A Case for Strain-Induced Fluid Flow as a Regulator of BMU-Coupling and Osteonal Alignment

Smit, Theo H.; Burger, E. H.; Huyghe, Jmrj Jacques

doi:10.1359/jbmr.2002.17.11.2021

Cited by 110 publications

(88 citation statements)

References 60 publications

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“…The exact factors involved in this ''coupling'' are not known but proposed mechanisms include release of growth factors from bone matrix, mediators (''coupling factors'') released from osteoclasts, changes in the local strain environment, TRAP signaling, and surface contour effects. [46][47][48][49] Osteoblast activity and bone formation may therefore have been affected by inhibition in osteoclast activity with reduced remodeling along the SFx line.…”

Section: Discussionmentioning

confidence: 99%

Selective and non‐selective cyclooxygenase inhibitors delay stress fracture healing in the rat ulna

Kidd

Cowling

et al. 2012

Journal Orthopaedic Research

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Anti-inflammatory drugs are widely used to manage pain associated with stress fractures (SFxs), but little is known about their effects on healing of those injuries. We hypothesized that selective and non-selective anti-inflammatory treatments would retard the healing of SFx in the rat ulna. SFxs were created by cyclic loading of the ulna in Wistar rats. Ulnae were harvested 2, 4 or 6 weeks following loading. Rats were treated with non-selective NSAID, ibuprofen (30 mg/kg/day); selective COX-2 inhibition, [5,5-dimethyl-3-3 (3 fluorophenyl)-4-(4 methylsulfonal) phenyl-2 (5H)-furanone] (DFU) (2.0 mg/kg/day); or the novel c5a anatagonist PMX53 (10 mg/kg/ day, 4 and 6 weeks only); with appropriate vehicle as control. Quantitative histomorphometric measurements of SFx healing were undertaken. Treatment with the selective COX-2 inhibitor, DFU, reduced the area of resorption along the fracture line at 2 weeks, without affecting bone formation at later stages. Treatment with the non-selective, NSAID, ibuprofen decreased both bone resorption and bone formation so that there was significantly reduced length and area of remodeling and lamellar bone formation within the remodeling unit at 6 weeks after fracture. The C5a receptor antagonist PMX53 had no effect on SFx healing at 4 or 6 weeks after loading, suggesting that PMX53 would not delay SFx healing. Both selective COX-2 inhibitors and non-selective NSAIDs have the potential to compromise SFx healing, and should be used with caution when SFx is diagnosed or suspected. ß

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Section: Discussionmentioning

confidence: 99%

Selective and non‐selective cyclooxygenase inhibitors delay stress fracture healing in the rat ulna

Kidd

Cowling

et al. 2012

Journal Orthopaedic Research

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“…This value is low compared to published measurements (2,000-5,000 me) measured from muscle contractions with daily activities. 4,10,20,27,28 These strain measurements were expected, however, because weight-bearing and ground reaction forces normally associated with muscle activity were purposely limited in our model, and the strength of the TENS-induced muscle contractions was minimized by the low-intensity settings. Furthermore, the titanium housing of the BCI deflected stress around the chamber compartment, thus limiting load transfer and strains to the bone tissue within the chamber.…”

Section: Discussionmentioning

confidence: 99%

“…Fluid flow induced by mechanical deformation is hypothesized to stimulate bone cells via mechanotransduction and initiate bone remodeling. 4,5 Parameters often overlooked in this theory are the significant stimulatory effects bone blood flow has on interstitial bone fluid flow and influences of skeletal muscle contraction on bone circulation. When muscle contracts around bone, blood vessels outside and within muscle compartments are compressed, emptying the veins, and generating pressure waves through veins and arteries toward bone capillaries.…”

mentioning

confidence: 99%

Skeletal muscle contractions uncoupled from gravitational loading directly increase cortical bone blood flow rates in vivo

