No abstract available.
Anti-Inflammatory Agents/*administration & dosage ; Cytokines/blood ; Diphosphonates/*administration & dosage ; Humans ; Injections, Intravenous ; Osteoporosis/*drug therapy

BACKGROUND: Pamidronate is a potent inhibitor of osteoclast-mediated bone resorption. Recently, the drug has been known to relieve bone pain. We hypothesized that direct epidural administration of pamidronate could have various advantages over oral administration with respect to dosage, side effects, and efficacy. Therefore, we evaluated the neuronal safety of epidurally-administered pamidronate. METHODS: Twenty-seven rats weighing 250-350 g were equally divided into 3 groups. Each group received an epidural administration with either 0.3 ml (3.75 mg) of pamidronate (group P), 0.3 ml of 40% alcohol (group A), or 0.3 ml of normal saline (group N). A Pinch-toe test, motor function evaluation, and histopathologic examination of the spinal cord to detect conditions such as chromatolysis, meningeal inflammation, and neuritis, were performed on the 2nd, 7th, and 21st day following administration of each drug. RESULTS: All rats in group A showed an abnormal response to the pinch-toe test and decreased motor function during the entire evaluation period. Abnormal histopathologic findings, including neuritis and meningeal inflammation were observed only in group A rats. Rats in group P, with the exception of 1, and group N showed no significant sensory/motor dysfunction over a 3-week observation period. No histopathologic changes were observed in groups P and N. CONCLUSIONS: Direct epidural injection of pamidronate (about 12.5 mg/kg) showed no neurotoxic evidence in terms of sensory/motor function evaluation and histopathologic examination.
Administration, Oral ; Animals ; Bone Resorption ; Diphosphonates ; Inflammation ; Injections, Epidural ; Neuritis ; Neurons ; Rats ; Spinal Cord

The average life expectancy has been increased, so the proportion of elderly patients that visit to the dental clinic for prosthetic restoration has increased. Elderly patients have various chronic diseases. Recent trends show an increase of osteoporosis in elderly patients, and thus, the number of osteoporosis patients is expected to escalate. Currently, the most widely used drug for osteoporosis is bisphosphonate. However, osteonecrosis of the jaw has been reported as a side effect derived from long-term oral administration or injection treatment of the drug. Surgical dental treatment was the main cause of medication related osteonecrosis of the jaw (MRONJ). As MRONJ is very difficult to cure, it is important to take preventive measures. Surgical operation may be needed for the mouth preparation before prosthetic restoration. For successful treatment, the dentist should have a full understanding of osteoporosis and show a continued interest toward this disease for careful management.
Administration, Oral ; Aged ; Chronic Disease ; Dental Clinics ; Dentists ; Diphosphonates ; Humans ; Jaw ; Life Expectancy ; Mouth ; Osteonecrosis ; Osteoporosis*

Bisphosphonates are used effectively for many medical conditions, such as multiple myeloma, Paget's disease, osteoporosis, etc. However, recently, osteonecrosis of the jaw was observed in patients receiving long-term bisphosphonate therapy, including oral administration. This osteonecrosis is refractory, and complete recovery is not guaranteed despite a standard treatment protocol being established by many associations related to oral and maxillofacial surgery. The treatment outcome of oral bisphosphonate-related osteonecrosis of jaw (BRONJ) is reported with a review of the relevant literature.
Administration, Oral ; Clinical Protocols ; Diphosphonates ; Humans ; Jaw ; Multiple Myeloma ; Osteonecrosis ; Osteoporosis ; Surgery, Oral ; Treatment Outcome

BACKGROUNDSystemic administration of bisphosphonates has shown promising results in the treatment of osteonecrosis of the femoral head (ONFH). However, few studies have evaluated the efficacy of local zoledronate (ZOL) administration in the treatment of ONFH. The purpose of this study was to investigate whether local administration of bisphosphonate-soaked hydroxyapatite (HA) could improve bone healing in an experimental rabbit model of ONFH.

