Age-Related Changes in Bone Mineral Density, Cross-Sectional Area and the Strength of Long Bones in the Hind Limbs and First Lumbar Vertebra in Female Wistar Rats

Fukuda, Satoshi; Iida, Haruzo

doi:10.1292/jvms.66.755

Cited by 27 publications

(18 citation statements)

References 29 publications

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“…Interestingly, the aging mesenchymal progenitors in mice (31, 61) and humans (46) also appear to cause a shift in lineage determination, such that cells preferentially differentiate toward the adipogenic, rather than the osteoblastic, phenotype in the bone marrow (42). However, progenitors from aging rodents appear to maintain some capacity to respond to osteogenic stimuli, such as bone morphogenetic protein (BMP) type 2 (BMP2) (62) and lasofoxifene (32), which protect against these deleterious effects of aging.Despite the fact that disuse in the elderly poses the risk of exacerbating age-related bone loss, there are few reports on effects of disuse in aged humans or animals (21,29). Because controlled experimental studies of disuse in elderly patients are ethically questionable, studies on this subject have been limited to animals.…”

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confidence: 99%

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Aging alters the skeletal response to disuse in the rat

Perrien¹,

Akel²,

Dupont‐Versteegden³

et al. 2007

American Journal of Physiology-Regulatory, Integrative and Comp

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Perrien DS, Akel NS, Dupont-Versteegden EE, Skinner RA, Siegel ER, Suva LJ, Gaddy D. Aging alters the skeletal response to disuse in the rat. Am J Physiol Regul Integr Comp Physiol 292: R988 -R996, 2007. First published October 26, 2006; doi:10.1152/ajpregu.00302.2006.-Disuse has been shown to cause a rapid and dramatic loss of skeletal mass and strength in the loadbearing bones of young and mature animals and humans. However, little is known about the skeletal effects of disuse in aged mammals. The present study was designed to determine whether the skeletal effects of disuse are maintained with extreme age. Fischer 344/Brown Norway male rats (6 and 32 mo old) were hindlimb suspended (HS) or housed individually for 2 wk. Trabecular volume and microarchitecture in the proximal tibia were significantly decreased by HS only in young rats. HS significantly reduced cortical bone mineral density and increased cortical porosity only in old rats by inducing new pore formation. Cortical pore diameter was also increased in old rats, regardless of loading condition. Ex vivo osteogenic and adipogenic cultures established from each group demonstrated that age and HS decreased osteoblastogenesis. Age, but not HS, decreased sensitivity to endogenous bone morphogenetic protein stimulation, as measured by treatment with exogenous Noggin. Adipocyte development increased with age, whereas HS suppressed sensitivity to peroxisome proliferator-activated receptor-␥-induced differentiation. Serum insulin-like growth factor I levels were reduced with HS in young rats and with age in control and HS rats. These results suggest that the site of bone loss due to disuse is altered with age and that the loss of osteogenic potential with disuse in the old rats may be due to the combined effects of decreased insulin-like growth factor I levels and sensitivity, as well as diminished bone morphogenetic protein production. hindlimb suspension; osteopenia; osteoblast; bone morphogenetic protein; insulin-like growth factor I AGING IS ASSOCIATED WITH FUNCTIONAL changes in many tissues, such as a decline in muscle mass and strength and reduced bone density (8,16,30,38,42,59). With aging, bone and muscle mass regress in a parallel fashion (51). The osteopenia has far-reaching consequences on the ability of the elderly to perform tasks of daily living and to be functionally independent. Indeed, one of the major concerns of aging is the loss of bone mass and strength, which is associated with an increased risk of fractures (1,9,18,51). Moreover, the elderly are often subjected to periods of inactivity, such as bed rest, due to diseases or surgeries. The association of inactivity with decreases in muscle mass and bone density in young people and animals is well documented, and the mechanisms responsible for these losses have been the subject of intense investigation (2,20,23,39,40,49,51).Recent evidence suggests that the increased bone fragility that occurs with aging is multifactorial: decreased bone mineral density (BMD), as well as changes in bone m...

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confidence: 99%

“…Despite the fact that disuse in the elderly poses the risk of exacerbating age-related bone loss, there are few reports on effects of disuse in aged humans or animals (21,29). Because controlled experimental studies of disuse in elderly patients are ethically questionable, studies on this subject have been limited to animals.…”

mentioning

confidence: 99%

Aging alters the skeletal response to disuse in the rat

Perrien¹,

Akel²,

Dupont‐Versteegden³

et al. 2007

American Journal of Physiology-Regulatory, Integrative and Comp

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“…When we chemically substituted butyryl moieties, replacing some of the acetyl moieties on the glucosamines of low molecular mass hyaluronic acid, we demonstrated anti-inflammatory cytokine activity of these mixed GlcNBu polymers on cultured macrophages [18]. These antiinflammatory effects are likely mediated through the TLR-4 receptor system [13] and could represent a mechanism of action for GlcNBu, if it were to be efficiently incorporated into newly synthesized hyaluronic acid. Additionally, we have recently demonstrated that human acetylCoA: glucosamine-6-phosphate N-acetyltransferase 1 has a relaxed donor specificity and transfers acyl groups up to the butyryl moiety (i.e.…”

Section: Discussionmentioning

confidence: 91%

“…At the start of the study, the rat age was 8 weeks and a Sham-OVX, Glc-fed control group was included; accordingly, gain of bone mass attributable to age could be differentiated from changes due to ovariectomy or GlcNBu feeding [6]. There are several considerations [13][14][15] related to our model: the skeleton of a rat reaches maturity after 10 months. In older, intact female rats age-related decreases in cortical BMD have been reported to start in the lumbar vertebrae at the age of 15 months.…”

