Microstructural changes associated with osteoporosis negatively affect loading-induced fluid flow around osteocytes in cortical bone

Abstract

Loading-induced interstitial fluid flow in the microporosities of bone is critical for osteocyte mechanotransduction and for the maintenance of tissue health, enhancing convective transport in the lacunar-canalicular system. In recent studies, our group has reported alterations of bone's vascular porosity and lacunar-canalicular system microarchitecture in a rat model of postmenopausal osteoporosis. In this work, poroelastic finite element analysis was used to investigate whether these microstructural changes can affect interstitial fluid flow around osteocytes. Animal-specific finite element models were developed combining micro-CT reconstructions of bone microstructure and measures of the poroelastic material properties. These models were used to quantify and compare loading-induced fluid flow in the lacunar-canalicular system of ovariectomized and sham-operated rats. A parametric analysis was also used to quantify the influence of the lacunar-canalicular permeability and vascular porosity on the fluid velocity magnitude. Results show that mechanically-induced interstitial fluid velocity can be significantly reduced in the lacunar-canalicular system of ovariectomized rats. Interestingly, the vascular porosity is shown to have a major influence on interstitial fluid flow, while the lacunar-canalicular permeability influence is limited when larger than 10m. Altogether our results suggest that microstructural changes associated with the osteoporotic condition can negatively affect interstitial fluid flow around osteocytes in the lacunar-canalicular system of cortical bone. This fluid flow reduction could impair mechanosensation of the osteocytic network, possibly playing a role in the initiation and progression of age-related bone loss and postmenopausal osteoporosis.

Assessment of the human bone lacuno-canalicular network at the nanoscale and impact of spatial resolution

“…The average length, width and depth of lacuna (Lc.L1, Lc.L2 and Lc.L3) at 30 nm were 17.2 µm, 9.4 µm, 4.8 µm. All parameters are consistent with previous works 8,31,47,49 . For instance the lacunar volumes Lc.V are found in a range varying from 50 to 730 µm 3 15,30 .…”

“…density of canaliculi 0.18 ± 0.03 µm −2 or 0.21 ± 0.05 µm −2 for mice samples 35,52 . The estimation of the number of canaliculi is an important parameter for the modeling of fluid flow transport and permeability measurements 49,50 . The measurements at 30 nm were compared to those made on site-matched registered volumes acquired at 120 nm.…”

Botox‐induced muscle paralysis alters intracortical porosity and osteocyte lacunar density in skeletally mature rats

“…Interestingly, recent work from our group has shown similar vascular canal changes in the proximal tibial metaphysis of skeletally mature rats in response to estrogen deficiency, a condition associated with the development of postmenopausal osteoporosis . An increase in vascular porosity has been shown to diminish interstitial fluid flow in the lacunar‐canalicular system, possibly altering molecular transport and the transduction of mechanical signals to the osteocytes . While not measured in the present study, the higher cortical porosity could also contribute to the loss in bone strength shown to occur in the proximal tibia in the rat Botox disuse model .…”

“…To assess bone formation activity, rats received intraperitoneal injections of calcein (15 mg/kg body weight, Sigma‐Aldrich) and xylenol orange (90 mg/kg body weight, Sigma‐Aldrich) 12 and 3 days prior to sacrifice, respectively. The BTX and CTRL groups were sacrificed four weeks after injection, a time period shown to induce bone changes in rodents …”

“…Recent studies from our lab have demonstrated alterations of both the vascular and osteocyte lacunar porosities in skeletally mature rats that underwent ovariectomy, a model for postmenopausal osteoporosis . In the rat ovariectomy model, we have shown that an increase in vascular porosity reduces interstitial fluid flow due to mechanical loading, potentially altering bone mechanotransduction and negatively affecting the bone formation/resorption balance …”