Tag Archives: quote

Lipids, Obesity, and Bone Density

Abstract

Lipid profile, obesity and bone mineral density: the Hertfordshire Cohort Study.

Body mass index (BMI) and bone mineral density (BMD) are positively correlated in several studies, but few data relate bone density, lipid profile and anthropometric measures.
To investigate these relationships in a large, well-characterized cohort of men and women (The Hertfordshire Cohort Study).Men (n = 465) and women (n = 448) from Hertfordshire, UK were recruited. Information was available on demographic and lifestyle factors, anthropometric measurements, body fat percentage, fasting triglycerides, cholesterol (total, HDL, LDL), apolipoprotein (a) and apolipoprotein (b); bone mineral density (BMD) was recorded at the lumbar spine and total femur.
BMD at the lumbar spine (males r = 0.15, p = 0.001; females r = 0.14, p = 0.003) and total femoral region (males r = 0.18, p = 0.0001; females r = 0.16, p = 0.0008) was related to serum triglyceride level, even after adjustment for waist-hip ratio, age, social class and lifestyle factors, but not if body fat percentage was substituted for waist-hip ratio in the regression model. Fasting HDL cholesterol level was related to lumbar spine BMD in women (r = -0.15, p = 0.001) and total femoral BMD in both sexes (males r = -0.15, p = 0.002; females r = -0.23, p < 0.0001); these relationships were also attenuated by adjustment for body fat percentage but not waist-hip ratio. No relationships were seen between total or LDL cholesterol with BMD.
In this cohort, relationships between lipid profile and BMD were robust to adjustment for one measure of central obesity (waist-hip ratio), but not total body fat. This broadly supports the idea that adiposity may confound the relationship between lipids and bone mass.

Dennison EM, Syddall HE, Aihie Sayer A, Martin HJ…
QJM May 2007
PMID: 17449479 | Free Full Text

A number of studies have suggested a positive relationship between BMD and triglyceride level, in concordance with our own findings [10,13], while the literature concerning relationships between HDL cholesterol levels and BMD is conflicting [12, 13,15,15, 18,19]. While D’Amelio et al [12] found an inverse relationship similar to our own results, Yamaguchi et al [14] described a positive relationship, and Cui et al [13] and Poli et al [15] described no relationship.

Cholesterol Indirectly Linked to Osteoporosis

Abstract

Links between cardiovascular disease and osteoporosis in postmenopausal women: serum lipids or atherosclerosis per se?

Epidemiological observations suggest links between osteoporosis and risk of acute cardiovascular events and vice versa. Whether the two clinical conditions are linked by common pathogenic factors or atherosclerosis per se remains incompletely understood. We investigated whether serum lipids and polymorphism in the ApoE gene modifying serum lipids could be a biological linkage.
This was an observational study including 1176 elderly women 60-85 years old. Women were genotyped for epsilon (epsilon) allelic variants of the ApoE gene, and data concerning serum lipids (total cholesterol, triglycerides, HDL-C, LDL-C, apoA1, ApoB, Lp(a)), hip and spine BMD, aorta calcification (AC), radiographic vertebral fracture and self-reported wrist and hip fractures, cardiovascular events together with a wide array of demographic and lifestyle characteristics were collected.
Presence of the ApoE epsilon 4 allele had a significant impact on serum lipid profile, yet no association with spine/hip BMD or AC could be established. In multiple regression models, apoA1 was a significant independent contributor to the variation in AC. However, none of the lipid components were independent contributors to the variation in spine or hip BMD. When comparing the women with or without vertebral fractures, serum triglycerides showed significant differences. This finding was however not applicable to hip or wrist fractures. After adjustment for age, severe AC score (>or=6) and/or manifest cardiovascular disease increased the risk of hip but not vertebral or wrist fractures.
The contribution of serum lipids to the modulators of BMD does not seem to be direct but rather indirect via promotion of atherosclerosis, which in turn can affect bone metabolism locally, especially when skeletal sites supplied by end-arteries are concerned. Further studies are needed to explore the genetic or environmental risk factors underlying the association of low triglyceride levels to vertebral fractures.