Section: Discussionmentioning

confidence: 99%

The modified amino sugar N-Butyryl Glucosamine fed to ovariectomized rats preserves bone mineral through increased early mineralization, but does not affect body composition

Anastassiades

Rees-Milton²,

Hopman³

2017

FFHD

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Citation: Anastassiades T., Ress-Milton K., Hopman W.M., The modified amino sugar NButyryl Glucosamine fed to ovariectomized rats preserves bone mineral through increased early mineralization, but does not affect body composition. Functional Foods in Health and Disease 2017; 7(10): 795-815 ABSTRACT Background: The toxicities of pharmaceuticals for chronic arthritis and osteoporosis should be of concern to consumers. This partially accounts for the popularity of consumption of the amino sugar glucosamine, in-spite of controversy about its efficacy. We chemically synthesized Nbutyryl glucosamine (GlcNBu), which we discovered protected bone and cartilage in an inflammatory arthritis rat model when used as a feed supplement. GlcNBu can also be potentially synthesized biochemically, since we recently demonstrated that human acetyl-CoA: glucosamine-6-phosphate N-acetyltransferase 1 has a relaxed donor specificity and transfers acyl groups of up to four carbons in length, i.e. the butyryl moiety. Oral GlcNBu had no detectable toxicity and also protected against bone loss in ovariectomized (OVX) rats as a model for osteoporosis. However, we demonstrated this only for bones excised at 6 months. Thus, the current study aims to determine when bone mineralization is maximized during daily GlcNBu supplementation, in both OVΧ and Sham-OVX rats, in addition to the relationship of bone mineralization to body composition.Methods: Female Sprague-Dawley rats were randomized into 4 groups, containing 8 rats each. The groups consisted of OVX or Sham-OVX rats whose diets were supplemented with either 200 mg/kg/day of GlcNBu or an equimolar amount of glucose. We performed sequential bone density and body composition measurements, by dual-energy X-ray absorptiometry in the live, anesthetised rats, over a 6-month experimental period, starting at the age of 8 weeks. Results were analyzed by descriptive statistics and 2-way ANOVA. Results:The major increases in the mineral content and density of the spine and the femur in GlcNBu-supplemented rats occurred early, from the baseline to week 8. Ovariectomy resulted in a number of significant differences in body composition, while feeding GlcNBu had no significant effects on body composition. The significant effects of ovariectomy on body composition initially appeared at 8 weeks, while the GlcNBu effects on increased bone mineral initially appeared at 2 weeks. An interaction between OVX and GlcNBu was seen only at 16 weeks for the bone mineral density of the femoral head.Conclusions: Supplementation of the diet by GlcNBu in both OVX and Sham-OVX rats increases bone mineral as early as 2 weeks. Ovariectomy but not GlcNBu supplementation had a significant effect on body composition. The effect of GlcNBu occurs independently of changes in body composition, probably as a direct effect of stimulation of bone matrix synthesis which continues to be mineralized. This work represents an important step in the development and commercialization of GlcNBu for the prevention and treatment osteoporosis, wh...

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“…Small bore peripheral quantitative computed tomography (pQCT) is widely used for measuring the bone density of human extremities [1][2][3][4][5] and small animals in vivo [6][7][8][9][10]. The precision of BMD measurement by pQCT is high, with a coefficient of variation (CoV) of 2-3% in both humans [1,12] and small animals [13,14].…”

Section: Introductionmentioning

confidence: 99%

Rat lumbar vertebrae bone densitometry using multidetector CT

et al. 2008

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Peripheral quantitative CT (pQCT) is the main method of bone mineral density (BMD) measurement in small animals. However, pQCT is usually only available in specialized centers, while clinical multidetector computed tomography (MDCT) is much more widely available. This study investigated the feasibility of using clinical 64-slice MDCT for measuring the BMD of rat lumbar vertebrae. The lumbar vertebrae of 18 7-month-old female Sprague-Dawley rats were studied. Two MDCT protocols (General Electric LightSpeed), comprising single 2.5-mm and continuous 0.625-mm acquisitions, and a single pQCT protocol (Scanco Densiscan 2000), comprising 1-mm acquisitions, were performed. The following comparisons were carried out: 2.5-mm MDCT densitometry versus 0.625-mm MDCT densitometry; 0.625-mm MDCT densitometry compared to pQCT densitometry; same day repeatability of 0.625-mm MDCT densitometry; longitudinal repeatability of 0.625-mm MDCT densitometry on day 0 and day 28 and longitudinal 0.625-mm MDCT densitometry in ovariectomized rats on day 0 and day 28. Comparisons were made using intra-class correlation coefficient (ICC). Examination time per animal was 5 min for MDCT and 30 min for pQCT. Acquisitions of 2.5-mm MDCT had a larger coefficient of variation (CoV) than 0.625-mm acquisitions. MDCT densitometry had good agreement with pQCT densitometry (ICC = 0.85). Same-day MDCT densitometry with 0.625-mm acquisitions had a small CoV (1.61%). MDCT densitometry of non-ovariectomized animals at 28 days showed no BMD change, while MDCT densitometry of ovariectomized animals showed a 13.7 +/- 6.7% BMD reduction at 28 days. Clinical MDCT can reliably and accurately measure rat lumbar vertebral BMD and is much faster than pQCT.

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Age-Related Changes in Bone Mineral Density, Cross-Sectional Area and the Strength of Long Bones in the Hind Limbs and First Lumbar Vertebra in Female Wistar Rats

Cited by 27 publications

References 29 publications

Aging alters the skeletal response to disuse in the rat

Aging alters the skeletal response to disuse in the rat

The modified amino sugar N-Butyryl Glucosamine fed to ovariectomized rats preserves bone mineral through increased early mineralization, but does not affect body composition

Rat lumbar vertebrae bone densitometry using multidetector CT

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