OBJECTIVES: Root resorption is an unexpected complication after replantation procedures. Combining anti-osteoclastic medicaments with retrograde root filling materials may avert this resorptive activity. The purpose of this study was to assess effects of a cathepsin K inhibitor with calcium silicate-based cements on osteoclastic activity. METHODS: MC3T3-E1 cells were cultured for biocompatibility analyses. RAW 264.7 cells were cultured in the presence of the receptor activator of nuclear factor-kappa B and lipopolysaccharide, followed by treatment with Biodentine (BIOD) or ProRoot MTA with or without medicaments (Odanacatib [ODN], a cathepsin inhibitor and alendronate, a bisphosphonate). After drug treatment, the cell counting kit-8 assay and Alizarin red staining were performed to evaluate biocompatibility in MC3T3-E1 cells. Reverse-transcription polymerase chain reaction, tartrate-resistant acid phosphatase (TRAP) staining and enzyme-linked immunosorbent assays were performed in RAW 264.7 cells to determine the expression levels of inflammatory cytokines, interleukin (IL)-1β, IL-6, tumor necrosis factor-α (TNF-α) and prostaglandin E2 (PGE2). Data were analyzed by one-way analysis of variance and Tukey's post hoc test (p < 0.05). RESULTS: Biocompatibility results showed that there were no significant differences among any of the groups. RAW 264.7 cells treated with BIOD and ODN showed the lowest levels of TNF-α and PGE2. Treatments with BIOD + ODN were more potent suppressors of inflammatory cytokine expression (p < 0.05). CONCLUSION: The cathepsin K inhibitor with calcium silicate-based cement inhibits osteoclastic activity. This may have clinical application in preventing inflammatory root resorption in replanted teeth.
Acid Phosphatase ; Alendronate ; Calcium ; Cathepsin K ; Cathepsins ; Cell Count ; Cytokines ; Dinoprostone ; Enzyme-Linked Immunosorbent Assay ; Interleukin-6 ; Interleukins ; Miners ; Necrosis ; Osteoblasts ; Osteoclasts ; Pemetrexed ; Polymerase Chain Reaction ; RAW 264.7 Cells ; Receptor Activator of Nuclear Factor-kappa B ; Replantation ; Root Resorption ; Tooth

BACKGROUND: Bisphosphonate (BP) is an effective drug for the prevention and treatment of osteoporosis. However, gastrointestinal distress caused by BP is a well-known side effect for low compliance. The aim of our study was to compare the 1-year persistence, compliance and T-scores between the aperitif medication group and the postprandial medication group. METHODS: Three hundred patients were included in this study to determine their persistence and compliance with the prescribed daily BP (Maxmarvil®, alendronate 5 mg and calcitriol 0.5 µg; YuYu Pharm) following distal radius fractures. Patients in Group 1 (aperitif medication) were asked to adhere to the general guidelines for BPs before breakfast. Patients in Group 2 (postprandial medication) were recommended medication after breakfast. We compared the persistence and compliance of this daily BP therapy using the medication possession ratio (MPR) and T-scores between the 2 groups after 1 year. RESULTS: Bone mineral density in hip and lumbar spine was improved significantly in 2 groups (P < 0.001). Significant differences existed between 2 groups, including 73 of 150 patients (48.7%) in Group 1, and 111 of 150 patients (73.3%) in Group 2 for 1-year persistence (P=0.001). The mean MPR is 0.66 in Group 1 (range, 0.50–0.86) and 0.71 in Group 2 (range, 0.54–0.87). A significant difference was detected between the 2 groups (P=0.002). CONCLUSIONS: Postprandial administration improved persistence and compliance with daily BP therapy, resulting in better clinical outcomes.
Alendronate ; Bone Density ; Breakfast ; Calcitriol ; Compliance ; Hip ; Humans ; Osteoporosis ; Radius Fractures ; Spine

