Elsevier

Bone

Volume 30, Issue 6, June 2002, Pages 859-865
Bone

Original article
Osteocyte density in aging subjects is enhanced in bone adjacent to remodeling haversian systems

https://doi.org/10.1016/S8756-3282(02)00731-7Get rights and content

Abstract

The osteocyte is a candidate regulatory cell for bone remodeling. Previously, we demonstrated that there is a substantial (approximately 50%) loss of osteocytes from their lacunae in the cortex of the elderly femoral neck. Higher occupancy was evident in tissue exhibiting high remodeling and high porosity. The present study examines the distribution of osteocytes within individual osteonal systems at differing stages of the remodeling cycle. In 22 subjects, lacunar density, osteocyte density, and their quotient, the percent lacunar occupancy, was assessed up to a distance of 65 μm from the canal surface in six quiescent, resorbing, and forming osteons. In both forming (p = 0.024) and resorbing (p = 0.034) osteons, osteocyte densities were significantly higher in cases of hip fracture than controls. However, there were no significant between-group differences in lacunar occupancy. In both cases and controls, osteocyte density (p < 0.0001; mean difference ±SEM: 157 ± 34/mm2) and lacunar occupancy (p = 0.025; mean difference: 8.1 ± 3.4%) were shown to be significantly higher in forming compared with quiescent osteons. Interestingly, resorbing systems also exhibited significantly elevated osteocyte density in both the fracture and the control group combined (mean difference 76 ± 23/mm2; p = 0.003). Lacunar occupancy was also greater in resorbing compared with quiescent osteons (both groups combined: p = 0.022; mean difference: 5.7 ± 2.3%). Elevated osteocyte density and lacunar occupancy in forming compared with quiescent systems was expected because of the likely effects of aging on quiescent osteons. However, the higher levels of these parameters in resorbing compared with quiescent systems was the opposite of what we expected and suggests that, in addition to their postulated mechanosensory role in the suppression of remodeling and bone loss, osteocytes might also contribute to processes initiating or maintaining bone resorption.

Introduction

The osteocyte represents the final differentiation step in the osteoblastic lineage and arises when bone-forming osteoblasts become encased within the calcified matrix. Osteocytes form, through their dendritic processes, an intercommunicating network between individual cells and the bone surface lining cells. Although the functional role of the osteocyte remains partly unresolved, a key role in the regulation of remodeling the skeletal architecture in response to mechanical load has been suggested.4, 11, 18 A variety of mechanisms for explaining this role have been suggested; for example, stretch-activated ion channels7, 12 or shear stress from the flow of interstitial fluid,28 leading to the release of paracrine mediators or cell-cell communication. In addition to sensing mechanical strain, it has been proposed that osteocytes may also detect microdamage within bone3 and direct its removal through their apoptosis.20 The direction of remodeling though the generation and delivery of signals to cells populating the bone surface, the osteoblasts and lining cells, represents a possible key osteocytic function.

The true nature of the mechanism(s) by which osteocytes might influence and/or regulate the activity and numbers of effector cells of bone remodeling remains controversial. Marotti and coworkers proposed that osteoblast differentiation to the osteocyte cell type is regulated via an inhibitory signal relayed from already formed osteocytes.15, 16 This concept has recently been expanded by Martin to develop a hypothesis for the downregulation of remodeling by osteocytes.17 In this proposal, an osteocytic inhibitory signal acts on lining cells, located on quiescent bone surfaces, effectively preventing these cells from initiating a remodeling sequence. Regions of bone exhibiting high rates of remodeling might then be expected to correlate with relatively low numbers of viable osteocytes, because low osteocyte density would reduce the proposed functional brake to remodeling. Somewhat at variance with Martin’s concept is the proposal by Noble and Reeve that resorption is targeted to the matrix surrounding osteocytes undergoing apoptosis.20 According to this hypothesis, at times of stress, such as when osteocytes begin to undergo apoptosis, they may promote (rather than inhibit) remodeling. As a consequence, observed rates of osteocyte apoptosis would be expected to show a positive correlation with rates of remodeling. These investigators found that, within human infant and pathological bone, osteocyte apoptosis was positively associated with bone turnover,20 whereas a further study on iliac bone25 demonstrated that suppression of estrogen in women induced osteocyte apoptosis associated with reduced connectivity of cancellous bone.6 Furthermore, a recent study by Terai et al. implicated expression of the bone-specific protein, osteopontin, by osteocytes as a trigger of remodeling induced by mechanical stress.24

Previously, we have shown that femoral neck osteocyte lacunar occupancy (calculated as the ratio of identifiable cells to identifiable osteocyte lacunae) was not significantly different between controls and patients in their seventh or eighth decade who had suffered an osteoporotic hip fracture. A positive association was observed, however, between osteocyte viability and regions of relatively high cortical remodeling.23 The aim of the present investigation was first to determine whether the hypothesis that osteocytes disappear from their lacunae with advancing tissue age could be substantiated in osteonal bone. To do this, the lacunar occupancy and osteocyte density within quiescent osteons were compared with that of forming osteons. Second, these parameters were compared in bone surrounding quiescent and resorbing osteons so as to test the Martin hypothesis.17 The statistical influence of the distances from the canal surface on lacunar density, osteocyte density, and lacunar occupancy was also investigated.

Section snippets

Subjects

Samples used in the study were obtained from 22 subjects. Eleven were female patients who suffered intracapsular fracture of the femoral neck (mean age: 82.2 ± 3.0 years). The biopsies were taken 1–4 days after fracture. Informed written, witnessed consent, as approved by the local ethics committee, was obtained from each subject. Nonfractured, age-matched control material was obtained from 11 female postmortem cases (mean age: 82.2 ± 1.4) (Table 1). The postmortems were held between 1 and 4

Case-control differences

The data presented in Table 2 represent the overall mean values (mean of six canals, generating a single value for each osteon category [i.e., resorbing, forming, and quiescent osteons]) of lacunar density, osteocyte density, and percentage lacunar occupancy (±SEM). Of the canal types analyzed by single ANOVA only in the forming canals did lacunar density approach a significantly higher value in the fracture group compared with controls (p = 0.06). With regard to osteocyte density, both

Discussion

Previously, we reported a positive association between lacunar occupancy and regional indices of bone turnover within randomly selected cortical fields, including both osteonal and interstitial bone.23 To examine this association in more detail we analyzed the local osteocyte populations within the osteonal bone adjacent to both remodeling (forming and resorbing) and resting (quiescent) Haversian canals. For the first time, an assessment of the effect of distance from the Haversian canal

Acknowledgments

This work was supported by an MRC Programme Grant (9321536) and was presented in part at the 2000 Meeting of the Bone and Tooth Society.

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