Lacunar-canalicular network in femoral cortical bone is reduced in aged women and is predominantly due to a loss of canalicular porosity

Abstract

The lacunar-canalicular network (LCN) of bone contains osteocytes and their dendritic extensions, which allow for intercellular communication, and are believed to serve as the mechanosensors that coordinate the processes of bone modeling and remodeling. Imbalances in remodeling, for example, are linked to bone disease, including fragility associated with aging. We have reported that there is a reduction in scale for one component of the LCN, osteocyte lacunar volume, across the human lifespan in females. In the present study, we explore the hypothesis that canalicular porosity also declines with age. To visualize the LCN and to determine how its components are altered with aging, we examined samples from young (age: 20–23 y; n = 5) and aged (age: 70–86 y; n = 6) healthy women donors utilizing a fluorescent labelling technique in combination with confocal laser scanning microscopy. A large cross-sectional area of cortical bone spanning the endosteal to periosteal surfaces from the anterior proximal femoral shaft was examined in order to account for potential trans-cortical variation in the LCN. Overall, we found that LCN areal fraction was reduced by 40.6% in the samples from aged women. This reduction was due, in part, to a reduction in lacunar density (21.4% decline in lacunae number per given area of bone), but much more so due to a 44.6% decline in canalicular areal fraction. While the areal fraction of larger vascular canals was higher in endosteal vs. periosteal regions for both age groups, no regional differences were observed in the areal fractions of the LCN and its components for either age group. Our data indicate that the LCN is diminished in aged women, and is largely due to a decline in the canalicular areal fraction, and that, unlike vascular canal porosity, this diminished LCN is uniform across the cortex.

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

“…There are only few reports on the canalicular porosity, especially measured in 3D in human bones. For instance, Ashique 16 reported a canaliculi area percentage between 7.9% and 14.3% in human femora but the use of confocal microscopy is likely to overestimate the values. Our values of Ca.TV/BV are comparable to those measured from SR imaging reported in previous works 0.57% 34 , 2% 33 .…”

“…Conventional 2D imaging techniques such as light microscopy 10,11 , transmission electron microscopy (TEM) 12 , scanning electron microscopy (SEM) 13 , and atomic force microscopy (AFM) 14 have been previously used to investigate the LCN. Based on 2D data, lacunae are typically described as flattened ellipsoids with an average area of about 20-70 µm 2 , an average length of about 14-25 µm and an average width of about 5-10 µm 15,16 , and the canaliculi are described as channels with an average diameter of about 100-600 nm 17,18 . However, the 2D measurements present some uncertainty because the slicing direction may bias the results due to missing information about the third dimension.…”

The contribution of the pericanalicular matrix to mineral content in human osteonal bone

“…In the maturated mineralized bone matrix, the cell bodies of the osteocytes are located in cavities called osteocyte lacunae which radiate in around 300 nm wide canals, the canaliculi, that house the dendritic processes (3) . This so-called osteocyte lacunar-canalicular network (LCN) pervades all bones of mammals displaying a sophisticated geometry that differs between species (4) , skeletal sites (5) , loading and health conditions (6) , age (7,8) and is linked to the orientation of the surrounding collagen matrix (4,5,9,10) . The primary role of osteocytes and the LCN for bone health is related to its multiple functions (1,2) .…”

Aging and Mechanoadaptive Responsiveness of Bone

“…Aging is also linked to the greater number and activity of osteoclasts in both humans [24] and mice [25,26]. Bone lining cells and osteocyte density (and lacunar density) diminish with age [27][28][29], as does osteocyte canaliculi number [30]. Of note, aging may contribute by compromising bones' regenerative potential, evidenced in the age-related decline in osteogenic progenitor cell numbers in animal models and human samples, and within the bone marrow of adult versus younger animals.…”