Influence of Osteocyte Lacunar-Canalicular Morphology and Network Architecture on Osteocyte Mechanosensitivity.

PURPOSE OF REVIEW: The goal of this review is to summarize recent findings related to modifications in osteocyte lacunar and canalicular morphology due to physiological and pathological conditions. In addition, this review aims to outline how these modifications may influence the local mechanical environment of osteocytes and their mechanosensitivity. RECENT FINDINGS: Reduction in lacunar density with age and increasing lacunar size with lactation are confirmed in multiple studies in human and murine bone. There is also evidence of a reduction in canalicular density, length, and branching, as well as increasing sphericity and smaller lacunae with aging and disease. However, while some studies have found modifications in lacunar density, size, shape, and orientation, as well as canalicular density, length, and size due to specific physiological and pathological conditions, others have not observed any differences. Recent finite element models provide insights into how observed modifications in the lacunar-canalicular network (lacunar and canalicular density) and lacunar-canalicular morphology (lacunar area/volume, shape, and orientation as well as canalicular diameter and length) may influence the fluid flow and local strains around the lacunar-canalicular network and modify the local mechanical environment of osteocytes. Modifications in the lacunar-canalicular network morphology may lead to significant changes in the strains received by osteocytes and may influence bone's response to mechanical stimulation as osteocytes are the primary mechanosensing bone cells. Further experimental and computational studies will continue to improve our understanding of the relationship between lacunar-canalicular network morphology and osteocyte mechanosensitivity.

Isolating the Role of Bone Lacunar Morphology on Static and Fatigue Fracture Progression through Numerical Simulations.

Currently, the onset of bone damage and the interaction of cracks with the surrounding micro-architecture are still black boxes. With the motivation to address this issue, our research targets isolating lacunar morphological and densitometric effects on crack advancement under both static and cyclic loading conditions by implementing static extended finite element models (XFEM) and fatigue analyses. The effect of lacunar pathological alterations on damage initiation and progression is evaluated; the results indicate that high lacunar density considerably reduces the mechanical strength of the specimens, resulting as the most influencing parameter among the studied ones. Lacunar size has a lower effect on mechanical strength, reducing it by 2%. Additionally, specific lacunar alignments play a key role in deviating the crack path, eventually slowing its progression. This could shed some light on evaluating the effects of lacunar alterations on fracture evolution in the presence of pathologies.

Alterations in osteocyte lacunar morphology affect local bone tissue strains.

Osteocytes are capable of remodeling their perilacunar bone matrix, which causes considerable variations in the shape and size of their lacunae. If these variations in lacunar morphology cause changes in the mechanical environment of the osteocytes, in particular local strains, they would subsequently affect bone mechanotransduction, since osteocytes are likely able to directly sense these strains. The purpose of this study is to quantify the effect of alterations in osteocyte lacunar morphology on peri-lacunar bone tissue strains. To this end, we related the actual lacunar shape in fibulae of six young-adult (5-month) and six old (23-month) mice, quantified by high-resolution micro-computed tomography, to microscopic strains, analyzed by micro-finite element modeling. We showed that peak effective strain increased by 12.6% in osteocyte cell bodies (OCYs), 9.6% in pericellular matrix (PCM), and 5.3% in extra cellular matrix (ECM) as the lacunae volume increased from 100-200 µm3 to 500-600 µm3. Lacunae with a larger deviation (>8°) in orientation from the longitudinal axis of the bone are exposed to 8% higher strains in OCYs, 6.5% in PCM, 4.2% in ECM than lacunae with a deviation in orientation below 8°. Moreover, increased lacuna sphericity from 0 to 0.5 to 0.7-1 led to 25%, 23%, and 13% decrease in maximum effective strains in OCYs, PCM, and ECM, respectively. We further showed that due to the presence of smaller and more round lacunae in old mice, local bone tissue strains are on average 5% lower in the vicinity of lacunae and their osteocytes of old mice compared to young. Understanding how changes in lacunar morphology affect the micromechanical environment of osteocytes presents a first step in unraveling their potential role in impaired bone mechanoresponsiveness with e.g. aging.