scholarly journals Prevention of Osteoporosis in the Ovariectomized Rat by Oral Administration of a Nutraceutical Combination That Stimulates Nitric Oxide Production

2019 ◽  
Vol 2019 ◽  
pp. 1-11 ◽  
Author(s):  
Rebecca A. Rajfer ◽  
Manuel Flores ◽  
Andrea Abraham ◽  
Eduardo Garcia ◽  
Natalhy Hinojosa ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Bone Resorption ◽  
Bone Formation ◽  
Bone Mineral ◽  
Lumbar Vertebrae ◽  
Calcium Deposition ◽  
Mineral Density ◽  
Ovx Rats ◽  
Cgmp Pathway ◽  
Tracp 5B

Osteoporosis represents an imbalance between bone formation and bone resorption. As a result of low estrogen levels, it is markedly prevalent during menopause, thus making such patients susceptible to fractures. Both bone formation and resorption are modulated by nitric oxide (NO). Currently, there are no risk-free pharmaceutical prevention therapies for osteoporosis. COMB-4, a nutraceutical combination of Paullinia cupana, Muira puama, ginger, and L-citrulline, known to activate the NO-cGMP pathway, was reported to accelerate fracture healing in the rat. To determine whether COMB-4 could be effective in preventing menopausal osteoporosis, it was compared to estradiol (E2) in an ovariectomized (OVX) rat osteoporosis model. Nine-month-old female Sprague Dawley rats were divided into SHAM, OVX, OVX+E2, and OVX+COMB-4. After 100 days of treatment, bone mineral density (BMD) and bone mineral content (BMC) were measured by DXA scan. TRAP staining was performed in the femur and lumbar vertebrae. TRACP 5b and osteocalcin levels were assayed in the serum. MC3T3-E1 cells were differentiated into osteoblasts and treated with COMB-4 for one week in order to evaluate calcium deposition by Alizarin staining, cGMP production by ELISA, and upregulation of the nitric oxide synthase (NOS) enzymes by RT-PCR. OVX resulted in a decrease in BMD, BMC, and serum osteocalcin and an increase in serum TRACP 5b. Except for an increase in BMC with COMB-4, both E2 and COMB-4 reverted all bone and serum markers, as well as the number of osteoclasts in the vertebrae, to SHAM levels. Incubation of MC3T3-E1 cells with COMB-4 demonstrated an increase in the three NOS isoforms, cGMP, and calcium deposition. COMB-4 increased BMD in OVX rats by inhibiting bone resorption and increasing calcium deposition presumably via activation of the NO-cGMP pathway. It remains to be determined whether COMB-4 could be a potential nutraceutical therapy for the prevention of premenopausal bone loss.

scholarly journals Bone Density, Turnover, and Estimated Strength in Postmenopausal Women Treated With Odanacatib: A Randomized Trial

2013 ◽  
Vol 98 (2) ◽  
pp. 571-580 ◽  
Author(s):  
Kim Brixen ◽  
Roland Chapurlat ◽  
Angela M. Cheung ◽  
Tony M. Keaveny ◽  
Thomas Fuerst ◽  
...  
Keyword(s):  
Lumbar Spine ◽  
Bone Resorption ◽  
Bone Formation ◽  
Postmenopausal Women ◽  
Bone Strength ◽  
Bone Mineral ◽  
Bone Resorption Marker ◽  
Mineral Density ◽  
Volumetric Bmd ◽  
The Impact

