Long-Term Therapy with a New Chemically Modified Tetracycline (CMT-8) Inhibits Bone Loss in Femurs of Ovariectomized Rats

1998 ◽  
Vol 12 (1) ◽  
pp. 76-81 ◽  
Author(s):  
T. Sasaki ◽  
N.S. Ramamurthy ◽  
L.M. Golub
Keyword(s):  
Bone Loss ◽  
Bone Formation ◽  
Trabecular Bone ◽  
Female Rats ◽  
Ovariectomized Rats ◽  
Term Therapy ◽  
Ovx Rats ◽  
Trabecular Bone Loss ◽  
Bone Trabeculae

The effect of a new non-antimicrobial analog of tetracycline (CMT-8) on bone loss in ovariectomized (OVX) rats was examined. Three-month-old female rats were ovariectomized, and one week later, were distributed into 3 groups: sham-operated non-OVX controls, vehicle-treated OVX controls, and CMT-8-treated OVX rats. After 145 days of daily CMT-8 administration, the intact femurs were dissected and examined by several histological and histomorphometric techniques. OVX significantly (p < 0.01) decreased trabecular bone volume by 53.4% in the metaphyses compared with sham-operated controls. CMT-8 therapy produced a significant (p < 0.05) inhibition of trabecular bone loss and also induced bone formation in the OVX rats. Of interest, the newly synthesized bone in the CMT-treated OVX rats was found to increase the "connectivity" of the trabecular "struts" by bridging the adjacent longitudinal bone trabeculae, forming dense, platelike bone trabeculae. These results strongly suggest that long-term CMT-8 therapy effectively inhibits bone loss after OVX, not only by inhibiting bone resorption but also by inducing new bone formation in the trabecular areas of long bones.

scholarly journals Combination treatment with pioglitazone and fenofibrate attenuates pioglitazone-mediated acceleration of bone loss in ovariectomized rats

2011 ◽  
Vol 212 (2) ◽  
pp. 179-186 ◽  
Author(s):  
Rana Samadfam ◽  
Malaika Awori ◽  
Agnes Bénardeau ◽  
Frieder Bauss ◽  
Elena Sebokova ◽  
...  
Keyword(s):  
Bone Loss ◽  
Bone Mass ◽  
Trabecular Bone ◽  
Bone Mineral ◽  
Combination Treatment ◽  
Mass Gain ◽  
Ovariectomized Rats ◽  
Concomitant Treatment ◽  
Mineral Density ◽  
Ovx Rats

Peroxisome proliferator-activated receptor (PPAR) γ agonists, such as pioglitazone (Pio), improve glycemia and lipid profile but are associated with bone loss and fracture risk. Data regarding bone effects of PPARα agonists (including fenofibrate (Feno)) are limited, although animal studies suggest that Feno may increase bone mass. This study investigated the effects of a 13-week oral combination treatment with Pio (10 mg/kg per day)+Feno (25 mg/kg per day) on body composition and bone mass parameters compared with Pio or Feno alone in adult ovariectomized (OVX) rats, with a 4-week bone depletion period, followed by a 6-week treatment-free period. Treatment of OVX rats with Pio+Feno resulted in ∼50% lower fat mass gain compared with Pio treatment alone. Combination treatment with Pio+Feno partially prevented Pio-induced loss of bone mineral content (∼45%) and bone mineral density (BMD; ∼60%) at the lumbar spine. Similar effects of treatments were observed at the femur, most notably at sites rich in trabecular bone. At the proximal tibial metaphysis, concomitant treatment with Pio+Feno prevented Pio exacerbation of ovariectomy-induced loss of trabecular bone, resulting in BMD values in the Pio+Feno group comparable to OVX controls. Discontinuation of Pio or Feno treatment of OVX rats was associated with partial reversal of effects on bone loss or bone mass gain, respectively, while values in the Pio+Feno group remained comparable to OVX controls. These data suggest that concurrent/dual agonism of PPARγ and PPARα may reduce the negative effects of PPARγ agonism on bone mass.

scholarly journals Retraction: Effect of pre- and post-surgery treatment with risedronate on trabecular bone loss in ovariectomized rats

2018 ◽  
Vol 67 (3) ◽  
pp. R3 ◽  
Author(s):  
Jun IWAMOTO ◽  
Tsuyoshi TAKEDA ◽  
Yoshihiro SATO ◽  
Chwan-Li SHEN ◽  
James K. YEH
Keyword(s):  
Bone Loss ◽  
Trabecular Bone ◽  
Ovariectomized Rats ◽  
Post Surgery ◽  
Trabecular Bone Loss

