The objective of this study is to examine the effect of low-magnitude, high-frequency (LMHF) loading, and anti-osteoporosis medications such as parathyroid hormone (PTH) and bisphosphonates on peri-implant bone healing in an osteoporosis model, and to assess their combined effects on these processes. Thirteen-week-old ovariectomized rats (n = 44) were divided into three groups: PTH, alendronate, and saline. After 3 weeks of drug administration, titanium implants were inserted into the tibiae. Each group was subdivided into two groups: with or without LMHF loading via whole-body vibration (50 Hz at 0.5 g, 15 min per day, 5 days per week). Rats were killed 4 weeks following implantation. Removal torque test, micro-CT analyses (relative gray (RG) value, water = 0, and implant = 100), and histomorphometric analyses (bone-to-implant contact (BIC) and peri-implant bone formation (bone volume/tissue volume (BV/TV))) were performed. Removal torque values and BIC were significantly differed by loading and drug administration (ANOVA). Post hoc analysis showed that PTH-treated groups were significantly higher than the other drug-treated groups. BV/TV was significantly enhanced by PTH administration. In cortical bone, RG values were significantly increased by loading. In trabecular bone, however, RG values were significantly increased by PTH administration. These findings suggest that LMHF loading and PTH can act locally and additively on the bone healing process, improving the condition of implant osseointegration.
Alendronate ; administration & dosage ; pharmacology ; Animals ; Dental Implantation, Endosseous ; methods ; Dental Implants ; Female ; Implants, Experimental ; Osseointegration ; drug effects ; Ovariectomy ; Parathyroid Hormone ; administration & dosage ; pharmacology ; Rats ; Tibia ; surgery ; Vibration ; Wound Healing ; drug effects

To provide a support to the clinical application of alendronate (Alen) on cytology, we studied the effects of Alen on the function of osteoblasts. In this experiment, we observed the influence of MG63 cell line co-incubation with Alen at concentrations of 1 x 10(-9) mol/L, 1 x 10(-7) mol/L or 1 x 10(-5) mol/L on the osteoblastic function (proliferation, cell morphology, alkali phosphatase (ALP) activity, expression of type I collagen and effect of calcium deposition). The proliferation, cell morphology, ALP activity and type I collagen synthesis of MG63 were not affected by Alen at concentration of 1 x 10(-9) mol/L and 1 x 10(-7) mol/L, but the ALP activity as well as type I collagen production were promoted at higher concentration (1 x 10(-5) mol/L). The calcium deposition of MG63 could be increased at the lower concentration (1 x 10(-9) mol/L), while it was inhibited at the higher concentration. In conclusion, Alen at low concentration can promote the mineralization ability of osteoblasts to a certain extent, and this benefits the bone formation.
Alendronate ; pharmacology ; Alkaline Phosphatase ; metabolism ; Bone Density Conservation Agents ; pharmacology ; Cell Line ; Cell Proliferation ; drug effects ; Collagen Type I ; metabolism ; Humans ; Osteoblasts ; cytology ; Osteogenesis ; drug effects

OBJECTIVETo investigate the effect of alendronate on the expressions of osteoprotegerin (OPG) and receptor activator of nuclear factor-κB ligand (RANKL) in mouse osteoblasts.

METHODSMouse calvarial osteoblasts cultured in vitro were identified by alkaline phosphatase (ALP) staining and immunofluorescence assay of OPG and RANKL expressions. The second passage of the osteoblasts were treated with different concentrations of alendronate (10(-4) to 10(-7) mol/L) for 48 h, and the changes in OPG and RANKL mRNA and protein expressions were examined using real-time PCR and Western blotting, respectively.

RESULTSThe isolated osteoblasts were positive for ALP and expressed OPG and RANKL. Real-time PCR and Western blotting showed that at the concentration of 1×10(-4) mol/L, alendronate caused an obvious down-regulation of OPG and RANKL expressions in the cells, whereas at lower concentrations, alendronate increased the expressions of both genes with the highest expressions occurring after treatment with 1×10(-5) mol/L.

CONCLUSIONHigh concentrations of alendronate (>1×10(-4) mol/L) decrease the expressions of OPG and RANKL, whereas low concentrations (1×10(-5) to 1×10(-7) mol/L) increase their expressions in mouse osteoblasts cultured in vitro.

