OBJECTIVETo explore the effect of recombinant human parathyroid hormone 1-34 [rhPTH(1-34)] on bone regeneration rabbit mandible during distraction osteogenesis (DO).

METHODS40 Japanese white rabbit (weight 2.0-2.5 kg) were randomly divided into control group and groups. The experimental groups were divided inito 12.5, 25 and 50 µg/kg group according to the dosage of rhPTH (1-34) in each group. Each group involved 10 rabbits, and unilateral DO models were established at the right mandible of the rabbits. From the first day of distraction to the day of execution, the rabbits in the experimental groups were injected subcutaneously rhPTH (1-34) of the corresponding dose respectively, and the rabbits in the control group were injected subcutaneously 2% heat inactivated rabbit serum 1 ml respectively.. Five rabbits in each group were executed respectively at 1 week and 3 weeks after completion of distraction, and the specimens of DO were harvested. The gross observation, X-ray examination, and histological study were performed.

RESULTSGross appearance: At the first week of consolidation, the dense and opaque white tissue was seen in the distraction gap of the 50 µg/kg group, and the white translucent tissue was seen in the distraction gaps of the rest groups. At the third week of consolidation, the greyish white tissue was seen in the distraction gap of the control group, while the cartilage-like tissue was seen in the buccal side of the distraction gap of the 12.5 µg/kg group, the color of new-formed tissues was close to that of normal bone tissue in the lingual side. The buccal tissue at the edge of the distraction gap of the 25 µg/kg group fitted together with the primary bone tissue in its two sides. It was difficult to distinguish the boundaries between the distraction gap and the bone tissues in its two sides in the 50 µg/kg group. X-ray findings: At the first week of consolidation, a sparse opaque image was seen in the distraction gap of the 50 µg/kg group, and a low-density image was seen in the distraction gap of the rest groups. At the third week of consolidation, a sparse bone image was seen in the control group, and the edge of the bone was not continuous. With the increase of the dose in the experimental groups, the image of the distraction gap became more and more opaque, and the image of the distraction gap in the 50 µg/kg group was close to that of the normal bone tissue. HISTOLOGICAL FINDINGS: At the first week of consolidation, few osteoblasts were present at the edge of the distraction gap of the control group. A large number of bone cells and bone trabecular were present in the distraction gap of the 12.5 µg/kg group, the network of the bone trabecula was present in the 25 µg/kg group, and a few new bones were found in the 50 µg/kg group. At the third week of consolidation, the network of the trabecular bone was present in the distraction gap of the control group, while the network of the bone trabecula was present in the 12.5 µg/kg group, a lot of bone-like tissues in the 25 µg/kg group, and near-mature bone in the 50 µg/kg group.

CONCLUSIONSrhPTH(1-34) can promote the formation of new bone in the distracted gap during mandibular DO in rabbits.

Animals ; Bone Density ; Bone Regeneration ; drug effects ; physiology ; Humans ; Mandible ; drug effects ; surgery ; Osteogenesis, Distraction ; methods ; Parathyroid Hormone ; pharmacology ; Rabbits ; Random Allocation ; Recombinant Proteins ; pharmacology

PURPOSE: Bone metastasis invariably increases morbidity and mortality. This study compares the effects of ibandronate and paclitaxel on bone structure and its mechanical properties and biochemical turnover in resorption markers using an immunocompetent Walker 256-Sprague-Dawley model, which was subjected to tumor-induced osteolysis. MATERIALS AND METHODS: Seventy rats were divided equally into 4 groups: 1) sham group (SHAM), 2) tumor group (CANC), 3) ibandronate treated group (IBAN), and 4) paclitaxel treated group (PAC). Morphological indices [bone volume fraction (BV/TV), trabecular number (Tb.N), trabecular thickness (Tb.Th), trabecular separation (Tb.Sp)] and mechanical properties (failure load, stiffness) were evaluated after thirty days of treatment period. Bone resorption rate was analysed using serum deoxypyridinoline (Dpd) concentrations. RESULTS: Morphological indices showed that ibandronate (anti-resorptive drug) had a better effect in treating tumor-induced architectural changes in bone than paclitaxel (chemotherapeutic drug). The deterioration in bone architecture was reflected in the biomechanical properties of bone as studied with decreased failure load (F(x)) and stiffness (S) of the bone on the 30th day postsurgery. Dpd concentrations were significantly lower in the IBAN group, indicating successful inhibition of bone resorption and destruction. CONCLUSION: Ibandronate was found to be as effective as higher doses of paclitaxel in maintaining stiffness of bone. Paclitaxel treatment did not appear to inhibit osteoclast resorption, which is contrary to earlier in-vitro literature. Emphasis should be placed on the use of immunocompetent models for examining drug efficacy since it adequately reflects bone metastasis in clinical scenarios.
Amino Acids ; Animals ; Biomechanical Phenomena/*drug effects/physiology ; Bone Density/drug effects/physiology ; Bone Neoplasms/*drug therapy ; Bone Resorption/*chemically induced ; Diphosphonates/*pharmacology ; Immunocompetence ; Male ; *Neoplasm Metastasis ; *Osteolysis ; Paclitaxel/*pharmacology ; Rats ; Rats, Sprague-Dawley