Caulkins

Ebramzadeh

Winet

2008

Journal Orthopaedic Research

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The direct and indirect effects of muscle contraction on bone microcirculation and fluid flow are neither well documented nor explained. However, skeletal muscle contractions may affect the acquisition and maintenance of bone via stimulation of bone circulatory and interstitial fluid flow parameters. The purposes of this study were to assess the effects of transcutaneous electrical neuromuscular stimulation (TENS)-induced muscle contractions on cortical bone blood flow and bone mineral content, and to demonstrate that alterations in blood flow could occur independently of mechanical loading and systemic circulatory mechanisms. Bone chamber implants were used in a rabbit model to observe real-time blood flow rates and TENS-induced muscle contractions. Video recording of fluorescent microspheres injected into the blood circulation was used to calculate changes in cortical blood flow rates. TENS-induced repetitive muscle contractions uncoupled from mechanical loading instantaneously increased cortical microcirculatory flow, directly increased bone blood flow rates by 130%, and significantly increased bone mineral content over 7 weeks. Heart rates and blood pressure did not significantly increase due to TENS treatment. Our findings suggest that muscle contraction therapies have potential clinical applications for improving blood flow to cortical bone in the appendicular skeleton. Keywords: bone blood flow; bone; muscle; bone healing A large body of evidence supports the premise that skeletal muscle contractions affect the acquisition and maintenance of bone mass. In general, muscle contraction loading of bone is not independent of physical activity or body weight forces, however, isolated contractions apply greater loads than do gravitational forces associated with weight and contribute to over 70% of the bending moments placed on bone. 1Animal models for disuse osteoporosis demonstrated that maintenance of muscle contraction within castimmobilized limbs via electrical stimulation resulted in a decreased rate of bone loss compared to nonstimulated immobilized animals.2,3 In tail-suspended rats, lowfrequency electrically stimulated contractions of the hindlimb muscles prevented bone loss compared to nonstimulated animals and further resulted in elevated periosteal and cancellous bone formation rates.3 Disuse created by casting rabbit hindlimbs with the ankle in plantarflexion caused a faster, more intensive rate of bone loss than casting with 908 joint angles.2 Plantarflexion was thought to inhibit contraction power of the calf muscles, thus reducing mechanical loading to the immobilized tibia. These findings support the hypothesis that skeletal muscle contractions play a significant role in bone homeostasis and adaptation. However, the specific mechanism remains unclear.Popular models for regulation of bone adaptation involve fluid flow. Fluid flow induced by mechanical deformation is hypothesized to stimulate bone cells via mechanotransduction and initiate bone remodeling. 4,5 Parameters often overlooked ...

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“…Coupling signals to induce new bone formation include bone matrix-derived factors such as TGF-b, IGF-1, IGF-2, bone morphogenetic proteins (BMPs), PDGF, or fibroblast growth factor. The phase of bone resorption is mediated by the strain gradient in the lacunae [34].…”

Section: Bone Remodelingmentioning

confidence: 99%

Bone as a source of organism vitality and regeneration

Mackiewicz¹,

Niklińska²,

Kowalewska³

et al. 2012

Folia Histochem Cytobiol.

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Abstract:The most important features that determine the vital role of bone include: a) a continuous supply of calcium, which is indispensible for every cell of the entire organism at all times, and b) the delivery of circulating blood cells and some adult stem cells to keep the body vigorous, ready for self-reparation, and continuously rebuilding throughout life. These functions of bones are no less important than protecting the body cavities, serving as mechanical levers connected to the muscles, and determining the shape and dimensions of the entire organism. The aim of this review was to address some basic cellular and molecular knowledge to better understand the complex interactions of bone structural components. The apprehension of osteoblast differentiation and its local regulation has substantially increased in recent years. It has been suggested that osteocytes, cells within the bone matrix, act as regulatory mechanosensors. Therefore immobility as well as limited activity has a dramatic effect on bone structure and influences a broad spectrum of bone physiology-related functions as well as the functions of many other organs. Lifelong bone rebuilding is modulated through several pathways, including the Wnt pathway that regulates bone formation and resorption. In the adult skeleton, bone is continuously renewed in response to a variety of stimuli, such as the specific process of remodeling dependent on RANK/ /RANKL/OPG interactions. Better understanding of bone biology provides opportunities for the development of more effective prevention and treatment modalities for a variety of bone diseases, including new approaches to adult stem cell-based therapies.

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A Case for Strain-Induced Fluid Flow as a Regulator of BMU-Coupling and Osteonal Alignment

Cited by 110 publications

References 60 publications

Selective and non‐selective cyclooxygenase inhibitors delay stress fracture healing in the rat ulna

Selective and non‐selective cyclooxygenase inhibitors delay stress fracture healing in the rat ulna

Skeletal muscle contractions uncoupled from gravitational loading directly increase cortical bone blood flow rates in vivo

Bone as a source of organism vitality and regeneration

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