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

BACKGROUNDOsteogenesis imperfecta (OI) is a rare bone disease and its effective treatment is relatively deficient. We tried to assess the effects of new bisphosphonate, ibandronate on children with OI.

METHODSIn this open-label, prospective, controlled study, 30 children with OI were enrolled. They received either infusions of ibandronate (2 mg) in every three months or oral calcitriol 0.25 µg daily for 24 months. All patients took 500 mg calcium plus 200 U vitamin D daily together. The endpoints were the change of annual new fracture rate (observed by case history and X ray films of spine), bone mineral density (BMD, measured by dual energy X-ray absortiometry), serum concentration of carboxy-telopeptide cross-links of type I collagen (CTX, bone resorption marker) and alkaline phosphatase (ALP, bone formation marker) during the follow-up.

RESULTSAfter the cyclic infusions of ibandronate, the annual new fracture rate was significantly decreased from 1.9 to 0.13 time, obviously lower than that of calcitriol group, which decreased from 1.8 to 1.0 time after the treatment (P < 0.001). The significant increase of BMD at the lumbar spine, femoral neck, trochanter, total hip was found in the group of ibandronate by 59.0%, 42.0%, 47.5% and 36.6% in time dependent manner (compared with the baseline, P < 0.001). The increase of BMD in ibandronate group was greater than that of calcitriol group (P < 0.001). The concentrations of ALP and CTX were obviously decreased in ibandronate group, and the reduction of CTX was more significant than that of ALP (P < 0.001). The tolerance of the children to ibandronate was quite well. Mild fever and muscle pain were found in 9 cases within 1 - 3 days after the first infusion of ibandronate, which could relieve after 1 - 2 days without special management.

CONCLUSIONSThe benefits of cyclic infusions of ibandronate to children with OI are significant because ibandronate could significantly reduce annual bone fracture rate, increase lumbar and hip BMD, preserve vertebral morphometry of patients through inhibition of bone resorption.

Bone Density Conservation Agents ; administration & dosage ; Child ; Child, Preschool ; Diphosphonates ; administration & dosage ; Female ; Humans ; Infant ; Infant, Newborn ; Infusions, Intravenous ; Male ; Osteogenesis Imperfecta ; drug therapy ; Prospective Studies

OBJECTIVETo investigate the effect of local application of zoledronic acid (ZA) on the expression of type I collagen and vascular endothelial growth factor (VEGF).

METHODSFifty-four male Wistar rats were divided into ZA group, gelatin sponge group, and blank control group after one-side tooth extraction. The expression of type I collagen and VEGF were detected with SP immunohistochemistry method 1, 2 and 4 weeks after operation.

RESULTSThe gray value of type I collagen in ZA group (60.00 ± 1.81, 63.47 ± 3.02) was lower than those in gelatin sponge group (68.58 ± 2.90, 71.15 ± 5.57) and blank control group (69.16 ± 9.63, 72.50 ± 4.10, P < 0.05) in the 1 and 2 week. In the ZA and gelatin sponge groups, the gray values of type I collagen were higher in the 4th week than in the 1st and 2nd week (P < 0.05). The expression of VEGF was higher in ZA group (69.93 ± 2.74) than in gelatin sponge group (60.86 ± 4.79) and blank control group (61.52 ± 2.28) in the 1st week (P < 0.05). There was significant difference in VEGF expression between the 2nd week and 1st and 4th week (P < 0.05).

CONCLUSIONSLocal application of ZA could enhance the expression of type I collagen but inhibit the expression of VEGF in the early stage.

Administration, Topical ; Animals ; Bone Density Conservation Agents ; administration & dosage ; pharmacology ; Bone Regeneration ; drug effects ; Diphosphonates ; administration & dosage ; pharmacology ; Imidazoles ; administration & dosage ; pharmacology ; Male ; Rats ; Rats, Wistar ; Tooth Extraction ; Vascular Endothelial Growth Factor A ; metabolism

OBJECTIVETo survey the incidence of acute febrile reaction in elderly patients receiving intravenous zoledronic acid for osteoporosis and identify the related factors.

