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ACE Inhibitor Moexipril Doesn’t Harm Bones in Ovariectomized Rats

Abstract

Impact of antihypertensive therapy on postmenopausal osteoporosis: effects of the angiotensin converting enzyme inhibitor moexipril, 17beta-estradiol and their combination on the ovariectomy-induced cancellous bone loss in young rats.

No data are available on whether angiotensin converting enzyme (ACE) inhibition affects the skeleton, though this might be of clinical relevance when antihypertensive therapy is initiated, particularly in hypertensive women after menopause who typically suffer from a concomitant rapid onset of osteoporosis. In the present study we investigated the effects of the new ACE inhibitor moexipril, 17beta-estradiol and their combination on the bone turnover in ovariectomized Sprague-Dawley rats, an established animal model for studying human postmenopausal osteoporosis.
We studied 119 12-week-old virgin female Sprague-Dawley rats. Seven rats were killed on day 0 as basal controls. The remaining rats were divided into sham-ovariectomy or ovariectomy groups. Vehicle, moexipril at 10 mg/kg per day alone (orally), 17beta-estradiol at 10 mu g/kg per day alone (subcutaneously) or both were administered to both groups immediately after the operation for 14 (short-term effects) or 56 (long-term effects) days. A stereology computer program was used for measurements. Static histomorphometric measurements, using a stereology computer program, were taken on double-fluorescent labeled undecalcified proximal tibial metaphyseal (cancellous bone site) and tibial shaft (cortical bone site) sections.
Ovariectomy induced dramatically cancellous bone loss due to increased bone turnover, with resorption exceeding formation. Moexipril had no effect on the cancellous bone site in either ovariectomized or sham-operated rats. 17beta-Estradiol treatment added extra cancellous bone in the sham-operated rats and prevented cancellous bone loss in the ovariectomized rats by inhibiting bone resorption. The combination of moexipril and 17beta-estradiol gave similar results to those of 17beta-estradiol alone. Comparable results were observed in the cortical bone site.
The results of this study show that ACE inhibition by moexipril has no effect on the skeleton when given alone and that it does not hamper the osteoprotective effects of 17beta-estradiol. These findings are relevant for the use of antihypertensive therapy in postmenopausal women treated or not with hormone replacement therapy.

Stimpel M, Jee WS, Ma Y, Yamamoto N…
J. Hypertens. Dec 1995
PMID: 8903666

Taurine No Benefit in Calcium Deficient Rats

Abstract

Effects of taurine supplementation on bone mineral density in ovariectomized rats fed calcium deficient diet.

Taurine supplementation has been shown to have a beneficial effect on femur bone mineral content in ovariectomized rats. It therefore seemed desirable to find out whether the beneficial effect of taurine on ovariectomized rats fed calcium deficient diet could also be reproduced. Forty female Sprague-Dawley rats were divided into two groups. One group was OVX and the other group received sham operation (SHAM), and received either control diet or a taurine supplemented diet for 6 weeks. All rats were fed on calcium deficient diet (AIN-93: 50% level of calcium) and deionized water. Bone mineral density (BMD) and bone mineral content (BMC) were measured in spine and femur. The serum and urine concentrations of calcium and phosphorus were determined. Bone formation was measured by serum osteocalcin and alkaline phosphatase (ALP) concentrations. Bone resorption rate was measured by deoxypyridinoline (DPD) crosslinks immunoassay and corrected for creatinine. Urinary calcium and phosphorus excretion, osteocalcin in blood and cross link value were not significantly different among the groups. Within the OVX group, the taurine supplemented group had not higher femur bone mineral content than the control group. This study established the need for a study on the taurine effect on bone with different calcium levels.

