Tag Archives: human

High Cholesterol May Cause Osteoporosis Long-Term

Abstract

High serum total cholesterol is a long-term cause of osteoporotic fracture.

Risk factors for osteoporotic fractures were evaluated in 1,396 men and women for a period of 20 years. Serum total cholesterol was found to be an independent osteoporotic fracture risk factor whose predictive power improves with time.
The purpose of this study was to evaluate long-term risk factors for osteoporotic fracture.
A population random sample of men and women aged 25-64 years (the Gothenburg WHO MONICA project, N = 1,396, 53% women) was studied prospectively. The 1985 baseline examination recorded physical activity at work and during leisure time, psychological stress, smoking habits, coffee consumption, BMI, waist/hip ratio, blood pressure, total, HDL and LDL cholesterol, triglycerides, and fibrinogen. Osteoporotic fractures over a period of 20 years were retrieved from the Gothenburg hospital registers. Poisson regression was used to analyze the predictive power for osteoporotic fracture of each risk factor.
A total number of 258 osteoporotic fractures occurred in 143 participants (10.2%). As expected, we found that previous fracture, smoking, coffee consumption, and lower BMI each increase the risk for osteoporotic fracture independently of age and sex. More unexpectedly, we found that the gradient of risk of serum total cholesterol to predict osteoporotic fracture significantly increases over time (p = 0.0377).
Serum total cholesterol is an independent osteoporotic fracture risk factor whose predictive power improves with time. High serum total cholesterol is a long-term cause of osteoporotic fracture.

Trimpou P, Odén A, Simonsson T, Wilhelmsen L…
Osteoporos Int May 2011
PMID: 20821192

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.

Low LDL Associated with Fractures in Hyperparathyroidism

Abstract

Low density lipoprotein-cholesterol levels affect vertebral fracture risk in female patients with primary hyperparathyroidism.

Although increased arterial sclerosis and dyslipidemia were observed in primary hyperparathyroidism (pHPT) patients in previous studies, it still remains unclear about the relationships between lipid and bone metabolism in pHPT patients, especially about fracture risk. The present study was performed to examine the relationships between lipid metabolism parameters including body composition and bone metabolism in 116 female patients with pHPT and 116 age-matched control subjects. Bone mineral density (BMD) and body composition were measured by dual-energy x-ray absorptiometry. Serum low density lipoprotein (LDL)-cholesterol (Chol) levels were negatively related to only z-score of BMD at femoral neck and serum creatinine levels. Serum levels of LDL-Chol were significantly lower in the group with vertebral fractures in pHPT patients, although body composition parameters were not significantly different. In univariate logistic regression analyses, age, height, BMD at lumbar spine and radius, serum levels of creatinine, total-Chol and LDL-Chol were significantly selected as a predictor of vertebral fractures. LDL-Chol was related to vertebral fractures independently of the other parameters. In conclusion, the present study demonstrated that lower serum LDL-Chol levels were related to vertebral fracture risk independent of renal function, age, body size, bone metabolism parameters and the severity of the disease in pHPT women.

Kaji H, Hisa I, Inoue Y, Sugimoto T
Exp. Clin. Endocrinol. Diabetes Jun 2010
PMID: 19609845

LDL, HDL, and Triglyceride Correlations with Bone Density in Postmenopausal Women

Abstract

Plasma lipids and osteoporosis in postmenopausal women.