Alendronate ; pharmacology ; Animals ; Cells, Cultured ; Mice ; Mice, Inbred BALB C ; Osteoblasts ; drug effects ; metabolism ; Osteoprotegerin ; metabolism ; RANK Ligand ; metabolism

We investigated acute effects of intermittent large dose bisphophonate therapy in osteoporotic patients. Peripheral blood mononuclear cells were incubated with alendronate (100 micrometer) for 18 hr, in vitro and cytokine expressions were measured by real-time RT-PCR. Pamidronate 30 mg was administered on 26 osteoporotic patients; and acute phase reactants, inflammatory cytokines and bone biomarkers were measured. The in vitro study showed significant increase in mRNA expression of IL-6, TNF-alpha and IFN-gamma. A notable rise in serum C-reactive protein (CRP) was observed over 3 days after pamidronate infusion (P=0.026). Serum levels of TNF-alpha, IL-6 and IFN-gamma were also significantly increased (P=0.009, 0.014, 0.035, respectively) and the increase in IL-6 levels were strongly correlated with CRP levels (P=0.04). Serum calcium and c-telopeptide levels rapidly decreased after the treatment (P=0.02, <0.001, respectively). This study showed that mRNA expression of inflammatory cytokines at peripheral blood mononuclear cells (PBMC) level were observed within 18 hr and marked elevation of inflammatory cytokines and acute phase reactants were demonstrated after pamidronate infusion at the dose for osteoporosis. Our studies confirmed that intermittent large dose aminobisphosphonate causes acute inflammation.
Acute-Phase Proteins/biosynthesis/genetics ; Adult ; Aged ; Aged, 80 and over ; Alendronate/pharmacology ; Biological Markers/blood ; Blood Cells/drug effects ; Bone Density Conservation Agents/*administration & dosage ; C-Reactive Protein/genetics/metabolism ; Calcium/blood ; Collagen Type I/blood ; Diphosphonates/*administration & dosage ; Female ; Humans ; Injections, Intravenous ; Interferon-gamma/blood/genetics ; Interleukin-6/blood/genetics ; Male ; Middle Aged ; Osteoporosis/*drug therapy ; Peptides/blood ; RNA, Messenger/metabolism ; Tumor Necrosis Factor-alpha/genetics/metabolism

PURPOSE: The comparative effects of alendronate and alfacalcidol on bone mineral density (BMD) and bone turnover have already been established in postmenopausal women with osteoporosis. An open-labeled prospective study was conducted to compare the treatment effects of alendronate and alfacalcidol on hip BMD and bone turnover in Japanese men with osteoporosis or osteopenia with clinical risk factors for fractures. MATERIALS AND METHODS: One hundred twelve men with osteoporosis or osteopenia with clinical risk factors for fractures (mean age: 71.4 years) were randomly divided into two groups of 56 patients each: the alendronate (5 mg daily) and alfacalcidol (1 microgram daily) groups. The BMD of the total hip, urinary level of cross-linked N-terminal telopeptides of type I collagen (NTX), and serum levels of bone-specific alkaline phosphatase (BSAP) were measured during the 12-month-treatment period. RESULTS: Forty-five patients in the alendronate group and 42 patients in the alfacalcidol group completed the trial. Alendronate increased BMD (+2.3% at 12 months) following reductions in the urinary level of NTX (-46.4% at 3 months) and serum level of BSAP (-34.1% at 12 months), while alfacalcidol sustained BMD (-1.9% at 12 months) as well as the urinary level of NTX (+13.2% at 3 months) and serum level of BSAP (+1.8% at 12 months). CONCLUSION: The present study confirmed that alendronate has better efficacy than alfacalcidol (active control) in increasing hip BMD and reducing bone turnover in Japanese men with osteoporosis or osteopenia with clinical risk factors for fractures.
Aged ; Aged, 80 and over ; Alendronate/pharmacology/therapeutic use ; Asian Continental Ancestry Group ; Bone Density/*drug effects ; *Bone Density Conservation Agents/pharmacology/therapeutic use ; Bone Diseases, Metabolic/*drug therapy ; Fractures, Bone/*prevention & control ; Hip Joint/*drug effects/pathology ; Humans ; *Hydroxycholecalciferols/pharmacology/therapeutic use ; Male ; Middle Aged ; Osteoporosis/*drug therapy ; Treatment Outcome

