Tag Archives: note

Vitamin E with Tocotrienols is an Anabolic Bone Agent in Nicotine Treated Rats

Abstract

Effects of palm vitamin e on bone-formation-related gene expression in nicotine-treated rats.

The study determines the effects of palm vitamin E on the gene expression of bone-formation-related genes in nicotine-treated rats. Male rats were divided into three groups: normal saline olive oil (NSO), nicotine olive oil (NO), and nicotine palm vitamin E (NE). The treatment was carried out in 2 phases. During the first 2 months, the NSO group received normal saline while the NO and NE groups received nicotine 7 mg/kg, 6 days a week, intraperitoneally. The following 2 months, normal saline and nicotine administration was stopped and was replaced with oral supplementation of olive oil for the NSO and NO groups and oral supplementation of palm vitamin E (60 mg/kg) for the NE group. Both femurs were harvested to determine the gene expression of bone morphogenetic protein-2 (BMP-2), Osterix (OSX), and Runt-related transcription factor 2 (RUNX2). Nicotine significantly downregulated the gene expression. This effect was reversed by palm vitamin E treatment. In conclusion, palm vitamin E may play a role in osteoblast differentiation and can be considered as an anabolic agent to treat nicotine-induced osteoporosis.

Abukhadir SS, Mohamed N, Makpol S, Muhammad N
Evid Based Complement Alternat Med 2012
PMID: 23049610 | Free Full Text

They used “Palm Vitamin E” in this study. Palm typically contains a high amount of Tocotrienols.

Vitamin E is an important fat-soluble vitamin with antioxidant properties. Of the two types of vitamin E, tocopherol is found in vegetable oils such as soy oil whereas tocotrienol is abundant in palm oil [7]. Previous studies have confirmed the beneficial effects of palm-oil-derived cotrcotrienol in several experimental osteoporosis; ovariectomized rats [8], steroid-induced rats [9], ferric-nitrilotriacetate-induced rats [10], and nicotine-induced rats [11, 12]. Furthermore, recent study has shown that supplementation of palm vitamin E, especially gamma isomer, can improve bone structural and biomechanical properties of normal male rats. Therefore, palm vitamin E has the potential to be used as an anabolic agent [13].

 

Myricetin Suppresses Osteoclasts

Abstract

Myricetin suppresses LPS-induced MMP expression in human gingival fibroblasts and inhibits osteoclastogenesis by downregulating NFATc1 in RANKL-induced RAW 264.7 cells.

Periodontitis is an inflammatory disease that affects connective tissue attachments and the supporting bone that surrounds the teeth. Gingival fibroblasts induce the overexpression of matrix metalloproteinase (MMP), which is involved in inflammatory progression in periodontitis. Osteoclasts are responsible for skeletal modeling and remodeling but may also destroy bone in several bone diseases, including osteoporosis and periodontitis. This study examined the anti-destructive effects of myricetin on human gingival fibroblasts (HGF) under lipopolysaccharide- (LPS-) induced inflammatory conditions, and the anti-osteoclastogenetic effect of myricetin on the receptor activator of NF-κB ligand (RANKL) induced RAW264.7 cells was also investigated.
The effects of myricetin on HGF were determined by measuring the cell viability and mRNA expression and enzyme activity of tissue-destructive proteins, including MMP-1, MMP-2 and MMP-8. The effects of myricetin on osteoclasts were examined by measuring the following: (1) the cell viability, (2) the formation of tartrate-resistant acid phosphatase (TRAP)(+) multinucleated cells, (3) MAPK signalling pathways (4) mRNA expression of osteoclast-associated genes and (5) tumor necrosis factor-α (TNF-α) and interleukin-1β (IL-1β) secretion.
The myricetin had no effects on the cell viability of the HGF and decreased the mRNA expression and enzyme activity of MMP-1, MMP-2 and MMP-8 in the HGF. Myricetin inhibited the formation of RANKL-stimulated TRAP(+) multinucleated cells. Myricetin also inhibited the RANKL-stimulated activation of p-38, ERK and cSrc signaling, and inhibited the RANKL-stimulated degradation of I(k)B in the RAW264.7 cells. In addition, the RANKL-stimulated induction of NFATc1 transcription factors was abrogated by myricetin. Myricetin decreased the mRNA expression of osteoclast-associated genes, including cFOS, TRAP and cathepsin K in the RAW264.7 cells. Myricetin inhibited the secretion of LPS-induced TNF-α and IL-1β in the RAW264.7 cells.
These findings suggest that myricetin has therapeutic effects on bone-destructive processes, such as those that occur in periodontal diseases.