METHODSThirty-eight elderly patients with osteoporosis were hospitalized and treated with intravenous infusion of 5 mg zoledronic acid in 2010. The incidence of acute fever reaction was observed in these patients , and the time of fever onset, duration, average maximum temperature, and antipyretic drug used were recorded. The patients with and without acute febrile reaction were compared for age, duration of osteoporosis, sex ratio, use of parathyroid hormone before zoledronic acid treatment, β-fragment of collagen breakdown, calcitonin, osteocalcin, serum calcium, and use of anti-osteoporosis drugs before the treatment.

RESULTSAcute fever reaction occurred in 12 (31.6%) of the patients. Two of the patients had fever on the day of zoledronic acid treatment, and the other patients developed fever after the first day of treatment, with a mean duration of 1 day and a maximum temperature of (38.5∓0.84) degrees celsius;. The fever was treated with a mean of 3.55∓1.21 pseudoephedrine tablets. The patients with fever showed significantly higher parathyroid hormone levels before treatment than those without fever (P<0.05); osteocalcin, calcitonin, β-fragment of collagen breakdown, or serum calcium showed no significant difference between the two groups.

CONCLUSIONAcute febrile reaction, often moderate and transient, is common in elderly patients receiving intravenous zoledronic acid for osteoporosis, and its occurrence is possibly associated with parathyroid hormone levels before the treatment.

Aged ; Aged, 80 and over ; Bone Density Conservation Agents ; administration & dosage ; adverse effects ; China ; epidemiology ; Diphosphonates ; administration & dosage ; adverse effects ; Female ; Fever ; chemically induced ; Humans ; Imidazoles ; administration & dosage ; adverse effects ; Incidence ; Infusions, Intravenous ; Male ; Osteoporosis ; drug therapy ; Parathyroid Hormone ; blood

BACKGROUND/AIMS: The aim of this study was to assess the efficacy and safety of monthly oral 150 mg ibandronate in women with postmenopausal osteoporosis (PMO). METHODS: A systematic review and meta-analysis were performed to determine treatment efficacy and safety outcomes between monthly oral 150 mg ibandronate and weekly 70 mg alendronate, daily 2.5 mg ibandronate, and a placebo. RESULTS: Eight randomized controlled trials were included in this systematic review and meta-analysis. Once-monthly 150 mg ibandronate therapy was clinically comparable to weekly 70 mg alendronate, showing increased bone mineral density (BMD) in both the lumbar spine and total hip. Pooled data from two cross-over trials showed that significantly more women with PMO preferred once-monthly ibandronate therapy to once-weekly alendronate therapy (relative risk [RR], 2.422; 95% confidence interval [CI], 2.111 to 2.825; p < 1 x 10(-8)) and found the monthly ibandronate regimen more convenient than the weekly alendronate regimen (RR, 3.096; 95% CI, 2.622 to 3.622; p < 1 x 10(-8)). Monthly 150 mg ibandronate therapy resulted in a significantly higher change in BMD of the lumbar spine than with the placebo. A once monthly 150 mg regimen produced greater increases in lumbar spine, total hip, femoral neck, and trochanter BMD than daily treatment, with a similar incidence of adverse events between the groups. CONCLUSIONS: Once monthly 150 mg ibandronate therapy was clinically comparable to weekly 70 mg alendronate, and patients strongly preferred the convenience of monthly ibandronate over weekly alendronate. Monthly 150 mg ibandronate was superior to, and as well tolerated as, the daily treatment.
Administration, Oral ; Alendronate/administration & dosage ; Bone Density/drug effects ; Bone Density Conservation Agents/*administration & dosage/adverse effects ; Bone and Bones/drug effects/radiography ; Diphosphonates/*administration & dosage/adverse effects ; Drug Administration Schedule ; Evidence-Based Medicine ; Female ; Humans ; Osteoporosis, Postmenopausal/*drug therapy/radiography ; Patient Preference ; Randomized Controlled Trials as Topic ; Time Factors ; Treatment Outcome