Bone modeling in bromocriptine-treated pregnant and lactating rats: possible osteoregulatory role of prolactin in lactation

2010 ◽  
Vol 299 (3) ◽  
pp. E426-E436 ◽  
Author(s):  
Panan Suntornsaratoon ◽  
Kannikar Wongdee ◽  
Suchandra Goswami ◽  
Nateetip Krishnamra ◽  
Narattaphol Charoenphandhu
Keyword(s):  
Bone Loss ◽  
Bone Formation ◽  
Trabecular Bone ◽  
Formation Rate ◽  
Bone Modeling ◽  
Mineral Density ◽  
Pregnant Rats ◽  
Bone Formation Rate ◽  
Bone Trabeculae ◽  
Bone Gain

The lactogenic hormone prolactin (PRL) directly regulates osteoblast functions in vitro and modulates bone remodeling in nulliparous rats, but its osteoregulatory roles in pregnant and lactating rats with physiological hyperprolactinemia remained unclear. Herein, bone changes were investigated in rats treated with bromocriptine (Bromo), an inhibitor of pituitary PRL release, or Bromo+PRL at different reproductive phases, from mid-pregnancy to late lactation. PRL receptors were strongly expressed in osteoblasts lining bone trabeculae, indicating bone as a target of PRL actions. By using dual energy X-ray absorptiometry, we found a significant increase in bone mineral density in the femora and vertebrae of pregnant rats. Such pregnancy-induced bone gain was, however, PRL independent and may have resulted from the increased cortical thickness. Bone trabeculae were modestly changed during pregnancy as evaluated by bone histomorphometry. On the other hand, lactating rats, especially in late lactation, showed massive bone loss in bone trabeculae but not in cortical shells. Further study in Bromo- and Bromo+PRL-treated rats suggested that PRL contributed to decreases in trabecular bone volume and number and increases in trabecular separation and eroded surface, as well as a paradoxical increase in bone formation rate in late lactation. Uncoupling of trabecular bone formation and resorption was evident in lactating rats, with the latter being predominant. In conclusion, pregnancy mainly induced cortical bone gain, whereas lactation led to trabecular bone loss in both long bones and vertebrae. Although PRL was not responsible for the pregnancy-induced bone gain, it was an important regulator of bone modeling during lactation.

scholarly journals Short- and long-term effects of calcium and exercise on bone mineral density in ovariectomized rats

2001 ◽  
Vol 86 (4) ◽  
pp. 521-527 ◽  
Author(s):  
Joseé Gala ◽  
Manuel Di´az-curiel ◽  
Concepcioó de la Piedra ◽  
Jesu´s Calero
Keyword(s):  
Bone Mineral Density ◽  
Bone Loss ◽  
Bone Mineral ◽  
Exercise Programme ◽  
Female Rats ◽  
Ovariectomized Rats ◽  
Standard Diet ◽  
Mineral Density ◽  
Left Femur ◽  
Ovx Rats

At the level of prevention of bone mineral loss produced by ovariectomy, the aim of the present study was to determine the effect produced by supplementation of Ca in the diet and a moderate exercise programme (treadmill), simultaneously or separately, in ovariectomized rats, an experimental model of postmenopausal bone loss. Female Wistar rats (n110, 15 weeks old) were divided into five groups: (1) OVX, rats ovariectomized at 15 weeks of age, fed a standard diet; (2) SHAM, rats sham operated at 15 weeks of age, fed a standard diet; (3) OVX–EX, ovariectomized rats, fed a standard diet and performing the established exercise programme; (4) OVX–Ca, ovariectomized rats fed a diet supplemented with Ca; (5) OVX–EXCa, ovariectomized rats with the exercise programme and diet supplemented with Ca. The different treatments were initiated 1 week after ovariectomy and were continued for 13 weeks for subgroup 1 and 28 weeks for subgroup 2, to look at the interaction of age and time passed from ovariectomy on the treatments. Bone mineral density (BMD) was determined, at the end of the study, in the lumbar spine (L2, L3 and L4) and in the left femur using a densitometer. Bone turnover was also estimated at the end of the study, measuring the serum formation marker total alkaline phosphatase (AP) and the resorption marker serum tartrate-resistant acid phosphatase (TRAP). As expected, OVX rats showed a significant decrease (P<0·05) in BMD, more pronounced in subgroup 2, and a significant increase in AP and TRAP with regard to their respective SHAM group. The simultaneous treatment with Ca and exercise produced the best effects on lumbar and femoral BMD of ovariectomized rats, partially avoiding bone loss produced by ovariectomy, although it was not able to fully maintain BMD levels of intact animals. This combined treatment produced a significant increase in AP, both in subgroups 1 and 2, and a decrease in TRAP in subgroup 1, with regard to OVX group. The exercise treatment alone was able to produce an increase in BMD with regard to OVX group only in subgroup 1 of rats (younger animals and less time from ovariectomy), but not in subgroup 2. In agreement with this, there was an increase of AP in both subgroups, lower than that observed in animals submitted to exercise plus Ca supplement, and a decrease of TRAP in subgroup 1, without significant changes in this marker in the older rats. Ca treatment did not produce any significant effect on BMD in OVX rats in both subgroups of animals, showing a decrease of AP and TRAP levels in the younger animals with no significant variations in markers of bone remodelling in the older female rats compared with their respective OVX group.

