The Effects of Berry Anthocyanin-Rich Diets for the Protection Against Ovariectomy-Induced Bone Loss

Abstract Objectives Osteoporosis is a condition of low bone mass that may affect women due to an abrupt cessation of ovarian hormones and increased level inflammation and oxidation. As the United States population increases and longevity rises, low bone mass that could lead to fractures poses an even greater health issue and cause for unnecessary health expenses. More and more, individuals are seeking alternatives such as functional foods as oppose to drug medications to attenuate the bone loss. Fruits like dried plums and certain berries are purported to have beneficial effects as strong antioxidants in retarding bone loss resulting from aging. To provide further in vivo evidence of blueberry effects and determine whether strawberry is supportive of bone health for the benefit of human consumption. The hypothesis of this study is that blueberry- and strawberry-rich diets will prevent or slow the progression of ovariectomy-induced bone loss in a rat model (Sprague Dawley) of osteoporosis. Methods We fed 15 estrogen-deficient female rats (3-month old) with either a blueberry-rich (10% w/w), strawberry-rich (10% w/w), or normal diet (Ovx), and 3 intact (Sham) rats a normal diet for 13 weeks. Upon sacrifice, we collected major organs, blood, vertebrae, femora, and tibiae for analysis. Three-point bending tests were performed using a compressive hydraulic system on the femora and tibiae to asses bone fracture point, stiffness, and elasticity. Tissue mineralization of the 6th lumbar vertebrae were measured as ratio of ash to dry weight burning at 800°C in a muffled furnace. Serum bone alkaline phosphatase and tartrate-resistant acid phosphatase 5b are being measured currently for presentation of results at the conference. Results There were no differences in body weight between groups at the start or termination of the study, nor were changes in body weight different (P > 0.05). Tissue mineralization trended to significance (P < 0.08) between Sham and Ovx groups, but not when comparing blueberry and strawberry groups to Ovx. The remaining data will be reported at the conference. Conclusions Thus far, we cannot conclude that berry-rich diets are sufficient to protect against ovariectomy-induced bone loss in female rats. Funding Sources The Agricultural Research Institute (ARI) of California State University.

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Hypothalamic leptin gene therapy reduces body weight without accelerating age-related bone loss

Journal of Endocrinology ◽

10.1530/joe-15-0280 ◽

2015 ◽

Vol 227 (3) ◽

pp. 129-141 ◽

Cited By ~ 6

Author(s):

Russell T Turner ◽

Michael Dube ◽

Adam J Branscum ◽

Carmen P Wong ◽

Dawn A Olson ◽

...

Keyword(s):

Gene Therapy ◽

Body Weight ◽

Bone Loss ◽

Bone Mass ◽

Bone Turnover ◽

Cancellous Bone ◽

Mass Density ◽

Female Rats ◽

Bone Mass Density ◽

Age Related

Excessive weight gain in adults is associated with a variety of negative health outcomes. Unfortunately, dieting, exercise, and pharmacological interventions have had limited long-term success in weight control and can result in detrimental side effects, including accelerating age-related cancellous bone loss. We investigated the efficacy of using hypothalamic leptin gene therapy as an alternative method for reducing weight in skeletally-mature (9 months old) female rats and determined the impact of leptin-induced weight loss on bone mass, density, and microarchitecture, and serum biomarkers of bone turnover (CTx and osteocalcin). Rats were implanted with cannulae in the 3rd ventricle of the hypothalamus and injected with either recombinant adeno-associated virus encoding the gene for rat leptin (rAAV-Leptin,n=7) or a control vector encoding green fluorescent protein (rAAV-GFP,n=10) and sacrificed 18 weeks later. A baseline control group (n=7) was sacrificed at vector administration. rAAV-Leptin-treated rats lost weight (−4±2%) while rAAV-GFP-treated rats gained weight (14±2%) during the study. At study termination, rAAV-Leptin-treated rats weighed 17% less than rAAV-GFP-treated rats and had lower abdominal white adipose tissue weight (−80%), serum leptin (−77%), and serum IGF1 (−34%). Cancellous bone volume fraction in distal femur metaphysis and epiphysis, and in lumbar vertebra tended to be lower (P<0.1) in rAAV-GFP-treated rats (13.5 months old) compared to baseline control rats (9 months old). Significant differences in cancellous bone or biomarkers of bone turnover were not detected between rAAV-Leptin and rAAV-GFP rats. In summary, rAAV-Leptin-treated rats maintained a lower body weight compared to baseline and rAAV-GFP-treated rats with minimal effects on bone mass, density, microarchitecture, or biochemical markers of bone turnover.