OBJECTIVE: To study and compare the clinical effects of Rehmannia Decoction and alendronate sodium for the treatment of primary osteoporosis. METHODS: From January 2016 to December 2017, 72 patients with primary osteoporosis who took Dihuang Decoction(DHD) orally and alendronate regularly for more than one year were randomly divided into 2 groups:experimental group and control group. The experimental group consisted of 14 males and 22 females, with an average age of(63.97±3.70) years old. The patients in the experimental group took Chinese medicine DHD, one dose each time, one time in the morning and one time in the evening, twice a week. The control group consisted of 16 males and 20 females with an average age of(63.36±3.07) years old. Patients in the control group were given alendronate 70 mg orally once a week. The basic treatment for osteoporosis remained unchanged in both groups(600 mg of calcium carbonate D3 and 0.5 μg of calcitriol capsules were taken daily). Bone mineral density (BMD) of femoral neck and lumbar vertebrae was measured by dual energy X-ray absorptiometry before and after treatment for one year. The levels of serum collagen type I C-terminal peptide (beta-CTX) and serum osteoclast (SOST) were measured before and after treatment for two groups. RESULTS: The age, bone mineral density, SOST and beta-CTX baseline values between the two groups before and after anti-osteoporosis treatment were compared. The difference was not statistically significant(>0.05). Compared with the two groups, the BMD of femoral neck and lumbar vertebrae were increased after 1 year of anti-osteoporosis treatment. The differences were statistically significant (<0.001). The value of serum beta-CTX was significantly lower than before. The values were 52.002 and 50.071 respectively. The value of serum SOST was increased than that before treatment. The values were -29.242 and -30.807 respectively. The differences were statistically significant (<0.001). BMD of the femoral neck and lumbar spine was compared between the two groups after treatment. The P values were 0.294 and 0.478 respectively. The difference was not statistically significant (>0.05). The serum beta-CTX values were compared between the two groups after treatment. The value was 0.908. The serum SOST values were compared between the two groups after treatment. The value was 0.888. The difference was not statistically significant (>0.05). CONCLUSIONS In this study, traditional Chinese medicine DHD is used to treat osteoporosis. It is found that DHD and alendronate have a good effect. The DHD can be used as a choice of Chinese medicine in the treatment of primary osteoporosis.
Absorptiometry, Photon ; Aged ; Alendronate ; therapeutic use ; Bone Density ; Bone Density Conservation Agents ; therapeutic use ; Female ; Humans ; Male ; Middle Aged ; Osteoporosis ; drug therapy

No abstract available.
Alendronate ; Cell Proliferation

BACKGROUND: Alendronate (AL), a drug for inhibiting osteoclast-mediated bone-resorption, was intercalated into an inorganic drug delivery nanovehicle, layered double hydroxide (LDH), to form a new nanohybrid, AL-LDH, with 1:1 heterostructure along the crystallographic C-axis. Based on the intercalation reaction strategy, the present AL-LDH drug delivery system (DDS) was realized with an enhanced drug efficacy of AL, which was confirmed by the improved proliferation and osteogenic differentiation of osteoblast-like cells (MG63). METHODS: The AL-LDH nanohybrid was synthesized by conventional ion-exchange reaction and characterized by powder X-ray diffraction (PXRD), high-resolution transmission electron microscopy (HR-TEM), and Fourier transform infrared (FT-IR) spectroscopy. Additionally, in vitro efficacy tests, such as cell proliferation and alkaline phosphatase (ALP) activity, were analyzed. RESULTS: The AL was successfully intercalated into LDH via ion-exchange reaction, and thus prepared AL-LDH DDS was X-ray single phasic and chemically well defined. The accumulated AL content in MG63 cells treated with the AL-LDH DDS nanoparticles was determined to be 10.6-fold higher than that within those treated with the intact AL after incubation for 1 hour, suggesting that intercellular permeation of AL was facilitated thanks to the hybridization with drug delivery vehicle, LDH. Furthermore, both in vitro proliferation level and ALP activity of MG63 treated with the present hybrid drug, AL-LDH, were found to be much more enhanced than those treated with the intact AL. This is surely due to the fact that LDH could deliver AL drug very efficiently, although LDH itself does not show any effect on proliferation and osteogenic differentiation of MG63 cells. CONCLUSION: The present AL-LDH could be considered as a promising DDS for improving efficacy of AL.
Alendronate ; Alkaline Phosphatase ; Cell Proliferation ; Drug Delivery Systems ; Fourier Analysis ; In Vitro Techniques ; Microscopy, Electron, Transmission ; Nanoparticles ; Spectrum Analysis ; X-Ray Diffraction

OBJECTIVETo compare the efficacy differences between catgut implantation at stellate ganglion combined with oral administration of alendronate sodium and oral administration of alendronate sodium alone on postmenopausal osteoporosis (PO).

METHODSSixty patients of PO were randomly divided into an observation group and a control group, 30 cases in each one. The patients in the control group were treated with oral administration of alendronate sodium. Based on the treatment of control group, the patients in the observation group were treated with catgut implantation at stellate ganglion. The treatment was given once a week in the two groups; the consecution treatment of four weeks constituted one session, and totally six sessions were given. The changes of total syndrome score, bone mineral density of lumbar vertebra (L to L) and femeral neck (FN) and estradiol were observed before and after treatment; the clinical efficacy was compared between the two groups.