Ko SY
Arch. Oral Biol. Dec 2012
PMID: 22795564

Myricetin may suppress melatonin.

Animal Protein Increases Bone Loss and Fracture in Postmenopausal Women – 2001

Abstract

A high ratio of dietary animal to vegetable protein increases the rate of bone loss and the risk of fracture in postmenopausal women. Study of Osteoporotic Fractures Research Group.

Different sources of dietary protein may have different effects on bone metabolism. Animal foods provide predominantly acid precursors, whereas protein in vegetable foods is accompanied by base precursors not found in animal foods. Imbalance between dietary acid and base precursors leads to a chronic net dietary acid load that may have adverse consequences on bone. We wanted to test the hypothesis that a high dietary ratio of animal to vegetable foods, quantified by protein content, increases bone loss and the risk of fracture. This was a prospective cohort study with a mean (+/-SD) of 7.0+/-1.5 y of follow-up of 1035 community-dwelling white women aged >65 y. Protein intake was measured by using a food-frequency questionnaire and bone mineral density was measured by dual-energy X-ray absorptiometry. Bone mineral density was not significantly associated with the ratio of animal to vegetable protein intake. Women with a high ratio had a higher rate of bone loss at the femoral neck than did those with a low ratio (P = 0.02) and a greater risk of hip fracture (relative risk = 3.7, P = 0.04). These associations were unaffected by adjustment for age, weight, estrogen use, tobacco use, exercise, total calcium intake, and total protein intake. Elderly women with a high dietary ratio of animal to vegetable protein intake have more rapid femoral neck bone loss and a greater risk of hip fracture than do those with a low ratio. This suggests that an increase in vegetable protein intake and a decrease in animal protein intake may decrease bone loss and the risk of hip fracture. This possibility should be confirmed in other prospective studies and tested in a randomized trial.

Sellmeyer DE, Stone KL, Sebastian A, Cummings SR
Am. J. Clin. Nutr. Jan 2001
PMID: 11124760 | Free Full Text

More recent studies and randomized trials have discredited the conclusions of this study.

There are two published comments on this study. The full text is available for both.

Protein intake and bone health: the influence of belief systems on the conduct of nutritional science.
Heaney RP
PMID: 11124741 | Free Full Text

Dietary ratio of animal to vegetable protein and rate of bone loss and risk of fracture in postmenopausal women.
Sebastian A, Sellmeyer DE, Stone KL, Cummings SR
Am. J. Clin. Nutr. Sep 2001
PMID: 11522569 | Free Full Text

Hypothesis: Animal Protein Associated with Hip Fracture – 1992

Abstract

Cross-cultural association between dietary animal protein and hip fracture: a hypothesis.

Age-adjusted female hip fracture incidence has been noted to be higher in industrialized countries than in nonindustrialized countries. A possible explanation that has received little attention is that elevated metabolic acid production associated with a high animal protein diet might lead to chronic bone buffering and bone dissolution. In an attempt to examine this hypothesis, cross-cultural variations in animal protein consumption and hip fracture incidence were examined. When female fracture rates derived from 34 published studies in 16 countries were regressed against estimates of dietary animal protein, a strong, positive association was found. This association could not plausibly be explained by either dietary calcium or total caloric intake. Recent studies suggest that the animal protein-hip fracture association could have a biologically tenable basis. We conclude that further study of the metabolic acid-osteoporosis hypothesis is warranted.

Abelow BJ, Holford TR, Insogna KL
Calcif. Tissue Int. Jan 1992
PMID: 1739864

This study from 1992 was one of the earlier proposals that animal protein may cause osteoporosis. The hypothesis has since been discredited.

Isoflavones + Calcium Better Than Isoflavones or Calcium in Ovariectomized Rats

Abstract

Isoflavones with supplemental calcium provide greater protection against the loss of bone mass and strength after ovariectomy compared to isoflavones alone.