BACKGROUNDRenal osteodystrophy is one of the commonest complications of chronic renal failure. It may have a severe impact on the quality of life of patients on maintenance dialysis therapy. Besides post-menopausal women and elderly people, the dialysis patients are another high risk group. But at present, there is no research on how to prevent osteoporosis in maintenance dialysis patients. This study was conducted to observe the bone density of maintenance dialysis patients and to evaluate the clinical outcomes and safety of different administration dosage of salmon calcitonin to prevent osteoporosis in maintenance dialysis patients.

METHODSOne hundred and forty-eight patients on maintenance dialysis were involved in the 12-month, randomized, controlled trial. Fifty patients (experiment I group) received subcutaneous injection of salmon calcitonin (50 U) three times a week for 12 months. Fifty patients (experiment II group) received subcutaneous injection of salmon calcitonin (100 U) three times a week for 12 months. At the same time, both of them received oral calcium carbonate 1500 mg tid and rocaltrol 0.25 microg qn for 12 months. The control group only received oral calcium carbonate 1500 mg tid and rocaltrol 0.25 microg qn for 12 months. The levels of bone mass density (BMD) of the lumbar spine and femoral neck, serum intact parathyroid hormone (iPTH), osteocalcin (OC), calcium, phosphorus, alkaline phosphatase (ALP) were assessed at baseline and then again after 3, 6 and 12 months of treatment.

RESULTSThe values of BMD at the lumbar spine and femoral neck before the treatment were not significantly different from those 3, 6, and 12 months after the treatment in trial groups I and II (all P > 0.05) and there were no significant differences in the BMD values at different time points between trial groups I and II. In the control group, the BMD values at the lumbar spine and femoral neck 3, 6, and 12 months after the beginning of trial were significantly lower than those before the trial, and significantly lower than the corresponding values of trial groups I and II (all P < 0.05). The serum OC 3, 6, and 12 months after the treatment was significantly lower than that before the experiment (all P < 0.05) in the control group. However, there was no significant difference in the value of serum OC before and 3, 6, and 12 months after the treatment in trial groups I and II (all P > 0.05).

CONCLUSIONSThe dose of salmon calcitonin 50 U three times a week plus calcium carbonate and active vitamin D can effectively preserve the BMD and prevent bone loss in maintenance dialysis patients, and it is well tolerated by patients on maintenance dialysis.

Adult ; Alkaline Phosphatase ; blood ; Bone Density ; drug effects ; Bone Density Conservation Agents ; administration & dosage ; therapeutic use ; Calcitonin ; administration & dosage ; therapeutic use ; Calcium ; blood ; Calcium Carbonate ; administration & dosage ; therapeutic use ; Drug Administration Schedule ; Female ; Femur Neck ; drug effects ; metabolism ; Humans ; Lumbar Vertebrae ; drug effects ; metabolism ; Male ; Middle Aged ; Osteocalcin ; blood ; Osteoporosis, Postmenopausal ; blood ; prevention & control ; Parathyroid Hormone ; blood ; Phosphorus ; blood ; Renal Dialysis

