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

2015 ◽  
Vol 227 (3) ◽  
pp. 129-141 ◽  
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.

scholarly journals Sex Steroids and the Construction and Conservation of the Adult Skeleton

2002 ◽  
Vol 23 (3) ◽  
pp. 279-302 ◽  
Author(s):  
B. Lawrence Riggs ◽  
Sundeep Khosla ◽  
L. Joseph Melton
Keyword(s):  
Bone Loss ◽  
Bone Mass ◽  
Cancellous Bone ◽  
Sex Steroids ◽  
Peak Bone Mass ◽  
Dietary Calcium Intake ◽  
Growth Spurt ◽  
Slow Phase ◽  
Age Related ◽  
Aging Men

Abstract Here we review and extend a new unitary model for the pathophysiology of involutional osteoporosis that identifies estrogen (E) as the key hormone for maintaining bone mass and E deficiency as the major cause of age-related bone loss in both sexes. Also, both E and testosterone (T) are key regulators of skeletal growth and maturation, and E, together with GH and IGF-I, initiate a 3- to 4-yr pubertal growth spurt that doubles skeletal mass. Although E is required for the attainment of maximal peak bone mass in both sexes, the additional action of T on stimulating periosteal apposition accounts for the larger size and thicker cortices of the adult male skeleton. Aging women undergo two phases of bone loss, whereas aging men undergo only one. In women, the menopause initiates an accelerated phase of predominantly cancellous bone loss that declines rapidly over 4–8 yr to become asymptotic with a subsequent slow phase that continues indefinitely. The accelerated phase results from the loss of the direct restraining effects of E on bone turnover, an action mediated by E receptors in both osteoblasts and osteoclasts. In the ensuing slow phase, the rate of cancellous bone loss is reduced, but the rate of cortical bone loss is unchanged or increased. This phase is mediated largely by secondary hyperparathyroidism that results from the loss of E actions on extraskeletal calcium metabolism. The resultant external calcium losses increase the level of dietary calcium intake that is required to maintain bone balance. Impaired osteoblast function due to E deficiency, aging, or both also contributes to the slow phase of bone loss. Although both serum bioavailable (Bio) E and Bio T decline in aging men, Bio E is the major predictor of their bone loss. Thus, both sex steroids are important for developing peak bone mass, but E deficiency is the major determinant of age-related bone loss in both sexes.

Modeling of Ultrasonic Wave Propagation Path through Cancellous Bone and Quantitative Estimation of Bone Density and Bone Quality

2006 ◽  
Vol 321-323 ◽  
pp. 857-861
Author(s):  
Takahiko Otani
Keyword(s):  
Bone Density ◽  
Bone Mass ◽  
Ultrasonic Wave ◽  
Cancellous Bone ◽  
Mass Density ◽  
Propagation Path ◽  
Bone Mass Density ◽  
Ultrasonic Wave Propagation ◽  
Fast And Slow Waves ◽  
Ultrasonic Parameters

Osteoporosis is a disease characterized by decreasing bone density, and is assessed by the bone mass density of cancellous bone. An X-ray method is widely used for noninvasive measurement of bone mass density [mg/cm3]. An ultrasonic method has the potential to evaluate the elastic properties, however measured ultrasonic parameters are the slope of frequency dependent attenuation (BUA [dB/MHz]) and the speed of sound (SOS [m/s]), not the bone mass density [mg/cm3]. In previous study, two longitudinal waves, the fast and slow waves, were observed in cancellous bone. In this study, the propagation path through cancellous bone is modeled to specify the causality between ultrasonic wave parameters and bone density. Then bone density and bone elasticity are quantitatively formulated. A novel ultrasonic bone densitometry, prototype LD-100, have been developed. The bone density [mg/cm3] and the bone elasticity [GPa] are evaluated by ultrasonic parameters based on the fast and slow waves in cancellous bone using a modeling of ultrasonic wave propagation path.

scholarly journals Probiotics (Bifidobacterium longum) Increase Bone Mass Density and UpregulateSparcandBmp-2Genes in Rats with Bone Loss Resulting from Ovariectomy

2015 ◽  
Vol 2015 ◽  
pp. 1-10 ◽  
Author(s):  
Kolsoom Parvaneh ◽  
Mahdi Ebrahimi ◽  
Mohd Redzwan Sabran ◽  
Golgis Karimi ◽  
Angela Ng Min Hwei ◽  
...  
Keyword(s):  
Bone Resorption ◽  
Bone Loss ◽  
Bone Formation ◽  
Bone Mass ◽  
Bone Structure ◽  
Mass Density ◽  
Bifidobacterium Longum ◽  
Bone Mass Density ◽  
Beneficial Effects ◽  
Ovx Rats

Probiotics are live microorganisms that exert beneficial effects on the host, when administered in adequate amounts. Mostly, probiotics affect the gastrointestinal (GI) tract of the host and alter the composition of gut microbiota. Nowadays, the incidence of hip fractures due to osteoporosis is increasing worldwide. Ovariectomized (OVX) rats have fragile bone due to estrogen deficiency and mimic the menopausal conditions in women. Therefore, this study aimed to examine the effects ofBifidobacterium longum(B. longum) on bone mass density (BMD), bone mineral content (BMC), bone remodeling, bone structure, and gene expression in OVX rats. The rats were randomly assigned into 3 groups (sham, OVX, and the OVX group supplemented with 1 mL ofB. longum108–109colony forming units (CFU)/mL).B. longumwas given once daily for 16 weeks, starting from 2 weeks after the surgery. TheB. longumsupplementation increased (p<0.05) serum osteocalcin (OC) and osteoblasts, bone formation parameters, and decreased serum C-terminal telopeptide (CTX) and osteoclasts, bone resorption parameters. It also altered the microstructure of the femur. Consequently, it increased BMD by increasing (p<0.05) the expression ofSparcandBmp-2genes.B. longumalleviated bone loss in OVX rats and enhanced BMD by decreasing bone resorption and increasing bone formation.