Choi MJ
Nutr Res Pract 2009
PMID: 20016710 | Free Full Text

This experiment was originally designed to test the ability of a taurine supplement to minimize bone loss during postmenopausal model with low calcium intake. Sulfur is predominantly responsible for determining the net endogenous acid production from protein because it is the acid precursor that is oxidized to sulfuric acid (Frassetto et al., 1998). It would therefore make sense that a dietary supplement with excess sulfur-containing amino acids (taurine) could yield increased sulfuric acid production in the body. However, these data suggest that bone mineral density per weight was increased, without changes in bone resorption and bone formation, in the taurine supplemented group, and therefore have the potential to increase bone mineral density if either the study is extended or more taurine is supplemented. The beneficial effect of taurine on ovariectomized rats fed calcium deficient diet was not reproduced. Because in this study, the control and taurine groups consumed identical diets as in the previous study (besides the calcium content), and we do not know whether intestinal calcium absorption will be increased by more taurine supplement. These results indicate that no significant differences in spine and femur BMD were found due to 2% taurine diet in OVX rats fed calcium deficient diet for 6 weeks. No positive effects of taurine on bone mineral density were found in the present study. Our failure to see an association between taurine supplementation and bone mineral density may have been related to the fact that we used calcium deficient diet and the same amount of taurine. Further investigations of the relation between taurine and calcium intake level for bone mineral density are warranted.

Coffee Not Associated with Bone Density in Premenopausal Korean Women

Abstract

Coffee consumption and bone mineral density in korean premenopausal women.

Although Asian people are known to have lower bone mass than that of Caucasians, little is known about coffee-associated bone health in Asian. This study aimed to assess the relationship between coffee consumption and bone mineral density (BMD) in Korean premenopausal women.
Data were obtained from the Fourth Korea National Health and Nutrition Examination Survey 2008-2009. The study population consisted of 1,761 Korean premenopausal women (mean age 36 years) who were measured for lumbar spine and femoral neck BMD and who completed a standardized questionnaire about coffee intake frequency. We excluded the participants who took hormone replacement therapy or medication for osteoporosis. The cross-sectional relationship between coffee consumption and impaired bone health (osteopenia or osteoporosis) was investigated by bone densitometry.
Coffee consumption showed no significant association with BMD of either femoral neck or lumbar spine, independent of other factors. The adjusted odds ratios for BMD for those who consumed once in a day, twice a day and three times a day were 0.94 (0.70-1.26), 0.93 (0.67-1.28), and 1.02 (0.69-1.50), respectively (P for trend = 0.927).
This study does not support the idea that coffee is a risk factor for impaired bone health in Korean premenopausal women.

Choi EJ, Kim KH, Koh YJ, Lee JS…
Korean J Fam Med Jan 2014
PMID: 24501665 | Free Full Text

 This study shows that high consumption of coffee is not associated with increased risk for impaired bone health. Our results are in agreement with some recent cross-sectional studies showing no association between caffeine and impaired bone health, and in disagreement with others which focused on BMD of various skeletal sites.22-26) Habitual dietary caffeine intake was found not to be associated with impaired bone health in healthy postmenopausal women in a longitudinal study in Pennsylvania (USA), on the basis of self-reported questionnaires collected in 2000.23) In elderly men and women from the population-based Framingham Osteoporosis Study, the same results were found.24) These studies are in agreement with our study. Although the frequency consumed and the species of coffee could be significantly affected by cultural differences and socioeconomic status, and the metabolism of caffeine and other constituents can be affected by genetic predisposition, our results in Korean premenopausal women did not appear to contradict those of previous studies.

The role of coffee intake in bone health, however, seems controversial. There are several studies showing a negative association between caffeine and bone health. Daily intake of 330 mg of caffeine, equivalent to 4 cups (600 mL) of coffee, or more may be associated with a modestly increased risk of osteoporotic fractures, especially in women with a low intake of calcium, as shown in a study on Swedish women aged 40 to 76 years.4) Also, in a cohort study, Men consuming 4 cups of coffee or more per day had 4% lower BMD at the proximal femur (P = 0.04) compared with low or non-consumers of coffee. This difference was not observed in women, suggesting that rapid metabolizers of caffeine may constitute a risk group for bone loss induced by coffee.24)

Tea, but Not Coffee, Reduces Hip Fracture

Abstract

Coffee, tea, and the risk of hip fracture: a meta-analysis.