RESULTSCompared before treatment, the total syndrome score, bone mineral density of lumbar vertebra (L to L) and FN and estradiol were significantly improved after treatment (all <0.05); which were more significant in the observation group (all <0.05). Compared before treatment, the level of estradiol in the control group was not significantly changed after treatment (>0.05), while that in the observation group was significantly changed after treatment (<0.05). After treatment, the level of estradiol in the observation group was higher than that in the control group (<0.05). The total effective rate was 93.3% (28/30) in the observation group, which was significantly higher than 83.3% (25/30) in the control group (<0.05).

CONCLUSIONCatgut implantation at stellate ganglion combined with oral administration of alendronate sodium are superior to oral administration of alendronate sodium alone for postmenopausal osteoporosis, which improve the clinical symptoms, regulate the hormone level and increase bone mineral density.

Acupuncture Therapy ; Alendronate ; administration & dosage ; Bone Density ; Catgut ; Female ; Humans ; Osteoporosis, Postmenopausal ; therapy ; Stellate Ganglion

BACKGROUND: In South Korea, 22.3% of women ≥50 years of age and 37% of women ≥70 years of age visit the doctor to obtain treatment for osteoporosis. According to the analysis of the National Health Insurance Services claim data between 2008 and 2012, the number and incidence of hip and vertebral fractures increased during the same period. Denosumab, a newly marketed medicine in Korea, is the first RANK inhibitor. METHODS: A cost-utility analysis was conducted from a societal perspective to prove the superiority of denosumab to alendronate. A Markov cohort model was used to investigate the cost-effectiveness of denosumab. A 6-month cycle length was used in the model, and all patients were individually followed up through the model, from their age at treatment initiation to their time of death or until 100 years of age. The model consisted of eight health states: well; hip fracture; vertebral fracture; wrist fracture; other osteoporotic fracture; post-hip fracture; post-vertebral fracture; and dead. All patients began in the well-health state. In this model, 5% discounted rate, two-year maximum offset time, and persistence were adopted. RESULTS: The total lifetime costs for alendronate and denosumab were USD 5,587 and USD 6,534, respectively. The incremental costeffectiveness ratio (ICER) for denosumab versus alendronate was USD 20,600/QALY. Given the ICER threshold in Korea, the results indicated that denosumab was remarkably superior to alendronate. CONCLUSION: Denosumab is a cost-effective alternative to the oral anti-osteoporotic treatment, alendronate, in South Korea.
Alendronate ; Cohort Studies ; Cost-Benefit Analysis ; Denosumab* ; Economics, Pharmaceutical ; Female ; Hip ; Humans ; Incidence ; Korea* ; National Health Programs ; Osteoporosis ; Osteoporosis, Postmenopausal* ; Osteoporotic Fractures ; Wrist

BACKGROUND: Recent evidence from in vitro and in vivo studies indicates that bisphosphonates may promote osteoblastic bone formation and potently inhibit osteoclast activity. However, little is known about the potential effect of bisphosphonates on the recruitment of osteoblastic precursors from patient-derived bone marrow stromal cells due to difficulties in accessing human bone marrow from healthy and disease subjects. METHODS: In this study, we evaluated the potential of using FDA-approved and clinically utilized bisphosphonates such as alendronate, ibandronate, and zoledronate to enhance the development of bone forming osteoblasts from osteoporosis patient- and healthy-person derived hBMSCs (op-MSCs and hp-MSCs, respectively). hBMSCs were obtained from postmenopausal women without endocrine diseases or receiving hormone replacement therapy. Cells were treated with or without a bisphosphonate (alendronate, ibandronate, and zoledronate) and analyzed over 21 days of culture. RESULTS: hBMSC from osteoporosis-patient with bisphosphonates treatment demonstrated a significant increase in Alizarin red staining after 7 days compared to that from healthy-person. Calcium contents and alkaline phosphatase (ALP) enzyme activity also demonstrated an increased propensity in hMSCs from osteoporosis-patient compared to those from healthy-person, although there were inter-individual variations.Gene expression levels varied among different donors. There were no significant differences in the effect on the osteoblastic differentiation of hBMSCs among alendronate, ibandronate, and zoledronate. Statistical significance in the osteoblastic differentiation of hBMSCs between the positive control group cultured in osteogenic mediumalone and groups cultured in osteogenic mediumsupplemented with bisphosphonate was not shown either.These results might be due to various cell types of hBMSCs from individual clinical patients and concentrations of bisphosphonate used. CONCLUSION: Our study using a clinically relevant in vitro model suggests that bisphosphonate treatment is more effective for patients with osteoporosis than its preventive effect for healthy person. In addition, patient-specific responses to bisphosphonates should be considered rather than bisphosphonate type prior to prescription. Further investigations are needed to determine how bisphosphonates influence hBMSCs function to mediate bone quality and turnover in osteoporotic patients. Such studies can generate novel approaches to treat age-related osteoporotic bone loss.
Alendronate ; Alkaline Phosphatase ; Bone Marrow ; Calcium ; Diphosphonates* ; Endocrine System Diseases ; Female ; Hormone Replacement Therapy ; Humans ; In Vitro Techniques ; Mesenchymal Stromal Cells* ; Osteoblasts ; Osteoclasts ; Osteogenesis ; Osteoporosis* ; Prescriptions ; Tissue Donors