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Comparison of the effects of add-back therapy with various natural oestrogens on bone metabolism in rats administered a long-acting gonadotrophin-releasing hormone agonist

Journal of Endocrinology ◽

10.1677/joe.0.1650467 ◽

2000 ◽

Vol 165 (2) ◽

pp. 467-473 ◽

Cited By ~ 10

Author(s):

Y Wang ◽

T Yano ◽

A Kikuchi ◽

N Yano ◽

H Matsumi ◽

...

Keyword(s):

Body Weight ◽

Bone Loss ◽

Lumbar Vertebrae ◽

Female Rats ◽

Mineral Apposition Rate ◽

Uterine Weight ◽

Mineral Density ◽

Bone Formation Rate ◽

Releasing Hormone ◽

Gonadotrophin Releasing Hormone

The hypoestrogenic state induced by gonadotrophin-releasing hormone agonist (GnRHa) has been shown to be effective in the treatment of oestrogen-dependent disorders but to induce bone loss. Adding back low doses of oestrogen in GnRHa therapy has been proposed to prevent bone loss. The purpose of this study is to assess the efficacy of add-back therapy with different natural oestrogens such as oestrone (OE(1)), oestradiol (OE(2)) and oestriol (OE(3)). Three-month-old female rats (250 g) were subcutaneously administered microcapsules of leuprorelin acetate in doses of 1 mg/kg of body weight every 4 weeks. GnRHa therapy lasted 16 weeks, and pellets of OE(1), OE(2) or OE(3) (0.5 mg/pellet, 60 day release), as an add-back agent, were implanted at 8 weeks of treatment. At the end of treatment, GnRHa alone decreased bone mineral density of the femur and lumbar vertebrae, and increased serum levels of bone metabolic markers such as alkaline phosphatase and osteocalcin levels. As for cancellous bone histomorphometry, GnRHa decreased bone volume while it increased osteoid volume, osteoid surface, eroded surface, mineral apposition rate and bone formation rate. All the oestrogens tested prevented these changes caused by GnRHa therapy. GnRHa induced a significant increase in body weight and a marked reduction in uterine weight, which was not observed in OE(1) or OE(2) add-back group. Body weight and uterine weight of the OE(3) add-back group were the same as those of the GnRHa group. These findings indicate that GnRHa induces high turnover bone loss which can be prevented by concomitant administration of natural oestrogens such as OE(1), OE(2) and OE(3) to the same extent. In addition, OE(3) is unique in that it is much less effective than OE(1) and OE(2) in blocking body weight gain and in promoting growth of uterine tissues. Because of its tissue-selective actions, OE(3) could be considered as one of the most appropriate oestrogens used for GnRHa add-back therapy.

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Loss of milk fat globule-epidermal growth factor 8 (MFG-E8) in mice leads to low bone mass and accelerates ovariectomy-associated bone loss by increasing osteoclastogenesis

Bone ◽

10.1016/j.bone.2015.04.003 ◽

2015 ◽

Vol 76 ◽

pp. 107-114 ◽

Cited By ~ 8

Author(s):

Kathrin Sinningen ◽

Elise Albus ◽

Sylvia Thiele ◽

Sylvia Grossklaus ◽

Thomas Kurth ◽

...