The present meta-analysis shows no clear association between coffee consumption and the risk of hip fractures. There was a nonlinear association between tea consumption and the risk of hip fracture. Compared to no tea consumption, drinking 1-4 cups of tea daily was associated with a lower risk of hip fracture.
Prospective cohort and case-control studies have suggested that coffee and tea consumption may be associated with the risk of hip fracture; the results have, however, been inconsistent. We conducted a meta-analysis to assess the association between coffee and tea consumption and the risk of hip fracture.
We performed systematic searches using MEDLINE, EMBASE, and OVID until February 20, 2013, without limits of language or publication year. Relative risks (RRs) with 95% confidence intervals (CI) were derived using random-effects models throughout all analyses. We conducted categorical, dose-response, heterogeneity, publication bias, and subgroup analyses.
Our study was based on 195,992 individuals with 9,958 cases of hip fractures from 14 studies, including six cohort and eight case-control studies. The pooled RRs of hip fractures for the highest vs. the lowest categories of coffee and tea consumption were 0.94 (95% CI 0.71-1.17) and 0.84 (95% CI 0.66-1.02), respectively. For the dose-response analysis, we found evidence of a nonlinear association between tea consumption and the risk of hip fracture (p(nonlinearity) < 0.01). Compared to no tea consumption, 1-4 cups of tea per day may reduce the risk of hip fracture by 28% (0.72; 95% CI 0.56-0.88 for 1-2 cups/day), 37% (0.63; 95% CI 0.32-0.94 for 2-3 cups/day), and 21% (0.79; 95% CI 0.62-0.96 for 3-4 cups/day).
We found no significant association between coffee consumption and the risk of hip fracture. A nonlinear association emerged between tea consumption and the risk of hip fracture; individuals drinking 1-4 cups of tea per day exhibited a lower risk of hip fractures than those who drank no tea. The association between 5 daily cups of tea, or more, and hip fracture risk should be investigated.

Sheng J, Qu X, Zhang X, Zhai Z…
Osteoporos Int Jan 2014
PMID: 24196722

Caffeine Not Associated with Bone Loss in Postmenopausal Women

Abstract

Dietary caffeine intake and bone status of postmenopausal women.

Dietary caffeine intake has been suggested as a risk factor for bone loss in postmenopausal women. We measured the bone density of both hips and the total body in 138 healthy, postmenopausal women aged 55-70 y who had either never used hormone replacement therapy (HRT) or had used HRT for < 1 y. In this cross-sectional study, participants were stratified according to their reported current and long-time caffeinated beverage use into one of three groups: low [0-2 cups (180 mL, or 6 oz per cup) caffeinated coffee per day], moderate (3-4 cups caffeinated coffee per day), or high (> or = 5 cups caffeinated coffee per day). Caffeine intake was measured from diet records and by gas chromatography of each subject’s brewed, caffeinated beverages. No association between caffeine intake and any bone measurement was observed. The anthropometric and nutrient intakes of the three groups were similar. Compared with caffeine intake based on chemical analysis of brewed beverages, 3-d prospective food records and computer-assisted analysis overestimated caffeine intake by nearly two-thirds. In conclusion, the habitual dietary caffeine intake of this cohort of 138 postmenopausal women ranged from 0-1400 mg/d and was not associated with total body or hip bone mineral density measurements. This study does not support the notion that caffeine is a risk factor for bone loss in healthy postmenopausal women.

Lloyd T, Rollings N, Eggli DF, Kieselhorst K…
Am. J. Clin. Nutr. Jun 1997
PMID: 9174479 | Free Full Text

Caffeine Not an Important Risk in Young Women

Abstract

Is caffeine associated with bone mineral density in young adult women?

By increasing the urinary excretion of calcium, caffeine consumption may reduce bone mineral density (BMD) and subsequently increase the risk for osteoporotic fracture. Although negative associations between caffeine consumption and BMD have been reported for postmenopausal women, in particular for those who consume low amounts of dietary calcium, the relation between caffeine and BMD in younger women is unclear. Therefore, we evaluated the association between caffeine consumption and BMD in a cross-sectional study of 177 healthy white women, age 19-26 years, who attended a Midwestern university.
Average caffeine intake (milligrams per day) was calculated from self-reports of the consumption of coffee, decaffeinated coffee, tea, colas, chocolate products, and select medications during the previous 12 months (mean caffeine intake = 99. 9 mg/day). BMD (grams per square centimeter) at the femoral neck and the lumbar spine was measured by dual-energy X-ray absorptiometry.
After adjusting in linear regression models for potential confounders, including height, body mass index, age at menarche, calcium intake, protein consumption, alcohol consumption, and tobacco use, caffeine consumption was not a significant predictor of BMD. For every 100 mg of caffeine consumed, femoral neck BMD decreased 0.0069 g/cm(2) (95% confidence in terval [CI] = -0.0215, 0. 0076) and lumbar spine BMD decreased 0.0119 g/cm(2) (95% CI = -0. 0271, 0.0033). No single source of caffeine was significantly associated with a decrease in BMD. Furthermore, the association between caffeine consumption and BMD at either site did not differ significantly between those who consumed low levels of calcium (< or =836 mg/day) and those who consumed high levels of calcium (>836 mg/day).
Caffeine intake in the range consumed by young adult women is not an important risk factor for low BMD.