PURPOSE: The comparative effects of alendronate and alfacalcidol on bone mineral density (BMD) and bone turnover have already been established in postmenopausal women with osteoporosis. An open-labeled prospective study was conducted to compare the treatment effects of alendronate and alfacalcidol on hip BMD and bone turnover in Japanese men with osteoporosis or osteopenia with clinical risk factors for fractures. MATERIALS AND METHODS: One hundred twelve men with osteoporosis or osteopenia with clinical risk factors for fractures (mean age: 71.4 years) were randomly divided into two groups of 56 patients each: the alendronate (5 mg daily) and alfacalcidol (1 microgram daily) groups. The BMD of the total hip, urinary level of cross-linked N-terminal telopeptides of type I collagen (NTX), and serum levels of bone-specific alkaline phosphatase (BSAP) were measured during the 12-month-treatment period. RESULTS: Forty-five patients in the alendronate group and 42 patients in the alfacalcidol group completed the trial. Alendronate increased BMD (+2.3% at 12 months) following reductions in the urinary level of NTX (-46.4% at 3 months) and serum level of BSAP (-34.1% at 12 months), while alfacalcidol sustained BMD (-1.9% at 12 months) as well as the urinary level of NTX (+13.2% at 3 months) and serum level of BSAP (+1.8% at 12 months). CONCLUSION: The present study confirmed that alendronate has better efficacy than alfacalcidol (active control) in increasing hip BMD and reducing bone turnover in Japanese men with osteoporosis or osteopenia with clinical risk factors for fractures.
Aged ; Aged, 80 and over ; Alendronate/pharmacology/therapeutic use ; Asian Continental Ancestry Group ; Bone Density/*drug effects ; *Bone Density Conservation Agents/pharmacology/therapeutic use ; Bone Diseases, Metabolic/*drug therapy ; Fractures, Bone/*prevention & control ; Hip Joint/*drug effects/pathology ; Humans ; *Hydroxycholecalciferols/pharmacology/therapeutic use ; Male ; Middle Aged ; Osteoporosis/*drug therapy ; Treatment Outcome

BACKGROUNDBiphasic calcium phosphate (BCP) ceramics has a potential advantage as an osteoconductive matrix and has an optimal resorption rate for bone formation. Using BCP ceramics as a bone graft during spinal fusion requires osteogenesis within the material and subsequent bridging between adjacent vertebrae to provide long-term support. Bisphosphonates have been reported to prolong the process of bone healing. The influence of bisphosphonate treatment on bone formation within BCP ceramics in spinal fusion remains unknown. The aim of this study was to evaluate the influence of alendronate on BCP osteogenesis in posterolateral spinal fusion.

METHODSPosterolateral spinal fusion with pedicle screw fixation was performed at the lumbar spine in twenty-two pigs. BCP ceramics were applied as a bone graft to obtain bone fusion between adjacent transverse processes. Eleven pigs in the treatment group received oral alendronate 10 mg/d for three months postoperatively. Eleven pigs in the control group did not receive treatment with alendronate. All animals underwent posterolateral spinal fusion with BCP ceramics. The fusion rate was evaluated three months after the operation.

RESULTSThe fusion rates evaluated by X-ray were 27.3% in the treatment group and 20% in the control group. The fusion rates using histological evaluation were 18.2% in the treatment group and 20% in the control group. The mean volumes of fusion mass were (3.64 +/- 0.86) cm(3) in the treatment group and (4.26 +/- 0.63) cm(3) in the control group. No significant differences were found in either trabecular bone volume or residual BCP volume between treatment and control groups using histological evaluation. The new bone formation within BCP ceramics was greater in the area adjacent to transverse process (P < 0.01).

CONCLUSIONOral alendronate with a dose of 10 mg daily do not inhibit bone formation within BCP ceramics or affect the fusion rate in posterolateral spinal fusion from porcine models.