Abstract Context: Odanacatib, a cathepsin K inhibitor, increases spine and hip areal bone mineral density (BMD) in postmenopausal women with low BMD and cortical thickness in ovariectomized monkeys. Objective: The objective of the study was to examine the impact of odanacatib on the trabecular and cortical bone compartments and estimated strength at the hip and spine. Design: This was a randomized, double-blind, 2-year trial. Setting: The study was conducted at a private or institutional practice. Participants: Participants included 214 postmenopausal women with low areal BMD. Intervention: The intervention included odanacatib 50 mg or placebo weekly. Main Outcome Measures: Changes in areal BMD by dual-energy x-ray absorptiometry (primary end point, 1 year areal BMD change at lumbar spine), bone turnover markers, volumetric BMD by quantitative computed tomography (QCT), and bone strength estimated by finite element analysis were measured. Results: Year 1 lumbar spine areal BMD percent change from baseline was 3.5% greater with odanacatib than placebo (P < .001). Bone-resorption marker C-telopeptide of type 1 collagen was significantly lower with odanacatib vs placebo at 6 months and 2 years (P < .001). Bone-formation marker procollagen I N-terminal peptide initially decreased with odanacatib but by 2 years did not differ from placebo. After 6 months, odanacatib-treated women had greater increases in trabecular volumetric BMD and estimated compressive strength at the spine and integral and trabecular volumetric BMD and estimated strength at the hip (P < .001). At the cortical envelope of the femoral neck, bone mineral content, thickness, volume, and cross-sectional area also increased from baseline with odanacatib vs placebo (P < .001 at 24 months). Adverse experiences were similar between groups. Conclusions: Over 2 years, odanacatib decreased bone resorption, maintained bone formation, increased areal and volumetric BMD, and increased estimated bone strength at both the hip and spine.

The effect of monthly ibandronate on bone mineral density and bone turnover markers in patients with haemophilia A and B and increased risk for fracture

2013 ◽  
Vol 110 (08) ◽  
pp. 257-263 ◽  
Author(s):  
Timoleon-Achilleas Vyzantiadis ◽  
Maria Charizopoulou ◽  
Fotini Adamidou ◽  
Spyridon Karras ◽  
Dimitrios Goulis ◽  
...  
Keyword(s):  
Bone Mineral Density ◽  
Bone Resorption ◽  
Bone Formation ◽  
Bone Mineral ◽  
Tartrate Resistant Acid Phosphatase ◽  
Haemophilia A ◽  
Mineral Density ◽  
Risk Of Fracture ◽  
Increased Risk ◽  
Turnover Markers

SummaryHaemophilia A and B have been associated with increased prevalence of low bone mineral density (BMD). However, no study has so far evaluated the effects of anti-osteoporotic therapy on BMD in haemophilia. The primary endpoint of this prospective study was to estimate the effect of 12-month therapy of oral ibandronate 150 mg/ month on BMD in patients with haemophilia A and B. Secondary endpoint was its effect on turnover markers (BTM) of bone resorption [serum C-terminal telopeptide of type 1 collagen (sCTX), tartrate-resistant acid phosphatase band 5b] and bone formation (osteocalcin and bone-specific alkaline phosphatase. Ten adult patients with T-score < −2.5 SD or Z-score < −2 and/or increased risk of fracture according to FRAX model were included. All received 1,000 mg/day calcium carbonate with 800 IU/d cholecalciferol. Males with haemophilia A (n=7) or B (n=3) (mean age 43.5 ± 13.5 years) were studied. Ibandronate resulted in an increase in lumbar BMD (from 0.886 ± 0.169 to 0.927 ± 0.176 g/cm2, 4.7%, p=0.004). No change in BMD of total hip (from 0.717 ± 0.128 to 0.729 ± 0.153 g/cm2, p=0.963) or femoral neck (0.741 ± 0.135 to 0.761 ± 0.146 g/cm2, p=0.952) was noticed. Ibandronate led to a decrease in sCTX (from 0.520 ± 0.243 to 0.347 ± 0.230 ng/ml, −29.9%, p=0.042). No change was observed in other BTM. Ibandronate was generally well-tolerated. In conclusion, ibandronate significantly improved BMD in lumbar spine and reduced bone resorption in adults with haemophilia at increased risk of fracture. Its effect on hip BMD and bone formation markers was not significant.

