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

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 ; Arcuate Nucleus of Hypothalamus ; physiopathology ; Bone and Bones ; physiopathology ; Disease Models, Animal ; Female ; Osteoporosis ; chemically induced ; pathology ; Ovariectomy ; Rats

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 ; Dexamethasone ; Nitric Oxide Donors/*therapeutic use ; Nitroglycerin/pharmacology ; Nitroglycerin/*therapeutic use ; Osteoporosis/chemically induced ; Osteoporosis/*prevention & control ; Random Allocation ; Rats, Wistar

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

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

OBJECTIVETo investigate the effects of systemic transplantation of allogenic adipose-derived stem cells (ADSCs), the main undifferentiated cells in the supporting-storing system based on the fasciology hypothesis, on the bone mineral density (BMD) and histomorphometry in rats with glucocorticoid-induced osteoporosis (GIOP) rats, and explore a new therapeutic approach for osteoporosis.

METHODSForty female adult Wistar rats were randomized equally into blank control group (A), model group (B), control treatment group (C) and treatment group (D). In groups B, C, and D, osteoporosis was induced by injection of prednisolone (8 mg/kg) via the tail vein 3 times a week for 12 consecutive weeks. After successful establishment of osteoporosis, allogenic ADSCs (3×10(6)/ml) were transplanted via the tail vein. The BMD at the L3-L5 levels and of the right femurs were detected, and the histomorphometry of the right tibias was analyzed in all the rats.

RESULTSAfter prednisolone injection, the BMD of L3-L5 vertebrae and the right femurs, the percent trabecular area, trabecular thickness and trabecular number of the right tibias were all obviously lowered while the trabecular separation and osteoclast number increased in group B as compared to those in group A (P<0.05). Four weeks after ADSC transplantation, all these indices were significantly improved in group D, showing significant differences from those in group B (P<0.05) and also group C.

CONCLUSIONTransplantation of allogenic ADSCs can restore the BMD and bone histomorphometric properties of rats with GIOP, and may serve as a potential treatment for GIOP. These results also provide partial experimental evidence supporting the hypothesis of fasciaology.

Adipocytes ; cytology ; Animals ; Bone Density ; Female ; Glucocorticoids ; adverse effects ; Osteoporosis ; chemically induced ; surgery ; Rats ; Rats, Wistar ; Stem Cell Transplantation ; Transplantation, Homologous

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

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

Aged ; Bone Density Conservation Agents ; adverse effects ; Female ; Humans ; Organometallic Compounds ; adverse effects ; Osteoporosis, Postmenopausal ; drug therapy ; Stevens-Johnson Syndrome ; chemically induced ; diagnosis ; physiopathology ; Thiophenes ; adverse effects

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