Femoral osteocyte lacunar density, volume and morphology in women across the lifespan Yasmin Carter a , C. David L. Thomas b , John G. Clement b , David M.L. Cooper a,⇑ a Department of Anatomy & Cell Biology, University of Saskatchewan, Saskatoon, Canada b Melbourne Dental School, University of Melbourne, Victoria, Australia article info Article history: Received 30 November 2012 Received in revised form 3 July 2013 Accepted 6 July 2013 Available online 18 July 2013 Keywords: Synchrotron Micro-CT Human cortical bone Osteocyte Lacuna abstract Osteocytes are believed to be the primary agents of mechanosensing in bone. Due to this important role in the structure–function relationship of bone, osteocytes and the spaces they occupy (lacunae) are of increasing interest. Changes in lacunae with age are of particular interest in women since they are more susceptible to bone loss and fragility associated with senescent diseases including osteoporosis. This study’s purpose was to test whether differences exist in lacunar density (lacunae/mm 3 of bone), orienta- tion and morphology in the cortex of adult women spanning the human lifespan. Anterior blocks from the femoral shaft from 30 women aged 20–86 years were imaged by synchrotron-radiation micro-CT. No sig- nificant relation between lacunar density and age was detected. A significant reduction in lacunar volume with age (p < 0.001) was observed, alongside changes in lacunar morphology. When divided into two groups (<50 and >50 years) the younger group’s lacunae were 30% larger and were flatter (p < 0.001) and less equant (spherical) (p < 0.001). To our knowledge the observation that lacunar volume and mor- phology change over the human lifespan is novel, potentially resulting from preferential surface infilling within the extracellular space. The functional impact of this infilling is unclear but such a change in scale likely impacts the mechanosensing function of the osteocyte network. Limitations in resolution pre- vented us from assessing if this infilling is associated with disruption of the canaliculi. This hypothesis warrants further investigation as, if confirmed, it would represent a profound negative impact on the osteocyte network and may provide new insights into age-related bone loss. Ó 2013 Elsevier Inc. All rights reserved. 1. Introduction During life, human bone undergoes a constant process of remodeling, in which old bone is removed (resorption) and re- placed with new bone (formation). In the young, these twinned processes are balanced; however, with advancing age there comes a net increase in bone resorption and a loss of bone architectural quality leading to fragility and fractures associated with diseases such as osteoporosis (Rodan and Martin, 2000). Studies examining the effect of aging at the cellular level have been restricted due to the encasement of the bone cells, osteocytes, deep within the bone matrix. Because the osteocytes themselves cannot be visualized using X-ray based techniques the spaces in which they reside, lacu- nae, are used as proxy. Osteocytes are the most ubiquitous cells found in bone and are connected through an extensive network of cell processes which al- low for communication and nutrient transportation (Busse et al., 2010). Together the lacunae and the spaces formed around the cell processes, the canaliculi, form a network considered vital to main- taining bone homeostasis. The exact role of the lacuno-canalicular network (LCN), however, is not yet fully understood. Several func- tions of the LCN have been proposed including initiation of bone remodeling via ion-sensation and regulation of osteoid matrix mat- uration and mineralization (Kamioka et al., 2001). Currently a gen- eral consensus exists that osteocytes play a role in translating mechanical stimuli into biochemical signals, forming the basis of the mechanosensation and transduction systems (Knothe Tate et al., 2004). The surface area of the LCN is immense and in the adult male has been calculated to be 400 times larger than that of the Haversian systems and 130 times greater than the surface area of the trabecular rods and plates (Johnson, 1966). The sheer scale of this network of connected spaces and cells suggests that differences in the scale or morphology of the LCN could affect mechanosensa- tion/transduction (Schneider et al., 2010). Changes in LCN with age are of particular interest, especially in women since they are more susceptible to the bone loss and 1047-8477/$ - see front matter Ó 2013 Elsevier Inc. All rights reserved. http://dx.doi.org/10.1016/j.jsb.2013.07.004 ⇑ Corresponding author. Address: Department of Anatomy & Cell Biology, University of Saskatchewan, 107 Wiggins Road, Saskatoon, SK, Canada S7 N 5E5. Fax: +1 (306) 966 4298. E-mail addresses: yasmin.carter@usask.ca (Y. Carter), cdthomas@unimelb.edu.au (C. David L. Thomas), johngc@unimelb.edu.au (J.G. Clement), dml.cooper@usask.ca (D.M.L. Cooper). Journal of Structural Biology 183 (2013) 519–526 Contents lists available at ScienceDirect Journal of Structural Biology journal homepage: www.elsevier.com/locate/yjsbi