Keyword(s):

Growth Factor ◽

Epidermal Growth Factor ◽

Bone Loss ◽

Bone Mass ◽

Milk Fat ◽

Low Bone Mass ◽

Milk Fat Globule ◽

Epidermal Growth ◽

Fat Globule

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Constitutive Activation of β-Catenin in Differentiated Osteoclasts Induces Bone Loss in Mice

Cellular Physiology and Biochemistry ◽

10.1159/000492549 ◽

2018 ◽

Vol 48 (5) ◽

pp. 2091-2102 ◽

Cited By ~ 3

Author(s):

Xin Sui ◽

Shijian Deng ◽

Mengmeng Liu ◽

Linlin Fan ◽

Yunfei Wang ◽

...

Keyword(s):

Bone Loss ◽

Bone Mass ◽

Bone Growth ◽

Osteoclast Differentiation ◽

Marker Genes ◽

Tartrate Resistant Acid Phosphatase ◽

Bone Homeostasis ◽

Micro Computed Tomography ◽

Constitutive Activation

Background/Aims: Activation of the Wnt/β-catenin signalling pathway has been widely investigated in bone biology and shown to promote bone formation. However, its specific effects on osteoclast differentiation have not been fully elucidated. Our study aimed to identify the role of β-catenin in osteoclastogenesis and bone homeostasis. Methods: In the present study, exon 3 in the β-catenin gene (Ctnnb1) allele encoding phosphorylation target serine/threonine residues was flanked by floxP sequences. We generated mice exhibiting conditional β-catenin activation (Ctsk-Cre;Ctnnb1flox(exon3)/+, designated CA-β-catenin) by crossing Ctnnb1flox(exon3)/flox(exon3) mice with osteoclast-specific Ctsk-Cre mice. Bone growth and bone mass were analysed by micro-computed tomography (micro-CT) and histomorphometry. To further examine osteoclast activity, osteoclasts were induced from bone marrow monocytes (BMMs) isolated from CA-β-catenin and Control mice in vitro. Osteoclast differentiation was detected by tartrate-resistant acid phosphatase (TRAP) staining, immunofluorescence staining and reverse transcription-quantitative PCR (RT–qPCR) analysis. Results: Growth retardation and low bone mass were observed in CA-β-catenin mice. Compared to controls, CA-β-catenin mice had significantly reduced trabecular bone numbers under growth plates as well as thinner cortical bones. Moreover, increased TRAP-positive osteoclasts were observed on the surfaces of trabecular bones and cortical bones in the CA-β-catenin mice; consistent results were observed in vitro. In the CA-β-catenin group, excessive numbers of osteoclasts were induced from BMMs, accompanied by the increased expression of osteoclast-associated marker genes. Conclusion: These results indicated that the constitutive activation of β-catenin in osteoclasts promotes osteoclast formation, resulting in bone loss.

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Sclareol prevents ovariectomy-induced bone loss in vivo and inhibits osteoclastogenesis in vitro via suppressing NF-κB and MAPK/ERK signaling pathways

Food & Function ◽

10.1039/c9fo00206e ◽

2019 ◽

Vol 10 (10) ◽

pp. 6556-6567 ◽

Cited By ~ 5

Author(s):

Haiming Jin ◽

Zhenxuan Shao ◽

Qingqing Wang ◽

Jiansen Miao ◽

Xueqin Bai ◽

...

Keyword(s):

Bone Loss ◽

Bone Mass ◽

Postmenopausal Women ◽

Postmenopausal Osteoporosis ◽

Bone Quality ◽

Progressive Disease ◽

Erk Signaling ◽

Low Bone Mass

Postmenopausal osteoporosis (PMO) is a progressive disease occurring in elderly postmenopausal women that is characterized by low bone mass and impaired bone quality.

