The study aims to investigate the embryo-fetus development toxicity of the novel PPAR-δ agonist HS060098 on SD rats. The pregnant rats that were randomly divided into the solvent control group (1% hydroxypropyl methyl cellulose water solution) and HS060098 suspension groups (10, 30 and 100 mg x kg(-1) xd(-1)) were orally administered with HS060098 suspension or vehicle during the gestation of 6 -15 days (GD6-15). At termination (GD20), female rats were sacrificed. The pregnant females were evaluated by corpora lutea count, implantation sites, existence and death of embryos. Fetal sex, weight, externals, variations and malformations of viscus and skeleton were observed. The results show that there were no significant abnormality in maternal general conditions and fetal appearance as well as viscera, but in the 100 mg x kg(-1) x d(-1) group, the maternal weight gain decreased greatly (P < 0.01) and the skeletal ossification delayed remarkably (P < 0.01); in the 30 mg x kg(-1) xd(-1) group, the fatal and litter number of incompletely ossified sternebrae II was higher than those of the control group (P < 0.05); the skeletal malformations occurred in all dose groups, which indicate that the novel PPAR-δ agonist HS060098 had maternal toxicity and adversely effected fetal skeletal development under the experimental conditions.
Animals ; Bone and Bones ; drug effects ; Embryonic Development ; drug effects ; Female ; Fetal Weight ; PPAR delta ; agonists ; Pregnancy ; Rats ; Toxicity Tests

The purpose of the present study was to observe the structure and functional change of the bone-coating-prosthesis interface in vivo and to evaluate the histocompatibility of self-made prosthetic femoral components in the body and the degree of their bonding with the surrounding bone tissues as well as their stability. Six mature beagle dogs underwent bilateral hip replacement with prosthetic femur components. Three groups were established in terms of different coating of prothesis (four joints in each group): atmosphere (A) plasma-sprayed pure titanium (Ti) prosthetic joint with hydroxyapatite (HA) coating (HA+Ti+A group); vacuum (V) plasma-sprayed pure Ti prosthetic joint with HA coating (HA+Ti+V group); vacuum plasma-sprayed pure Ti prosthetic joint with Ti-HA stepped coating (Ti+HAG+Ti+V group). The hip joints were functionally evaluated, and subjected to X-ray examination, biomechanics inspection, and histological examination. As a result, X-ray imaging revealed all prosthetic joints were in a good location and no dislocation of joint was found. Shear strength of interface was significantly higher in Ti+HAG+Ti+V group than in HA+Ti+V group (P<0.05) and HA+Ti+A group (P<0.05) at 28th week. Histological examination showed the amount of newborn bone in Ti+HAG+Ti+V group was more than in HA+Ti+V group and HA+Ti+A group after 28 weeks. It was suggested that vacuum plasma-sprayed pure Ti prosthetic joint with TI-HA stepped coating could improve the bonding capacity of bone-prosthesis, enhance the stability of prosthesis, and increase the fixion of prosthetic femoral components because of better bone growth. This new type of biological material in prosthetic femoral components holds promises for application in clinical practice.
Animals ; Biomechanical Phenomena ; drug effects ; physiology ; Bone Development ; drug effects ; physiology ; Coated Materials, Biocompatible ; pharmacology ; Dogs ; Durapatite ; pharmacology ; Femur ; drug effects ; physiology ; Prostheses and Implants ; Titanium ; pharmacology ; Vacuum

Animals ; Body Weight ; drug effects ; Bone Remodeling ; drug effects ; Growth and Development ; drug effects ; physiology ; Isoflavones ; pharmacology ; Male ; Rats ; Rats, Sprague-Dawley ; Testosterone ; blood

OBJECTIVEBased on peer-reviewed random-control studies, effects of calcium supplement and intake of milk on bone mineral density (BMD) and growth in children were evaluated.

METHODSMeta-analysis was applied to review published data in random-control studies related to the effects of calcium supplement and milk consumption on BMD, body height and body weight in children.