Many clinical studies have shown that osteoporosis is associated with atherosclerosis and cardiovascular death. Although both high plasma levels of low density lipoprotein cholesterol (LDL-C) and low plasma levels of high density lipoprotein cholesterol (HDL-C) are known to be risk factors for atherosclerosis, it is unclear whether such lipid derangements are also associated with the pathogenesis of osteoporosis. In this study, we evaluated the relationships between plasma levels of total C, LDL-C, HDL-C, or triglyceride (TG) versus bone mineral density (BMD) at the lumbar spine, femoral neck, radius, or total body as well as the presence of vertebral fractures in 214 Japanese postmenopausal women (age range, 47-86 years, mean 62.7). Multiple regression analysis was performed between BMD at each skeletal site versus each lipid level adjusted for age, years after menopause, body mass index (BMI), and %fat. Plasma LDL-C levels were significantly and inversely correlated with the absolute values of both one-third radial (1/3R) and distal radial (UDR) BMD (p<0.01), and tended to be inversely correlated with the absolute values of L-BMD (p=0.051). In contrast, plasma HDL-C levels were significantly and positively correlated with the absolute values of L, 1/3R and UDR BMD (p<0.05). On the other hand, plasma TG levels were significantly lower in women with vertebral fractures than in those without fractures (97.0+/-36.5 vs. 126.4+/-65.8 mg/dl, mean+/-SD, p<0.05). When multivariate logistic regression analysis was performed with the presence of vertebral fractures as a dependent variable and each lipid level adjusted for age, years after menopause, BMI, and %fat as independent variables, TG alone was selected as an index affecting the presence of vertebral fractures (odds ratio: 0.51, 95% confidential interval: 0.29-0.89 per SD increase, p<0.05). Our study showed that plasma LDL-C and HDL-C levels were inversely and positively correlated with both R- and L-BMD values, respectively, while low plasma TG levels were associated with the presence of vertebral fractures in postmenopausal women. Thus, plasma lipids might be related to bone mass and bone fragility, and might be the common factor underlying both osteoporosis and atherosclerosis.

Yamaguchi T, Sugimoto T, Yano S, Yamauchi M…
Endocr. J. Apr 2002
PMID: 12081241 | Free Full Text

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

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.

Tea Protects Bone in Older Women

Abstract

Tea drinking is associated with benefits on bone density in older women.

Impaired hip structure assessed by dual-energy X-ray absorptiometry (DXA) areal bone mineral density (aBMD) is an independent predictor for osteoporotic hip fracture. Some studies suggest that tea intake may protect against bone loss.
Using both cross-sectional and longitudinal study designs, we examined the relation of tea consumption with hip structure. Randomly selected women (n = 1500) aged 70-85 y participated in a 5-y prospective trial to evaluate whether oral calcium supplements prevent osteoporotic fractures. aBMD at the hip was measured at years 1 and 5 with DXA. A cross-sectional analysis of 1027 of these women at 5 y assessed the relation of usual tea intake, measured by using a questionnaire, with aBMD. A prospective analysis of 164 women assessed the relation of tea intake at baseline, measured by using a 24-h dietary recall, with change in aBMD from years 1 to 5.
In the cross-sectional analysis, total hip aBMD was 2.8% greater in tea drinkers (x: 806; 95% CI: 797, 815 mg/cm(2)) than in non-tea drinkers (784; 764, 803 mg/cm(2)) (P < 0.05). In the prospective analysis over 4 y, tea drinkers lost an average of 1.6% of their total hip aBMD (-32; -45, -19 mg/cm(2)), but non-tea drinkers lost 4.0% (-13; -20, -5 mg/cm(2)) (P < 0.05). Adjustment for covariates did not influence the interpretation of results.
Tea drinking is associated with preservation of hip structure in elderly women. This finding provides further evidence of the beneficial effects of tea consumption on the skeleton.

Devine A, Hodgson JM, Dick IM, Prince RL
Am. J. Clin. Nutr. Oct 2007
PMID: 17921409 | Free Full Text

Cola Associated with Low Bone Density in Older Women

Abstract

Colas, but not other carbonated beverages, are associated with low bone mineral density in older women: The Framingham Osteoporosis Study.