Although hormone replacement therapy (HRT) and calcium (Ca) supplementation preserve bone mass more when combined, there is a growing concern over the safety of HRT that necessitates thorough investigation of effective, alternative treatments for bone loss. While plant-derived estrogen-like compounds such as isoflavones preserve bone, it is not known whether isoflavones and Ca supplementation attenuate losses in bone mass and strength to a greater extent when combined. This study compared the effects of an isoflavone extract + high Ca to isoflavone extract or high Ca alone on preservation of bone mineral density (BMD) and biomechanical strength in ovariectomized (ovx) rats. Rats were sham-operated (n = 10) or ovx (n = 40). Shams were fed a 0.2% Ca diet. Ovx rats were randomized to a 0.2% Ca diet alone (OVX) or with isoflavone extract (IE; 1.6 g/kg diet) or to a high Ca diet (Ca; 2.5%) alone or a high Ca diet with the isoflavone extract (IE + Ca) for 8 weeks. BMD of femur and lumbar spine were measured by dual-energy X-ray absorptiometry. The biomechanical strength of femurs and individual vertebra was measured by three-point bending and compression testing, respectively. The average food intake was lowest (P < 0.05) among sham and IE groups and greatest (P < 0.05) among the OVX group. Final body weight was lowest (P < 0.05) among shams and highest (P < 0.05) among the OVX group while IE + Ca were lighter (P < 0.05) than all ovx groups. Femur and vertebra BMD was greater (P < 0.05) among IE + Ca and sham rats compared to IE, Ca, or OVX rats. Although there were differences in femur BMD among groups, biomechanical properties at the femur midpoint did not differ among groups, possibly due to the lack of cortical bone loss at this site. Conversely, vertebra biomechanical strength was greater (P < 0.05) among IE + Ca and Ca alone groups compared to IE alone. Uterine weight was higher (P < 0.05) among shams than OVX and IE with no difference among shams, Ca, or IE + Ca rats, suggesting that the isoflavones did not have an uterotrophic effect. In conclusion, isoflavones combined with high Ca are more protective against the loss of femur and vertebra BMD than isoflavones or high Ca diet alone.

Breitman PL, Fonseca D, Cheung AM, Ward WE
Bone Oct 2003
PMID: 14555264

Also, it’s interesting that Calcium alone was superior to Isoflavones alone.

Carnitine Slows Bone Growth (and Loss) in Ovariectomized Rats

Abstract

Dietary l-carnitine supplementation improves bone mineral density by suppressing bone turnover in aged ovariectomized rats.

Postmenopausal bone loss is a major public health concern. Although drug therapies are available, women are interested in alternative/adjunct therapies to slow down the bone loss associated with ovarian hormone deficiency. The purpose of this study was to determine whether dietary supplementation of l-carnitine can influence bone density and slow the rate of bone turnover in an aging ovariectomized rat model. Eighteen-month-old Fisher-344 female rats were ovariectomized and assigned to two groups: (1) a control group in which rats were fed ad libitum a carnitine-free (-CN) diet (AIN-93M) and (2) another fed the same diet but supplemented with l-carnitine (+CN). At the end of 8 weeks of feeding, animals were sacrificed and bone specimens were collected for measuring bone mineral content (BMC) and density (BMD) using dual energy X-ray absorptiometry. Femoral microarchitectural properties were assessed by microcomputed tomography. Femoral mRNA levels of selected bone matrix proteins were determined by northern blot analysis. Data showed that tibial BMD was significantly higher in the rat fed the +CN diet than those fed the -CN (control) diet. Dietary carnitine significantly decreased the mRNA level of tartrate-resistant acid phosphatase (TRAP), an indicator of bone resorption by 72.8%, and decreased the mRNA abundance of alkaline phosphatase (ALP) and collagen type-1 (COL), measures of bone formation by 63.6% and 61.2%, respectively. The findings suggest that carnitine supplementation slows bone loss and improves bone microstructural properties by decreasing bone turnover.

Hooshmand S, Balakrishnan A, Clark RM, Owen KQ…
Phytomedicine Aug 2008
PMID: 18539446 | Free Full Text

The part in red above is negative for bone growth. The full text notes:

Our data here showed that carnitine decreased the mRNA levels of TRAP as well as ALP and COL, suggesting that carnitine may suppress bone turnover by decreasing the rates of both bone resorption and formation.