scholarly journals New Bone Formation with Teriparatide [Human Parathyroid Hormone-(1–34)] Is Not Retarded by Long-Term Pretreatment with Alendronate, Estrogen, or Raloxifene in Ovariectomized Rats

Endocrinology ◽  
2003 ◽  
Vol 144 (5) ◽  
pp. 2008-2015 ◽  
Author(s):  
Yanfei L. Ma ◽  
Henry U. Bryant ◽  
Qingqiang Zeng ◽  
Allen Schmidt ◽  
Jennifer Hoover ◽  
...  
Keyword(s):  
Bone Loss ◽  
Bone Formation ◽  
Formation Rate ◽  
Prior Exposure ◽  
Ovariectomized Rats ◽  
Mineral Density ◽  
Bone Formation Rate ◽  
Teriparatide Treatment ◽  
Antiresorptive Agents ◽  
Ovx Rats

With the ready availability of several osteoporosis therapies, teriparatide [human PTH-(1–34)] is likely to be prescribed to postmenopausal women with prior exposure to agents that prevent bone loss, such as bisphosphonates, estrogen, or selective estrogen receptor modulators. Therefore, we evaluated the ability of once daily teriparatide to induce bone formation in ovariectomized (Ovx) rats with extended prior exposure to various antiresorptive agents, such as alendronate (ABP), 17α-ethinyl estradiol (EE), or raloxifene (Ral). Sprague Dawley rats were Ovx and treated with ABP (28 μg/kg, twice weekly), EE (0.1 mg/kg·d), or Ral (1 mg/kg·d) for 10 months before switching to teriparatide 30 μg/kg·d for another 2 months. Analysis of the proximal tibial metaphysis showed that all three antiresorptive agents prevented ovariectomy-induced bone loss after 10 months, but were mechanistically distinct, as shown by histomorphometry. Before teriparatide treatment, ABP strongly suppressed activation frequency and bone formation rate to below levels in other treatment groups, whereas these parameters were not different from sham values for EE or Ral. Trabecular area for ABP, EE, and Ral were greater than that in Ovx controls. However, the trabecular bone effects of ABP were attributed not only to effects on the secondary spongiosa, but also to the preservation of primary spongiosa, which was prevented from remodeling. After 2 months of teriparatide treatment, lumbar vertebra showed relative bone mineral density increases of 18%, 7%, 11%, and 10% for vehicle/teriparatide, ABP/teriparatide, EE/teriparatide, and Ral/teriparatide, respectively, compared with 10 month levels. Histomorphometry showed that trabecular area was increased by 105%, 113%, 36%, and 48% for vehicle/teriparatide, ABP/teriparatide, EE/teriparatide, and Ral/teriparatide, respectively, compared with 10 month levels. Teriparatide enhanced mineralizing surface, mineral apposition rate, and bone formation rate in all groups. Compression testing of vertebra showed that teriparatide improved strength (peak load) and toughness in all groups to a proportionately similar extent compared with 10 month levels. These data showed a surprising ability of the rat skeleton to respond to teriparatide despite extensive pretreatment with ABP, EE, or Ral. Therefore, the mature skeleton of Ovx rats remains highly responsive to the appositional effects of teriparatide regardless of pretreatment status in terms of cancellous bone area or rate of bone turnover.

scholarly journals Red wine polyphenols modulate bone loss in the ovariectomized rat model of postmenopausal osteoporosis

