Tag Archives: negative

Review: Cyclists Have Low Bone Density

Abstract

Cycling and bone health: a systematic review.

Cycling is considered to be a highly beneficial sport for significantly enhancing cardiovascular fitness in individuals, yet studies show little or no corresponding improvements in bone mass.
A scientific literature search on studies discussing bone mass and bone metabolism in cyclists was performed to collect all relevant published material up to April 2012. Descriptive, cross-sectional, longitudinal and interventional studies were all reviewed. Inclusion criteria were met by 31 studies.
Heterogeneous studies in terms of gender, age, data source, group of comparison, cycling level or modality practiced among others factors showed minor but important differences in results. Despite some controversial results, it has been observed that adult road cyclists participating in regular training have low bone mineral density in key regions (for example, lumbar spine). Conversely, other types of cycling (such as mountain biking), or combination with other sports could reduce this unsafe effect. These results cannot yet be explained by differences in dietary patterns or endocrine factors.
From our comprehensive survey of the current available literature it can be concluded that road cycling does not appear to confer any significant osteogenic benefit. The cause of this may be related to spending long hours in a weight-supported position on the bike in combination with the necessary enforced recovery time that involves a large amount of time sitting or lying supine, especially at the competitive level.

Olmedillas H, González-Agüero A, Moreno LA, Casajus JA…
BMC Med 2012
PMID: 23256921 | Free Full Text

Curcumin Decreases Proliferation and Mineralization of Human Osteoblasts In Vitro

Abstract

Effects of curcumin on the proliferation and mineralization of human osteoblast-like cells: implications of nitric oxide.

Curcumin (diferuloylmethane) is found in the rhizomes of the turmeric plant (Curcuma longa L.) and has been used for centuries as a dietary spice and as a traditional Indian medicine used to treat different conditions. At the cellular level, curcumin modulates important molecular targets: transcription factors, enzymes, cell cycle proteins, cytokines, receptors and cell surface adhesion molecules. Because many of the curcumin targets mentioned above participate in the regulation of bone remodeling, curcumin may affect the skeletal system. Nitric oxide (NO) is a gaseous molecule generated from L-arginine during the catalization of nitric oxide synthase (NOS), and it plays crucial roles in catalization and in the nervous, cardiovascular and immune systems. Human osteoblasts have been shown to express NOS isoforms, and the exact mechanism(s) by which NO regulates bone formation remain unclear. Curcumin has been widely described to inhibit inducible nitric oxide synthase expression and nitric oxide production, at least in part via direct interference in NF-κB activation. In the present study, after exposure of human osteoblast-like cells (MG-63), we have observed that curcumin abrogated inducible NOS expression and decreased NO levels, inhibiting also cell prolifieration. This effect was prevented by the NO donor sodium nitroprusside. Under osteogenic conditions, curcumin also decreased the level of mineralization. Our results indicate that NO plays a role in the osteoblastic profile of MG-63 cells.

Moran JM, Roncero-Martin R, Rodriguez-Velasco FJ, Calderon-Garcia JF…
Int J Mol Sci 2012
PMID: 23443113 | Free Full Text

Curcumin Helps Kill Osteoblasts In Vitro

Abstract

Dosage effects of curcumin on cell death types in a human osteoblast cell line.

Curcumin, the yellow pigment of Curcuma longa, is known to have antioxidant and anti-inflammatory properties, as well as their ability to either induce or prevent cell apoptosis. However, the precise molecular mechanisms of these effects are unknown. Here, we demonstrate that curcumin can induce apoptotic changes, including JNK activation, caspase-3 activation, and cleavage of PARP and PAK2, at treatment concentrations lower than 25 microM in human osteoblast cells. In contrast, treatment with 50-200 microM of curcumin does not induce apoptosis, but rather triggers necrotic cell death in human osteoblasts. Using the cell permeable dye 2′,7′-dichlorofluorescin diacetate (DCF-DA) as an indicator of reactive oxygen species (ROS) generation, we found that while treatment with 12.5-25 microM curcumin directly increased intracellular oxidative stress, 50-200 microM curcumin had far less effect. Pretreatment of cells with N-acetyl cysteine or alpha-tocopherol, two well known ROS scavengers, attenuated the intracellular ROS levels increases and converted the apoptosis to necrosis induced by 12.5-25 microM curcumin. Moreover, we observed a dose-dependent decrease in intracellular ATP levels after treatment of osteoblast cells with curcumin and pretreatment of cells with antimycin or 2-deoxyglucose to cause ATP depletion significantly converted 12.5-25 microM curcumin-induced apoptosis to necrosis, indicating that ATP (a known mediator of apoptotic versus necrotic death) is most likely involved in the switching mechanism. Overall, our results signify that curcumin dosage treatment determines the possible effect on ROS generation, intracellular ATP levels, and cell apoptosis or necrosis in osteoblast cells.