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Commentary-FSH and bone 2010: evolving evidence

Acta Endocrinologica ◽

10.1530/eje-10-0397 ◽

2010 ◽

Vol 163 (1) ◽

pp. 173-176 ◽

Cited By ~ 8

Author(s):

Jameel Iqbal ◽

Li Sun ◽

Mone Zaidi

Keyword(s):

Bone Loss ◽

Bone Mass ◽

Current Issue ◽

Scientific Evidence ◽

Primary Role ◽

Low Bone Mass ◽

Genetic Studies ◽

High Bone ◽

Estrogen Effect

Bone loss due to menopause, natural or artificial, has been attributed solely to low estrogen. However, in a woman's life, the most precipitous bone loss begins 2 years prior to the last menstrual period, during which time estrogen levels are unperturbed whereas FSH is elevated. Our cell-based and mouse genetic studies have shown that FSH stimulates bone resorption by osteoclasts directly in a pituitary–bone axis, independently of the estrogen effect. On the basis of this and evolving clinical and scientific evidence, we propose that elevated FSH contributes to bone loss across the menopausal transition, particularly during late perimenopause. In the current issue of theEuropean Journal of Endocrinology, Rendinaet al.strengthen the view for a primary role of FSH signaling in the regulation of bone mass and bone remodeling in humans by demonstrating that an ‘activating’ polymorphism AA rs6166 causes low bone mass and high bone turnover.

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Preventive Effects of Collagen Peptide from Deer Sinew on Bone Loss in Ovariectomized Rats

Evidence-based Complementary and Alternative Medicine ◽

10.1155/2014/627285 ◽

2014 ◽

Vol 2014 ◽

pp. 1-9 ◽

Cited By ~ 6

Author(s):

He Zhang ◽

Ying Dong ◽

Bin Qi ◽

Li Liu ◽

Guangxin Zhou ◽

...

Keyword(s):

Body Weight ◽

Bone Loss ◽

Female Rats ◽

Ovariectomized Rats ◽

Uterine Weight ◽

Mineral Density ◽

Active Constituent ◽

Collagen Peptide ◽

Calcium Phosphorus ◽

Serum Biochemical

Deer sinew (DS) has been used traditionally for various illnesses, and the major active constituent is collagen. In this study, we assessed the effects of collagen peptide from DS on bone loss in the ovariectomized rats. Wister female rats were randomly divided into six groups as follows: sham-operated (SHAM), ovariectomized control (OVX), OVX given 1.0 mg/kg/week nylestriol (OVX + N), OVX given 0.4 g/kg/day collagen peptide (OVX + H), OVX given 0.2 g/kg/day collagen peptide (OXV + M), and OVX given 0.1 g/kg/day collagen peptide (OXV + L), respectively. After 13 weeks of treatment, the rats were euthanized, and the effects of collagen peptide on body weight, uterine weight, bone mineral density (BMD), serum biochemical indicators, bone histomorphometry, and bone mechanics were observed. The data showed that BMD and concentration of serum hydroxyproline were significantly increased and the levels of serum calcium, phosphorus, and alkaline phosphatase were decreased. Besides, histomorphometric parameters and mechanical indicators were improved. However, collagen peptide of DS has no effect on estradiol level, body weight, and uterine weight. Therefore, these results suggest that the collagen peptide supplementation may also prevent and treat bone loss.

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Low bone mass and fast rate of bone loss at menopause: equal risk factors for future fracture. A 15-year follow-up study

Maturitas ◽

10.1016/s0378-5122(97)88490-3 ◽

1997 ◽

Vol 26 (2) ◽

pp. 154-155

Author(s):

B.J. Riis ◽

M.A. Hansen ◽

A.M. Jensen ◽

K. Overgaard ◽

C. Christiansen

Keyword(s):

Risk Factors ◽

Bone Loss ◽

Bone Mass ◽

Fast Rate ◽

Low Bone Mass ◽

Follow Up Study ◽

Future Fracture ◽

Rate Of Bone Loss

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Evaluación de causas secundarias de baja masa ósea en mujeres colombianas con osteoporosis posmenopáusica

Revista Colombiana de Endocrinología, Diabetes & Metabolismo ◽

10.53853/encr.3.4.5 ◽

2017 ◽

Vol 3 (4) ◽

pp. 12-16

Author(s):

Edwin Antonio Wandurraga ◽

Lisseth Fernanda Marín Carrillo ◽

Annie Katherine Natera Melo ◽

Claudia Milena Gómez Giraldo ◽

Juan Camilo Mendoza Díaz

Keyword(s):

