Heparin-Induced Osteoporosis in Rats

1986 ◽  
Vol 56 (03) ◽  
pp. 293-294 ◽  
Author(s):  
Thomas Matzsch ◽  
David Bergqvist ◽  
Ulla Hedner ◽  
Bo Nilsson ◽  
Per Østergaard
Keyword(s):  
Body Weight ◽  
Bone Mass ◽  
Experimental Model ◽  
Bone Mineral ◽  
Female Rats ◽  
Bone Mineral Mass ◽  
Mineral Mass

SummaryIn order to study the effect of heparin in inducing osteoporosis, 30 female rats were divided in two groups and treated with daily injections of 2 IU heparin/g body weight for 33 and 65 days and compared with the same number of rats acting as controls. The mineral bone mass in the femora of the animals was measured quantitatively. A significant (p <0.001) reduction in bone mineral mass was found in the heparin-treated animals. This effect was present to the same degree after 33 days as after 65 days of treatment. It is concluded that heparin in this dose causes osteoporosis in rats after 33 days and that the described method can be used as an experimental model for further studies on this topic.

scholarly journals A Dynamic Model of Calcium Metabolism for Predicting the Effects of Treatments on Bone Mineral Mass in Young Growing Rats (P24-046-19)

2019 ◽  
Vol 3 (Supplement_1) ◽  
Author(s):  
Joanna Hodges ◽  
Meryl Wastney ◽  
Emily Hohman ◽  
Connie Weaver
Keyword(s):  
Bone Mass ◽  
Dynamic Model ◽  
Bone Mineral ◽  
Calcium Metabolism ◽  
Calcium Absorption ◽  
Male Rats ◽  
Total Calcium ◽  
Growing Rats ◽  
Bone Mineral Mass ◽  
Mineral Mass

Abstract Objectives Quantifying the long-term effects of nutritional or drug treatments on bone is challenging due to the delay in time between treatment and changes in bone mass. The objective of this study was to develop a dynamic (non-steady state) mathematical model of calcium metabolism in young growing rats as an analogue for human adolescents and to use that model to predict the effects of treatments on calcium mass in bone. Methods A dynamic model of calcium metabolism was developed using kinetic data collected from Sprague-Dawley male rats (n = 54) dosed intraperitoneally with 50 μCi of 45Ca at 4 wk of age. Total calcium and 45Ca levels measured in serum and 24-h urine samples collected periodically for 45 d after treatment were analyzed by compartmental modeling using WinSAAM software. Concurrently, tracer (45Ca) and tracee (total calcium) models, together called the ‘dynamic model’, were developed. Growth of the rats was modeled using a formula based on body weight. Calcium absorption was decreased by about 50% at wk 6 to account for the reduction in bone mineral accretion in late puberty. During the first 40 d after weaning, the model included a 4-fold decrease in bone resorption and a 20-fold decrease in bone formation, consistent with previous findings of studies conducted in growing rats. Data were fitted by iterative least squares regression analysis. To mimic the effects of dietary and drug interventions during adolescence, the absorption efficiency was manipulated in terms of degree, timing, and duration and the subsequent changes in bone mass were quantified. Results The dynamic model predicted that, if absorption decreased by 25% instead of 50% during growth, the rate of bone accretion would be 32% higher and the bone mineral mass at d 50 would be 24% larger, suggesting that a dietary or drug intervention that minimizes the drop in absorption, would result in a higher bone mineral mass. Conclusions A dynamic model of calcium metabolism during growth was developed and used to predict the effect of interventions on bone mass. These predictions would be tested in future studies. Funding Sources Purdue University Graduate School and Amgen, Inc., Thousand Oaks, CA.

Comparative effects of Venlafaxine and Alendronate on Biochemical, Bone mechanical and Anti-inflammatory properties in ovariectomized rats

2021 ◽  
pp. 3553-3558
Author(s):  
Vadivelan Ramachandran ◽  
Punitha Nanjundan ◽  
Triveni Jasti ◽  
Manogaran Elumalai
Keyword(s):  
Alkaline Phosphatase ◽  
Body Weight ◽  
Inflammatory Cytokines ◽  
Bone Mineral ◽  
Serum Calcium ◽  
Serum Alkaline Phosphatase ◽  
Ovariectomized Rats ◽  
Bone Mineral Mass ◽  
Anti Inflammatory ◽  
Mineral Mass