Effects of tower climbing exercise on bone mass, strength, and turnover in orchidectomized growing rats

2002 ◽  
Vol 93 (3) ◽  
pp. 1152-1158 ◽  
Author(s):  
Takuya Notomi ◽  
Yuichi Okazaki ◽  
Nobukazu Okimoto ◽  
Yuri Tanaka ◽  
Toshitaka Nakamura ◽  
...  
Keyword(s):  
Bone Mineral Density ◽  
Bone Formation ◽  
Bone Mass ◽  
Bone Mineral Content ◽  
Trabecular Bone ◽  
Bone Mineral ◽  
Mineral Content ◽  
Lumbar Vertebrae ◽  
Mineral Density ◽  
Sedentary Group

To determine the effects of a tower climbing exercise on mass, strength, and local turnover of bone, 70 9-wk-old Sprague-Dawley rats were assigned to seven groups: a baseline control and three groups of sham-operated sedentary, orchidectomized (ORX)-sedentary and ORX-exercise rats. Rats voluntarily climbed a 200-cm tower to drink water from a bottle set at the top. At 4 wk, the periosteal bone formation rate (BFR), moment of inertia, bone mineral content, bone mineral density, and bending load at the midfemur were maintained in ORX-exercise rats, whereas these parameters were reduced in ORX-sedentary rats. At 8 wk, the periosteal mineral apposition rate and BFR in ORX-exercise rats were significantly higher, whereas the parameters in ORX-sedentary rats did not differ compared with sham-sedentary rats. In ORX-exercise rats, the trabecular mineralizing surface, BFR, and bone volume of the lumbar vertebrae were maintained at the same levels as those in the sham-sedentary group, whereas the osteoclast surface decreased compared with the ORX-sedentary group. However, the climbing exercise did not affect bone mineral content, bone mineral density, or the compression load of the lumbar vertebrae. These results show that, in the midfemur, the voluntary climbing exercise maintained cortical bone mass and strength by stimulating periosteal bone formation and partially prevented ORX-induced trabecular bone loss, depressing the elevation of turnover. Interestingly, in ORX rats, the climbing exercise had the opposite effect on bone formation at the periosteal femoral cortical bone, where the exercise increased the bone formation compared with vertebral trabecular bone, where the exercise decreased it.

scholarly journals A case of hepatitis C-associated osteosclerosis: accelerated bone turnover controlled by pulse steroid therapy

2016 ◽  
Vol 2016 ◽  
Author(s):  
Nobuhiro Miyamura ◽  
Shuhei Nishida ◽  
Mina Itasaka ◽  
Hirofumi Matsuda ◽  
Takeshi Ohtou ◽  
...  
Keyword(s):  
Hepatitis C ◽  
Bone Resorption ◽  
Bone Formation ◽  
Bone Turnover ◽  
Bone Mineral ◽  
Steroid Therapy ◽  
Bone Markers ◽  
List Type ◽  
Mineral Density ◽  
Bone Disorder

Summary Hepatitis C-associated osteosclerosis (HCAO), a very rare disorder in which an extremely rapid bone turnover occurs and results in osteosclerosis, was acknowledged in 1990s as a new clinical entity with the unique bone disorder and definite link to chronic type C hepatitis, although the pathogenesis still remains unknown. Affected patients suffer from excruciating deep bone pains. We report the 19th case of HCAO with diagnosis confirmed by bone biopsy, and treated initially with a bisphosphonate, next with corticosteroids and finally with direct acting antivirals (DAA: sofosbuvir and ribavirin) for HCV infection. Risedronate, 17.5 mg/day for 38 days, did not improve the patient’s symptoms or extremely elevated levels of bone markers, which indicated hyper-bone-formation and coexisting hyper-bone-resorption in the patient. Next, intravenous methylprednisolone pulse therapy followed by high-dose oral administration of prednisolone evidently improved them. DAA therapy initiated after steroid therapy successfully achieved sustained virological response, but no additional therapeutic effect on them was observed. Our results strongly suggested that the underlying immunological alteration is the crucial key to clarify the pathogenesis of HCAO. Bone mineral density of lumbar vertebrae of the patient was increased by 14% in four-month period of observation. Clarification of the mechanisms that develop osteosclerosis in HCAO might lead to a new therapeutic perspective for osteoporosis. Learning points: HCAO is an extremely rare bone disorder, which occurs exclusively in patients affected with HCV, of which only 18 cases have been reported since 1992 and pathogenesis still remains unclear. Pathophysiology of HCAO is highly accelerated rates of both bone formation and bone resorption, with higher rate of formation than that of resorption, which occur in general skeletal leading to the diffuse osteosclerosis with severe bone pains. Steroid therapy including intravenous pulse administration in our patient evidently ameliorated his bone pains and reduced elevated values of bone markers. This was the first successful treatment for HCAO among cases reported so far and seemed to propose a key to solve the question for its pathogenesis. The speed of increase in the bone mineral content of the patient was very high, suggesting that clarification of the mechanism(s) might lead to the development of a novel therapy for osteoporosis.