Soft drink consumption may have adverse effects on bone mineral density (BMD), but studies have shown mixed results. In addition to displacing healthier beverages, colas contain caffeine and phosphoric acid (H3PO4), which may adversely affect bone.
We hypothesized that consumption of cola is associated with lower BMD. BMD was measured at the spine and 3 hip sites in 1413 women and 1125 men in the Framingham Osteoporosis Study by using dual-energy X-ray absorptiometry. Dietary intake was assessed by food-frequency questionnaire. We regressed each BMD measure on the frequency of soft drink consumption for men and women after adjustment for body mass index, height, age, energy intake, physical activity score, smoking, alcohol use, total calcium intake, total vitamin D intake, caffeine from noncola sources, season of measurement, and, for women, menopausal status and estrogen use.
Cola intake was associated with significantly lower (P < 0.001-0.05) BMD at each hip site, but not the spine, in women but not in men. The mean BMD of those with daily cola intake was 3.7% lower at the femoral neck and 5.4% lower at Ward’s area than of those who consumed <1 serving cola/mo. Similar results were seen for diet cola and, although weaker, for decaffeinated cola. No significant relations between noncola carbonated beverage consumption and BMD were observed. Total phosphorus intake was not significantly higher in daily cola consumers than in nonconsumers; however, the calcium-to-phosphorus ratios were lower.
Intake of cola, but not of other carbonated soft drinks, is associated with low BMD in women. Additional research is needed to confirm these findings.

Tucker KL, Morita K, Qiao N, Hannan MT…
Am. J. Clin. Nutr. Oct 2006
PMID: 17023723 | Free Full Text

Mediterranean Diet or Nuts May Benefit Bones

Abstract

Mediterranean diet and bone mineral density in two age groups of women.

We hypothesized that adherence to the Mediterranean diet measured as a Mediterranean diet score (MDS) has a beneficial effect on bone mineral density (BMD). For the purposes of this study, a sample of healthy women from Southern Spain was chosen. Subjects were grouped into two major groups: a first group consisted of women of reproductive age (premenopausal, pre-M) and a second group consisted of postmenopausal women (pos-M). The consumption of vegetables and fruit was found to be significantly related to BMD in both groups of subjects studied. In the pre-M group, the lipid ratio was positively associated with BMD and in pos-M women nuts intake was also associated with BMD. After implementing the analysis of covariance analysis, significant linear trends between the MDS and BMD were observed in all subjects studied. Our results indicate that a varied diet based on Mediterranean diet patterns may be beneficial in the prevention of osteoporosis.

Rivas A, Romero A, Mariscal-Arcas M, Monteagudo C…
Int J Food Sci Nutr Mar 2013
PMID: 22946650

Mediterranean Diet + Nuts Does Not Significantly Increase Resorption

Abstract

Mediterranean diet and high dietary acid load associated with mixed nuts: effect on bone metabolism in elderly subjects.

Objectives: To analyze the effect of differing diet on the acid load content on bone metabolism.
Design: Multicentric, randomized, single-blind, parallel-group clinical trial.
Setting: Outpatient clinics.
Two hundred thirty-eight elderly men and women aged 60 to 80 at high risk for cardiovascular disease were randomly assigned to three interventional groups: a recommended low-fat diet (control diet group), a Mediterranean diet supplemented with virgin olive oil, or a Mediterranean diet supplemented with mixed nuts.
Main outcomes were 12-month changes from baseline in bone formation and resorption markers and bone mass measured according to quantitative ultrasound scanning.
The baseline data on the anthropometric, bone densitometry, and biochemical variables did not differ between the three groups. Dietary potential renal acid load (PRAL) and daily net endogenous acid production (NEAP) at baseline did not differ between groups. After intervention, subjects allocated to the Mediterranean diet with mixed nuts had a significant increase of PRAL and NEAP. In comparison, subjects in the Mediterranean diet with nuts group had higher parathyroid hormone (PTH) levels (2.63, 95% confidence interval (CI)=-1.01-6.35, P=.02) and a nonsignificantly higher (0.31, 95% CI=-0.13-0.74, P=.14) urine free deoxypyridoxine:creatinine ratio, a marker of bone resorption, than the control group and the Mediterranean diet with virgin olive oil group.
A Mediterranean dietary pattern associated with a high dietary acid load derived from consumption of mixed nuts does not seem to have a much greater effect on bone metabolism biomarkers, with the exception of PTH levels, than a Mediterranean diet without mixed nuts or a control diet in elderly subjects.

Bulló M, Amigó-Correig P, Márquez-Sandoval F, Babio N…
J Am Geriatr Soc Oct 2009
PMID: 19807791