Tag Archives: positive

Folate Prevents Bone Loss in Cyclosporine-Treated Rats

Abstract

Protective effect of folic acid on cyclosporine-induced bone loss in rats.

Hyperhomocysteinemia is seen in patients with decreased bone mineral density. Cyclosporine can cause alveolar bone loss and osteopenia. It is also associated with elevated serum homocysteine levels. We aimed to investigate the effect of cyclosporine on serum homocysteine level, bone volume, and bone density, and determine whether folic acid had a protective effect against bone loss. In an experimental study, 40 male Sprague-Dawley rats were randomly assigned to five groups and received dietary supplementation for 6 weeks with olive oil (Group A), cyclosporine (Group B), folic acid (Group C), and cyclosporine plus folic acid (Group D), or no supplementation (Group F, control). Serum homocysteine, calcium, alkaline phosphatase, total bone volume, periodontal ligament volume, and volume density of bone were compared between groups. Mean serum homocysteine level (10.84 ± 0.93 μmol/l) was significantly higher in group B (cyclosporine supplementation) compared with the other groups (P = 0.001). Mean total mandibular volume was 46.3 ± 13.6 mm(3) in rats treated with cyclosporine, 80.4 ± 15.70 mm(3) in rats treated with folic acid (P = 0.004), and 73.9 ± 21.3 mm(3) in rats treated with cyclosporine plus folic acid (P = 0.028). In our experimental model, cyclosporine increased serum homocysteine levels and decreased bone volume and density. Folic acid may have a preventive role against bone loss in rats treated with cyclosporine.

Mohammadi A, Omrani L, Omrani LR, Kiani F…
Transpl. Int. Jan 2012
PMID: 22039919

B6 and Riboflavin Associated with Increased Bone Density

Abstract

Effect of dietary B vitamins on BMD and risk of fracture in elderly men and women: the Rotterdam study.

A mildly elevated homocysteine (Hcy) level is a novel and potentially modifiable risk factor for age-related osteoporotic fractures. Elevated Hcy levels can have a nutritional cause, such as inadequate intake of folate, riboflavin, pyridoxine or cobalamin, which serve as cofactors or substrates for the enzymes involved in the Hcy metabolism. We examined the association between intake of Hcy-related B vitamin (riboflavin, pyridoxine, folate and cobalamin) and femoral neck bone mineral density BMD (FN-BMD) and the risk of fracture in a large population-based cohort of elderly Caucasians. We studied 5304 individuals aged 55 years and over from the Rotterdam Study. Dietary intake of nutrients was obtained from food frequency questionnaires. Incident non-vertebral fractures were recorded during a mean follow-up period of 7.4 years, and vertebral fractures were assessed by X-rays during a mean follow-up period of 6.4 years. We observed a small but significant positive association between dietary pyridoxine (beta = 0.09, p = 1 x 10(-8)) and riboflavin intake (beta = 0.06, p = 0.002) and baseline FN-BMD. In addition, after controlling for gender, age and BMI, pyridoxine intake was inversely correlated to fracture risk. As compared to the three lowest quartiles, individuals in the highest quartile of age- and energy-adjusted dietary pyridoxine intake had a decreased risk of non-vertebral fractures (HR = 0.77, 95% CI = 0.65-0.92, p = 0.005) and of fragility fractures (HR = 0.55, 95% CI = 0.40-0.77, p = 0.0004). Further adjustments for other dietary B vitamins (riboflavin, folate and cobalamin), dietary intake of calcium, vitamin D, vitamin A and vitamin K, protein and energy intake, smoking and BMD did not essentially modify these results. We conclude that increased dietary riboflavin and pyridoxine intake was associated with higher FN-BMD. Furthermore, we found a reduction in risk of fracture in relation to dietary pyridoxine intake independent of BMD. These findings highlight the importance of considering nutritional factors in epidemiological studies of osteoporosis and fractures.

