1.Investigation on the role on perindopril for prevention and treatment of glucocorticoid-induced osteoporosis in rabbits.
Feng ZHOU ; Chun RONG ; Kai WANG ; Chun-sheng WANG ; Yong-tao ZHANG
China Journal of Orthopaedics and Traumatology 2016;29(1):52-57
OBJECTIVETo investigate the role of perindopril for prevention and treatment of glucocorticoid-induced osteoporosis (GIOP) in rabbits.
METHODSA total of 45 male New Zealand white rabbits (10 months old, weight 3.0 to 3.5 kg) were randomly divided into 3 groups involving normal control group (muscle injection of saline solution, n = 15, group NC), model group (muscle injection of dexamethasone, n = 15, group GIOP), and treatment group (muscle injection of dexamethasone combined with oral perindopril, n = 15, group GIOP+ACEI). All rabbits put to death after 12 weeks' treatment. The changes of bone mass and strength were observed and analyzed by bone histomorphology, biomechanics, metabolic bone related serological indexes and mRNA expression.
RESULTSAt 12 weeks, the analysis of bone histomorphology and biomechanics results showed that the bone mass and bone strength of group GIOP were significantly lower than that of group NC (P < 0.05); after perindopril treatment, the bone mass and bone strength of group GIOP+ACEI were higher obviously than that of group GIOP (P < 0.05). Mineralizing surface,mineral apposition rate and serum osteocalcin in group GIOP decreased than group NC; however, osteoclast number, osteoclast surface, eroded surface, and urinary deoxypyridinoline in group GIOP increased than group NC (P < 0.05); these changes were inhibited after perindopril treatment (P < 0.05). Quantitative RT-PCR revealed that after dexamethasone treatment, the ratio of SOST mRNS expression and RANKL/OPG mRNA expression obviously increased than that of group NC (P < 0.05); and Runx2 expression decreased significantly (P < 0.05); while the changes of mRNA expression were improved by perindopril treatment.
CONCLUSIONPerindopril can promote bone formation and inhibit bone resorption to deduce glucocorticoid-induced osteoporosis. This study provides a new method for prevention and treatment of GIOP.
Animals ; Biomechanical Phenomena ; Glucocorticoids ; adverse effects ; Male ; Osteoporosis ; chemically induced ; prevention & control ; Perindopril ; therapeutic use ; Rabbits
2.Interrelation between the hypothalamic arcuate nucleus and the bone variation of osteoporosis in rats.
Acta Physiologica Sinica 2013;65(5):525-532
This study investigated the interrelation between the hypothalamic arcuate nucleus (ARC) and the bone variation of osteoporosis in rats. Four animal models of ovariectomy-induced osteoporosis (OVX), glucocorticoid-induced osteoporosis (GIOP), retinoic acid-induced osteoporosis (RAOP) and senile osteoporosis (SOP) were used to study the influence of osteoporosis on ARC. Ovariectomized rats were further treated with thymopeptide, ciclosporin and exercise respectively to detect the changes of ARC nerve cells number. The results showed that: (1) The OVX, GIOP, RAOP and SOP models were successfully established, showing osteoporosis as well as decrease of the number of ARC nerve cells; (2) Thymopeptide and exercise respectively alleviated the bone loss induced by ovariectomy, accompanied by increase of the number of ARC nerve cells, while ciclosporin further increased the bone loss of ovariectomized rats, accompanied by further decrease of the number of ARC nerve cells. These results suggest that there is a close interrelationship between ARC and osteoporosis in rat. There is a hypothalamus-pituitary-bone (HPB) axis, and HPB axis regulates the mechanism of osteoporosis in rats.
Animals
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Arcuate Nucleus of Hypothalamus
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physiopathology
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Bone and Bones
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physiopathology
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Disease Models, Animal
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Female
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Osteoporosis
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chemically induced
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pathology
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Ovariectomy
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Rats
3.Preventive effects of nitroglycerine on glucocorticoid-induced osteoporosis in growing rats.
