Tag Archives: negative

Beta Blockers Increase Bone Loss from Steroids in Rats

Abstract

Effects of propranolol on the development of glucocorticoid-induced osteoporosis in male rats.

Glucocorticoid-induced osteoporosis is the most frequently occurring type of secondary osteoporosis. Antagonists of β-adrenergic receptors are now considered to be potential drugs under investigation for osteoporosis. The aim of the present study was to investigate the effects of propranolol, a nonselective β-receptor antagonist, on the skeletal system of mature male rats and on the development of bone changes induced by glucocorticoid (prednisolone) administration. The experiments were performed on 24-week-old male Wistar rats. The effects of prednisolone 21-hemisuccinate sodium salt (7 mg/kg, sc daily) or/and propranolol hydrochloride (10 mg/kg, ip daily) administered for 4 weeks on the skeletal system were studied. Bone and bone mineral mass in the tibia, femur and L-4 vertebra, length and diameter of the long bones, mechanical properties of tibial metaphysis, femoral diaphysis and femoral neck, bone histomorphometric parameters and turnover markers in serum were determined. Prednisolone-induced unfavorable skeletal changes led to disorders in bone mechanical properties. Propranolol not only did not improve bone parameters, but even caused deleterious effects on the skeletal system. Concurrent administration of propranolol with prednisolone did not counteract the changes induced by prednisolone. The results of this study may help to understand the equivocal results of human studies on the effects of β-blockers on the skeletal system. It is possible that the drugs exert biphasic effects on the skeletal system, both favorable and deleterious, depending on the dose or individual susceptibility.

Folwarczna J, Pytlik M, Sliwiński L, Cegieła U…
Pharmacol Rep 2011
PMID: 22001992 | Free Full Text

Berberine Impairs Muscle Growth and Energy

Abstract

Atrogin-1 affects muscle protein synthesis and degradation when energy metabolism is impaired by the antidiabetes drug berberine.

Defects in insulin/IGF-1 signaling stimulate muscle protein loss by suppressing protein synthesis and increasing protein degradation. Since an herbal compound, berberine, lowers blood levels of glucose and lipids, we proposed that it would improve insulin/IGF-1 signaling, blocking muscle protein losses.
We evaluated whether berberine ameliorates muscle atrophy in db/db mice, a model of type 2 diabetes, by measuring protein synthesis and degradation in muscles of normal and db/db mice treated with or without berberine. We also examined mechanisms for berberine-induced changes in muscle protein metabolism.
Berberine administration decreased protein synthesis and increased degradation in muscles of normal and db/db mice. The protein catabolic mechanism depended on berberine-stimulated expression of the E3 ubiquitin ligase, atrogin-1. Atrogin-1 not only increased proteolysis but also reduced protein synthesis by mechanisms that were independent of decreased phosphorylation of Akt or forkhead transcription factors. Impaired protein synthesis was dependent on a reduction in eIF3-f, an essential regulator of protein synthesis. Berberine impaired energy metabolism, activating AMP-activated protein kinase and providing an alternative mechanism for the stimulation of atrogin-1 expression. When we increased mitochondrial biogenesis by expressing peroxisome proliferator-activated receptor gamma coactivator-1alpha, berberine-induced changes in muscle protein metabolism were prevented.
Berberine impairs muscle metabolism by two novel mechanisms. It impairs mitochonidrial function stimulating the expression of atrogin-1 without affecting phosphorylation of forkhead transcription factors. The increase in atrogin-1 not only stimulated protein degradation but also suppressed protein synthesis, causing muscle atrophy.

Wang H, Liu D, Cao P, Lecker S…
Diabetes Aug 2010
PMID: 20522589 | Free Full Text

If this study is correct, it is damning for Berberine!

Ukrain No Benefit in Rats #2

Abstract

Intermittent three-month treatment with Ukrain in intact and ovariectomized rats. Part II: Effect on bone mineral density of the femur.

Ukrain, an acid alkaloid derivative of Chelidonium majus L., was administered intraperitoneally to ovariectomized and control sexually mature female rats at doses of 7, 14 and 28 mg/kg once daily for 10 days, followed by 10-day break. This procedure was repeated five times. At the end of the Ukrain treatment (24 h after the last dose of the drug) the right femora of the rats were harvested and the bone densitometric parameters of the whole bone and distal metaphysial and intertrochanteric subregions were assessed using the dual energy x-ray absorptiometry densitometric method. The results showed no apparent decrease in bone mineral density in groups of rats studied. A nearly significant (p = 0.08) decrease of bone mineral content was observed in ovariectomized rats treated with 14 mg/kg of Ukrain.