8-Prenylnaringenin > Genistein for Preventing Osteoporosis in Ovariectomized Rats; Resveratrol Has no Effect

Abstract

Comparison of the phytohormones genistein, resveratrol and 8-prenylnaringenin as agents for preventing osteoporosis.

As the average age of society increases, identifying and preventing osteoporosis becomes more important. According to the results of the Women’s Health Initiative study, substitution of estradiol is not recommended in hormone replacement therapy (HRT), although phytoestrogens might be a safe alternative. In this study, the osteoprotective effects of genistein (Gen), resveratrol (Res) and 8-prenylnaringenin (8PN) were evaluated by analysing bone biomechanical strength and bone mineral density. After ovariectomy, 88 female rats received soy-free food (C), and according to their grouping, were fed estradiol (E), GEN, RES or 8PN for 12 weeks. The phytohormones were given in two dosages. To analyse the osteoprotective effects of the tested substances, bone biomechanical properties and bone mineral density (BMD) were evaluated on the upper tibial metaphysis. Bone biomechanical properties were significantly improved after treatment with E (F (max): 90.6 N) and 8PN (85.0 N) compared to GEN (76.0 N), RES (72.6 N) and C (76.6 N). Bone biomechanical properties with 8PN (yL: 55.7 N) supplementation reached a level similar to that seen after E (49.3 N) supplementation. Treatment with GEN (38.5 N) was not as effective as E and 8PN, but demonstrated improved biomechanical properties compared to C (40.1 N) and RES (36.3 N). E (Cn.Dn. 217 mg/cm (3)) and 8PN (165 mg/cm3) showed superior results in the analysis of bone mineral density compared to C (112 mg/cm (3)). GEN (164 mg/cm (3)) also demonstrated superior results, though not as good as E and 8PN. RES (124 mg/cm (3)) revealed no effect on bone density. Treatment with 8PN resulted in very good biomechanical properties and showed an increased BMD. GEN had a smaller effect on bone biomechanical strength, while RES did not have an effect on bone biomechanical strength or BMD. Therefore, 8PN might be a safe alternative for HRT, but further studies are needed.

Sehmisch S, Hammer F, Christoffel J, Seidlova-Wuttke D…
Planta Med. Jun 2008
PMID: 18537073

It is surprising and disappointing that resveratrol had no effect on bone density in this study.

Quercetin Inhibits Bone Loss Without Affecting Osteoclasts or Estrogen Receptors in Ovariectomized Mice

Abstract

Dietary quercetin inhibits bone loss without effect on the uterus in ovariectomized mice.

Quercetin is a major dietary flavonoid found in onions and other vegetables, and potentially has beneficial effects on disease prevention. In the present study, we demonstrate for the first time the effects of dietary quercetin on bone loss and uterine weight loss by ovariectomy in vivo. Female mice were ovariectomized (OVX) and were randomly allocated to 3 groups: a control diet or a diet with 0.25% (LQ) or 2.5% quercetin (HQ). After 4 weeks, dietary quercetin had no effects on uterine weight in OVX mice, but bone mineral density of the lumbar spine L4 and femur measured by peripheral quantitative computed tomography (pQCT) was higher in both the sham and the HQ groups than in the OVX group. Histomorphometric analysis showed that the HQ group restored bone volume (BV/TV) completely in distal femoral cancellous bone, but did not reduce the osteoclast surface area and osteoclast number when compared with the OVX group. In in-vitro experiments using mouse monocyte/macrophage cell line RAW264.7 cells, however, quercetin and its conjugate, quercetin-3-O-beta-D: -glucuronide dose-dependently inhibited the receptor activator of nuclear factor-kappa B ligand (RANKL)-induced osteoclast differentiation, and the RANKL-stimulated expression of osteoclast related genes was also inhibited by quercetin. The luciferase reporter assay showed that quercetin did not appear to have estrogenic activity through estrogen receptors. These results suggest that dietary quercetin inhibits bone loss without effect on the uterus in OVX mice and does not act as a potent inhibitor of osteoclastogenesis or as a selective estrogen receptor modulator in vivo.