Bagger YZ, Rasmussen HB, Alexandersen P, Werge T…
Osteoporos Int Apr 2007
PMID: 17109061 | Free Full Text

In summary, the results of the present observational study provide further evidence for the independent association of peripheral vascular disease with osteoporosis in the proximal femur. Since the association of lipids and lipoproteins to BMD and non-vertebral fractures is not independent of the severity of AC, it seems unlikely that these metabolites exert direct and clinically significant effects on bone turnover in postmenopausal women. Their contribution is via promotion of atherogenesis, in which regard ApoA1 levels seem to take a leading role. The remaining issue to be clarified is which genetic or environmental factors underlie the association of low triglycerides levels to vertebral fractures.

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].

 

Review: Melatonin Effects on Bones and Teeth

Abstract

Melatonin effects on hard tissues: bone and tooth.

Melatonin is an endogenous hormone rhythmically produced in the pineal gland under the control of the suprachiasmatic nucleus (SCN) and the light/dark cycle. This indole plays an important role in many physiological processes including circadian entrainment, blood pressure regulation, seasonal reproduction, ovarian physiology, immune function, etc. Recently, the investigation and applications of melatonin in the hard tissues bone and tooth have received great attention. Melatonin has been investigated relative to bone remolding, osteoporosis, osseointegration of dental implants and dentine formation. In the present review, we discuss the large body of published evidence and review data of melatonin effects on hard tissues, specifically, bone and tooth.

Liu J, Huang F, He HW
Int J Mol Sci 2013
PMID: 23665905 | Free Full Text

From the full text:

Bone remolding processes are mediated by hormones, cytokines, growth factors and other molecules [22]. One of the hormones modulating bone formation and resorption is melatonin. It is hypothesized that melatonin, perhaps through three principle actions, modulates bone metabolism. Firstly, melatonin directly affects the actions of osteoblast and osteoclast. Numerous studies documented that melatonin increases pre-osteoblast/osteoblast/osteoblast-like cell proliferation, promotes the expression of type I collagen and bone marker proteins (e.g., alkaline phosphatase, osteopontin, bone sialoprotein and osteocalcin), and stimulates the formation of a mineralized matrix in these cells [23–27]. Besides, melatonin inhibits the differentiation of osteoclasts via decreases in the expression of RANK mRNA and increases in both the mRNA and protein levels of osteo-protegerin [28,29]. Secondly, melatonin indirectly regulates bone metabolism through the interaction with systemic hormones (e.g., PTH, calcitonin, and estrogen) or other moleculars. Ladizesky et al. [15] revealed that estradiol treatment could prolong the effect of melatonin to augment bone remodeling in ovariectomized rats; it indicates that appropriate circulating estradiol levels might be needed for melatonin effects on bone. Thirdly, osteoclasts generate high levels of superoxide anions during bone resorption that contribute to the degradative process. Melatonin is a significant free-radical scavenger and antioxidant. It can clear up the free radicals generated by osteoclast during the bone resorption process and protect bone cells from oxidative attacks [18,30,31].

And:

Some studies revealed the possible etiologic role of melatonin in osteoporosis. Nocturnal plasma melatonin levels decline with age. It has also been reported that melatonin secretion decreases sharply during menopause, which is associated with post-menopausal osteoporosis [46,47]. A correlation between decreased plasma melatonin levels and an increased incidence of bone deterioration as seen in post-menopausal women has been examined [48]. Furthermore, Ostrowska et al. [49] found that a pinealectomy in rats promotes the induction of bone metabolism biomarkers. In addition, Feskanich et al. [50] reported that twenty or more years of nightshift work significantly increased the risk of wrist and hip fractures in post-menopausal women. Nightshift work leads to disturbances of melatonin secretion as well as severe circadian rhythm disruption. These observations taken together suggest that melatonin may be involved in the pathogenesis of osteoporosis.

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.

Review: Malnutrition Associated with Decreased Bone Mass

Abstract

Assessment and management of nutrition in older people and its importance to health.

Nutrition is an important element of health in the older population and affects the aging process. The prevalence of malnutrition is increasing in this population and is associated with a decline in: functional status, impaired muscle function, decreased bone mass, immune dysfunction, anemia, reduced cognitive function, poor wound healing, delayed recovery from surgery, higher hospital readmission rates, and mortality. Older people often have reduced appetite and energy expenditure, which, coupled with a decline in biological and physiological functions such as reduced lean body mass, changes in cytokine and hormonal level, and changes in fluid electrolyte regulation, delay gastric emptying and diminish senses of smell and taste. In addition pathologic changes of aging such as chronic diseases and psychological illness all play a role in the complex etiology of malnutrition in older people. Nutritional assessment is important to identify and treat patients at risk, the Malnutrition Universal Screening Tool being commonly used in clinical practice. Management requires a holistic approach, and underlying causes such as chronic illness, depression, medication and social isolation must be treated. Patients with physical or cognitive impairment require special care and attention. Oral supplements or enteral feeding should be considered in patients at high risk or in patients unable to meet daily requirements.