Yuming, LI ; Yongguo, LI ; Weihong, YANG
Journal of Huazhong University of Science and Technology (Medical Sciences) 2007;27(5):528-31
The preventive effects of nitroglycerine (NG) on glucocorticoid-induced osteoporosis in growing rats were studied. Three-month-old female Wistar rats were randomly divided into control group (CON), dexamethasone group (DXM), DXM plus a low dose NG group (NG-L), DXM plus a middle dose NG group (NG-M) and DXM plus a high dose NG group (NG-H), 8 rats in each group. The rat model of osteoporosis was developed by intramuscular injection of dexamethasone twice a week. NG 0.2, 0.4 and 1.0 mg/kg was administered by oral gavages to the treatment groups every day for 12 weeks. Rats in CON group and DXM group were treated with normal saline of the same amount. After the treatment, the bone mineral density (BMD) and bone metabolism-associated biochemical markers were determined. Compared with CON group, BMD of lumbar spine and femur in DXM group was decreased significantly (P<0.05 and P<0.01 respectively), blood BGP levels and NO levels reduced (both P<0.01), and TRAP level increased (P<0.05). As compared with DXM group, BMD, serum BGP and NO were increased, and TRAP decreased in NG-L group and NG-M group, but had no significant difference in comparison to CON group. All the markers other than serum NO and TRAP levels had no significant difference between NG-H group and DXM group. It was concluded that low or middle doses of NG could prevent glucocorticoid-induced bone loss in growing rats, but high dose of NG could not. Supplement with NO donor could be considered as a preventive treatment for glucocorticoid-induced osteoporosis in a developing skeleton.
Bone Density/*drug effects
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Dexamethasone
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Nitric Oxide Donors/*therapeutic use
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Nitroglycerin/pharmacology
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Nitroglycerin/*therapeutic use
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Osteoporosis/chemically induced
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Osteoporosis/*prevention & control
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Random Allocation
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Rats, Wistar
4.X-ray analysis on 114 patients with moderate endemic skeletal fluorosis by treatment of Guo's Chinese herbal.
Zhi-Cheng SANG ; Wei ZHOU ; Zhao-Jie ZHANG ; Guan-Nan WU ; Pei-Hua GUO ; Hui-Ming WANG ; Shu-Wen SI ; Jing ZHAO ; Shi-Xiu GUO
China Journal of Orthopaedics and Traumatology 2010;23(5):379-382
OBJECTIVETo observe the X-ray features of bone damage in patients with moderate endemic skeletal fluorosis and the changes of X-ray after treatment with herbal therapy.
METHODSFrom 2007.12 to 2009.8,114 patients with moderate endemic skeletal fluorosis were randomly divided into treatment group and control group by central randomization system. There were 60 patients in treatment group including 26 males and 34 females,aged from 39 to 60 years with an average of (51.68 +/- 4.98) years; There were 54 patients in control group included 30 males and 24 females, aged from 39 to 60 years with an average of (52.15 +/- 4.86) years. Both treatment and control groups were treated with basic treatment including calcium supplementation and preparation stage with herb decoction. Patients were orally given 600 mg Caltrate everyday for calcium suptrointestinal function and promoting the digestion and absorption of herb decoction for 3 days. Patients in treatment group were rally given Guo's Maqian decoction(200 ml,twice daily) for 8 weeks. Eight weeks later,Guo 's Maqian decoction was replaced y Guokangning capsule (0.44 g per cansule,2 capsules,three times daily) for 4 weeks. The treatment course lasted 12 weeks. The time for followed-up after treatment was 24 weeks. When the treatment finished, 7 experts on orthopaedics and radiology evaluated and statistically analyzed the X-ray features pre and post treatment,using expert evaluation scale (including the appearance and changes of osteosclerosis,osteoporosis softening,joint changes close to the bone and mixed changes) designed referring endemic skeletal fluorosis X-ray findings and sub-degree standard(WS192-2008).
