OBJECTIVES: The purpose of this study was to investigate the influences of interruption and reinitiation of monthly minodronate therapy on the bone mineral density (BMD) and bone metabolism markers in postmenopausal women with osteoporosis. METHODS: Study patients were included if they had been administered monthly minodronate therapy for ≥6 months, interrupted the therapy, and reinitiated the therapy for ≥12 months. The BMD and bone metabolism markers were assessed at 4 time points: initiation, interruption, reinitiation and 1 year after reinitiation of therapy. RESULTS: A total of 23 patients were enrolled. The mean monthly minodronate treatment period was 23.8 ± 12.9 months following a mean interruption period of 11.9 ± 5.4 months. Once increased by monthly minodronate treatment for 2 years on average, the BMD of lumbar spine and radius did not significantly decrease even after an interruption for 1 year on average. However, the BMD of the femoral neck did decrease after interruption. The BMD of the lumbar spine and radius increased further after 1 year of monthly minodronate retreatment. The BMD of the femoral neck did not change. Once decreased after the treatment for an average of 2 years followed by an interruption for 1 year, bone metabolism markers increased gradually but did not recover to baseline levels. A potent suppressive effect on bone resorption was noted. The change rate was greater for the bone formation marker procollagen 1 N-terminal propeptide. CONCLUSIONS: Monthly minodronate treatment increases BMD and reduces bone metabolism markers. The effect lessens after treatment interruptions, and can be restored by retreatment.
Bone Density ; Bone Resorption ; Female ; Femur Neck ; Humans ; Metabolism ; Osteogenesis ; Osteoporosis ; Procollagen ; Radius ; Retreatment ; Spine

PURPOSE: To examine the influence of ovariectomy (OVX) on bone turnover and trabecular bone mass at the 3 clinically important skeletal sites in mature cynomolgus monkeys. MATERIALS AND METHODS: Six female cynomolgus monkeys, aged 17-21 years, were randomized into 2 groups by the stratified weight: the OVX and sham-operation groups (n = 3 in each group). The experimental period was 16 months. Lumbar bone mineral density (BMD) in vivo and serum and urinary bone turnover markers were longitudinally measured, and peripheral quantitative computed tomographic and bone histomorphometric analyses were performed on trabecular bone of the lumbar vertebra, femoral neck, and distal radius at the end of the experiment. RESULTS: OVX induced in a reduction in lumbar BMD compared with the sham controls and the baseline, as a result of increased serum levels of bone-specific alkaline phosphatase and urinary levels of cross-lined N- and C-terminal telopeptides of type I collagen. Furthermore, OVX induced reductions in trabecular volumetric BMD and trabecular bone mass compared with the sham controls, with increased bone formation rate at the lumbar vertebra, femoral neck, and distal radius. CONCLUSION: The results indicated that OVX in mature cynomolgus monkeys (17-21 years of age) increased bone turnover and induced trabecular bone loss at the three skeletal sites compared with the sham controls. Thus, mature cynomolgus monkeys could be utilized for preclinical studies to examine the effects of interventions on bone turnover and trabecular bone mass at the 3 clinically important skeletal sites.
Alkaline Phosphatase/blood ; Animals ; *Bone Density ; Collagen Type I/urine ; Female ; Femur Neck/metabolism ; Lumbar Vertebrae/metabolism ; Macaca fascicularis/*physiology ; Ovariectomy/*adverse effects ; Radius/metabolism ; Random Allocation

OBJECTIVETo study the effect of vascular endothelial growth factor (VEGF)and anti-VEGF on the expression of fracture healing-related factors and observe pathological changes at fractured sites.

METHODSFracture models were established in 105 New Zealand white rabbits and they were randomly divided into control group, VEGF group and anti-VEGF group. The relevant factors expression at fractured sites was assayed and pathological changes were observed in decalcified samples at 8, 24, 72 hours and 1,3,5,8 weeks after fracture.

RESULTSAfter application of VEGF, the expression of BMP appeared earlier and expression time lasted longer. On the contrary, anti-VEGF completely inhibited the expression of BMP. The fractured sites were filled with fibrous callus, cartilaginous callus and bony callus at the 3rd week and woven bone was constructed at the 5th week. Fracture healing was accomplished at the 8th week in VEGF group. In anti-VEGF polyclonal antibody group, cellular necrosis increased at early period. Continuous focal necrosis was seen in the fractured sites from the 1st week to 5th week. Vascularization reduced obviously at the 3rd week.

CONCLUSIONSFracture healing is a result of mutual regulation and coordination among many factors. VEGF may be an important factor in fracture healing.