Yazdanpanah N, Zillikens MC, Rivadeneira F, de Jong R…
Bone Dec 2007
PMID: 17936100

AKG Prevents Bone Loss in Dexamethasone-Treated Pigs

Abstract

Postnatal administration of 2-oxoglutaric acid improves articular and growth plate cartilages and bone tissue morphology in pigs prenatally treated with dexamethasone.

The potential effects of prenatal administration of dexamethasone (DEX) and postnatal treatment with 2-oxoglutaric acid (2-Ox) on postnatal development of connective tissue of farm animals were not examined experimentally. The aim of this study was to establish changes in morphological parameters of bone and articular and growth plate cartilages damaged by the prenatal action of DEX in piglets supplemented with 2-Ox. The 3 mg of DEX was administered by intramuscular route every second day from day 70 of pregnancy to parturition and then piglets were supplemented with 2-Ox during 35 days of postnatal life (0.4 g/kg body weight). The mechanical properties, BMD and BMC of bones, and histomorphometry of articular and growth plate cartilages were determined. Maternal treatment with DEX decreased the weight by 48%, BMD by 50% and BMC by 61% of the tibia in male piglets while such action of DEX in female piglets was not observed. DEX led to thinning of articular and growth plate cartilages and trabeculae thickness and reduced the serum GH concentration in male piglets. The administration of 2-Ox prevented the reduction of trabeculae thickness, the width of articular and growth plate cartilages in male piglets connected with higher growth hormone concentration compared with non-supplemented male piglets. The result showed that the presence of 2-Ox in the diet had a positive effect on the development of connective tissue in pigs during suckling and induced a complete recovery from bone and cartilage damage caused by prenatal DEX action.

Tomaszewska E, Dobrowolski P, Wydrych J
J. Physiol. Pharmacol. Oct 2012
PMID: 23211309 | Free Full Text

AKG shows Only a Slight Influence on Bone in Rats

Abstract

The effect of dietary administration of 2-oxoglutaric acid on the cartilage and bone of growing rats.

2-Oxoglutaric acid (2-Ox), a precursor to hydroxyproline – the most abundant amino acid in bone collagen, exerts protective effects on bone development during different stages of organism development; however, little is known about the action of 2-Ox on cartilage. The aim of the present study was to elucidate the influence of dietary 2-Ox supplementation on the growth plate, articular cartilage and bone of growing rats. A total of twelve male Sprague-Dawley rats were used in the study. Half of the rats received 2-oxoglutarate at a dose of 0·75 g/kg body weight per d in their drinking-water. Body and organ weights were measured. Histomorphometric analyses of the cartilage and bone tissue of the femora and tibiae were conducted, as well as bone densitometry and peripheral quantitative computed tomography (pQCT). Rats receiving 2-Ox had an increased body mass (P<0·001) and absolute liver weight (P=0·031). Femoral length (P=0·045) and bone mineral density (P=0·014), overall thickness of growth plate (femur P=0·036 and tibia P=0·026) and the thickness of femoral articular cartilage (P<0·001) were also increased. 2-Ox administration had no effect on the mechanical properties or on any of the measured pQCT parameters for both bones analysed. There were also no significant differences in histomorphometric parameters of tibial articular cartilage and autofluorescence of femoral and tibial growth plate cartilage. Dietary supplementation with 2-Ox to growing rats exerts its effects mainly on cartilage tissue, having only a slight influence on bone. The effect of 2-Ox administration was selective, depending on the particular bone and type of cartilage analysed.

Dobrowolski P, Tomaszewska E, Bienko M, Radzki RP…
Br. J. Nutr. Aug 2013
PMID: 23308390

AKG Helps Prevent Induced Osteopenia in Pigs

Abstract

2-Oxoglutaric acid administration diminishes fundectomy-induced osteopenia in pigs.