Conlisk AJ, Galuska DA
Prev Med Nov 2000
PMID: 11071837

Nasal Calcitonin No Benefit After Hip Replacement

Abstract

Salmon calcitonin (Miacalcic ns 200 IU) in prevention of bone loss after hip replacement.

Loosening of a hip prosthesis after total arthroplasty is related to periprosthetic bone loss. Calcitonin has been used in the treatment of bone loss in osteoporosis and prevention of fractures. The main purposes of the study were firstly to evaluate the effect of calcitonin on periprosthetic bone after total hip arthroplasty, secondly investigate possible loosening of the prosthesis and thirdly examine further clinical outcome.
60 patients who underwent total hip arthroplasty using cemented Exeter prosthesis were randomized in the treatment group (salmon calcitonin 200 IU nasal spray daily + calcium 500 mg) and the placebo group (inactive nasal spray + calcium 500 mg) for six months. Bone mineral density (BMD) was measured from different locations at the time of discharge and after six and 12 months. Dynamic histomorphometry on bone biopsies taken from femoral collum was performed. Serum bone-specific alkaline phosphatase (BAP), serum osteocalcine (OC) and cross-linked N-telopeptides (NTX) were measured after one week, one month, three months and 12 months. Clinical manifestations and the incidence of fractures and loosening of the prosthesis were followed up to eight years.
Statistically there was not significant difference in bone histomorphometry between the groups. In both groups there was a significant BMD decrease in periprosthetic bone. However, the difference between the groups was not statistically significant. In the biochemical analysis NTX increased more in the Miacalcic group than in the placebo group (p = 0.013). There were no significant differences between the groups in serum BAP or OC even though the changes within the groups were statistically significant. No loosening of the prosthesis was seen during the follow-up and there was no need for revision of any reason. Four fractures were recorded in three patients. One patient sustained a periprosthetic fracture. All the patients with fractures were allocated in the placebo group.
Nasal salmon calcitonin 200 IU on a daily basis does not promote any additional value on calcium substitution to prevent bone loss after hip replacement. The durability of the Exeter prosthesis was good.

Arnala IO
Scand J Surg 2012
PMID: 23238499 | Free Full Text

Nitroglycerin Not Effective in Postmenopausal Bone Loss

Abstract

Transdermal nitroglycerin therapy may not prevent early postmenopausal bone loss.

Osteoporosis is common among postmenopausal women; animal studies and human pilot studies support the concept of nitric oxide (NO) donors reducing bone mineral density loss. The objective of the study was to evaluate whether NO donor, nitroglycerin, prevents postmenopausal bone loss.
 This was a 3-yr randomized, double blinded, single-center, placebo-controlled clinical trial.
The single-center study was conducted at the University of Medicine and Dentistry-Robert Wood Johnson Medical School (New Brunswick, NJ).
Participants included 186 postmenopausal women aged 40-65 yr, with lumbar bone mineral density (BMD) T-scores of 0 to -2.5.
Women, stratified by lumbar T-score (<-1.50 and >or=-1.50) and years since menopause (<or=5 and >5 yr), were randomized to receive nitroglycerin ointment (22.5 mg as Nitro-Bid) or placebo ointment received daily for 3 yr. Both groups took 630 mg daily calcium plus 400 IU vitamin D supplements.
BMD was measured at 6 months and annually by dual-energy x-ray absorptiometry. Percent change in lumbar vertebrae BMD was the primary outcome. Hip BMD, total body bone mineral content, and height were secondary outcomes.
After 36 months of therapy, changes of -2.1% in the active group (n = 88) and -2.5% in the placebo group (n = 82) in lumbar spine BMD were seen (P = 0.59; 95% confidence interval -1.001, 1.975). Secondary outcomes also did not differ by intervention arm. The active group reported more headaches compared with the placebo group (57 vs. 14%, P < 0.001). Other adverse and serious adverse events were not different.
BMD changes did not substantially differ between postmenopausal women who received the dose of nitroglycerin tested, in comparison with a placebo. Once-daily dosing with 22.5 mg of transdermal-administered nitroglycerin was not effective (compliance adjusted dose was only approximately 16 mg/d); a sub-therapeutic dose.