Ahmed T, Haboubi N
Clin Interv Aging 2010
PMID: 20711440 | Free Full Text

The full study also has this comment about protein:

Concerns about the detrimental affects of increased protein intake on bone health, renal function, neurological function and cardiovascular function are generally unfounded. It has been recommended that the RDA intake of 1.5 g protein/kg body weight per day is a reasonable intake in older people to optimize protein intake in terms of health and function.

GH Therapy Cuts Number With Osteopenia in Half in GH-Deficient Adults

Abstract

Effects of 42 months of GH treatment on bone mineral density and bone turnover in GH-deficient adults.

To study the effects of GH treatment for up to 42 months on bone mineral density (BMD) and bone turnover.
BMD with dual energy X-ray absorptiometry, serum type I procollagen carboxy-terminal propeptide (PICP), serum type I collagen carboxy-terminal telopeptide (ICTP) and serum IGF-I were assessed in 71 adults with GH deficiency. There were 44 men and 27 women, aged 20 to 59 (median 43) years. Thirty-two patients completed 36 months and 20 patients 42 months of treatment.
The BMD increased for up to 30-36 months and plateaued thereafter. In the whole study group, the maximum increase of BMD was 5.0% in the lumbar spine (P<0. 001), 5.9% (P<0.01) in the femoral neck, 4.9% (NS, P>0.05) in the Ward’s triangle and 8.2% (P<0.001) in the trochanter area. The serum concentrations of PICP (202.6+/-11.5 vs 116.3+/-5.4 microg/l; mean+/-s.e.m.) and ICTP (10.5+/-0.6 vs 4.4+/-0.3 microg/l) doubled (P<0.001) during the first 6 months of GH treatment but returned to baseline by the end of the study (130.0+/-10.4 and 5.6+/-0.7 microg/l respectively), despite constantly elevated serum IGF-I levels (39. 6+/-4.1 nmol/l at 42 months vs 11.9+/-0.9 nmol/l at baseline; P<0.001). The responses to GH treatment of serum IGF-I, PICP, ICTP (P<0.001 for all; ANOVA) and of the BMD in the lumbar spine (P<0.05), in the femoral neck and the trochanter (P<0.001 for both) were more marked in men than in women. At the end of the study the BMD had increased at the four measurement sites by 5.7-10.6% (P<0.01-0.001) in patients with at least osteopenia at baseline and by 0.1-5.3% (NS P<0.05) in those with normal bone status (P<0.001 for differences between groups; ANOVA). Among patients who completed 36-42 months of treatment, the number of those with at least osteopenia was reduced to more than a half. The response of BMD to GH treatment was more marked in young than in old patients at three measurement sites (P<0. 05-<0.001; ANOVA). In the multiple regression analysis the gender and the pretreatment bone mass appeared to be independent predictors of three measurement sites, whereas the age independently determined only the vertebral BMD.
GH treatment in GH-deficient adults increased BMD for up to 30-36 months, with a plateau thereafter. Concurrently with the plateau in BMD the bone turnover rate normalized. From the skeletal point of view GH-deficient patients exhibiting osteopenia or osteoporosis should be considered as candidates for GH supplementation of at least 3-4 years.

Välimäki MJ, Salmela PI, Salmi J, Viikari J…
Eur. J. Endocrinol. Jun 1999
PMID: 10377504 | Free Full Text

From the full text:

Moreover, in more than a half of the patients the criteria of osteopenia disappeared or there was an improvement of the bone state from osteoporosis to osteopenia.

Cissus Inhibits Bone Loss in Mice

Abstract

Inhibition of Bone Loss by Cissus quadrangularis in Mice: A Preliminary Report.