OBJECTIVES: The purpose of this study was to investigate the demographic and clinical characteristics of patients with medication-related osteonecrosis of the jaw (MRONJ) and to elucidate factors affecting recurrence in surgical treatment. MATERIALS AND METHODS: A total of 51 patients who were diagnosed with MRONJ were analyzed according to demographic and clinical features and treatment results through a retrospective chart review from 2013 to 2017 in the Department of Oral and Maxillofacial Surgery, Korea University Anam Hospital, Seoul in Korea. RESULTS: Alendronate composed the majority of medication doses (55.6%), followed by ibandronate (20.0%), risedronate (15.6%), and zoledronate (6.7%). Forty patients (88.9%) were given oral medication, and five patients (11.1%) were intravenously treated, and the mean duration of medication use was 61.1±42.9 months. A total of 10 patients (22.2%) had a drug holiday before MRONJ-induced dental treatment lasting an average of 6.8±7.0 months. MRONJ occurred 2.7 times more in the mandible, with 41 cases (73.2%) occurring in the mandible and 15 cases (26.8%) occurring in the maxilla, and the prevalence of affected posterior parts (premolar-molar) was six times greater than that of the anterior parts (incisor-canine) (48 cases vs 8 cases, 85.7% vs 14.3%). The most common dental cause of MRONJ was tooth extraction (69.6%). Regarding recurrence, there was no statistical difference in recurrence rate according to either site or stage. However, recurrence occurred in 4 out of 34 cases (11.8%) in the primary closure group and 9 out of 20 cases (45.0%) in the secondary healing group, and there was a statistical difference with respect to closure technique. CONCLUSION: The identified risk factors in patients taking bone resorption inhibitors can aid dental clinicians in ensuring prevention and proper treatment of MRONJ.
Alendronate ; Bone Density Conservation Agents ; Holidays ; Humans ; Jaw* ; Korea ; Mandible ; Maxilla ; Osteonecrosis* ; Prevalence ; Recurrence ; Retrospective Studies ; Risedronate Sodium ; Risk Factors ; Seoul ; Surgery, Oral ; Surgical Procedures, Operative ; Tooth Extraction

OBJECTIVES: The purpose of this study was to evaluate the synergic effect of recombinant human bone morphogenetic protein-2 (rhBMP-2) and low-level laser therapy (LLLT) on bisphosphonate-treated osteoblasts. MATERIALS AND METHODS: Human fetal osteoblast cells (hFOB 1.19) were cultured with 100 µM alendronate. Low-level Ga-Al-As laser alone or with 100 ng/mL rhBMP-2 was then applied. Cell viability was measured with MTT assay. The expression levels of receptor activator of nuclear factor kappa-B ligand (RANKL), macrophage colony-stimulating factor (M-CSF), and osteoprotegerin (OPG) were analyzed for osteoblastic activity inducing osteoclastic activity. Collagen type and transforming growth factor beta-1 were also evaluated for bone matrix formation. RESULTS: The results showed that rhBMP-2 and LLLT had a synergic effect on alendronate-treated osteoblasts for enhancing osteoblastic activity and bone matrix formation. Between rhBMP-2 and LLLT, rhBMP-2 exhibited a greater effect, but did not show a significant difference. CONCLUSION: rhBMP-2 and LLLT have synergic effects on bisphosphonate-treated osteoblasts through enhancement of osteoblastic activity and bone formation activity.
Alendronate ; Bone Matrix ; Bone Morphogenetic Protein 2 ; Cell Survival ; Collagen ; Humans* ; Low-Level Light Therapy ; Macrophage Colony-Stimulating Factor ; Osteoblasts* ; Osteoclasts ; Osteogenesis ; Osteoprotegerin ; Transforming Growth Factors