Jabłoński M, Gorzelak M, Patyra M, Jagiełło-Wójtowicz E
Drugs Exp Clin Res 2000
PMID: 11345047

Ukrain No Benefit in Rats

Abstract

Effect of intermittent three-month treatment with different doses of Ukrain on subregional femoral bone mineral density of sexually mature female rats.

Sexually mature but still growing female Wistar rats received i.p. injections of Ukrain (7, 14 or 28 mg/kg in a volume of 0.5 ml/100g) every other day for 10 days, followed by a 10-day break, and this procedure was performed five times. The control animals received the same volume of injected water. At the end of the experiment the rat right femora were harvested and the bone densitometric parameters of the entire bone, distal metaphyseal and basicervical subregions were assessed using the dual-energy X-ray absorptiometry (DXA) densitometric method. No significant changes were observed in the bone mineral density in experimental groups in comparison with control animals that received the vehicle. A slight decrease in the bone mineral content value was observed in the distal metaphyseal region in animals that were treated with the highest dose of Ukrain.

Gorzelak M, Jabłoński M, Patyra M, Jagiello-Wójtowicz E
Drugs Exp Clin Res 1998
PMID: 10190094

Saturated Fat Associated with Lower Bone Density; Protein or Vitamin C No Help

Abstract

Dietary saturated fat intake is inversely associated with bone density in humans: analysis of NHANES III.

Mounting evidence indicates that the amount and type of fat in the diet can have important effects on bone health. Most of this evidence is derived from animal studies. Of the few human studies that have been conducted, relatively small numbers of subjects and/or primarily female subjects were included. The present study assessed the relation of dietary fat to hip bone mineral density (BMD) in men and women using NHANES III data (n = 14,850). Multivariate models using SAS-callable SUDAAN were used to adjust for the sampling scheme. Models were adjusted for age, sex, weight, height, race, total energy and calcium intakes, smoking, and weight-bearing exercise. Data from women were further adjusted for use of hormone replacement therapy. Including dietary protein, vitamin C, and beta-carotene in the model did not influence the outcome. Analysis of covariance was used to generate mean BMD by quintile of total and saturated fat intake for 4 sex/age groups. Saturated fat intake was negatively associated with BMD at several hip sites. The greatest effects were seen among men < 50 y old (linear trend P = 0.004 for the femoral neck). For the femoral neck, adjusted mean BMD was 4.3% less among men with the highest compared with the lowest quintile of saturated fat intake (BMD, 95% CI: highest quintile: 0.922 g/cm2, 0.909-0.935; lowest quintile: 0.963 g/cm2, 95% CI: 0.950-0.976). These data indicate that BMD is negatively associated with saturated fat intake, and that men may be particularly vulnerable to these effects.

Corwin RL, Hartman TJ, Maczuga SA, Graubard BI
J. Nutr. Jan 2006
PMID: 16365076 | Free Full Text

Review: Depression and Bone Mass

Abstract

Depression and bone mass.

Although it has been repeatedly suggested that low bone mineral density (BMD) is disproportionately prevalent among patients with depressive disorders, so far depression has not been officially acknowledged as a risk factor for osteoporosis. In a recent meta-analysis comparing depressed with nondepressed individuals we report that BMD is lower in depressed than nondepressed subjects. The association between depression and BMD is stronger in women than men, and in premenopausal than postmenopausal women. Only women psychiatrically diagnosed for major depression display significantly low BMD; women diagnosed by self-rating questionnaires do not. Using a mouse model for depression, we demonstrate a causal relationship between depressive-like behavior and bone loss. The depression-induced bone loss is associated with increases in skeletal norepinephrine and serum corticosterone levels. Bone loss, but not the depressive behavior, could be prevented by a beta-blocker. Hence, depression appears as a significant risk factor for low BMD, causing bone loss through stimulation of the sympathetic nervous system.

Bab IA, Yirmiya R
Ann. N. Y. Acad. Sci. Mar 2010
PMID: 20392233

Lipoic Acid Prevents the Bone Inhibition and Resorption from a High Fat Diet and Dyslipidemia in Mice

Abstract

Dyslipidemic high-fat diet affects adversely bone metabolism in mice associated with impaired antioxidant capacity.