Women drastically loose bone during and after menopause leading to osteoporosis, a disease characterized by low bone mass increasing the risk of fractures with minor trauma. Existing therapies mainly reduce bone resorption, however, all existing drugs have severe side effects. Recently, the focus is to identify alternative medicines that can prevent and treat osteoporosis with minimal or no side effects. We used Cissus quadrangularis (CQ), a medicinal herb, to determine its effects on bone loss after ovariectomy in C57BL/6 mice. Two-month old mice were either sham operated or ovariectomized and fed CQ diet. After eleven weeks, mice were sacrificed and the long bones scanned using pQCT and μCT. In the distal femoral metaphysis, femoral diaphysis, and proximal tibia, control mice had decreased cancellous and cortical bone, while CQ-fed mice showed no significant differences in the trabecular number, thickness, and connectivity density, between Sham and OVX mice, except for cortical bone mineral content in the proximal tibia. There were no changes in the bone at the tibio-fibular junction between groups. We conclude that CQ effectively inhibited bone loss in the cancellous and cortical bones of femur and proximal tibia in these mice.

Banu J, Varela E, Bahadur AN, Soomro R…
J Osteoporos 2012
PMID: 22779034 | Free Full Text

The full study is available using the link above.

CQ may primarily attenuate bone resorption in OVX mice through the downregulation of proinflammatory cytokines but it does not rule out the possibility that it may also act through other pathways. There are reports that CQ also enhances bone mineralization by accumulating mucopolysaccharides at the site of bone formation [The following popper user interface control may not be accessible. Tab to the next button to revert the control to an accessible version.Destroy user interface control14]. Moreover, CQ is reported to increase calcium uptake and mechanical properties of bone in rats [The following popper user interface control may not be accessible. Tab to the next button to revert the control to an accessible version.Destroy user interface control15]. Phytochemical analyses of CQ show the presence of high levels of calcium, vitamin C, β-carotene [The following popper user interface control may not be accessible. Tab to the next button to revert the control to an accessible version.Destroy user interface control38, The following popper user interface control may not be accessible. Tab to the next button to revert the control to an accessible version.Destroy user interface control39], and flavanoids [The following popper user interface control may not be accessible. Tab to the next button to revert the control to an accessible version.Destroy user interface control25] some of these substances have established beneficial properties on bone. In vitro studies have shown that ethanolic extracts of CQ increased mRNA and proteins related to the bone formation pathway and IGF-I, IGF-II, and IGF binding protein [The following popper user interface control may not be accessible. Tab to the next button to revert the control to an accessible version.Destroy user interface control40, The following popper user interface control may not be accessible. Tab to the next button to revert the control to an accessible version.Destroy user interface control41]. More investigations are necessary to elucidate the mechanism(s) by which CQ influences bone metabolism. However, it is very encouraging to note that in studies done with CQ using very high doses (5000mg/kgbodyweight) [The following popper user interface control may not be accessible. Tab to the next button to revert the control to an accessible version.Destroy user interface control9] have not reported any toxic side effects. In the present study, we have used only 500mg/kgbodyweight of CQ and observed that the liver, spleen, and kidney weights were not altered significantly, suggesting that CQ may not have any severe side-effects….

We conclude that CQ can reduce OVX induced bone loss and it does this in the long bones in a site-specific manner with more effects on the cancellous bone of femur followed by tibia. CQ probably reduces bone resorption primarily by downregulating proinflammatory cytokines that are often increased after ovariectomy. The beneficial effects of CQ are probably due to the flavanoids present.

 

No Bone Benefit in Young Healthy Women from 3 Months Resistance Training or Protein

Abstract

Effects of resistance training and protein supplementation on bone turnover in young adult women.