OBJECTIVE: To investigate the effects of continuous pumping of teriparatide (TPTD) on bone metabolism in ovariectomized and normal mice and provide experimental evidence for the selection of animal models for studying the effects of TPTD and its related peptides on osteoclasts. METHODS: Twenty-four female C57BL mice (6-weeks old) were subjected to ovariectomy (OVX) or sham operation followed 7 days later by continuous pumping of TPTD or the solvent vehicle (VEH) a micropump (SHAM-VEH, SHAM-TPTD, OVX-VEH, and OVX-TPTD groups; =6). Two weeks later, the tibial and femoral bones were harvested for micro-CT scanning to measure the parameters of the tibia and the femoral cortical bone. Histopathological examinations of the tibial tissue were conducted using HE staining and TRAP staining and the number of osteoclasts and the growth plate thickness were determined. The serum Ca2 + levels of the mice were measured. The primary osteoblasts from the cranial bone were treated with estradiol (E2) and TPTD for 48 h, and the expressions of β-catenin and RANKL protein in the cells were analyzed. RESULTS: The trabecular bone mass of OVX mice was significantly lower than that of sham-operated mice ( < 0.05). Continuous TPTD pumping significantly reduced tibial cancellous bone mass and femoral cortical bone area in the sham-operated mice, while in the castrated mice, TPTD pumping increased the cancellous bone mass without changing the cortical bone area. TRAP staining showed that cancellous osteoblasts in the tibia increased significantly in the castrated mice as compared with the sham-operated mice, and TPTD pumping significantly increased the number of cancellous osteoblasts in the sham-operated mice ( < 0.05). In the primary cultured osteoblasts, treatment with both E2 and TPTD obviously lowered the expression of β-catenin and increased the expression of RANKL as compared with TPTD treatment alone. CONCLUSIONS Continuous pumping of TPTD promotes bone resorption in normal mice but does not produce obvious bone resorption effect in the ovariectomized mice, suggesting that castrated mice are not suitable models for studying the effect of TPTD and the related peptides on the osteoclasts.
Animals ; Bone Density ; Bone Density Conservation Agents ; administration & dosage ; pharmacology ; Bone Resorption ; drug therapy ; Bone and Bones ; drug effects ; metabolism ; Female ; Growth Plate ; drug effects ; Mice ; Mice, Inbred C57BL ; Osteoclasts ; drug effects ; Ovariectomy ; RANK Ligand ; metabolism ; Teriparatide ; administration & dosage ; pharmacology ; beta Catenin ; metabolism

PURPOSE: Teriparatide markedly increases bone formation and strength, while reducing the incidence of new-onset osteoporotic vertebral compression fractures (OVCFs). In some countries, expenses for teriparatide use are covered by medical insurance for up to 6 months; however, the national medical insurance of the authors' country does not cover these expenses. This retrospective cohort study compared the therapeutic effects of teriparatide on the initial onset of a new OVCF after treatment of osteoporosis and/or related OVCFs with regard to therapeutic durations of longer than 3 months (LT3M) or shorter than 3 months (ST3M). MATERIALS AND METHODS: From May 2007 to February 2012, 404 patients who were prescribed and administered teriparatide and who could be followed-up for longer than 12 months were enrolled. They were divided into two groups depending on teriparatide duration: LT3M (n=132) and ST3M (n=272). RESULTS: The group with the teriparatide duration of LT3M showed significantly less development of an initial OVCF within 1 year (p=0.004, chi-square). Duration of teriparatide use, body mass index, pre-teriparatide lowest spinal bone mineral density, and severity of osteoporosis significantly affected multiple regression analysis results (p<0.05). Survival analysis of first new-onset OVCFs demonstrated a significantly better survival rate for the LT3M group (log rank, p=0.005). Also, the ST3M group showed a higher odds ratio of 54.00 for development of an initial OVCF during follow-up than the LT3M group (Mantel-Haenzel common odds ratio, p=0.006). CONCLUSION: At least one cyclic teriparatide administration is recommended to provide a protective effect against the initial onset of a new OVCF for up to one year after therapy.
Aged ; Aged, 80 and over ; Bone Density/drug effects ; Bone Density Conservation Agents/*administration & dosage/pharmacology ; Cohort Studies ; Drug Administration Schedule ; Female ; Fractures, Compression/*drug therapy/etiology ; Humans ; Incidence ; Male ; Middle Aged ; Osteoporosis/complications ; Osteoporotic Fractures/*drug therapy/etiology ; Retrospective Studies ; Spinal Fractures/*drug therapy/etiology ; Teriparatide/*administration & dosage/pharmacology ; Time Factors ; Treatment Outcome