Partial surgical removal of the stomach (fundectomy, FX) leads to osteopenia in animals and humans. FX adversely affects the bone. 2-oxoglutaric acid is a precursor of glutamine and hydroxyproline–the most abundant amino acid of collagen. The aim of the study was to investigate the effects of 2-oxoglutaric acid on FX-evoked osteopenia in pigs.

Eighteen castrated male pigs of the Puławska breed were used. Twelve pigs were subjected to FX and divided into two groups: FX + AKG (the AKG group; AKG at the daily dosage of 0.4 g/kg of body weight) and FX + Placebo (the FXC group; received CaCO(3) as placebo). Remaining six pigs were sham-operated (the SHO group). The pigs were euthanized at the age of 8 months and long bones were collected. Area bone mineral density (aBMD) and bone mineral content (BMC) were measured; morphology, geometry and biomechanical properties were determined. Moreover, the serum concentrations of selected hormones and one marker of bone metabolism were determined. FX caused osteopenia in the pigs and treatment with AKG greatly reduced these effects of FX in pigs. Negative effect of fundectomy on the skeletal system leading to decreased bone mass in pigs is associated with lowered body gain and activity of the gastric-hypothalamic-pituitary axis. Better definitions of each of the local and systemic hormonal and structural components associated with fundectomy-induced decreased bone mass that separately and together determine the whole bone properties may lead to identify opportunities for prevention.

Śliwa E
J Anim Physiol Anim Nutr (Berl) Oct 2010
PMID: 20487101

PGE2 Increases Bone Strength in Rats

Abstract

Prostaglandin E2 increases bone strength in intact rats and in ovariectomized rats with established osteopenia.

It is well documented that prostaglandin E2 (PGE2) has the ability to stimulate bone formation, improve bone structure, and increase bone mass in intact or osteopenic rat models. However, the effects of PGE2 on the mechanical properties of bone have not been investigated previously.The purpose of our study was to determine the effects of PGE2 on the mechanical strength of bones in rapidly growing, adult, and ovariectomized rat models. In study I, PGE2 at 3 mg/kg per day, or vehicle, was given by daily subcutaneous injections for 30 days to rapidly growing (3-month-old) intact male rats. Compared with controls, PGE2 significantly increased initial maximal load and stiffness of cancellous bone at the distal femoral metaphysis (DFM) as determined by an indentation test. As determined by a compression test, rats treated with PGE2 showed a significant increase in maximal load, and a nonsignificant increase in stiffness in the fifth lumbar vertebral body (L5) when compared with controls. In study II, PGE2 at 3 mg/kg per day, or vehicle, was given by daily subcutaneous injection for 30 days to mature (10-month-old) intact male rats. PGE2 treatment significantly increased initial maximal load and stiffness of the DFM and L5. PGE2 induced a significant increase in maximal load, but not stiffness, in the femoral neck (FN), as determined by a cantilever compression test. There was an increase in maximal load in a three-point bending test at the femoral shaft (FS) although the increase did not achieve statistical significance. No change in stiffness in the FS was found after PGE2 treatment. In study III, 3-month-old female rats were sham-operated or ovariectomized (ovx) for 30 days. Thereafter, PGE, at 1 or 3 mg/kg, or vehicle, were given by daily subcutaneous injection to these rats for 30 days. After 30 and 60 days, ovx induced a significant decrease in initial maximal load and stiffness of cancellous bone at the DFM as compared with sham controls. In ovx rats with established osteopenia, PGE2 at 1 mg/kg per day nonsignificantly increased the initial maximal load and stiffness, whereas, at 3 mg/kg per day, PGE2 completely restored the initial maximal load and stiffness of DFM to sham control levels. Similarly, maximal load and stiffness of L5 decreased significantly in ovx rats compared with sham controls at 30 days postsurgery. PGE2 at 1 mg/kg per day partially restored the maximal load, whereas, at 3 mg/kg per day, it completely restored the maximal load and stiffness of L5 in the established osteopenia, ovx rats. At the FS, PGE2 at 3 mg/kg per day nonsignificantly increased maximal load (+11%) and significantly increased stiffness (+25%) compared with ovx controls. Neither ovx nor PGE2 treatment caused a significant change in the maximal load and stiffness of the FN in this study. These results reveal that PGE2 significantly increased the mechanical strength at various skeletal sites in rapidly growing and mature male rats, although the increase in femoral shafts was not statistically different. Furthermore, PGE2 completely restored mechanical strength to the cancellous bone in ovx rats with established osteopenia.