Alkaline Phosphatase ◽

Bone Loss ◽

Bone Mass ◽

Postmenopausal Osteoporosis ◽

Inverse Correlation ◽

Low Bone Mass ◽

Mineral Density ◽

History Of ◽

Las Mujeres ◽

Secondary Causes

Introducción: La osteoporosis posmenopáusica puede coexistir con otras entidades que aumentan la pérdida ósea.Objetivo: Determinar la frecuencia de causas secundarias de baja masa ósea en mujeres con osteoporosis posmenopáusica en una población colombiana.Diseño: Estudio descriptivo retrospectivo.Población: Mujeres mayores de 50 años con diagnóstico reciente de osteoporosis posmenopáusica antes de iniciar tratamiento.Mediciones: Se incluyeron variables demográficas, densitométricas y bioquímicas como hemoglobina, fosfatasa alcalina, transaminasas, creatinina, 25-hidroxivitamina D, calcio, fósforo, magnesio, calciuria en 24 horas, PTH y TSH.Resultados: Se incluyeron 129 mujeres con edad promedio de 67+/-8,8 años. Cuarenta y nueve mujeres (36%) presentaban antecedente de fractura por fragilidad. En el 86,8% se encontró al menos una alteración bioquímica asociada con pérdida de masa ósea, documentándose insuficiencia de vitamina D en 71,8%, hiperparatiroidismo normocalcémico en 18,1% e hipercalciuria en 6,4%. Las mujeres con antecedente de fractura presentaron valor promedio de fosfatasa alcalina superior (111,6 +/- 61,3 vs 87,1 +/- 30,4 U/L, p= 0,0143) y promedio de hemoglobina inferior (12,9 +/- 1,2 vs. 14,2 +/- 1,2gr/dl, p<0,0001) al compararse con las mujeres sin fractura. Se encontró correlación inversa entre los niveles de fosfatasa alcalina y la densidad mineral ósea de la columna lumbar (p<0,001) y la cadera (p=0,003).Conclusiones: Las causas secundarias de baja masa ósea en mujeres con OPM son frecuentes en nuestro medio. Con base en una frecuencia de alteraciones mayor al 5%, sugerimos la evaluación de toda mujer con OPM con hemoglobina, calcio, calciuria en 24 horas, 25-hidroxivitamina D, AST, PTH y TSH.Abstract Introduction: Postmenopausal osteoporosis can coexist with other entities that increase bone loss. Aim: To determine the frequency of secondary causes of low bone mass in women with postmenopausal osteoporosis in a Colombian population. Materials and methods: A retrospective descriptive study was conducted, including women over 50 years with newly diagnosed postmenopausal osteoporosis without treatment. Demographic, densitometric and biochemical variables such as hemoglobin, alkaline phosphatase, transaminases, creatinine, 25 hydroxivitamin D, calcium, phosphorus, magnesium, calciuria in 24 hours, PTH and TSH were evaluated.Results: 129 women with a mean age of 67 +/- 8,8 years were included. 49 patients (36%) had history of fragility fracture. At least one biochemical disorder associated with bone loss was reported in 86,8% of cases, vitamin D insufficiency was documented in 71,8%, normocalcemic hyperparathyroidism in 18,1% and hypercalciuria in 6,4%. Women with history of fracture showed higher average value of alkaline phosphatase (111,6 +/- 61,3 vs 87,1 +/- 30,4 U/L, p=0,0143) and lower mean hemoglobin (12,9 +/- 1,2 vs 14,2 +/- 1,2 gr/dl, p<0,0001) compared with women without fracture. Inverse correlation was found between levels of alkaline phosphatase and bone mineral density of lumbar spine (p<0,001) and hip (p=0,003). Conclusions: Secondary causes of low bone mass in women with PMO are frequent in our clinical practice. Based on a frequency of laboratory abnormalities greater than 5%, we suggest that all women with PMO should be studied with hemoglobin, serum calcium, urinary calcium in 24 hours, 25 hydroxivitamin D, AST, PTH and TSH. Keywords: ; ; etiology;; .

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