RESULTSAll X-ray features of endemic skeletal fluorosis appeared in the X-ray of the 114 patients with moderate endemic skeletal fluorosis. Osteosclerosis: 4 cases in forearm, 7 in calf,4 in pelvis,4 in lumbar vertebrae ;Osteoporosis and bone softening: 23 cases in forearm patients, 23 in calf, 5 in pelvis, 8 in lumbar vertebrae; Mixed changes: 6 cases in forearm, 9 in calf, 10 in pelvis, 1 in lumbar vertebrae patients; oint changes: 107 cases in forearm, 47 in calf, 28 in pelvis, 19 in lumbar vertebrae. There were X-ray no changes before and after the treatment in all of parts in control group. In treatment group, there were only 2 patients showed extraperiostealin and joint changes after the treatment, in which one showed better ossification of interosseous membrane of leg and another one showed disappearance of the lateral hyperplasia of the left pelvic acetabulum. There were no changes between before and after treatment in X-ray of all parts in the rest patiens of the treatment group. There was no significant difference between before and after treatment in both groups (P > 0.05).
CONCLUSIONThere is no obvious improvement in radiology of patients with skeletal fluorosis treated by Guo's therapy.
Adult ; Bone Diseases ; chemically induced ; diagnostic imaging ; drug therapy ; epidemiology ; Drugs, Chinese Herbal ; therapeutic use ; Endemic Diseases ; Female ; Fluorine ; adverse effects ; Humans ; Joint Diseases ; chemically induced ; diagnostic imaging ; drug therapy ; epidemiology ; Male ; Middle Aged ; Osteoporosis ; chemically induced ; diagnostic imaging ; drug therapy ; epidemiology ; Osteosclerosis ; chemically induced ; diagnostic imaging ; drug therapy ; epidemiology ; Tomography, X-Ray Computed ; Treatment Outcome
5.Gastrointestinal Side Effect Profile Due to the Use of Alendronate in the Treatment of Osteoporosis.
Semih AKI ; Nurten ESKIYURT ; Ulku AKARIRMAK ; Fikret TUZUN ; Merih ERYAVUZ ; Serap ALPER ; Oktay ARPACIOGLU ; Fatma ATALAY ; Vural KAVUNCU ; Siren KOKINO ; Omer KURU ; Kemal NAS ; Onder OZERBIL ; Gursoy SAVAS ; Omer Faruk SENDUR ; Derya SOY ; Gulseren AKYUZ
Yonsei Medical Journal 2003;44(6):961-967
The aim of our study was to evaluate the upper gastrointestinal (GI) tract side effect profile in 759 female patients that had taken alendronate (10 mg/day), for at least 6 months, for the treatment of osteoporosis, in relation to the safety of alendronate and the compliance of patients to its absorption rules. This study was a multicentered retrospective, clinical, non- placebo controlled, study of 759 female subjects carried out at 26 centres in 6 different regions of Turkey. The mean age of our patients was 62.6+/-8.6, with 51.2%in the age range 60 to 69 years. 158 patients (20.8%) were considered to have upper GI tract complaints with nausea as the most often encountered symptom. Of the subjects with upper GI tract complaints, 20% reported discontinued drug use, and 30% reported the requirement of an additional drug in order to abolish their complaints. Approximately 537 (71%) of the patients stated they had been given written information about the administration of the drug, and at least 93 patients (12%) and 73 patients (18.4%) acknowledged non compliance with the safety and absorption rules, respectively. In our study, no significant difference was found between the adherence to the safety measures and upper GI tract complaints (p > 0.05), but that upper GI tract complaints were higher in patients taking additional medication to alendronate (p < 0.05).
Adult
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Aged
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Aged, 80 and over
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Alendronate/*adverse effects
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Female
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Gastrointestinal Diseases/*chemically induced
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Human
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Middle Aged
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Osteoporosis/*drug therapy
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Retrospective Studies
7.Methods and evaluations on the sterioid-induced osteoporosis mice model with the type of Kidney-Yin deficiency.
Bing-jiang XIA ; Pei-jian TONG ; Yan SUN ; Luo-yu ZHOU ; Hong-ting JIN
China Journal of Orthopaedics and Traumatology 2014;27(8):673-679
OBJECTIVETo establish the steriod-induced osteoporosis model with the type of Kidney-Yin deficiency.