Ke HZ, Shen VW, Qi H, Crawford DT…
Bone Sep 1998
PMID: 9737347

AKG Decreases a Marker of Bone Turnover in Postmenopausal Women with Osteopenia

Abstract

Alpha-ketoglutarate decreases serum levels of C-terminal cross-linking telopeptide of type I collagen (CTX) in postmenopausal women with osteopenia: six-month study.

Several studies have shown that alpha-ketoglutaric acid (AKG) increases serum levels of proline and has beneficial effects on skeletal development. We studied the effect of alpha-ketoglutaric (AKG) acid calcium salt (6 g AKG and 1.68 Ca/day) or calcium alone (1.68 Ca/day) on serum C-terminal cross-linked telopeptide of type I collagen (CTX) and osteocalcin (OC), as well as on lumbar spine bone mineral density (BMD) in a randomized, parallel group, double-blind, 6-month study conducted on 76 postmenopausal women with osteopenia. The maximum decrease of the mean CTX level in the AKG-Ca group was observed after 24 weeks (37.0%, p = 0.006). The differences in CTX between study groups were statistically significant after 12 and 24 weeks. The OC serum level was not affected by treatments. The BMD of the AKG-Ca group increased by 1.6% from baseline; however, the difference between treatment groups was estimated as 0.9% (non-significant). This study suggests the potential usefulness of AKG-Ca in osteopenic postmenopausal women. AKG-Ca induced beneficial changes in serum CTX, which was consistent with preserving the bone mass in the lumbar spine; however, the long-term effect needs to be further investigated.

Filip RS, Pierzynowski SG, Lindegard B, Wernerman J…
Int J Vitam Nutr Res Mar 2007
PMID: 17896582

AKG Reduces Gastrectomy-Evoked Bone Loss in Rats

Abstract

Dietary alpha-ketoglutarate reduces gastrectomy-evoked loss of calvaria and trabecular bone in female rats.

Surgical removal of the stomach (gastrectomy, Gx) leads to osteopenia in animals and in humans. In the rat, Gx adversely affects calvaria and trabecular bone. alpha-Ketoglutarate (AKG) is a precursor of hydroxyproline–the most abundant amino acid in bone collagen. The purpose of this study was to investigate the effects of dietary AKG on Gx-induced osteopenia.
Twenty female Sprague-Dawley rats were subjected to Gx and divided between two groups: Gx+AKG in the drinking water and Gx+Vehicle (i.e. drinking water without AKG). Another 20 rats were sham-operated and divided between two groups: Sham+AKG and Sham+Vehicle. The daily dose of AKG was 0.43 g per 100 g rat. All the rats were killed 8 weeks later and the calvariae, femora and tibiae were collected. The integrity of the calvariae was analysed planimetrically, following transillumination and photography. The bone mineral content (BMC) and bone mineral density (BMD) were measured in the right femorae and tibiae (bone densitometry), leaving the left femorae and tibiae to be analysed histomorphometrically (measurement of trabecular bone volume and trabecular fractal dimension).
Gx caused calvarial bone degradation, reduced trabecular bone (femur and tibia) and impaired trabecular architecture. In addition, Gx lowered the femoral/tibial BMC and BMD (mainly cortical bone). Dietary AKG counteracted the Gx-evoked impairment of calvaria and trabecular bone but failed to affect the BMC and the BMD in either sham- operated or Gx rats.
Gx resulted in loss of calvarial, trabecular and cortical bone in the rat. AKG counteracted the effect of Gx on calvaria and trabecular bone but not on cortical bone.