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

2020 ◽  
Vol 4 (Supplement_2) ◽  
pp. 391-391
Author(s):  
Marcus Elam ◽  
Jacquenlyn Valenzuela ◽  
Olivia Bouffard ◽  
Dalia Vasquez ◽  
Karenna Alexandra Martin ◽  
...  
Keyword(s):  
Body Weight ◽  
Bone Loss ◽  
Bone Mass ◽  
Agricultural Research ◽  
Lumbar Vertebrae ◽  
The United States ◽  
Normal Diet ◽  
Female Rats ◽  
Tartrate Resistant Acid Phosphatase ◽  
Low Bone Mass

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 &gt; 0.05). Tissue mineralization trended to significance (P &lt; 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.

scholarly journals Correlations between bone turnover markers, serum magnesium and bone mass density in postmenopausal osteoporosis

2018 ◽  
Vol Volume 13 ◽  
pp. 1383-1389 ◽  
Author(s):  
Ovidiu Alexandru Mederle ◽  
Melania Balas ◽  
Sorin Dumitru Ioanoviciu ◽  
Camelia-Vidita Gurban ◽  
Anca Tudor ◽  
...  
Keyword(s):  
Bone Mass ◽  
Bone Turnover ◽  
Postmenopausal Osteoporosis ◽  
Bone Turnover Markers ◽  
Mass Density ◽  
Serum Magnesium ◽  
Bone Mass Density ◽  
Turnover Markers

scholarly journals ANALISIS KADAR OSTEOKALSIN SERUM OSTEOPENIA DAN OSTEOPOROSIS

2018 ◽  
Vol 12 (2) ◽  
pp. 49
Author(s):  
N Sennang AN ◽  
Mutmainnah Mutmainnah ◽  
RDN Pakasi ◽  
Hardjoeno Hardjoeno
Keyword(s):  
Bone Mass ◽  
Bone Turnover ◽  
Bone Disease ◽  
Metabolic Bone Disease ◽  
Mass Density ◽  
Bone Mass Density ◽  
Serum Osteocalcin ◽  
Osteocalcin Level ◽  
Serum Osteocalcin Level ◽  
Metabolic Bone

Osteoporosis is a metabolic bone disease, characterized by decreased of bone mass density. Its incidence is higher in older population.Serum osteocalcin level is related to the rate of bone turnover. To analyze serum osteocalcin level on osteopenic and osteoporosis subjects.We examined 61 subjects for detecting osteopenia and osteoporosis by Sahara densitometer and measuring serum osteocalcin level byElecsys N-MID Osteocalsin Assay test. Of 21 men and 40 women, prevalence of osteopenia and osteoporosis were higher in women(57.5% and 32.5%) than men (42.9% and 23.8%). Most of osteoporosis subjects were in ≥ 60 years group and osteopenic subjects werein 50–59 years group (p<0.05). Mean of serum osteocalcin on osteoporosis subjects (26.70 ng/mL) was higher than osteopenic (23.78ng/mL) and normal (19.16 ng/mL) subjects (p<0.005). Prevalence of osteopenia and osteoporosis were higher in women than men. Theincidence of osteoporosis was related to the increase of age. Serum osteocalcin level was related to the severity of diagnosis category.

Impaired Estrogen Sensitivity in Bone by Inhibiting Both Estrogen Receptor a and b Pathways*

2020 ◽  
Author(s):  
Lungwani Muungo
Keyword(s):  
Bone Mineral Density ◽  
Estrogen Receptor ◽  
Bone Loss ◽  
Bone Turnover ◽  
Bone Mineral ◽  
Female Rats ◽  
Wild Type ◽  
Mineral Density ◽  
Transgenic Rats ◽  
Estrogen Sensitivity

Although it is well established that estrogen deficiencycauses osteoporosis among the postmenopausalwomen, the involvement of estrogen receptor (ER) in itspathogenesis still remains uncertain. In the presentstudy, we have generated rats harboring a dominantnegative ERa, which inhibits the actions of not only ERabut also recently identified ERb. Contrary to our expectation,the bone mineral density (BMD) of the resultingtransgenic female rats was maintained at the same levelwith that of the wild-type littermates when sham-operated.In addition, ovariectomy-induced bone loss wasobserved almost equally in both groups. Strikingly, however,the BMD of the transgenic female rats, after ovariectomized,remained decreased even if 17b-estradiol(E2) was administrated, whereas, in contrast, the decreaseof littermate BMD was completely prevented byE2. Moreover, bone histomorphometrical analysis ofovariectomized transgenic rats revealed that the higherrates of bone turnover still remained after treatmentwith E2. These results demonstrate that the preventionfrom the ovariectomy-induced bone loss by estrogen ismediated by ER pathways and that the maintenanceof BMD before ovariectomy might be compensatedby other mechanisms distinct from ERa and ERbpathways.

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