Intramedullary pressure and matrix strain induced by oscillatory skeletal muscle stimulation and its potential in adaptation

Abstract

Intramedullary pressure (ImP) and low-level bone strain induced by oscillatory muscle stimulation (MS) has the potential to mitigate bone loss induced by disuse osteopenia, i.e., hindlimb suspension (HLS). To test this hypothesis, we evaluated a) MS induced ImP and bone strain as function of stimulation frequency, and b) the adaptive responses to functional disuse, and disuse plus 1Hz and 20Hz stimulation in vivo. Femoral ImP and bone strain generated by MS were measured in the frequencies of 1Hz-100Hz in four rats. Forty retired breeder rats were used for the in vivo HLS study. The quadriceps muscle was stimulated at frequencies of 1 Hz and 20 Hz, 10min/d for 4 weeks. The metaphyseal trabecular bone quantity and microstructure at the distal femur were evaluated using μCT, while bone formation indices were analyzed using histomorphometric techniques. Oscillatory MS generated a maximum ImP of 45±9 mmHg at 20 Hz and produced a maximum matrix strain of 128±19 με at 10 Hz. Our analyses from the in vivo study showed that MS at 20 Hz was able to attenuate trabecular bone loss and partially maintain the microstructure induced by HLS. Conversely, there was no evidence of an adaptive effect of stimulation at 1 Hz on disused skeleton. The results suggested that oscillatory MS regulates fluid dynamics and mechanical strain in bone, which serves as a critical mediator of adaptation. These results clearly demonstrated the ability of MS in attenuating bone loss from the disuse osteopenia and could hold potential in mitigating skeletal degradation imposed by conditions of disuse, which may serve as a biomechanical intervention in clinic application.

Alteration of contraction-to-rest ratio to optimize trabecular bone adaptation induced by dynamic muscle stimulation

“…The close relationship between muscle and bone hypothesizes that a change in vascular perfusion within skeletal muscle can indeed cascade to a change in fluid pressure in bone. [10, 21] The decline in femoral ImP due to hindlimb suspension and the increase in femoral ImP induced by MS firmly demonstrated the importance of fluid flow in medicating bone physiological processes. [10, 21] Bone fluid flow can enhance mechanosensitivity at the cellular level has been illustrated via various studies.…”

“…[25] However, MS at 50 Hz generated extremely low level of bone strain, which is below 10με. [10] This discrepancy may be explained by the differences in stimulation and its frequency. It has been shown that the strain magnitude decreases in an inverse relation with the induced loading frequency.…”

“…[10, 21] The decline in femoral ImP due to hindlimb suspension and the increase in femoral ImP induced by MS firmly demonstrated the importance of fluid flow in medicating bone physiological processes. [10, 21] Bone fluid flow can enhance mechanosensitivity at the cellular level has been illustrated via various studies. [32–35] Mechanical loading accentuates fluid shear stress on bone cells, thus releasing signaling molecules, e.g., nitric oxide, to further mediate bone remodeling.…”

“…[21] On the contrary, dynamic MS, applied at mid-stimulation frequency, significantly increased the ImP. [10]…”

Blood and interstitial flow in the hierarchical pore space architecture of bone tissue

“…Also, the mechanosensory function of osteocytes was proved in vivo in a murine model of osteocyte ablation (Tatsumi et al, 2007), and apoptosis of osteocytes was shown to be a controlling step of activation of intracortical resorption (Cardoso et al, 2009). In addition to IFF in the LCP, IFF in the vascular porosity can also prevent bone loss and lead to bone formation, as shown by in vivo studies in which fluid flow was decoupled from bone matrix strains (Qin et al, 2003; 2009; Kwon et al, 2010). More recently, it has been shown that intramedullary-driven IFF in the vascular system can also prevent bone loss and lead to bone formation, even in the absence of osteocytes, suggesting that bone cells other than osteocytes (i.e.…”