The drug of choice in the treatment of postmenopausal osteoporosis is alendronate. Antidepressive agents are currently used in combination with alendronate to protect against depression and may affect the condition of osteoporosis. The aim is to study the comparative effects of venlafaxine and alendronate on biochemical, bone mechanical and anti-inflammatory properties in osteoporotic induced rats. 36 female Wistar albino rats were included (6 rats/group). Treated groups were ovariectomized bilaterally to induce osteoporosis. Rats were treated orally with alendronate (3mg/kg/day) and venlafaxine (20mg/kg/day) and combined alendronate and venlafaxine for 28 days. Body weight, serum alkaline phosphates, serum calcium, three point bending test, bone mineral mass and inflammatory cytokines The induction of osteoporosis showed significant elevated serum alkaline phosphatase, decreased serum calcium, body weight, bone mineral mass and inflammatory cytokines. Venlafaxine treatment did not ameliorate the changes in tested parameters, where at end of the experiment alendronate has significant improved with serum alkaline phosphatase, serum calcium, bone mineral mass, bone mineral density. The improvement was not affected by combining venlafaxine with alendronate whereas the venlafaxine treatment alone caused a significant deterioration of tested parameters. Venlafaxine is an anti-depressive agent that inhibits brain serotonin which leads to decrease in bone formation. Hence, from the above findings the combination of alendronate and venlafaxine showed worsen the condition of osteoporosis rats.

Effects of Low Molecular Weight Heparin and Unfragmented Heparin on Induction of Osteoporosis in Rats

1990 ◽  
Vol 63 (03) ◽  
pp. 505-509 ◽  
Author(s):  
Thomas Mätzsch ◽  
David Bergqvist ◽  
Ulla Hedner ◽  
Bo Nilsson ◽  
Per Østergaar
Keyword(s):  
Molecular Weight ◽  
Bone Mineral ◽  
Low Molecular Weight Heparin ◽  
Zinc Content ◽  
Low Molecular Weight ◽  
Dependent Manner ◽  
Bone Mineral Mass ◽  
Bone Ash ◽  
Dose Dependent ◽  
Mineral Mass

SummaryA comparison between the effect of low molecular weight heparin (LMWH) and unfragmented heparin (UH) on induction of osteoporosis was made in 60 rats treated with either UH (2 IU/ g b w), LMWH in 2 doses (2 Xal U/g or 0.4 Xal U/g) or placebo (saline) for 34 days. Studied variables were: bone mineral mass in femora; fragility of humera; zinc and calcium levels in serum and bone ash and albumin in plasma. A significant reduction in bone mineral mass was found in all heparin-treated rats. There was no difference between UH and LMWH in this respect. The effect was dose-dependent in LMWH-treated animals. The zinc contents in bone ash were decreased in all heparin-treated rats as compared with controls. No recognizable pattern was seen in alterations of zinc or calcium in serum. The fragility of the humera, tested as breaking strength did not differ between treatment groups and controls. In conclusion, if dosed according to similar factor Xa inhibitory activities, LMWH induces osteoporosis to the same extent as UH and in a dose-dependent manner. The zinc content in bone ash was decreased after heparin treatment, irrespective of type of heparin given.

Bone mineral mass consolidation in young British adults

2009 ◽  
Vol 11 (2) ◽  
pp. 264-274 ◽  
Author(s):  
Tessa J. Parsons ◽  
Ann Prentice ◽  
Elisabeth A. Smith ◽  
Tim J. Cole ◽  
Juliet E. Compston
Keyword(s):  
Bone Mineral ◽  
Bone Mineral Mass ◽  
Mineral Mass

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 New method for assessing bone mineral mass

1996 ◽  
Vol 64 (4) ◽  
pp. 664-664
Author(s):  
M Fukunaga ◽  
M Sakamoto
Keyword(s):  
Bone Mineral ◽  
New Method ◽  
Bone Mineral Mass ◽  
Mineral Mass

Effect of nitric oxide synthase inhibitors on bone metabolism in growing rats

1996 ◽  
Vol 270 (5) ◽  
pp. E840-E845 ◽  
Author(s):  
H. Tsukahara ◽  
M. Miura ◽  
S. Tsuchida ◽  
I. Hata ◽  
K. Hata ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Bone Mass ◽  
Bone Mineral ◽  
Normal Serum ◽  
Bone Mineral Status ◽  
Growing Rats ◽  
Bone Mineral Mass ◽  
Bone Degradation ◽  
Cross Links

We examined the effects of chronic nitric oxide (NO) blockade on bone mineral status in growing rats. Oral administration of NG-nitro-L-arginine methyl ester (L-NAME) for 4 wk caused hypertension and a significant reduction in urinary NO2- and NO3- excretion. Four-week oral aminoguanidine (AG, 400 mg/dl of drinking water) did not alter blood pressure but caused a significant decrease in urinary NO2- and NO3-. Rats treated with L-NAME at doses of 20 and 50 mg/dl had normal bone mineral mass in the lumbar spine, but the highest dose (80 mg/dl) caused a slight decrease in bone mass. Chronic AG induced a significant spine osteopenia. This effect of AG was abolished by the simultaneous administration of L-arginine (2.0 g/dl). AG-induced osteopenia was associated with a significant increase in urine excretion of collagen cross-links with normal serum osteocalcin. These findings indicate that chronic AG administration can cause an imbalance between bone resorption and formation, resulting in a decrease in bone mass in growing rats, and suggest that NO produced by inducible NO synthase plays an important role in basal osteoclast bone degradation activity in vivo.

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