The strength of aging bone depends on the balance between the resorption and formation phases of the remodeling process. The purpose of this study was to examine the interaction of two factors with the potential to exert opposing influences on bone turnover, resistance exercise training and high dietary protein intake. It was hypothesized that resistance training by young, healthy, untrained women with protein intakes near recommended levels (0.8 g.kg(-1).d(-1)) would promote bone formation and/or inhibit bone resorption, and that subsequent supplementation to provide 2.4 g protein.kg(-1).d(-1) would reverse these effects.
Bone formation was assessed with serum bone-specific alkaline phosphatase (BAP) and osteocalcin (OC), and bone resorption with urinary calcium and deoxypyridinoline (DPD). Biochemical, strength, anthropometric, dietary, and physical activity data were obtained from 24 healthy, untrained, eumenorrheic women (18-29 y) at baseline, after eight weeks of resistance training (3 d.wk(-1), approximately 1 hr.d(-1); 3 sets, 6-10 repetitions, 13 exercises, 75-85% maximum voluntary contraction), and after 12 weeks of resistance training and 10 days of protein/placebo supplementation. Subjects were randomized (double-blind) to either a high protein (HP) or training control (TC) group and, during the final 10 days, consumed either enough purified whey protein to bring daily protein intake to 2.4 g.kg(-1).d(-1), or an equivalent dose of isoenergetic, carbohydrate placebo.
Strength, lean tissue mass, and DPD increased significantly in both groups over time, while percent body fat and BAP decreased (repeated measures ANOVA, p < or = 0.05, Bonferroni correction). No significant changes were observed for serum OC or urinary calcium, and no significant group (TC, HP) x time (baseline, week 8, week 12) interactions emerged for any of the biochemical measures.
(1) Twelve weeks of high-intensity resistance training did not appear to enhance bone formation or inhibit bone resorption in young adult women, as assessed by biochemical markers of bone metabolism. (2) Subsequent maintenance of a high protein intake for 10 days in these regularly-training, calcium-replete women also showed no effects on bone metabolism.

Mullins NM, Sinning WE
Nutr Metab (Lond) Aug 2005
PMID: 16098231 | Free Full Text

The results are surprising. The full study is available using the link above. The authors note that these women were taking calcium supplements.

…to exclude the potential effects of calcium deficiency, each subject was given a supply of calcium supplements … to begin consuming for the duration of the study. Each was instructed to carry the calcium tablets in her purse or backpack, and was regularly reminded to consume one 500-mg tablet, twice per day.

There may not have been much more bone enhancement to gain.

…the subjects were healthy, eumenorrheic, calcium-replete women, regularly participating in high-intensity exercise.

They measured alkaline phosphatase, serum osteocalcin, urinary calcium. and urinary deoxypyridinoline.

It is possible that other biomarkers may have produced different results, and that, given a longer time frame, bone densitometry could detect osteogenic effects.

 

Chocolate Bad for Bones

Abstract

Chocolate consumption and bone density in older women.

Nutrition is important for the development and maintenance of bone structure and for the prevention of osteoporosis and fracture. The relation of chocolate intake with bone has yet to be investigated.
We investigated the relation of chocolate consumption with measurements of whole-body and regional bone density and strength.
Randomly selected women aged 70-85 y (n=1460) were recruited from the general population to a randomized controlled trial of calcium supplementation and fracture risk. We present here a cross-sectional analysis of 1001 of these women. Bone density and strength were measured with the use of dual-energy X-ray absorptiometry, peripheral quantitative computed tomography, and quantitative ultrasonography. Frequency of chocolate intake was assessed with the use of a questionnaire and condensed into 3 categories: or=1 time/d.
Higher frequency of chocolate consumption was linearly related to lower bone density and strength (P<0.05). Daily (>or=1 times/d) consumption of chocolate, in comparison to Older women who consume chocolate daily had lower bone density and strength. Additional cross-sectional and longitudinal studies are needed to confirm these observations. Confirmation of these findings could have important implications for prevention of osteoporotic fracture.

Hodgson JM, Devine A, Burke V, Dick IM…
Am. J. Clin. Nutr. Jan 2008
PMID: 18175753 | Free Full Text

This is disappointing. Cocoa is normally so healthy. My first thought was that they may be seeing the effects of sugar. Reading the full study, which is available for free using the link above, the authors made these comments:

Chocolate is usually also rich in sugar and contains the methylxanthines, theobromine and caffeine (27), and oxalate (11, 12)….

Oxalate is a potent inhibitor of calcium absorption (13). Furthermore, a single 100-g dose of dark chocolate was found to increase calcium excretion by 147% (14). The basis for this is not clear, but it is likely to include an effect of sugar to increase urinary calcium excretion (14, 15), dependent in part on an increase in plasma insulin that itself stimulates calciuria (29).

I wonder what would happen if you consumed a very dark chocolate (so very low in sugar) and supplemented calcium and vitamin D? The idea being that the very dark chocolate would avoid most of the sugar, and the calcium and vitamin D would hopefully overcome the reduced calcium absorption.