Enhanced trabecular bone resorption and microstructural bone changes in rats after removal of the cecum

2012 ◽  
Vol 303 (8) ◽  
pp. E1069-E1075 ◽  
Author(s):  
Narattaphol Charoenphandhu ◽  
Panan Suntornsaratoon ◽  
Prapaporn Jongwattanapisan ◽  
Kannikar Wongdee ◽  
Nateetip Krishnamra
Keyword(s):  
Bone Resorption ◽  
Bone Formation ◽  
Trabecular Bone ◽  
Calcium Absorption ◽  
Lumbar Vertebrae ◽  
The Body ◽  
Computer Assisted ◽  
Calcium Balance ◽  
Mineral Density ◽  
Bone Formation Rate

The cecum, the proximal part of the large intestine, has the highest rate of calcium absorption compared with other intestinal segments. Previously, we showed that rats with the cecum surgically removed (cecectomized rats) had severe negative calcium balance, low bone mineral density (BMD), and a compensatory increase in colonic calcium absorption. Herein, we used the computer-assisted bone histomorphometric technique and microcomputed tomography (μCT) to analyze bone microstructural defects in cecectomized rats at 1 and 3 mo postsurgery compared with age-matched sham-operated control rats. Relatively low BMD as determined by dual energy X-ray absorptiometry was observed in the femora, tibiae, and lumbar vertebrae of the 3-mo cecectomized rats. μCT analysis revealed decreases in the tibial cortical thickness, periosteal and endosteal perimeters, and moment of inertia in cecectomized rats. The histomorphometric results further showed that trabecular bone volume and number were markedly decreased, whereas trabecular separation was increased in the proximal tibial metaphysis of cecectomized rats, thus leading to a decrease in trabecular volumetric BMD. Since osteoclast surface and eroded surface were increased after cecectomy, such bone loss in cecectomized rats appeared to result from an enhanced bone resorption. Moreover, decreases in bone formation rate and osteoblast surface indicated a suppression of osteoblast-mediated bone formation. In conclusion, cecectomy induced widespread osteopenia in rats presumably by enhancing the osteoclast-mediated bone resorption and suppressing bone formation. The present results underline the important role of cecum in the body calcium homeostasis.

scholarly journals Sclerostin antibodies as novel anabolic therapy for osteoporosis

2019 ◽  
Vol 21 (3) ◽  
pp. 21-29
Author(s):  
Elizaveta O. Mamedova ◽  
Tatiana A. Grebennikova ◽  
Zhanna E. Belaya ◽  
Liudmila Y. Rozhinskaya
Keyword(s):  
Bone Mineral Density ◽  
Bone Resorption ◽  
Bone Formation ◽  
Bone Mineral ◽  
Human Monoclonal Antibody ◽  
Wnt Signaling Pathway ◽  
Osteoporosis Treatment ◽  
Anabolic Effect ◽  
Mineral Density ◽  
Anabolic Therapy

Osteoporosis medications are divided into two groups: those inhibiting bone resorption and formation (bisphosphonates and denosumab), and those stimulating bone formation i.e. having an anabolic effect. The latter include teriparatide, parathyroid hormone 1-84 and abaloparatide, all of which stimulate bone resorption as well as bone formation, which limits their anabolic effect. The discovery of sclerostin – the key inhibitor of bone formation – has led to development of the concept that inhibition of this protein could stimulate bone formation. Romosozumab is a human monoclonal antibody to sclerostin that binds to sclerostin and enables Wnt-signaling pathway ligands and their co-receptors to interact with each other, which, in turn, leads to increased bone formation and bone mineral density. Unlike classical anabolic drugs in osteoporosis treatment, romosozumab stimulates bone formation and inhibits bone resorption. In clinical trials, romosozumab showed marked increase in lumbar spine and hip bone mineral density. Presented article contains information about pre-clinical and clinical studies of romosozumab.

