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

Abstract

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 ...

Effects of high-intensity resistance training and low-intensity resistance training with vascular restriction on bone markers in older men

“…Capillary endothelial cells have an impact on bone remodeling by synthesizing and releasing different molecules including free radicals, local regulatory factors (e.g., interleukin-6, nitric oxide), and growth factors that may inhibit osteoclast activity and stimulate osteoblast activity (McCarthy 2006;Parfitt 2000), therefore blood flow restriction in combination with resistance exercise might be affecting the secretory function of the endothelial cells leading to improvements in bone remodeling. Furthermore, even though the magnitude of mechanical loading during LI-VRT training sessions was low, fluid shifts occurring during muscular contractions (Caulkins et al 2009) may stimulate piezoelectric potentials on osteocytes to stimulate remodeling (Frost 2001). Finally, endocrine responses to resistance training (Kraemer and Ratamess 2005) may either directly affect bone metabolism, or may alter the mechanosensitivity of bone cells, leading to decreases in bone resorption.…”

The Key Role of the Blood Supply to Bone

“…Whether and how changes in mechanical loading and/or IMP may affect bone blood circulation and the tone of the intramedullary blood vessel is not clear (99), but it is likely that muscle contraction plays a role through the modulation of vascular resistance regulation the flow of blood exiting bone (102)(103). Further research in this area is required to understand whether skeletal blood perfusion and mechanoadaptation to exerciseinduced bone strain may induce synergistic effects on bone formation.…”

Skeletal Adaptation to Intramedullary Pressure-Induced Interstitial Fluid Flow Is Enhanced in Mice Subjected to Targeted Osteocyte Ablation

“…Mechanical loading has been demonstrated to induce skeletal IFF through two distinct mechanisms that give rise to distinct spatial patterns of flow: poroelastic interactions within the lacunar-canalicular system (LCS) between the interstitial fluid and bone tissue [15], [16], and intramedullary pressurization [2], [17], [18], [19]. Whereas poroelastic interactions within the LCS are expected to give rise to IFF primarily within the lacunar-canalicular network, pressurization of the intramedullary cavity is expected to result in significant levels of IFF at the endosteal surface as well as within the LCS due to the gross outward pressure gradient from the intramedullary cavity to the periosteal surface [2], [12].…”