RESULTSEleven peer-reviewed papers published during 1993 to 2006 were selected in this study. Homogeneity test showed that random effect model should be selected for weighting and pooling data. The combined means of improvement in BMD, height and body weight in children with milk intervention were 2.01 (0.92 - 3.09), 0.25 (0.09 - 0.41) and 0.63 (0.33 - 0.93), respectively, and the data from children with calcium intervention were 1.05 (0.66 - 1.43), -0.10 (-0.25 - 0.05) and -0.75 (-1.98 - 0.49), respectively.

CONCLUSIONBoth milk and calcium intakes could improve BMD of children significantly, and the difference in BMD gain through milk intake was the same as that with calcium intervention, however, compared with the control group, increasing milk intake did significantly promote growth and development of children compared to the calcium supplement group.

Animals ; Body Height ; drug effects ; Body Weight ; drug effects ; Bone Density ; drug effects ; Bone Development ; drug effects ; Calcium, Dietary ; administration & dosage ; pharmacology ; Child ; Dietary Supplements ; Humans ; Milk ; Randomized Controlled Trials as Topic

AIMTo explore the effect of hypothalamic arcuate nucleus (ARC) on the skeleton in rat.

METHODSNewborn SD rats were injected by 10% MSG 4 g/kg hypodermically once every other day until the 10th day postnatally, meanwhile, the newborn rats in control group were given by equal volume of normal saline. After surviving for 200 days, 6 female rats in each group were killed and their hypothalami were made into sections (4 microm) and stained with HE. The length, diameter, weight and volume of the femora, the tibia, the humeri, the radii and the ulnae were measured.

RESULTSThe number of the hypothalamic arcuate nucleus nervous cell were obviously less than those in control group as well as the length, diameter, weight, volume but the weight/volume (g/cm3) of the femora, the tibia, the humeri, the radii and the ulnae decreased significantly as compared with the control group. Levels of serum GH E2 in rats of MSG group were obviously lower than that in control group.

CONCLUSIONThe hypothalamic arcuate nucleus participated in the regulation of the growth and development of skeleton in rats.

Animals ; Animals, Newborn ; Arcuate Nucleus of Hypothalamus ; drug effects ; Bone Development ; drug effects ; Female ; Rats ; Rats, Sprague-Dawley ; Sodium Glutamate ; adverse effects

Zebrafish was selected as model animal, and glucocorticoid dexamethasone was used as a model compound to establish a rapid and high efficient osteopenia model. Zebrafish larvae at 4 days post fertilization (dpf) were exposed to a serial concentrations of dexamethasone solutions, and 0.5% DMSO was selected as the vehicle control group. All groups were incubated in 24-well plates (28.5 degrees C) until 9 dpf. In addition, effects of 10 micromol x L(-1) dexamethasone on preventing against osteopenia induced by etidronate disodium were also investigated. Zebrafish bones at 9 dpf were stained with alizarin red. Quantitative analysis of the stained area was performed by microscopic inspection and digital imaging methods to reflect the amount of bone mineralization. Results showed that dexamethasone group at 2.5, 10 and 25 micromol x L(-1) can decrease the staining area and the staining optical density values of zebrafish head bones when compared with the vehicle control group (0.5% DMSO), which suggested that dexamethasone can significantly reduce the zebrafish mineralized bone and the bone mineral density. Results also showed that 15 and 30 microg x mL(-1) etidronate disodium can increase the mineralized matrix of zebrafish head bone and prevent against osteopenia induced by dexamethasone. In conclusion, the study indicated that zebrafish can be an idea osteopenia model induced by dexamethasone.
Animals ; Bone Density ; drug effects ; Bone Density Conservation Agents ; pharmacology ; therapeutic use ; Bone Diseases, Metabolic ; chemically induced ; prevention & control ; Calcification, Physiologic ; drug effects ; Dexamethasone ; toxicity ; Disease Models, Animal ; Etidronic Acid ; pharmacology ; therapeutic use ; Larva ; drug effects ; growth & development ; Zebrafish

OBJECTIVETo investigate the efficacy of letrozole for delaying bone maturation and increasing predicted adult height in boys with idiopathic central precocious puberty (ICPP) who have a bone age above 13 years and a short stature, and its adverse effects.