Bones are stained into red color with feeding madder, but we do not know whether the fed madder can change the bone biomechanical properties and bone mineral contents in animals. In this research, we established a rat model with feeding madder. The bone biomechanical properties were detected by universal material mechanics, bone mineral contents were detected by inductively coupled plasma mass spectrometry and spectrometer, and red color material in bone was analyzed by high performance liquid chromatography. The results showed that bone biomechanical parameters in femur diaphysis in the 10% and 15% group rats were significantly higher than those in the control group after feeding madder for 6 months. The level of calcium, magnesium and zinc in femur diaphysis in 10% and 15% group rats were higher than those in the control group after feeding madder for 6 months. However, it was shown that the kidney congestion and hyperemia and the level of blood urea nitrogen and creatinine in the 15% group rats were significantly different compared to those in the control group rats after feeding madder for 6 months. The red colored material in bone is related to alizarin analyzed with high-performance liquid chromatography. The conclusion could be drawn that feeding 10% madder in diet was not toxic to the rats fed for 6 months, and it could improve bone biomechanical properties and increase bone mineral elements.
Animals ; Anthraquinones ; toxicity ; Biomechanical Phenomena ; Bone Density ; Bone and Bones ; drug effects ; physiology ; Calcium ; Femur ; Magnesium ; Rats ; Zinc

OBJECTIVEInjection of insulin-like growth factor-1 (IGF-1) can prevent bone loss in sciatic nerve transaction rats. We try to investigate the action mechanism of IGF-1 on bone formation.

METHODSA total of 40 adult male Spragne-Dawley rats were divided into two groups (experimental group and control group) with 20 animals in each. Sciatic neurectomy was performed to model disuse osteoporosis in all rats. IGF-1 was administered in experimental group with the dose of 100 microgramme/kilogram per day for 3 days. Meanwhile, the rats in control group were treated with saline. Bone mineral density was measured by dual-energy X-ray absorptiometry 4 and 6 weeks after neurectomy respectively. Expression of Osterix and Runx2 was determined by reverse transcription-polymerase chain reaction (RT-PCR) assay.

RESULTSThere was a significant increase in the bone mineral density of experimental group compared with control group. There was a significant decrease in the level of receptor activator of nuclear factor-kappaB-ligand but an increase in the level of osteoprotegerin 4 and 6 weeks after neurectomy in the experimental group compared with control one. The expression of Osterix and Runx2 was up-regulated in the bone marrow of experimental group compared with control group.

CONCLUSIONIGF-1 can increase bone formation by stimulation of osteoblast number and activity, and reduce bone resorption by restriction of differentiation of osteoclast, suggesting that IGF-1 may improve the therapeutic efficacy for disuse osteoporosis.

Animals ; Bone Density ; drug effects ; Bone Resorption ; prevention & control ; Cell Differentiation ; Core Binding Factor Alpha 1 Subunit ; metabolism ; Immunohistochemistry ; Injections ; Insulin-Like Growth Factor I ; administration & dosage ; Male ; Osteoblasts ; drug effects ; Rats ; Rats, Sprague-Dawley ; Sciatic Nerve ; surgery ; Transcription Factors ; metabolism ; Up-Regulation ; physiology

OBJECTIVETo compare the effects of icariin (ICA) and genistein (GEN) on rats bone peak mass and thus screen for a drug that can more effectively prevent osteoporosis.

METHODSTotally 36 one-month SD rats were randomly divided into three groups: ICA group [25 mg/(kg·d), intragastric administration], GEN group [10 mg/(kg·d), intragastric administration], and control group (fed with equal volume of distilled water). The body weight was monitored weekly and the bone mineral density of total body was measured monthly. All rats were sacrificed three months later. The femoral bone mineral density and the serum levels of osteocalcin and anti-tartaric acid phosphatase 5b, N-terminal propeptide of type 1 procollagen, and C-terminal propeptide of type 1collagen were measured. The bone microarchitectures were analyzed with micro-CT and the bone biomechanics properties were tested with universal material machine.