Wimalawansa SJ, Grimes JP, Wilson AC, Hoover DR
J. Clin. Endocrinol. Metab. Sep 2009
PMID: 19549739 | Free Full Text

Fruit + Vegetables Fails to Improve Bone Over 16 Weeks

Abstract

Effect of increased fruit and vegetable consumption on bone turnover in older adults: a randomised controlled trial.

Evidence suggests that increased fruit and vegetable (FV) intake may be associated with improved bone health, but there is limited evidence from intervention trials to support this. This 16-week study showed that increased FV consumption (five or more portions per day) does not have any effect on the markers of bone health in older adults.
Observational evidence suggests that increased FV consumption may be associated with improved bone health. However, there is lack of evidence from intervention trials to support this. This study examined the effect of increased FV consumption on bone markers among healthy, free-living older adults.
A randomised controlled trial was undertaken. Eighty-three participants aged 65-85 years, habitually consuming less than or equal to two portions of FV per day, were randomised to continue their normal diet or to consume five or more portions of FV per day for 16 weeks. FV were delivered to all participants each week, free of charge. Compliance was assessed at baseline and at 6, 12 and 16 weeks by diet histories and biomarkers of micronutrient status. Fasting serum bone markers (osteocalcin (OC) and C-terminal telopeptide of type 1 collagen (CTX)) were measured using enzyme-linked immunosorbent assay.
Eighty-two participants completed the intervention. The five portions per day group showed a significantly greater change in daily FV consumption compared to the two portions per day group (p < 0.001), and this was reflected in significant increases in micronutrient status. No significant differences were evident in change in bone markers between the two portions per day group and the five portions per day group over the 16 weeks (geometric mean of week 16 to baseline ratio (95% confidence interval): OC-0.95 (0.89-1.02) and 1.04 (0.91-1.18), respectively, p = 0.25; CTX-1.06 (0.95-1.19) and 0.98 (0.90-1.06) respectively, p = 0.20).
Increased FV consumption had no effect on bone markers in older adults. Larger intervention studies of longer duration are warranted to establish whether long-term FV consumption can benefit bone health.

Neville CE, Young IS, Gilchrist SE, McKinley MC…
Osteoporos Int Jan 2014
PMID: 23716039

Cranberry Juice No Effect on Bone Quality in Rats

Abstract

Cranberry juice improved antioxidant status without affecting bone quality in orchidectomized male rats.

We reported that drinking citrus juice improves bone quality in orchidectomized senescent male rats. Because cranberry juice, like citrus, is rich in nutrients and phenolic compounds, beneficial effects of citrus juice might also be seen with cranberry juice. An experiment evaluated effect of drinking cranberry juice on bone quality in orchidectomized rats.
Thirty-two 1-year-old male rats were randomized to two groups: a sham-control group (n=8) and an orchidectomized group (n=24). The treatments for the 4 months duration of the study were SHAM, orchidectomy (ORX), ORX+drinking either 27% or 45% cranberry juice concentrate added to drinking water. At the termination of the study, the rats were euthanized, blood was collected for plasma antioxidant status and IGF-I. The femur, tibia and the 4th lumbar were evaluated for bone quality. Total calcium and magnesium concentration in the femurs were also evaluated.
ORX did not affect red blood cell (RBC)-induced hemolysis despite lowering (p<0.05) plasma antioxidant capacity; reduced (p<0.05) plasma IGF-I, femoral density, femoral strength, time-induced femoral fracture, bone mineral content, bone mineral area; numerically (p=0.07) lowered 4th lumbar density; decreased (p<0.05) trabecular connectivity, trabecular number, femoral ash; increased (p<0.05) trabecular separation in comparison to the SHAM group. Drinking cranberry juice increased (p<0.05) plasma antioxidant status, protected RBC against hemolysis, but had no positive effect on bone quality or bone mineral status.
Cranberry juice increases plasma antioxidant status without affecting bone quality.

Villarreal A, Stoecker BJ, Garcia C, Garcia K…
Phytomedicine Dec 2007
PMID: 17481874