BACKGROUND/AIMS: Increased osteoclast activity is a pivotal finding in osteoporosis. This increase is mediated via the mevalonate-to-cholesterol pathway, which is involved in producing the intermediates required for osteoclast activity. D-003, a mixture of high molecular weight sugarcane wax acids, has been shown to inhibit cholesterol synthesis prior to mevalonate production, resulting in a reduction of bone loss and resorption in ovariectomized rats. Moreover, previous studies have demonstrated that short-term D-003 treatment reduces urinary excretion of deoxypyridinoline/creatinine in postmenopausal women. METHODS: We performed a double-blinded, placebo-controlled study to investigate the effects of D-003 (10 mg/day) treatment for 3 years on bone mineral density (BMD) in 83 postmenopausal women with low BMD. RESULTS: Over 3 years, D-003 treatment increased lumbar spine BMD (5.1%, p < 0.01) and improved osteoporosis-related quality of life scores as compared with placebo-treated controls. D-003 was also well tolerated; the frequency of adverse events in the bone, joints, or muscle with D-003 treatment (p < 0.05) was lower than in the placebo group. CONCLUSIONS: D-003 treatment (10 mg/day) for 3 years increased lumbar spine BMD and produced clinical improvements in postmenopausal women with low BMD. Further studies, however, will be required to confirm these results.
Absorptiometry, Photon ; Adult ; Aged ; Analysis of Variance ; Bone Density/*drug effects ; Bone Density Conservation Agents/*administration & dosage/adverse effects ; Cuba ; Double-Blind Method ; Fatty Acids/*administration & dosage/adverse effects ; Female ; Femur Neck/*drug effects/radiography ; Humans ; Lipids/blood ; Lumbar Vertebrae/*drug effects/radiography ; Middle Aged ; Osteoporosis, Postmenopausal/blood/*drug therapy/psychology/radiography ; Quality of Life ; Questionnaires ; Time Factors ; Treatment Outcome

BACKGROUND/AIMS: This study was performed to compare the mucosal findings after esophagogastroduodenoscopy in two groups before and after the use of alendronate only and following administration of the enteric-coated alendronate (5 mg) and calcitriol (0.5 microg) combined drug (Maxmarvil, Yuyu Co.). METHODS: The study population consisted of 33 postmenopausal healthy female volunteers, aged 50 to 70 years (mean age, 58 +/- 5) without gastrointestinal symptoms and with normal baseline endoscopic findings. Esophagogastroduodenoscopy was performed at baseline and was repeated 2 weeks later after daily intake of Maxmarvil (n = 17 subjects) or alendronate only (n = 16 subjects). Mucosal injury scores were reported by an endoscopist after 2 weeks of treatment with each medication schedule. RESULTS: Esophageal mucosal injuries developed in two of 16 subjects in the alendronate only group and 0 of 17 in the Maxmarvil group. Gastric mucosal injuries developed in eight subjects in the alendronate group and four subjects in the Maxmarvil group; this difference was statistically significant. CONCLUSIONS: The mucosal damage scores for the alendronate group (total score 24) were significantly higher than those for the Maxmarvil group (total score 9) in the esophagus and stomach. Therefore, this study suggested that enteric-coated Maxmarvil is less harmful to gastrointestinal mucosa than alendronate, and may improve the tolerability of osteoporosis medication in clinical practice.
Administration, Oral ; Age Factors ; Aged ; Alendronate/administration & dosage/*adverse effects ; Bone Density Conservation Agents/administration & dosage/*adverse effects ; Calcitriol/administration & dosage/*adverse effects ; Drug Combinations ; *Endoscopy, Digestive System ; Esophagus/*drug effects/pathology ; Female ; Gastric Mucosa/*drug effects/pathology ; Humans ; Middle Aged ; *Postmenopause ; Predictive Value of Tests ; Republic of Korea ; Sex Factors ; Tablets, Enteric-Coated ; Time Factors ; Treatment Outcome ; Vitamins/administration & dosage/*adverse effects