RESULTSThe body weight and organ index showed no significant difference among these three groups(P>0.05). No obvious pathological change was found. The bone mineral density was also not significantly different in the first and second months; however, in the third months, the ICA group had significant higher bone mineral density for both total body and femur than those in the control and GEN group (P<0.05). The same trends were found for both femur bone mineral density and whole-body bone mineral density (P<0.05). The ICA group also had significantly higher serum levels of osteocalcin (P<0.05) and lower level of anti-tartaric acid phosphatase 5b(P<0.05). Besides, rats in the ICA group had significantly larger bone volume/tissue volume, trabecular thickness, and trabecular number than the control group, whereas the trabecular spacing and model coefficients were signicantly lower(all P<0.05), which, however, were not significantly different between ICA group and GEN group (P>0.05). Femoral maximum load, Youg's modulus, and yield load were significantly higher in these two groups than in the control group (P<0.05), which, again, were not significantly different between ICA group and GEN group (P>0.05).

CONCLUSIONOrally administered ICA is more efficient than GEN in inhibiting resorption and promoting bone formation, and thus can dramatically improve the peak bone mineral density and bone quality.

Animals ; Bone Density ; drug effects ; Bone and Bones ; drug effects ; physiology ; Female ; Flavonoids ; pharmacology ; Genistein ; pharmacology ; Osteoporosis ; prevention & control ; Rats ; Rats, Sprague-Dawley

OBJECTIVETo investigate sex hormone deficiency related osteoporosis and efficacy of different therapies.

METHODSOrchiectomized and ovariectomized rat models are used to investigate sex hormone deficiency related osteoporosis and efficacy of different therapies. A rat vertebral body can be longitudinally divided into central portion, which contain more trabecular bone, and para-endplate portions which contain more compact bone. In matured male and female Wistar and Sprague-Dawley rat lumbar spines, we investigated baseline bone mineral density (BMD) characteristics and the differential segmental responses in bone loss within the lumbar vertebral body post gonadal surgery with clinical multidetector computed tomography.

RESULTSPara-endplate sections had a higher BMD than central sections. The cephalad para-endplate sections had a higher BMD than the caudad para-endplate sections. Eight weeks after gonadal removal, there was more bone loss in central sections than para-endplate sections. The relative difference of bone loss between para-endplate and central sections was more apparent in male rats than in female rats. There was more bone loss in caudad sections than cephalad sections; this lead to a further increase of BMD difference between caudad para-endplate sections and cephalad para-endplate sections post gonadal surgery.

CONCLUSIONThe approach described in this study provided a consistent way to study BMD change within predominantly compact bone portion and trabecular bone portion of the vertebral body.

Animals ; Bone Density ; drug effects ; Female ; Gonadal Steroid Hormones ; deficiency ; metabolism ; Lumbar Vertebrae ; physiology ; Male ; Orchiectomy ; Ovariectomy ; Rats ; Sex Factors

Dental implant is an advanced prosthodontic treatment widely accepted by patients with missing tooth. However, peri-implant bone loss is still an important reason which limits wider application of the implants to a certain extent. Bisphosphonates is an osteoclastic bone resorption inhibitor that is widely used in clinical practice with the function of inhibiting bone resorption and increasing bone density. As the defect of systemic BPs treatment, local application of BPs in implant has become a research hotspot recently. Calcium phosphate ceramics, polylactic acid, fibrinogen film and collagen membrane have been reported as BPs carriers. This article summarizes the researches on the mechanism of bone regulation and local delivering system of BPs.
Administration, Topical ; Bone Density Conservation Agents ; administration & dosage ; Bone Remodeling ; drug effects ; physiology ; Dental Implantation, Endosseous ; methods ; Dental Implants ; Diphosphonates ; administration & dosage ; Humans

OBJECTIVETo investigate the effect of calcium supplementation on bone mineral density (BMD) in Chinese women with different FokI vitamin D receptor (VDR) genotypes (FF, Ff, and ff) after weaning or resumption of menstruation during lactation.

METHODSA total of 40 subjects with the same FokI VDR genotype were randomly divided into two groups: one received calcium tablet (600 mg once daily as CaCO(3)) and the other placebo tablet once daily for 1 year. At baseline, BMD was measured by dual-energy X-ray absorptiometry at lumbar spine (L2-L4) and at left hip whereas serum PICP, serum OC, and urinary CTX, serum 25(OH)VitD(3), and serum estradiol were measured at weaning and 1 year thereafter.

