N-acylated glucosamines for bone and joint disorders: effects of N-butyryl glucosamine on ovariectomized rat bone

Anastassiades, Tassos; Rees-Milton, Karen; Xiao, Hao; Yang, Xiaojing; Willett, Thomas L.; Grynpas, Marc D.

doi:10.1016/j.trsl.2013.04.002

Cited by 9 publications

(10 citation statements)

References 23 publications

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“…We used relatively young rats, weighing approximately 180 g at the start of the experiment, when the daily supplementation of the OVX or Sham-OVX groups with GlcNBu or glucose (Glc) commenced. Additionally, we found that femurs are longer in GlcNBu-fed rats at the end of the six-month period, whether or not they were OVX [6]. Furthermore, the relationship between BMC, BMD, and body composition components, measured by DXA was not determined.…”

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confidence: 69%

“…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.…”

Section: Discussionmentioning

confidence: 99%

“…In a rat model of a destructive streptococcal cell wall-induced destructive arthritis of cartilage and bone, oral administration of GlcNBu at either 20 or 200 mg/kg/day had strong protective effects in both cartilage and subchondral bone, with a number of quantitative parameters being preserved in the latter in a dose-dependent fashion [17]. It was this effect of GlcNBu on bone that led us to investigate this compound as a dietary supplement in the ovarectomized rat model for increased bone loss at the dose of 200 mg/kg/day [6].…”

Section: Discussionmentioning

confidence: 99%

“…In terms of animal models, we initially observed in an experimental model of inflammatory arthritis in the rat that oral GlcNBu preserved both bone and cartilage, as discussed below. We then reported [6] that daily supplementation of 200 mg/kg/day of GlcNBu of the standard feed of ovariectomized (OVX) rats preserved bone mineral and some biomechanical properties of the spine and femurs. These observations were made at the end of a six-month experimental period and reached significance only in the OVX group fed GlcNBu.…”

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confidence: 99%

“…In our previous work [6], the animals were sacrificed at 6 months; it was not clear at what time frame the increases in bone mineral content (BMC) and bone mineral density (BMD), as measured by dual-energy X-ray absorptiometry (DXA), initially occurred. Furthermore, the relationship between BMC, BMD and body composition components, measured by DXA, was not determined.…”

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confidence: 99%

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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

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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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confidence: 69%