Chan WH, Wu HY, Chang WH
Food Chem. Toxicol. Aug 2006
PMID: 16624471

Curcumin Decreases Bone Density in Rats

Abstract

Effects of curcumin on the skeletal system in rats.

There is increasing interest in the discovery of natural compounds that could favorably affect the skeletal system. Curcumin is a constituent of turmeric, a plant which has been used for centuries as a dietary spice and a traditional Indian medicine. Curcumin has been reported to affect differentiation, activity and the lifespan of osteoblasts and osteoclasts in vitro. The aim of the present study was to investigate the effects of curcumin on the skeletal system of rats in vivo. Curcumin (10 mg/kg, po daily) was administered for four weeks to normal (non-ovariectomized) and bilaterally ovariectomized (estrogen-deficient) three-month-old female Wistar Cmd:(WI)WU rats. Ovariectomy was performed seven days before the start of curcumin administration. Bone mass, mineral and calcium content, macrometric and histomorphometric parameters, as well as the mechanical properties of the bone, were examined. Serum total cholesterol and estradiol levels were also determined. In rats with normal estrogen levels, curcumin decreased serum estradiol level and slightly increased cancellous bone formation, along with decreased mineralization. Estrogen deficiency induced osteoporotic changes in the skeletal system of the ovariectomized control rats. In ovariectomized rats, curcumin decreased body mass gain and serum total cholesterol level, slightly improved some bone histomorphometric parameters impaired by estrogen deficiency, but did not improve bone mineralization or mechanical properties. In conclusion, the results of the present in vivo study in rats did not support the hypothesis that curcumin, at doses that are readily achievable through dietary intake, could be useful for the prevention or treatment of osteoporosis.

Folwarczna J, Zych M, Trzeciak HI
Pharmacol Rep
PMID: 21098873 | Free Full Text

Curcumin, Japanese Apricot, and Others, Effects on Osteoclasts in Mice In Vitro

Abstract

Screening of Korean medicinal plants for possible osteoclastogenesis effects in vitro.

Bone undergoes continuous remodeling through bone formation and resorption, and maintaining the balance for skeletal rigidity. Bone resorption and loss are generally attributed to osteoclasts. Differentiation of osteoclasts is regulated by receptor activator of nuclear factor NF-kB ligand (RANKL), a member of tumor necrosis factor family. When the balance is disturbed, pathological bone abnormality ensues. Through the screening of traditional Korean medicinal plants, the effective molecules for inhibition and stimulation of RANKL-induced osteoclast differentiation in mouse bone marrow macrophages were identified. Among 222 methanol extracts, of medicinal plants, 10 samples exhibited ability to induce osteoclast differentiation. These include Dryobalanops aromatica, Euphoria longana, Lithospermum erythrorhizon, Prunus mume, Prunus nakaii, and Polygonatum odoratum. In contrast, Ailanthus altissima, Curcuma longa, Solanum nigrum, Taraxacum platycarpa, Trichosanthes kirilowii, and Daphne genkwa showed inhibitory effects in RANKL-induced osteoclast differentiation.

Youn YN, Lim E, Lee N, Kim YS…
Genes Nutr Feb 2008
PMID: 18850234 | Free Full Text

Curcumin Inhibits Rat Osteoblast Cells In Vitro

Abstract

Curcumin inhibits the proliferation and mineralization of cultured osteoblasts.