METHODSThis experimental study was conducted between October 2014 and June 2015. Forty-five rabbits underwent simulated ONFH surgery. Immediately following surgery, they were divided into three groups: model (untreated, n = 15), HA (treated with HA alone, n = 15), and HA + ZOL (treated with HA soaked in a low-dose ZOL solution, n = 15). Histological, immunohistochemical, and quantitative analyses were performed to evaluate bone formation and resorption 2, 4, and 8 weeks after surgery.

RESULTSGross bone matrix and hematopoietic tissue formation were observed in the HA + ZOL group 4 weeks after surgery. The immunohistochemical staining intensities for 5-bromodeoxyuridine, runt-related transcription factor 2, osteocalcin, osteopontin, and osteoprotegerin were significantly higher in the HA + ZOL group than that in the model (P < 0.001, P< 0.001, P< 0.001, P< 0.001, and P = 0.018, respectively) and HA groups (P = 0.003, P = 0.049, P< 0.001, P = 0.020, and P = 0.019, respectively), whereas receptor activator of the nuclear factor-κB ligand staining intensity was significantly lower in the HA + ZOL group than that in the model and HA groups (P = 0.029 and P = 0.015, respectively) 4 weeks after surgery. No significant differences in bone formation or bone resorption marker expression were found between the three groups 2 or 8 weeks after surgery (P > 0.05).

CONCLUSIONSLocal administration of HA soaked in a low-dose ZOL solution increased new bone formation while inhibiting bone resorption in an animal model of ONFH, which might provide new evidence for joint-preserving surgery in the treatment of ONFH.

Animals ; Diphosphonates ; administration & dosage ; therapeutic use ; Durapatite ; administration & dosage ; therapeutic use ; Female ; Femur Head Necrosis ; drug therapy ; metabolism ; Imidazoles ; administration & dosage ; therapeutic use ; Immunohistochemistry ; Male

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

PURPOSE: We evaluated changes in bone mineral density and biochemical bone turn over markers resulting from intravenous administration of zoledronic acid for the purpose of increasing bone mineral density and decreasing bone turnover rate in patients who had received operative treatment after hip fracture. MATERIALS AND METHODS: We carried out a retrospective study of 34 patients who had received injections of zoledronic acid after surgical treatment for hip fracture from January 2009 to June 2010, with a follow up period of more than one year. We evaluated pre and post T-scores of DXA in spine, proximal femur and femoral neck along with biochemical bone metabolic markers, and we then analyzed each factor. RESULTS: T score was enhanced in all cases with pre T-score -4.2 and post T-score -3.3 revealing statistical significance (P<0.05). In addition, two biochemical bone turnover markers were observed to decrease in most patients. Three days after drug administration, 7 patients(20.6%) had minor adverse effects. There were no serious complications such as atrial fibrillation. CONCLUSION: No major adverse effects were observed, only minor ones in patients who had been injected with zoledronic acid for the prevention of osteoporotic fracture after surgical treatment for hip fracture. We confirmed the affirmative effects on changes in bone mineral density and biochemical bone turn over markers associated with the use of this drug.
Administration, Intravenous ; Bone Density ; Diphosphonates ; Femur ; Femur Neck ; Follow-Up Studies ; Hip ; Humans ; Imidazoles ; Osteoporosis ; Osteoporotic Fractures ; Retrospective Studies ; Spine

A 59-year-old male who had suffered from multiple myeloma for nine years and had been administered bisphosphonates for seven years visited a dental hospital for pain relief due to extensive caries in his left maxillary molars. The molars were extracted, leaving an exposed wound for three months. The radiograph showed sequestra formation and irregular bone destruction in the left maxilla. Sudden pain and gingival swelling in the right mandibular molar area occurred six months later. The interseptum of the right lower second molar was observed to be necrotic during surgery. These findings coincided with the features of bisphosphonate-related osteonecrosis of the jaw (BRONJ). In this case, the long intravenous administration of bisphosphonates and tooth extraction were likely the etiologic factors of BRONJ in a patient with multiple myeloma; moreover, the bilateral occurrence of BRONJ is a characteristic feature.
Administration, Intravenous ; Bisphosphonate-Associated Osteonecrosis of the Jaw* ; Diphosphonates ; Humans ; Male ; Maxilla ; Middle Aged ; Molar ; Multiple Myeloma* ; Tooth Extraction ; Wounds and Injuries

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