Long-Term Electroacupuncture Stimulation Prevents Osteoporosis in Ovariectomised Osteopaenic Rats through Multiple Signalling Pathways

2018 ◽  
Vol 36 (3) ◽  
pp. 176-182 ◽  
Author(s):  
Xuefeng Zheng ◽  
Yan Nie ◽  
Chengtao Sun ◽  
Guangwen Wu ◽  
Qiaoyan Cai ◽  
...  
Keyword(s):  
Lumbar Vertebrae ◽  
Nuclear Factor Κb ◽  
Mitogen Activated Protein Kinase ◽  
Tartrate Resistant Acid Phosphatase ◽  
Sprague Dawley ◽  
Mineral Density ◽  
Ovx Rats ◽  
Mitogen Activated Protein ◽  
Tracp 5B ◽  
Turnover Markers

Background The pathogenic mechanisms of postmenopausal osteoporosis (PMOP) development are complex and are related to multiple cellular signalling transduction pathways. The aim of this study was to compare the effects of electroacupuncture (EA) at GV4/GV6 versus BL20/BL23 on the bones in ovariectomised (OVX) rats to explore the pathways that mediate the effects of EA on bone. Methods Forty female Sprague-Dawley rats were allocated to one of four groups (n=10 rats each) that received sham surgery (Sham group), OVX surgery only (OVX group), OVX surgery plus EA at GV4/GV6 (GV group) and OVX surgery plus EA at BL20/BL23 (BL group). Bone turnover markers osteocalcin (OC) and tartrate-resistant acid phosphatase 5b (TRACP 5b) were measured in serum, and bone mineral density (BMD) of the lumbar vertebrae and histomorphology of the femur were evaluated. Moreover, the expression of osteoprotegerin (OPG) and receptor activator of nuclear factor-κB ligand (RANKL) was detected by ELISA. The expression of lipoprotein receptor-related protein (LRP) 5, β-catenin, runt-related transcription factor (Runx) 2 involving Wnt/β-catenin signalling and p38, c-Jun N-terminal kinase (JNK) and extracellular regulated protein kinases 1/2 involving mitogen-activated protein kinase signalling were determined by Western blotting. Results The two EA-treated groups demonstrated increased levels of OC and the BMD of lumbar vertebrae, decreased levels of TRACP 5b and improved bone microstructure in the femur, compared with the untreated OVX group (P<0.05). Histomorphology analysis showed that EA treatment significantly increased the values of the trabeculae (µm), trabecular area (%) and trabecular bone number (per mm) and reduced trabecular separation (mm), compared with the OVX group. In addition, the ratio of OPG to RANKL and LRP5, β-catenin and Runx2 expression were significantly upregulated, while the expression of phosphorylated (p)-p38 and p-JNK were downregulated in EA-treated groups compared with the OVX group. Conclusion EA attenuates PMOP and it appears that the mechanism involves the regulation of multiple targets and pathways.

Teriparatide [rhPTH (1-34)], But Not Strontium Ranelate, Demonstrated Bone Anabolic Efficacy in Mature, Osteopenic, Ovariectomized Rats

Endocrinology ◽  
2011 ◽  
Vol 152 (5) ◽  
pp. 1767-1778 ◽  
Author(s):  
Yanfei L. Ma ◽  
Qing Q. Zeng ◽  
Leah L. Porras ◽  
Anita Harvey ◽  
Terry L. Moore ◽  
...  
Keyword(s):  
Bone Mineral Density ◽  
Bone Formation ◽  
Bone Mineral ◽  
Strontium Ranelate ◽  
Formation Rate ◽  
Ovariectomized Rats ◽  
Mineral Density ◽  
Bone Formation Rate ◽  
Ovx Rats ◽  
Dose Dependent