The present study examined impacts of dyslipidemic high-fat diet on the bone antioxidant system and bone metabolism in growing mice. Furthermore, the relationship was studied between them.
Male C57BL/6 mice (4 wk old) were fed with normal diet, high-fat diet (HFD), or HFD supplemented with 0.1% antioxidant lipoic acid (LA). After 13-wk feeding, the markers of plasma lipids status, bone metabolism in plasma and in urine, and femora oxidative stress were measured. To provide molecular evidence for abnormal bone metabolism affected by HFD, bone cell-specific mRNA levels were tested by real-time quantitative polymerase chain reaction. Moreover, insulin-like growth factor I and tumor necrosis factor-alpha in plasma and their mRNA levels in femur were measured.
The feeding dyslipidemic HFD induced both inhibitory bone formation reactions and enhancement of bone resorption reactions, accompanied by impaired bone antioxidant system, low levels of insulin-like growth factor I in plasma and in bone, and high levels of tumor necrosis factor-alpha in plasma but not in bone. In contrast, these alternatives were prevented completely or partially in mice fed LA supplement. Further, plasma propeptide of І collagen C-propeptide as a marker of bone formation was positively correlated with both total antioxidant capacity (r=0.683, P<0.001) and reduced glutathione/oxidized glutathione ratio (r=0.565, P<0.003) of bone. Cross-linked N-telopeptides of bone type І collagen as a marker of bone resorption was negatively correlated with both total antioxidant capacity (r=-0.753, P<0.001) and glutathione/oxidized glutathione ratio (r=-0.786, P<0.001).
Dyslipidemia induces impaired bone antioxidant system. Oxidative stress could be an important mediator of hyperlipidemia-induced bone loss.

Xiao Y, Cui J, Li YX, Shi YH…
Nutrition Feb 2011
PMID: 20392601

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.

Review: Reduction in Food Associated with Decreased Bone Mass in Older Persons

Abstract

Physiological and psychosocial age-related changes associated with reduced food intake in older persons.

Dietary intake changes during the course of aging. Normally an increase in food intake is observed around 55 years of age, which is followed by a reduction in food intake in individuals over 65 years of age. This reduction in dietary intake results in lowered levels of body fat and body weight, a phenomenon known as anorexia of aging. Anorexia of aging has a variety of consequences, including a decline in functional status, impaired muscle function, decreased bone mass, micronutrient deficiencies, reduced cognitive functions, increased hospital admission and even premature death. Several changes during lifetime have been implicated to play a role in the reduction in food intake and the development of anorexia of aging. These changes are both physiological, involving peripheral hormones, senses and central brain regulation and non-physiological, with differences in psychological and social factors. In the present review, we will focus on age-related changes in physiological and especially non-physiological factors, that play a role in the age-related changes in food intake and in the etiology of anorexia of aging. At the end we conclude with suggestions for future nutritional research to gain greater understanding of the development of anorexia of aging which could lead to earlier detection and better prevention.

de Boer A, Ter Horst GJ, Lorist MM
Ageing Res. Rev. Jan 2013
PMID: 22974653

Depression Associated with Bone Loss in Older Men

Abstract

Depressive symptoms and rates of bone loss at the hip in older men.

In this prospective cohort study, depressive symptoms were associated with higher rates of bone loss in older men. Poorer performance on physical function tests partly explained the association between depressive symptoms and bone loss, suggesting that efforts to increase exercise and improve physical performance in depressed men may be beneficial.
The aim of this study was to ascertain whether depressive symptoms are associated with increased rates of bone loss at the hip in older men.
A population-based prospective cohort study of 2,464 community-dwelling men, aged 68 and older, enrolled in the Osteoporosis in Men Sleep Ancillary Study had depressive symptoms assessed by the Geriatric Depression Scale (GDS). Subjects were categorized as depressed if GDS ≥6 at the initial examination. Bone mineral density (BMD) at the hip was measured using dual-energy X-ray absorptiometry at the initial and follow-up examination (average 3.4 years between exams). Use of antidepressant medications was assessed by interview and verified from medication containers at the two examinations. A computerized dictionary was used to categorize type of medication.
In a base model adjusted for age, race/ethnicity, and clinic site, the mean total hip BMD decreased 0.70 %/year in 136 men with a GDS score of ≥6 compared to 0.39 %/year in 2,328 men with a GDS score of <6 (p = 0.001). Walking speed and timed chair stand partly explained the association between depressive symptoms and rates of bone loss.
Depression, as defined by a score of 6 or greater on the Geriatric Depression Scale, is associated with an increased rate of bone loss at the hip in this cohort of older men. Adjustment for walking speed and timed chair stand attenuated the strength of the association, suggesting that differences in physical functioning do partially explain the observed association.

Diem SJ, Harrison SL, Haney E, Cauley JA…
Osteoporos Int Jan 2013
PMID: 22461074