METHODSTotally 45 female Kunming mice were randomly divided into normal group,model group and Liuwei Dihuang pills(Chinese character: see text)group. The model was established by intramuscular injecting of Dexamethasone. Liuwei Dihuang pills (Chinese character: see text) group was administered orally with Liuwei Dihuang pills (Chinese character: see text). The signs and symptoms of mice were observed dynamically. All the animals were sacrificed at the end of the 6th weeks. The level of ACTH, cAMP, cGMP, TSH and E2 in serum were detected to evaluate deficiency of Kidney-Yin. Morphological changes and bone density were observed to evaluate osteoporosis.
RESULTS(1) Compared with control group, mice in model group appeared obvious Kidney-Yin deficiency symptoms, including hair dry, restlessness, excitability, hard stool, and yellow. (2) Compared with control group,the weight of mice in model group gained slower (P<0.01); the index of adrenal gland,liver and spleen decreased (P<0.01, P<0.01 ,P<0.01); the level of ACTH and TSH increased (P<0.01 ,P<0.01), the level of E2 decreased (P<0.01) and the ratio of cAMP/cGMP increased (P< 0.05). (3)Compared with control group,the bone density of lumbar vertebra and femur in model group were significantly decreased (P<0.01, P<0.05); HE staining revealed osteoporosis in model group mice. (4)However, the Liuwei Dihuang pills (Chinese character: see text) group can partly antagonize the inhibition of the HPA axis, alter the disordered sex hormone and the ratio of cAMP/cGMP, and reverse the osteoporosis partly.
CONCLUSIONthe model of osteoporosis with type of Kidney-Yin deficiency could be established by Dexamethasone intramuscular injection. With less interference, it wight be a stable and reliable modeling method for integration of disease and syndrome in TCM.
Animals ; Bone Density ; Dexamethasone ; toxicity ; Disease Models, Animal ; Female ; Kidney Diseases ; etiology ; Medicine, Chinese Traditional ; Mice ; Osteoporosis ; chemically induced ; Yin Deficiency ; complications
8.Application of benchmark dose (BMD) in a bone-effect study on a general population environmentally exposed to cadmium.
Hai-lei QIAN ; Tai-yi JIN ; Qing-hu KONG ; Hong-fu WANG ; Guo-ying ZHU
Chinese Journal of Industrial Hygiene and Occupational Diseases 2006;24(1):23-26
OBJECTIVETo estimate the benchmark dose for osteoporosis caused by cadmium exposure in a Chinese general population with an epidemiological study.
METHODSThe inhabitants living in both cadmium polluted and non-polluted areas served as the exposure group and the control group. Urinary cadmium (UCd) and Blood cadmium (BCd) were used as exposure biomarkers while the Z score was used as effect biomarker for the osteoporosis.
RESULTSThe UCd and BCd in the habitants of the polluted areas were significantly higher than those in the habitants of the control area on average (P < 0.05) and the UCd and BCd in the habitants of the highly polluted areas were significantly higher than those in the habitants of the moderately polluted area on average (P < 0.05). The bone mineral density was significantly decreased in the groups of the highest UCd and BCd level compared with the 5 microg/g Cr group with the significant difference (P < 0.05). The morbidity of the osteoporosis would increase significantly with the increase of the cadmium exposure (P < 0.05) with the linear correlation (P < 0.05). BMDs were calculated using BMDS Version l.3.2 software and BMDLs were also determined. The BMDL of UCd for cadmium-induced osteoporosis was higher than those representing cadmium-induced renal dysfunction.
CONCLUSIONHigh level of cadmium exposure can induce osteoporosis, which occurs later than renal damage related to cadmium exposure. The BMD is a practical method.
Aged ; Bone Density ; drug effects ; Cadmium ; adverse effects ; metabolism ; China ; epidemiology ; Dose-Response Relationship, Drug ; Environmental Exposure ; Female ; Humans ; Male ; Middle Aged ; Osteoporosis ; chemically induced ; epidemiology
9.Effects of Xianling Gubao capsules for the treatment of bone loss induced by glucocorticoid.
