Changes in Bone Structure and Mass With Advancing Age in the Male C57BL/6J Mouse

Abstract

To determine whether the mouse loses bone with aging and whether the changes mimic those observed in human aging, we examined the changes in the tibial metaphysis and diaphysis in the male C57BL/6J mouse over its life span using microcomputed tomography (CT). Cancellous bone volume fraction (BV/TV) decreased 60% between 6 weeks and 24 months of age. Loss was characterized by decreased trabecular number (Tb.N), increased trabecular spacing (Tb.Sp), and decreased connectivity. Anisotropy decreased while the structure model index increased with age. Cortical bone thickness increased between 6 weeks and 6 months of age and then decreased continuously to 24 months (؊12%). Cortical bone area (Ct.Ar) remained constant between 6 and 24 months. Fat-free weight reached a peak at 12 months and gradually declined to 24 months. Total mass lost between 12 and 24 months reached 10%. Overall, the age-related changes in skeletal mass and architecture in the mouse were remarkably similar to those seen in human aging. Furthermore, the rapid early loss of cancellous bone suggests that bone loss is not just associated with old age in the mouse but rather occurs as a continuum from early growth. We conclude that the C57BL/6J male mouse maybe a useful model to study at least some aspects of age-related bone loss in humans. (J Bone Miner Res 2002;17:1044 -1050)

Characterization of skeletal alterations in a model of prematurely aging mice

“…Regarding the trabecular compartment, as expected (Halloran et al 2002), BV/TV, vBMD, BMC, and Tb.N significantly decreased, whereas Tb.Sp increased, without significant changes in Tb.Th, in NPAM with age. PAM showed a similar but non-significant pattern of changes with aging (Table 2).…”

“…Mice present a continuous growth at the metaphysis; they do not exhibit estrogen depletion, and they lack Haversian system. Nevertheless, the mouse is a wellrecognized model that generally mimics the human bone changes with aging (Bar-Shira- Maymon et al 1989;Halloran et al 2002). Bone structure deterioration has been described in the trabecular compartment of long bones and vertebra in aging rodents (Wang et al 2001;Banu et al 2002;Almeida et al 2007b;Glatt et al 2007).…”

“…PAM are characterized by an impairment in the immune and neurological functions, and by an increased oxidative stress (Guayerbas et al 2002;De la Fuente et al 2003;Guayerbas and De La Fuente 2003;De la Fuente and Gimenez-Llort 2010), but no data about the status of bone in these mice were available. Although an age-related increase in body weight has been observed in females of the CD-1 mouse strain until 11 weeks (Harlan Laboratories, Inc, Indianapolis, IN, USA), and in female C57BL/6L mice (Halloran et al 2002), as well as in several other mice strains as reflected in the Mouse Each value is the mean ± SEM (n06 mice)…”

“…In spite of the fact that some mouse strains exhibit a continuous increase in BMD, bone microarchitecture has been shown to consistently deteriorate with age in mice (Halloran et al 2002;Glatt et al 2007). In the present study, old NPAM showed a decrease in vBMD, BMC, and Tb.…”

Osteoblast-targeted overexpression of PPARγ inhibited bone mass gain in male mice and accelerated ovariectomy-induced bone loss in female mice

“…First, transgenic mice have decreased trabecular bone volume by approximately 45% from 1 to 30 months, indicating that overexpressed PPARg hindered bone mass gain in this growing phase. (49) Second, histomorphometric analysis showed a reduced bone-formation rate and reduced osteoblast number. Third, at the cellular level, BMSCs exhibited reduced ALP activity.…”