RESULTSAfter the intervention, BMD at lumbar spine and at left hip increased significantly in all these women with a trend among different FokI VDR genotypes such as FF > Ff > ff (P<0.05, <0.01, and <0.001, respectively). BMD at lumbar spine in women with FF VDR genotype increased much more rapidly than in those with ff VDR genotype (P<0.05). Compared with the control group women with the FF genotype regained more BMD after calcium supplementation (P<0.05).

CONCLUSIONDaily calcium 600 mg supplementation has beneficial effect on the bone health of women with FF VDR genotype.

Adult ; Asian Continental Ancestry Group ; Bone Density ; drug effects ; Calcium, Dietary ; administration & dosage ; pharmacology ; Female ; Genotype ; Humans ; Menstruation ; physiology ; Weaning ; Young Adult

OBJECTIVETo investigate the association of estrogen receptor alpha (ER-alpha) PvuII polymorphisms with the effect of calcium supplementation on bone development in Chinese pubertal girls, and to study the importance of calcium supplementation by maximizing the peak bone mass at their pubertal stage for bone development and osteoporosis prevention and the role of estrogen in regulating bone mass.

METHODSNinety-four pubertal girls were recruited in the study and divided into two groups and three sub-groups according to the ER-alpha PvuII polymorphisms. One year before and after calcium supplementation, bone mineral density (BMD) was measured by DEXA, while BGP, BAP, TRACP5b, and 25-OH-VitD(3), as well as estrogen were detected by ELISA. Analysis of covariance was used to examine the effect of ER-alpha polymorphisms on bone development.

RESULTSThe absolute increase and percentage change of BGP were significantly higher in the supplemented group than in the control group (P<0.05). In the intervened group, The increase and percentage change of the total body and radio distal 1/3 BMD were higher in PP than in PP genotype (P<0.05), and the increase of BAP in Pp was also higher than PP in the same group (P<0.05).

CONCLUSIONPP genotype shows a better response to calcium supplementation than the other PvuII polymorphisms.

Adolescent ; Asian Continental Ancestry Group ; Biomarkers ; Bone Density ; drug effects ; Calcium ; administration & dosage ; pharmacology ; Dietary Supplements ; Estrogen Receptor alpha ; genetics ; Female ; Humans ; Polymorphism, Genetic ; Puberty ; physiology

OBJECTIVETo investigate the molecular mechanism of TFE (total flavone of epimedium) in the treatment of osteoporosis, and then provide experimental evidence for modernization and further development of TFE as an traditional Chinese medicine.

METHODSSixty healthy female SD rats with aged 4 months were randomly divided into three groups (including control group in which rats received sham surgery, OVX group in which ovariectomized rats didn't give any medicine after the removal of ovaries and TFE group in which ovariectomized rats administrated TFE), 20 rats in each group. Compared bone mineral density (BMD) between before operation and at 4th week after operation in order to verify the establishment of osteoporotic model (criteria: BMD decreased more than 20% at 4th week after operation). The rats in TEF group were administrated total flavone of epimedium(concentration 30 mg/ml, 10 ml/kg, qd) orally for 4 weeks. After this, killed rats to harvest the lower part of the femur and detected BMD again. Applying the reverse transcriptase-polymerase chain reaction technique (RT-PCR) to detect expression of OPG, OPGL mRNA in bone tissue.

RESULTS(1) At 4th week after ovariectomy, the mean BMD of lumbar vertebra in TFE group fell to (0.084 +/- 0.020) g/cm2. Administrated with TFE for 4 weeks,the BMD increased to (0.112 +/- 0.009) g/cm2. There was significant improvement compare with the OVX group (P < 0.05). (2) Compared between OVX group and TFE group, The OPG mRNA expression of TFE group obviously enhanced. There was significant difference in statistics (P < 0.05). However,the promotion for OPGL mRNA expression were detected between OVX group and TFE group,there was no significant difference in statistics (P > 0.05).

CONCLUSIONThis study showed that TFE could inhibit differentiation and maturation of osteoclast through enhancing OPG mRNA expression, accordingly,to treat osteoporosis.

Animals ; Bone Density ; drug effects ; Drugs, Chinese Herbal ; pharmacology ; Epimedium ; chemistry ; Female ; Flavones ; Flavonoids ; pharmacology ; Gene Expression Regulation ; drug effects ; Osteoblasts ; drug effects ; metabolism ; physiology ; Osteoprotegerin ; genetics ; Ovariectomy ; RANK Ligand ; genetics ; RNA, Messenger ; genetics ; metabolism ; Rats