Animals ; Bone Morphogenetic Proteins ; metabolism ; Electrophoresis, Polyacrylamide Gel ; Fibroblast Growth Factor 2 ; metabolism ; Fracture Healing ; physiology ; Rabbits ; Radius Fractures ; physiopathology ; Vascular Endothelial Growth Factor A ; physiology

OBJECTIVES: Vitamin D is regarded as one of the major nutrients that significantly influence bone metabolism. This study aims to look at the effect of supplementary vitamin D on bone mineral density (BMD) in female osteoporosis patients. METHODS: The retrospective hospital record review was performed on 282 patients who were diagnosed with osteoporosis and treated with selective estrogen receptor modulators (SERMs) between January 2015 and December 2016. Of these patients, 151 were treated with SERMs only while 131 were treated using both SERMs and vitamin D supplements. The BMD and any occurrence of osteoporotic fracture episode were investigated after one year. The result of two groups was compared to find the significance of vitamin D. RESULTS: Overall, improvement in BMD score was observed in 76% of the patients. The BMD of the SERMs only group improved by 3% in spine and 1% in the hip while that of the SERMs with vitamin D group improved by 6% and 1% respectively. Statistical significance was noticed in the spine only. One distal radius fracture and one single level vertebral fracture occurred in patients of SERMs group while two distal radius fractures occurred in SERMs with vitamin D group. There was no occurrence of around hip fracture in both groups. CONCLUSION: The result of the current study suggests that additional vitamin D may have some additive effect on improving BMD of the spine. Further study with the larger study population and the extended study period is recommended.
Bone Density ; Female ; Hip ; Hospital Records ; Humans ; Metabolism ; Osteoporosis ; Osteoporotic Fractures ; Radius Fractures ; Retrospective Studies ; Selective Estrogen Receptor Modulators ; Spine ; Vitamin D ; Vitamins

This study was conducted to investigate osteopenia and osteoporosis prevalence of radius and tibia using Quantitative Ultrasound (QUS) and to identify affecting factors of osteoporosis. A total of 4,340 women aged 40 - 69 years, living in Ansung (rural) and Ansan (mid-sized) area, and free of illnesses affecting bone metabolism participated in the community-based cohort study. Among them 4,059 subjects measured radius bone density and 4,089 measured tibia. The T-score threshold, defined as < -1.0 and < or = -2.5, was used to identify subjects with osteopenia and osteoporosis by WHO criteria. The crude prevalence of osteoporosis in radius and tibia was 8.4% and 23.3% respectively; after adjustment for age, it changed 6.3% and 18.8%. In simple logistic regression analysis, the prevalence of osteoporosis increased by aging, non-marital status, low education, low income. Otherwise, high intakes of Ca/P, thiamin, riboflavin, vitamin B6, and vitamin E were decreased osteoporosis prevalence. Compared to the normal BMI (body mass index) group (18.5 < or = BMI < 23), the odds ratio (ORs) of the low BMI group (BMI < 18.5), and high BMI groups (BMI 25 - 30, BMI > or = 30) were significantly increased. The OR of osteoporosis decreased across increasing quartiles of intakes of Ca, P and Ca/P. Therefore, maintaining normal BMI and increasing Ca intake and Ca/P ratio may have a beneficial effect on bone health of Korean women.
Aging ; Bone Density ; Bone Diseases, Metabolic ; Cohort Studies* ; Education ; Female ; Genome* ; Gyeonggi-do ; Humans ; Logistic Models ; Metabolism ; Odds Ratio ; Osteoporosis* ; Prevalence* ; Radius* ; Riboflavin ; Tibia* ; Ultrasonography* ; Vitamin B 6 ; Vitamin E ; Vitamins

OBJECTIVETo investigate bone defect healing by true bone ceramic complex carrying core binding factor a1 (Cbfa1) gene modified rabbit skin fibroblasts.

METHODSTransfect rabbit skin fibroblasts (RSF) with both eukaryotic expression vector pSG5 which could express Cbfa1 gene and pSG5. After being cultured for 48 h, the transfected RSF were seeded into true bone ceramic (TBC) of 2 cm in length and 4 mm in diameter to construct pSG5-Cbfa1/RSF/TBC complex and pSG5/RSF/TBC complex. Forty-eight bone defect model rabbits were randomized into four groups, each has 6 rabbits (12 radius), due to different treatment. group I: with pSG5-Cbfa1/RSF/TBC complex, group II: with pSG5/RSF/TBC complex, group III: with TBC, Group IV: empty control. After being seeded and cultured for about 24 h the complexes were implanted into 2 cm long bone defects in the middle of bilateral radius of rabbits. The radius were inspected by X-ray and then the specimens were collected at the end of the fourth and twelfth weeks after operation. Then, the specimens were decalcified and histologically investigated with Hematoxylin eosin staining and Masson staining methods. Newly synthesized trabecular bone was inspected by image analysis system and the strength of bone defect area treated with graft-implantation was tested with biomechanical method-three point bending test.

RESULTSIn group I, trabecular bone was actively synthesized to generate a great amount of trabecular bone and osteon. Preliminary union and bone defect healing were completed with good biomechanical characteristics. There were no newly synthesized trabecular in the other three groups, and bone defect healing were not discovered. The amount of newly synthesized trabecular bone and the results of biomechanical testing differed significantly between group I and the other three (P < 0.01). The efficacy of group I was significantly better than that of the other three groups.