The effects of curcumin, which is an important constituent of rhizomes of the plant Curcuma longa Linn, on the metabolism of osteoblasts were examined in cultures of rat calvarial osteoblastic cells (ROB cells). The proliferation of cells was markedly inhibited upon exposure of cells to curcumin at 5×10(-6) to 1×10(-5) M. Curcumin at 1×10(-5) M did not induce apoptosis in ROB cells but arrested cells at the G1 phase of the cell cycle. In addition, curcumin stimulated the expression of mRNA for p21(WAF1/CIP1), which inhibits the activity of cyclin-dependent kinases, and inhibited the phosphorylation of histone H1. Furthermore, curcumin reduced the rate of deposition of calcium and the formation of mineralized nodules. Our results indicate that curcumin might inhibit the proliferation and mineralization of osteoblastic cells through the expression of p21(WAF1/CIP1).

Notoya M, Nishimura H, Woo JT, Nagai K…
Eur. J. Pharmacol. Mar 2006
PMID: 16476424

Omega-3 Inhibits Osteoclasts In Vitro

Abstract

The omega-6 arachidonic fatty acid, but not the omega-3 fatty acids, inhibits osteoblastogenesis and induces adipogenesis of human mesenchymal stem cells: potential implication in osteoporosis.

Arachidonic fatty acid (AA) induces adipogenesis in human mesenchymal stem cells cultures, and high concentrations inhibit osteoblastogenesis; whereas eicosapentaenoic and docosahexaenoic fatty acids do not induce adipogenesis and do not inhibit osteoblastogenesis. In mesenchymal stem cells, omega-6 arachidonic polyunsaturated fatty acid promotes the differentiation of adipocytes and inhibits the osteoblast differentiation. While omega-3 fatty acids do not affect the adipogenic differentiation their effects on osteoblastogenesis are less relevant. An increased ratio of omega-3/omega-6 fatty acid consumption can prevent bone mass loss.
Consumption of omega-3 may protect against osteoporosis since they may inhibit osteoclastogenesis. However, with aging, MSC in bone marrow are increasingly differentiated into adipocytes, reducing the number of osteoblasts. Products derived from omega-6 and omega-3 metabolism may affect MSC differentiation into osteoblasts and adipocytes.
Human MSC have been differentiated into osteoblasts or adipocytes in the presence of omega-6 (AA), or omega-3 (DHA and EPA), and osteoblastic and adipocytic markers have been analyzed.
AA decreases the expression of osteogenic markers and the osteoprotegerin/receptor activator of nuclear factor kappa β ligand gene expression ratio (opg/rankl). High concentrations of AA inhibit the mineralization and cause the appearance of adipocytes in MSC differentiating into osteoblasts to a higher extent than DHA or EPA. In MSC differentiated into adipocytes, AA increases adipogenesis, while DHA and EPA do not affect it. AA caused the appearance of adipocytes in undifferentiated MSC. The lipoxygenase gene (alox15b) is induced by omega-3 in MSC induced to osteoblasts, and by omega-6 in MSC induced to adipocytes.
An increase in the intake of omega-3 respect to omega-6 may provide protection against the loss of bone mass, since omega-6 favors the osteoclastic activity by diminishing the opg/rankl gene expression in osteoblasts and promotes MSC differentiation into adipocytes, thus diminishing the production of osteoblasts.

Casado-Díaz A, Santiago-Mora R, Dorado G, Quesada-Gómez JM
Osteoporos Int May 2013
PMID: 23104199

Fish Oil, EPA + DHA Correlated with Bone Mass in Postmenopausal Korean Women

Abstract

Positive correlation between erythrocyte levels of n-3 polyunsaturated fatty acids and bone mass in postmenopausal Korean women with osteoporosis.

Osteoporosis, a major health problem among postmenopausal women, is influenced by dietary factors. The purpose of the present study was to evaluate the hypothesis that erythrocyte levels of n-3 polyunsaturated fatty acid (PUFA) and the dietary intake of fish are associated with risk of osteoporosis and correlate with bone mass in postmenopausal Korean women with the disease.
Fifty cases and 100 controls were recruited. Osteoporosis was defined according to the International Society for Clinical Densitometry guideline as a score lower than -2.5 SD below the T-score for lumbar vertebrae L₁-L₄, femoral neck or femoral total.
The T-score of the femoral neck was positively correlated with erythrocyte levels of n-3 PUFA, eicosapentaenoic acid (EPA), docosahexaenoic acid (DHA) and the intake of fish, and was negatively correlated with the ratio of n-6/n-3 PUFA after adjusting for age, years after menopause and height. In addition, the risk of osteoporosis was positively associated with erythrocyte levels of saturated fatty acids but negatively associated with EPA + DHA.
Erythrocyte levels of n-3 PUFA and the intake of fish were positively correlated with bone mass. In particular, erythrocyte levels of EPA + DHA reduced the risk of osteoporosis in postmenopausal Korean women.