2019 ◽  
Vol 70 (2) ◽  
pp. 1541
Author(s):  
C. PASSALI ◽  
A. PATSAKI ◽  
P. LELOVAS ◽  
N. ALIGIANNIS ◽  
M. MAKROPOULOU ◽  
...  
Keyword(s):  
Bone Loss ◽  
Rat Model ◽  
Red Wine ◽  
Bending Test ◽  
Ovariectomized Rats ◽  
Mineral Density ◽  
Ovx Rats ◽  
Trabecular Bone Loss ◽  
Wine Polyphenols ◽  
Red Wine Polyphenols

The aim of this study was to examine the effect of Red Wine Polyphenols (RWPs) extract on bone mineral density (BMD) in the ovariectomized (OVX) rat model. Thirty-five 10-month-old Wistar rats were separated into controls (CTRL), OVX and OVX plus RWPs in their drinking water (dose, 50 mg/kg body weight per day), starting immediately after OVX for 6 months. Βody and uterine weight, BMD of the tibia at baseline, 3 and 6 months post-OVX, and 3-pointing bending of the femur, were examined. Statistical comparison of the total tibia BMD within groups during the study period showed a significant reduction in the OVX and OVX+RWPs groups both from baseline to 3 and 6 months and from 3 to 6 months, whereas in the CTRL group, there was no significant change. For the proximal tibial metaphysis, comparison of BMD percentage changes from baseline to 3 months and 6 months and from 3 to 6 months revealed highly statistical differences between OVX and OVX+RWPs groups (P = 0.000). OVX induced a significant reduction of biomechanical parameters as expected; the 3-point bending test showed that the maximum force before fracture, energy absorption and fracture stress significantly increased in the OVX group treated with RWPs compared with the nontreated OVX rats (P = 0.048, P = 0.002 and P = 0.003, respectively). Dietary intake of RWPs for 6 months significantly prevented trabecular bone loss and improved bone strength in estrogen-deficient ovariectomized rats.

scholarly journals Rhizoma drynariae total flavonoids combined with calcium carbonate ameliorates bone loss in experimentally induced Osteoporosis in rats via the regulation of Wnt3a/β-catenin pathway

2021 ◽  
Vol 16 (1) ◽  
Author(s):  
Yimei Hu ◽  
Panyun Mu ◽  
Xu Ma ◽  
Jingru Shi ◽  
Zhendong Zhong ◽  
...  
Keyword(s):  
Calcium Carbonate ◽  
Bone Loss ◽  
Bone Formation ◽  
Chinese Herb ◽  
Estrogen Deficiency ◽  
Ovariectomized Rats ◽  
Cartilage Tissue ◽  
Total Flavonoids ◽  
Ovx Rats ◽  
Rhizoma Drynariae

Abstract Background Rhizoma drynariae, a traditional Chinese herb, is commonly used in treatment of bone healing in osteoporotic fractures. However, whether the Rhizoma drynariae total flavonoids (RDTF) can promote the absorption of calcium and enhance the bone formation is unclear. The aim of the present study was to investigate the preventive effects of RDTF combined with calcium carbonate (CaCO3) on estrogen deficiency-induced bone loss. Methods Three-month-old Sprague–Dawley rats were ovariectomized (OVX) and then treated with CaCO3, RDTF, and their admixtures for ten weeks, respectively. The bone trabecular microstructure, bone histopathological examination, and serum biomarkers of bone formation and resorption were determined in the rat femur tissue. The contents of osteoprotegerin (OPG), receptor activator of the NF-κB (RANK), and its ligand (RANKL) in marrow were analyzed by ELISA, and the protein expressions of Wnt3a, β-catenin, and phosphorylated β-catenin (p-β-catenin) were analyzed by Western blot. Statistical analysis was conducted by using one-way analysis of variance (ANOVA) followed by LSD post hoc analysis or independent samples t test using the scientific statistic software SPSS version 20.0 Results RDTF combined with CaCO3 could promote osteosis and ameliorate bone loss to improve the repair of cracked bone trabeculae of OVX rats. Furthermore, RDTF combined with CaCO3 also could prevent OVX-induced decrease in collagen fibers in the femoral tissue of ovariectomized rats and promote the regeneration of new bone or cartilage tissue, while CaCO3 supplementation promoted the increase in bone mineral content. Nevertheless, there was no difference in the expression of Wnt3a, β-catenin and p-β-catenin between osteopenic rats and RDTF treated rats, but RDTF combined with CaCO3 could activate the Wnt3a/β-catenin pathway. Conclusions RDTF combined with CaCO3 could ameliorate estrogen deficiency-induced bone loss via the regulation of Wnt3a/β-catenin pathway.

