnar, 2006;Cardoso and Henderson, 2010;Thara et al., 2010;Havelkova et al., 2011). Using both qualitative and quantitative data to assess the expression of insertion morphology along long bone diaphyses, inferences are frequently made regarding both generalized and specific activities past humans participated in throughout their daily lives. Recognition of this potential relationship between mechanical strain and the osteotendinous interface has led many to refer to tendon insertions sites as musculoskeletal stress markers (MSM). However, more empirical analyses exploring the factors responsible for these proposed MSM are needed before we can confidently begin to assess individual behavior and draw population-based inferences from series of skeletal remains. With this lack of understanding in the etiology of periosteal tendon insertion morphology, particularly in the mechanical and structural relationship between soft and hard tissues, this interface should be referred to by the clinical term, enthesis.

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“…This is most commonly expressed as a percentage change [20,21] or alternatively as absolute units [22] ; the target for treatment with bisphosphonates being to reduce the bone markers by at least the LSC. The second approach is that the target for treatment is to decrease the BTM to the lower half of the premenopausal reference interval (RI) [9,23] . However not all women are above the RI mean before starting treatment.…”

Section: Introductionmentioning

confidence: 99%

Response of bone turnover markers to three oral bisphosphonate therapies in postmenopausal osteoporosis: the TRIO study

et al. 2015

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Introduction: Biochemical response to bisphosphonate therapy can be assessed using either a decrease in bone turnover marker beyond the least significant change (LSC) or a reduction to within a reference interval (RI). We compared the performance of these target responses and determined whether response was related to the type of bisphosphonate, compliance and baseline bone turnover markers.Methods: Biochemical responses to three oral bisphosphonates were assessed in an open, controlled trial comprising 172 postmenopausal osteoporotic women (age 53-84 years), randomized to alendronate, ibandronate or risedronate, plus calcium and vitamin D supplementation for two years. The LSC for each marker was derived within the study population whereas RIs were obtained from a control group of healthy premenopausal women (age 35-40 years).Results: Over 70% of women achieved a target response for serum CTX and PINP, irrespective of the approach used. The percentage decrease at 12 weeks was greater for women with baseline PINP above the RI -63% (difference 13%, 95%CI 0 to 27.1, P=0.049) and good compliance -67% (difference 15.9%, 95%CI 6.3 to 25.5, P=0.001). Responders had a greater increase in spine bone density compared to non-responders; for example 6.2% vs. 2.3%, (difference 3.9%, 95%CI 1.6 to 6.3, p=0.0011) for PINP LSC. The magnitude of change in bone markers was greater with ibandronate and alendronate than risedronate.Conclusions: Both approaches to response identified similar proportions of women as responders. Nonresponders had smaller increases in BMD and we suggest that biochemical assessment of response is a useful tool for the management of women with postmenopausal osteoporosis.Key words: postmenopausal osteoporosis, bone turnover markers, variability, bisphosphonate Mini Abstract (50 words)We used bone turnover markers to identify women who responded to bisphosphonate treatment for osteoporosis.Response was more likely with alendronate and ibandronate, than risedronate. There was a greater decrease in bone markers if baseline bone turnover markers were higher and if the patient took more than 80% of her medication.

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Loading and Skeletal Development and Maintenance

Cited by 59 publications

References 196 publications

Mechanosignaling in Bone Health, Trauma and Inflammation

Mechanosignaling in Bone Health, Trauma and Inflammation

Understanding Entheses: Bridging the Gap Between Clinical and Anthropological Perspectives

Response of bone turnover markers to three oral bisphosphonate therapies in postmenopausal osteoporosis: the TRIO study

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