METHODSTwenty ICPP boys with a bone age above 13 years and a short stature were randomly divided into letrozole treatment (n=10) and control groups (n=10). The letrozole treatment group received oral letrozole [2.5 mg/(m(2)·d), Qd] for 6 months, while the control group received no treatment and was observed periodically. Bone age, growth rate, height standard deviation (SD) score, predicted adult height SD score, sexual maturity, and levels of follicle-stimulating hormone (FSH), luteinizing hormone (LH), dehydroepiandrosterone, testosterone (T), estradiol (E2), progesterone (P), and androstenedione (ASD) were measured. The letrozole-related adverse reactions were evaluated.

RESULTSAfter 6 months of treatment, both groups had a significantly increased bone age, but the letrozole group had a significantly slowed increase in bone age compared with the control group (13.82 ± 0.23 years vs 14.47 ± 0.30 years; P<0.05); compared with the control group, the letrozole group had a significantly increased predicted adult height SD score (-1.69 ± 0.26 vs -1.91 ± 0.35; P<0.05) and a significantly increased T level (4.9 ± 0.9 nmol/L vs 4.4 ± 0.8 nmol/L; P<0.05). There was no significant difference in testicular volume between the two groups. The treatment led to no significant changes in growth rate, Tanner stage, and levels of FSH, LH, P, E2 and ASD in the two groups, and there was no significant difference in these indices between the two groups. No adverse reactions were observed during letrozole treatment.

CONCLUSIONSLetrozole delays bone maturation and increases predicted adult height in ICPP boys with a bone age above 13 years and a short stature, and it causes no obvious adverse reactions.

Adolescent ; Aromatase Inhibitors ; therapeutic use ; Body Height ; drug effects ; Bone Development ; drug effects ; Gonadal Steroid Hormones ; blood ; Humans ; Male ; Nitriles ; adverse effects ; therapeutic use ; Puberty, Precocious ; blood ; drug therapy ; Testis ; drug effects ; pathology ; Triazoles ; adverse effects ; therapeutic use

OBJECTIVEThis study was designed to explore the effects of zinc on bone development.

METHODSForelimbs of mice with 16 d gestation were cultured by a rotating device.

RESULTSContents of OC and (45)Ca and activities of AKP in the bone tissues cultured at zinc-deficiency media and at media with 120 micro mol/L of Zn(2+) decreased significantly. Synthesis of OC, absorption of calcium and activities of AKP in the bone tissues cultures at media with 45 and 70 micro mol/L of Zn(2+) increased significantly. Radiograph of bone tissues showed that length of long bone cultured at zinc-deficiency media and at media with 120 micro mol/L of Zn(2+) shortened and their density reduced, and those cultured at media with 45 and 70 micro mol/L of zinc increased, as compared with self-control bone. Histological analysis showed the death of bone cells and loss of stroma in the bone tissues cultured at media with 120 micro mol/L of Zn(2+), and active proliferation and differentiation of bone cells, and secretion and synthesis of osteoid increased in the bone tissues cultured at media with 45 and 70 micro mol/L of zinc.

CONCLUSIONSAdequate supplementation of zinc could promote formation and development of bone tissues and deficiency or excess of zinc could alter their growth and development and normal metabolism.

Animals ; Bone Density ; drug effects ; Bone Development ; drug effects ; Calcium ; metabolism ; Embryo, Mammalian ; drug effects ; physiology ; Extremities ; embryology ; Female ; Insulin-Like Growth Factor II ; Male ; Mice ; Proteins ; metabolism ; Zinc ; pharmacology

OBJECTIVELong-term inhaled corticosteroids are the preferred treatment for asthma, but their safety still controversial. The aim of the present study was to explore the effects of inhaled corticosteroids on bone age and growth in children with asthma.