CONCLUSIONTrue bone ceramic complex composed with Cbfa1 gene modified rabbit skin fibroblasts can effectively heal bone defect in rabbits.

Animals ; Bone Regeneration ; Bone Substitutes ; Bone Transplantation ; Cells, Cultured ; Core Binding Factor Alpha 1 Subunit ; genetics ; Disease Models, Animal ; Fibroblasts ; cytology ; metabolism ; Plasmids ; genetics ; Rabbits ; Radius ; injuries ; physiopathology ; surgery ; Random Allocation ; Skin ; cytology ; Tissue Engineering ; methods ; Transfection

Adenovirus carrying BMP-2 gene, after being mixed with fibrinous gel, was siphoned off on biodegradable scaffolds (PLA/PCL). The composite was used to repair 1.5 cm long radius defect in rabbits. Four methods were in use in the experiments: Ad-BMP-2 plus fibrinous gel and PLA/PCL (Group A), reconstructed hBMP-2 plus fibrinous gel and PLA/PCL (Group B), Ad-Lacz plus fibrinous gel and PLA/PCL (Group C), and fibrinous gel and PLA/PCL (Group D). Results showed that the defects treated in Group A were repaired with much more new bone regenerated, bridged earlier and stronger than those in Group B 12 weeks after operation. The defects treated in the other two groups could not attain osseous tissue healing. BMP-2 gene carried by biodegradable scaffold and fibrinous gel is easy to conduct and has very strong osteoinduction ability. It is really a good method to repair segmental bone defects.
Absorbable Implants ; Adenoviridae ; genetics ; metabolism ; Animals ; Biocompatible Materials ; Bone Morphogenetic Protein 2 ; biosynthesis ; genetics ; Bone Substitutes ; Caprolactam ; analogs & derivatives ; chemistry ; Fracture Healing ; Gels ; Genetic Therapy ; Humans ; Implants, Experimental ; Lactic Acid ; chemistry ; Polyesters ; Polymers ; chemistry ; Rabbits ; Radius Fractures ; therapy ; Tissue Engineering ; Tissue Scaffolds

OBJECTIVETo assess bone health in epileptic children who have been treated with carbamazepine (CBZ) or valproate (VPA) by using quantitative ultrasound (QUS) and determining the biochemical indices of bone metabolism, and to provide a proposal to improve quality of life of epileptic children.

METHODSNinety-two epileptic children who had been treated with CBZ or VPA for more than two years were evaluated for bone mineral density (BMD) at the mid-shaft tibia and the distal third of the radius. Biochemical indices of bone metabolism including urine deoxypyridinoline (DPD) and serum osteocalcin (OC), and daily calcium intake were also evaluated. Thirty-five age-matched healthy children were used as controls. Reduced BMD was defined as speed of sound (SOS) Z scores of the mid-shaft tibia and (or) the distal third of the radius less than -0.7.

RESULTSBMD was reduced in epileptic children significantly when compared to the controls (P < 0.05). In addition, a negative correlation was found between the duration of anti-epileptic drugs (AEDs) use and BMD (r(s) = -0.21 - -0.31, P < 0.05), the lowest BMD was observed in those who had been treated for the longest time. The serum values of OC in epileptic children were significantly reduced relative to the controls (P < 0.01), children who took VPA had the lowest value of OC. However, the urine values of DPD showed no significant difference between epileptic and healthy children (P > 0.05); children who took CBZ had the highest value of DPD. Thirty-two epileptic children (35%) and five (14%) sex- and age-matched healthy children had reduced BMD, significant difference was found between them (P < 0.05). Moreover, epileptic children with reduced BMD seemed to have higher body mass index (BMI) (P < 0.05), take less daily calcium intake (P < 0.01), and had longer duration of AEDs (P < 0.01). The two risk factors of having reduced BMD in epileptic children were those who had been treated with AEDs for more than five years and higher BMI, while the protective factor was daily calcium intake.

CONCLUSIONSLong-term use of CBZ or VPA is associated with bone metabolism abnormalities, which include reduced BMD and decreased bone turnover (mainly decreased bone formation). Long-term anti-epileptic therapy is an important factor for impaired bone health in epileptic children, and that low calcium intake and high BMI could be two aggravating factors. QUS is a useful method to evaluate BMD of epileptic children who are on long-term anti-epileptic therapy, and to recognize the status of bone health, in helping to promote bone health and improve quality of life in epileptic children by the use of calcium and vitamin D supplementation.

Amino Acids ; urine ; Anticonvulsants ; adverse effects ; therapeutic use ; Bone Density ; drug effects ; Bone and Bones ; diagnostic imaging ; drug effects ; metabolism ; Calcium, Dietary ; analysis ; Carbamazepine ; adverse effects ; therapeutic use ; Child ; Epilepsy ; drug therapy ; Female ; Humans ; Male ; Osteocalcin ; blood ; Radius ; diagnostic imaging ; Tibia ; diagnostic imaging ; Ultrasonography ; Valproic Acid ; adverse effects ; therapeutic use