Dobrowolski PJ, Piersiak T, Surve VV, Kruszewska D…
Scand. J. Gastroenterol. 2008
PMID: 18415747

AKG Increases Bone Length and Estrogen in Pigs

Abstract

The long-term effect of alpha-ketoglutarate, given early in postnatal life, on both growth and various bone parameters in pigs.

The long-term effect of alpha-ketoglutarate (AKG) given for 21-24 days post-partum, on the skeleton of commercial pigs, was investigated. In experiment A, 12 pigs were given AKG [0.1 g/kg of body weight (b.w.) per day per os], while 12 controls were administered vehicle. At day 169, the left and right femur, humerus and sixth ribs were analysed for mechanical and geometrical properties and quantitative computed tomography. In experiment B, 32 piglets were divided equally into an AKG group (0.3 g/kg of b.w. per day) or a control group. Blood, taken at days 24 and 53 was analysed for plasma 17 beta-oestradiol. The main bone effect of AKG was to increase bone length in the sixth rib (7.3%, p < 0.01), ultimate strength (23%, p < 0.05), Young s modulus (52%, p < 0.001) and maximum elastic strength (31%, p = 0.056) compared with controls. In both experiments, AKG preferentially increased the growth of female piglets, whilst for male piglets AKG had the opposite effect. In addition, AKG elevated plasma 17 beta-oestradiol levels compared to those of controls at the end of the period of treatment (20%, p = 0.002). It is concluded that AKG has long-term effects on rib properties when given early in postnatal life whilst it elevates plasma 17 beta-oestradiol levels only so long as it is being administered.

Andersen NK, Tatara MR, Krupski W, Majcher P…
J Anim Physiol Anim Nutr (Berl) Oct 2008
PMID: 19012595

AKG Improves Bone Mineralization in Ovariectomized Rats

Abstract

Anti-osteopenic effect of alpha-ketoglutarate sodium salt in ovariectomized rats.

The purpose of the study was to determine the effect of alpha-ketoglutarate sodium salt (AKG) treatment on the mineralization of the tibia in female rats during the development of osteopenia (Experiment-1) and in the condition of established osteopenia (Experiment-2). Thirty-two female rats were ovariectomized (OVX) to induce osteopenia and osteoporosis and another 32 female rats were sham-operated (SHO) and then randomly divided between the two experiments. In Experiment-1, the treatment with AKG started after a 7-day period of convalescence, whereas in Experiment-2 the rats were subjected to a 60-day period of osteopenia fixation, after which the actual experimental protocol commenced. AKG was administered in the experimental solution for drinking at a concentration of 1.0 mol/l and a placebo (PLC) was used as a control solution. After 60 days of experimental treatment the rats in both experiements were sacrificed, the body weight recorded, and blood serum and isolated tibia were stored for further analysis. The bones were analyzed using tomography and densitometry, and for estimation of mechanical properties the 3-point bending test was used. Serum concentrations of osteocalcin and collagen type I crosslinked C-telopeptide were measured. The anabolic effects of AKG on bone during osteopenia development in Experiment-1 not only stopped the degradation of bone tissue, but also stimulated its mineralization. The usage of AKG in animals with established osteopenia (Experiment-2) was not able to prevent bone atrophy, but markedly reduced its intensity. The stimulation of tibia mineralization after AKG treatment has been also argued in healthy SHO animals. The results obtained prove the effectiveness of AKG usage in the prophylaxis and therapy of osteopenia and osteoporosis, induced by bilateral gonadectomy. Additionally, the results clearly prove that treatment with AKG improves the mineralization of bone tissue in healthy animals.

Radzki RP, Bienko M, Pierzynowski SG
J. Bone Miner. Metab. Nov 2012
PMID: 22864414