We compared teriparatide (TPTD) and strontium ranelate (SR) efficacy on bone formation activity in a mature rat model of estrogen-deficiency bone loss. Rats were ovariectomized (OVX) at age 6 months and permitted to lose bone for 2 months to establish osteopenia before initiation of treatment with TPTD (5 or 15 μg/kg · d sc) or SR (150 or 450 mg/kg · d oral gavage). After 3 wk, RT-PCR analyses of bone formation genes in the distal femur metaphysis showed significant elevation of collagen 1α2, osteocalcin, bone sialoprotein, alkaline phosphatase, and Runx2 gene expression at both TPTD doses, relative to OVX controls. SR had no significant effect on expression of these genes. TPTD treatment for 12 wk dose dependently increased lumbar vertebral (LV) and femoral midshaft bone mineral content (BMC) and bone mineral density over pretreatment and age-matched OVX controls. SR 150 increased BMC, and SR 450 increased BMC and bone mineral density of femoral midshaft and LV over OVX controls. There were significant dose-dependent TPTD increases of LV and femoral neck strength, and TPTD 15 also increased midshaft strength compared with pretreatment and age-matched OVX controls. SR did not enhance bone strength relative to pretreatment or age-matched OVX controls. Histomorphometry of the proximal tibial metaphysis showed dose-dependent effects of TPTD on trabecular area, number, width, and osteoblast surface, bone mineralizing surface, and bone formation rate relative to pretreatment and age-matched OVX controls, whereas SR had no effect on these parameters. These findings confirmed the bone anabolic efficacy of teriparatide, but not SR in mature, osteopenic, OVX rats.

scholarly journals Different Molecular Mechanisms Underlie Ethanol-Induced Bone Loss in Cycling and Pregnant Rats

Endocrinology ◽  
2006 ◽  
Vol 147 (1) ◽  
pp. 166-178 ◽  
Author(s):  
Kartik Shankar ◽  
Mats Hidestrand ◽  
Rani Haley ◽  
Robert A. Skinner ◽  
William Hogue ◽  
...  
Keyword(s):  
Bone Resorption ◽  
Bone Loss ◽  
Bone Formation ◽  
Bone Mineral ◽  
Molecular Mechanisms ◽  
Nuclear Factor Κb ◽  
Tartrate Resistant Acid Phosphatase ◽  
Mineral Density ◽  
Pregnant Rats ◽  
Estradiol Levels

Chronic ethanol (EtOH) consumption can result in osteopenia. In the current study, we examined the modulation of EtOH-induced bone loss during pregnancy. Nonpregnant and pregnant dams were intragastrically infused either control or EtOH-containing diets throughout gestation (gestation d 5 through 20 or an equivalent period of 15 d) by total enteral nutrition. The effects of EtOH (8.5 to 14 g/kg/d) on tibial bone mineral density (BMD), mineral content (BMC), and bone mineral area were assessed at gestation d 20 via peripheral quantitative computerized tomography. EtOH caused a dose-dependent decrease in BMD and BMC without affecting bone mineral area. Trabecular BMD and BMC were significantly lower in EtOH-treated, nonpregnant dams, compared with pregnant cohorts at the same infused dose of EtOH and urinary ethanol concentrations. Static histomorphometric analysis of tibiae from pregnant rats after EtOH treatment showed decreased osteoblast and osteoid surface, indicating inhibited bone formation, whereas EtOH-treated cycling rats showed higher osteoclast and eroded surface, indicative of increased bone resorption. Circulating osteocalcin and 1,25-dihydroxyvitamin D3 were lower in both EtOH-fed nonpregnant and pregnant rats. Gene expression of osteoclast markers, 70 kDa v-ATPase, and tartrate-resistant acid phosphatase were increased selectively in nonpregnant EtOH-treated rats but not pregnant rats. Moreover, only nonpregnant EtOH-fed rats showed induction in bone marrow receptor activator of nuclear factor-κB ligand mRNA and decreased circulating 17β-estradiol levels. Our data suggest that EtOH-induced bone loss in pregnant rats is mainly due to inhibited bone formation, whereas in nonpregnant rats, the data are consistent with increased osteoclast activation and bone resorption concomitant with decreased estradiol levels.

Sign in / Sign up

Export Citation Format

Share Document