METHODSSeventy-three children with asthma received inhaled fluticasone treatment at a starting dosage of 250 μg/d for 3 months, when the dosage was reduced by a third. Three months later, the patients were treated with fluticasone at a dosage of 125 μg/d for 6 months. Bone age, heights and weights were measured before and one year of treatment.

RESULTSThe increase in the heights, weights and RUS (radius, ulna and short finger bones) bone age of the children with asthma after one year of treatment was not significantly different from healthy children. There were no significant differences in body mass index (BMI) before and after one year of treatment, however the level of carpal bone age [-0.2(-0.6,0.8) years] was delayed after therapy compared to before treatment [-0.5(-1.0,0.6) years] (P<0.05).

CONCLUSIONSTreatment with inhaled corticosteroids for 1 year may suppress the level of carpal bone age, but the level of RUS bone age, heights, weights and BMI are not affected. It is necessary to monitor the growth of children with asthma who receive long-term inhaled corticosteroid treatment.

Administration, Inhalation ; Age Determination by Skeleton ; Androstadienes ; administration & dosage ; adverse effects ; Asthma ; drug therapy ; physiopathology ; Body Height ; drug effects ; Body Mass Index ; Body Weight ; drug effects ; Bone Development ; drug effects ; Child ; Child, Preschool ; Female ; Fluticasone ; Humans ; Male

OBJECTIVETo study the effect of growth hormone (GH) combined with Radix Dipsaci on the body growth and the bone mineral content (BMC) of hypophysectomized rats.

METHODSThe GH deficiency rats model was established using the hypophysectomized operation through the skull and the throat. Qualified rats were divided into the sham-operation group (n = 15), the negative control group (n = 13), the GH intervention group (n = 13), and the GH combined with Radix Dipsaci group(n = 12). GH (0.25 mg/kg) was subcutaneously injected from the cervical part in the GH intervention group and the GH combined with Radix Dipsaci group at the same time, while equal volume of normal saline was injected to the rest groups. 0.7 mL/100 kg Radix Dipsaci was given by gastrogavage to the GH combined with Radix Dipsaci group at the same time, while equal volume of normal saline was given by gastrogave to the rest groups. The body weight, the tail length, and the body length were measured during the intervention period. Blood was withdrawn after 14-day intervention. The femoral bone and the tibial bone were taken out. The levels of GH, insulin-like growth factor 1 (IGF-1), alkaline phosphatase (ALP), and osteocalcin (OC) were measured. The width of the tibial epiphyseal plate was measured. The bilateral femur bone mineral density (BMD) and BMC were measured using the dual energy X-ray absorptiometry.

RESULTSThe body weight, the body length, the length of the femoral bone, the length of the tibial bone, the width of the epiphyseal plate, the levels of the GH, IGF-1, ALP, and OC increased in the GH intervention group and the GH combined with Radix Dipsaci group after 2-week intervention, showing statistical difference when compared with the model group (P < 0.01). But there was no statistical difference in the tail length though it also increased (P > 0.05). There was insignificant difference in the aforesaid indices between the two groups (P > 0.05). Compared with the model group, the BMD of the GH combined with Radix Dipsaci group increased with statistical difference (P < 0.01). Compared with the model group, the BMC of the GH intervention group and the GH combined with Radix Dipsaci group increased with statistical difference (P < 0.01). It was highest in the GH combined with Radix Dipsaci group (P < 0.01).

CONCLUSIONSGH combined with Radix Dipsaci showed unobvious effect on promoting the growth. But it could elevate BMD and BMC, and improve the bone metabolism.

Animals ; Bone Development ; drug effects ; Bone and Bones ; metabolism ; Dipsacaceae ; chemistry ; Drugs, Chinese Herbal ; pharmacology ; Growth Hormone ; pharmacology ; Hypophysectomy ; Male ; Rats ; Rats, Sprague-Dawley