scholarly journals Evaluation of the Bone Morphology Around Four Types of Porous Metal Implants Placed in Distal Femur of Ovariectomized Rats

2020 ◽  
Author(s):  
Stanislav Bondarenko ◽  
Nataliya Ashukina ◽  
Valentyna Maltseva ◽  
Gennadiy Ivanov ◽  
Ahmed Amine Badnaoui ◽  
...  
Keyword(s):  
Bone Formation ◽  
Histological Study ◽  
Porous Metal ◽  
Structural Features ◽  
Female Rats ◽  
Ovariectomized Rats ◽  
Control Group ◽  
Implant Materials ◽  
Normal Bone ◽  
Ovx Rats

Abstract Background To compare structural features of femoral bone of ovariectomized and non-ovariectomized rats after implantation of porous materials (TANTALUM, CONCELOC, TTM, ATLANT). Methods Experiments were carried out on 56 white laboratory female rats aged 6-months. Rats were randomly assigned into groups: Sham control group (SH) or ovariectomy group (OVX). Four different commercial implant materials (TTM, CONCELOC, TANTALUM, ATLANT) were placed into the defects (diameter 2.5mm, depth 3.0mm) in the distal metaphysis of femurs. Rats were sacrificed 45-days after surgery. Histological study was performed and the percentage of bone area (BA%) around the implant at a distance of 500μm in the cancellous area was measured. Results Formation of mature bone tissue of varying degrees around all of the implants was detected. In OVX rats cancellous bone defect zone was characterized by a high density of osteocytes on the surface. In the SH group, no differences in BA% among implant materials were found. In OVX rats the BA% around ATLANT implants was 1.5-time less (p=0.002) than around TANTALUM. The BA% around the rest of the materials was not statistically different. Conclusions Bone formation around the studied porous titanium and tantalum materials in the osteoporosis model was lower than in normal bone. There were differences in bone formation around the different materials in the osteoporosis model, while in the normal bone model these differences were absent.

Distinct effects of ovarian transplantation and exogenous 17 β-oestradiol on cancellous bone of osteopenic ovariectomized rats

1995 ◽  
Vol 133 (4) ◽  
pp. 483-488 ◽  
Author(s):  
Andrea C Gallagher ◽  
Timothy J Chambers ◽  
Jonathan H Tobias
Keyword(s):  
Bone Loss ◽  
Bone Metabolism ◽  
Cancellous Bone ◽  
Ovarian Function ◽  
Bone Volume ◽  
Female Rats ◽  
Ovariectomized Rats ◽  
Serum Progesterone ◽  
Ovarian Transplantation ◽  
Ovx Rats

Gallagher AC, Chambers TJ, Tobias JH. Distinct effects of ovarian transplantation and exogenous 17 β-oestradiol on cancellous bone of osteopenic ovariectomized rats. Eur J Endocrinol 1995;133:483–8. ISSN 0804–4643 Although 17 β-oestradiol (E2) is known to prevent bone loss, prolonged administration of E2 is unable to reverse this in female rats rendered osteopenic by ovariectomy. To determine whether this reflects a failure to replace other components of ovarian function involved in bone metabolism, we compared the effects of administering E2 to osteopenic ovariectomized (ovx) rats with those of ovarian transplantation. Ovariectomy was performed in female rats. After 13 weeks, by which time marked bone loss had occurred, one group of ovx animals received ovaries from donor rats, and, after a delay of 2 weeks to allow oestrus cycles to return, a further group received E2 5 μg · kg−1 · day−1 for 9 weeks. The dose of E2 was chosen as that which in preliminary studies restored mean serum E2 levels to that of intact female rats. The study was terminated 24 weeks after ovariectomy. Both E2 and ovarian transplantation largely restored indices of oestrogenic exposure in ovx rats to those of sham-ovx animals. Animals receiving ovarian transplants also showed a small increase in serum progesterone and full restoration of serum testosterone. However, while ovarian transplantation also returned indices of cancellous bone metabolism to those of sham-ovx animals, there was little increase in bone volume. Interestingly, exogenous E2 caused a greater increase in cancellous bone volume than ovarian transplantation but also caused more marked suppression of bone formation, as assessed at the end of the study. In conclusion, exogenous E2 and ovarian transplantation exerted distinct effects on skeletal metabolism in osteopenic ovx rats, although the basis for this difference is currently unclear. JH Tobias, Department of Histopathology, St George's Hospital Medical School, London SW17 ORE, UK

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