Moon HJ, Kim TH, Byun DW, Park Y
Ann. Nutr. Metab. 2012
PMID: 22507833

DHA prevents, and GLA Exacerbates, Bone Loss in Ovariectomized Rats

Abstract

Specific effects of gamma-linolenic, eicosapentaenoic, and docosahexaenoic ethyl esters on bone post-ovariectomy in rats.

Long chain polyunsaturated fatty acids (LCPUFAs) are involved in the regulation of bone metabolism. Increased dietary consumption of n-3, and possibly some n-6, LCPUFAs may limit postmenopausal bone loss. The aim of this study was to determine the effects on bone of specific fatty acids within the n-3 and n-6 LCPUFA families in ovariectomized (OVX) rats. Rats were OVX or sham-operated and fed either a control diet (OVX and sham) or a diet supplemented with 0.5 g/kg body weight/day of gamma-linolenic (GLA), eicosapentaenoic (EPA), docosahexaenoic (DHA) ethyl esters or a mixture of all three (MIX) for 16 weeks. Bone mineral content (BMC), area, and density and plasma concentrations of insulin-like growth factor-I, vitamin D, selected biochemical markers of bone metabolism, and parathyroid hormone (PTH) were determined. The OVX-induced decrease in lumbar spine BMC was significantly attenuated by DHA but not by EPA or GLA supplementation or supplementation with a mixture of all three LCPUFAs. Endosteal circumferences of tibiae were significantly greater in DHA and EPA compared to OVX. Plasma C-terminal telopeptide of type I collagen and osteocalcin concentrations were not significantly different in the DHA group compared to OVX. Femur BMC decreased by a significantly greater amount in GLA than OVX, and final plasma PTH concentrations were significantly higher in GLA compared to all other groups. In conclusion, DHA ameliorated OVX-induced bone mineral loss. GLA exacerbated post-OVX bone mineral loss, possibly as a result of PTH-induced bone catabolism.

Poulsen RC, Firth EC, Rogers CW, Moughan PJ…
Calcif. Tissue Int. Dec 2007
PMID: 18008020

High Cortisol is an Independent Predictor of Fractures in Older People

Abstract

The relation between cortisol excretion and fractures in healthy older people: results from the MacArthur studies-Mac.

In persons with depression, higher urinary cortisol is associated with lower bone mineral density.
To examine the relation between urinary free cortisol (UFC) and fractures.
Community-based samples from Durham, NC, East Boston, MA, and New Haven, CT.
684 men and women, aged 70 to 79 at baseline, who were part of the MacArthur Study of Successful Aging.
Cohort study. Participants with previous history of fractures at baseline were excluded.
The primary exposure variable was overnight (8:00 p.m. to 8:00 a.m.) UFC (microg/g creatinine) at baseline (1988). Outcomes were self-reported hip, arm, spine, wrist, or other fracture during the follow-up period (1988-1995). Covariates were baseline age, gender, race, body mass index, current physical activity, lower extremity strength, depression subscale of the Hopkins Symptom Checklist, and current use of cigarettes and alcohol.
Logistic regression was used to predict the occurrence of incident fractures (1988-1995) as a function of quartiles of baseline UFC. Models were adjusted for age, gender, and race and were also multiply adjusted for the remaining covariates listed above. Gender-stratified models and models that excluded corticosteroid users were also run.
In multiply adjusted models, higher baseline levels of UFC were significantly associated with incident fractures. Odds of fracture (95% Confidence Intervals) for increasing quartiles of baseline UFC, multiply adjusted, were: 2.28 (.91, 5.77); 3.40 (1.33, 8.69); 5.38 (1.68, 17.21). Results were not materially influenced by exclusion of persons using corticosteroids.
Higher baseline UFC is an independent predictor of future fracture.

Greendale GA, Unger JB, Rowe JW, Seeman TE
J Am Geriatr Soc Jul 1999
PMID: 10404922