Jian-jing WU ; Li-ping WEN ; Yun-gang WU ; Quan SHEN ; Yan HAN
China Journal of Orthopaedics and Traumatology 2009;22(3):193-195
OBJECTIVETo study the clinical effects of Xianling Gubao capsules for the treatment of glucocorticoid-induced osteoporosis.
METHODSFrom 2005.6 to 2007.8, 50 patients with primary glomerulonephritis treated with glucocorticoids were divided into two groups randomly. The treatment group were dealed with Xianling Gubao capsules and the control group with calcitriol and Caltrate D 600. TCM Synrdome integral before and after treatment were estimated. And the bone mineral density (BMD) of lumbar spine and femoral neek was measured by dual-energy X-ray absorptionm etry (DEXA). Osteo-calcin, intact parathyroidhormone (IPTH), urine excretion of calcium and phosphorus, serum calcium and phosphorus were detected before and after treatment, and adverse effects were investigated too.
RESULTSTCM Synrdome integral in two groups decresed apparently (P<0.05), which decresed more apparently in the treatment group than that in control group (P<0.05). BMD of lumbar spine and femoral neek increased in two groups (P<0.05), but there were no statistical deferences between them (P>0.05). Serum osteocalcin after treatment reduced significantly in two groups (P<0.05) compared with pre-treatment,but there were no statistical deferences between the treatment and the control group (P>0.05). In the control group, serum calcium after treatment increased significantly (P<0.05), but there were no statistical deferences compared with the treatment group (P>0.05). There were no statistical deferences in intact parathyroidhormone, urine excretion of calcium and phosphorus, serum phosphorus in the treatment and the control group before and after therapy.
CONCLUSIONBoth the treatment group and the control group have clinical effects in prevention and treatment of GC-induced osteoporosis, but the treatment group has more remarkable therapeutic effect and less adverse effects.
Adult ; Bone Density ; Drugs, Chinese Herbal ; therapeutic use ; Female ; Glucocorticoids ; adverse effects ; Humans ; Male ; Medicine, Chinese Traditional ; Middle Aged ; Osteoporosis ; chemically induced ; drug therapy
10.The influence of the different components of nourishing kidney herbs on osteoporosis rats.
He-di LIU ; Fu-shan LIN ; En LI ; Mi-shan WU ; Xiao-xu TONG
China Journal of Chinese Materia Medica 2003;28(3):262-265
OBJECTIVETo observe the influent of the different components of nourishing kidney herbs on the main items of bone metabolism in osteoporosis rats induced with Dexamethasona(DXM).
METHODModels of three-month old SD female rats with osteoporosis here made by being fed with low calcium diet (containing calcium 0.2%) and distilled water, and injected with DXM 0.1 mg/100 g weight intramuscularly, twice a week. Then the osteoporosis rats were treated with different components of nourishing kidney herbs, and the change of calcium, phosphate, alkaline phosphatase(ALP), calcitonin(CT), PTH, CT/PTH, estrogen(E2), testosterone(T), T/E2 and bone section and bone quantitative morphology in these osteoporosis rats were observed.
RESULTThe total components of nourishing kidney herbs could improve the general condition of osteoporosis rats, decrease PTH, increase CT, estrogen, testosterone, CT/PTH and T/E2. The total components of nourishing kidney herbs could improve osteoporotic state, promote bone formation, and inhibite bone resorption. But no effect of the A, B, C, D components of nourishing kidney herbs on the main items of bone metabolism in osteoporosis rats induced with DXM was found.
CONCLUSIONIt is possible that the purification and separation of these herbs weaken or destroy the integrative effect of nourishing kidney herbs or destroy effective components of nourishing kidney herbs during the process of purification and separation.
Animals ; Dexamethasone ; Drug Combinations ; Drugs, Chinese Herbal ; pharmacology ; Epimedium ; chemistry ; Lumbar Vertebrae ; pathology ; Male ; Osteoporosis ; chemically induced ; metabolism ; Plants, Medicinal ; chemistry ; Rats ; Rats, Sprague-Dawley ; Rehmannia ; chemistry