Tsuji M, Yamamoto H, Sato T, Mizuha Y…
J. Bone Miner. Metab. 2009
PMID: 19495926

Interesting, I wonder how it works if it doesn’t inhibit osteoclasts in vivo and isn’t estrogenic?

Beta Blockers Improved Bone in Hypertensive Rats from Beta2 Blockade

Abstract

Effects of propranolol on bone metabolism in spontaneously hypertensive rats.

The effects of propranolol (PRO), a nonselective beta-adrenergic receptor (beta-AR) antagonist with membrane-stabilizing action on bone metabolism, were examined in spontaneously hypertensive rats (SHR) showing osteoporosis with hyperactivity of the sympathetic nervous system. Treatment of SHR with PRO at 1 and 5 mg/kg p.o. for 12 weeks increased bone mass of the lumbar vertebra and proximal tibia without affecting blood pressure, but PRO at 50 and 100 mg/kg with hypotensive action did not increase bone mass. Next, the effects of PRO at 0.1, 1, and 10 mg/kg on bone status were examined in more detail. Compared with the SHR control, not only bone mass but also biomechanical parameters of strength and toughness of the lumbar vertebrae were increased in SHR treated with PRO at 0.1 and 1 mg/kg, suggesting antiosteoporotic action. PRO at 1 mg/kg statistically increased histomorphometry indices of bone formation, whereas PRO at doses of 0.1, 1, and 10 mg/kg decreased those of bone resorption. Antiosteoporotic effect of PRO is attenuated at 10 mg/kg compared with 0.1 and 1 mg/kg. In addition, treatment with timolol, a nonselective beta-AR antagonist without membrane-stabilizing action, or butoxamine, a selective beta2-AR antagonist, at 1 mg/kg increased bone mass in SHR. These results suggested that treatment of SHR with beta-blockers at low dose improved bone loss and bone fragility. This antiosteoporotic effect of beta-blockers seems to be caused by the blocking action of beta2-AR, regardless of the membrane-stabilizing action.

Sato T, Arai M, Goto S, Togari A
J. Pharmacol. Exp. Ther. Jul 2010
PMID: 20404011 | Free Full Text

It is possible that a beta1 blocker, like Metoprolol, would not be effective.

Beta Blockers May Blunt Exercise Benefits

Abstract

β-Adrenergic receptor blockade blunts postexercise skeletal muscle mitochondrial protein synthesis rates in humans.

β-Adrenergic receptor (AR) signaling is a regulator of skeletal muscle protein synthesis and mitochondrial biogenesis in mice. We hypothesized that β-AR blockade blunts postexercise skeletal muscle mitochondrial protein synthesis rates in adult humans. Six healthy men (mean ± SD: 26 ± 6 yr old, 39.9 ± 4.9 ml·kg(-1)·min(-1) peak O(2) uptake, 26.7 ± 2.0 kg/m(2) body mass index) performed 1 h of stationary cycle ergometer exercise (60% peak O(2) uptake) during 1) β-AR blockade (intravenous propranolol) and 2) administration of saline (control). Skeletal muscle mitochondrial, myofibrillar, and sarcoplasmic protein synthesis rates were assessed using [(2)H(5)]phenylalanine incorporation into skeletal muscle proteins after exercise. The mRNA content of signals for mitochondrial biogenesis was determined using real-time PCR. β-AR blockade decreased mitochondrial (from 0.217 ± 0.076 to 0.135 ± 0.031%/h, P < 0.05), but not myofibrillar or sarcoplasmic, protein synthesis rates. Peroxisome proliferator-activated receptor-γ coactivator-1α mRNA was increased ∼2.5-fold (P < 0.05) at 5 h compared with 1 h postexercise but was not influenced by β-AR blockade. We conclude that decreased β-AR signaling during cycling can blunt the postexercise increase in mitochondrial protein synthesis rates without affecting mRNA content.

Robinson MM, Bell C, Peelor FF, Miller BF
Am. J. Physiol. Regul. Integr. Comp. Physiol. Aug 2011
PMID: 21613574 | Free Full Text

Given that increased muscle tends to increase bone, this is somewhat negative, even though there is some evidence that beta blockers plus exercise is additive for bone.