Alendronate ; pharmacology ; Animals ; Calcium Phosphates ; chemistry ; Ceramics ; chemistry ; Female ; Osteogenesis ; drug effects ; Spinal Fusion ; Swine

PURPOSE: To compare the effects of alendronate and raloxifene on lumbar bone mineral density (BMD), bone turnover, and lipid metabolism in elderly women with osteoporosis. Subjects and Methods: One hundred twenty-two postmenopausal women with osteoporosis (mean age: 69.4 years) were randomly divided into 2 groups of 61 patients: the alendronate group and the raloxifene group. BMD of the lumbar spine, urinary level of cross-linked N-terminal telopeptides of type I collagen (NTX), and serum levels of alkaline phosphatase (ALP), total cholesterol (TC), high and low density lipoprotein cholesterols (LDL-C and HDL-C, respectively), and triglycerides (TG) were measured during the 12-month-treatment period. RESULTS: The trial in 50 patients in the alendronate group and 52 patients in the raloxifene group could be completed. Both alendronate and raloxifene increased lumbar BMD (+8.0% and +2.4% at 12 months, respectively), followed by reductions of urinary NTX level and serum ALP level; however, the effects of alendronate were more pronounced than those of raloxifene. Only raloxifene reduced the serum levels of TC and LDL-C (-3.9% and -7.7% at 12 months, respectively), without any significant effect on the serum HDL-C and TG levels. CONCLUSION: The present study confirmed the efficacy of alendronate greater than raloxifene in increasing lumbar BMD through its effect on marked reduction of the bone turnover more than by raloxifene, and some beneficial effects of raloxifene on lipid metabolism in elderly women with osteoporosis.
Aged ; Alendronate/adverse effects/pharmacology/*therapeutic use ; Biological Markers/blood ; Bone Density/*drug effects ; Calcium/blood ; Female ; Fractures, Bone/prevention & control ; Humans ; Lipid Metabolism/*drug effects ; Osteoporosis/*drug therapy/*metabolism ; Phosphorus/blood ; Raloxifene/adverse effects/pharmacology/*therapeutic use ; Spine/drug effects

OBJECTIVETo study the effect of combination rhOPG-Fc and alendronate on mature osteoclasts.

METHODSRecombinant human osteoprotegerin secretory expression in P. pastoris was performed. Osteoblasts were got from new born mouse skeletal bone and proved by ALP staining and incubated together with osteoclasts precursor cell line Raw 264.7 in 96 well plate. After 9 d, 10 micromol/L ALN, 10(-5) g/L rhOPG-Fc, 10 micromol/L ALN + 10(-5) g/L rhOPG-Fc, 5 micromol/L ALN + 5 x 10(-6) g/L rhOPG-Fc were added to these coculture systems. Osteoblasts cultured without the drugs mentioned above served as controls. TRAP stain positive cells counting and cortical bone pit formation counting were preformed in the following the 3rd and 7th d.

RESULTSSDS-PAGE and Western blot showed that molecular weight of the expressed protein was about 55 KD, and it could reach specifically with anti-IgG antibody. Many multi-nuclear TRAP stain positive cells were found in the coculture control group after 9 d incubation, and proved to be mature osteoclasts by TRAP stain. In the 3rd and 7th d after the addition of rhOPG-Fc, ALN or both, TRAP stain positive cells counting and cortical bone pit formation counting decreased significantly in the rhOPG-Fc, ALN or both groups than in the control group, and the combine group (10(-5) g/L rhOPG-Fc + 10 micromol/L ALN) decreased most significantly when compared with rhopG-FC or ALN single.

CONCLUSIONSrhOPG-Fc can decrease the number of osteoclasts and inhibit their function. The combination of both rhOPG-Fc and ALN shows the significant inhibition effect on mature osteoclasts.

Alendronate ; pharmacology ; Animals ; Drug Synergism ; Humans ; In Vitro Techniques ; Mice ; Mice, Inbred Strains ; Osteoclasts ; cytology ; drug effects ; Osteoprotegerin ; biosynthesis ; pharmacology ; Pichia ; metabolism ; Recombinant Proteins ; biosynthesis ; pharmacology

OBJECTIVETo assess efficacy and safety of alendronate sodium treatment in osteoporosis patients with hip fracture.

METHODSOne year randomized, double-blind clinical trial was carried out in 77 osteoporosis patients with hip fracture. The bone mineral density (BMD) in lumbar spine (L(2 - 4)), femoral neck (Neck), Wards triangle (Wards) and great trochanter (Troch) was measured by dual energy x-ray absorptiometer (DEXA).

RESULTSIn our study, alendronate sodium induced marked increases in BMD of the L(2 - 4) (7.0% +/- 13.0%), Neck (7.3% +/- 11.1%), Wards (4.6% +/- 5.9%), Troch (4.5% +/- 3.2%) (mean +/- s) versus decreases of 2.0% +/- 4.5%, -0.9% +/- 6.9%, 3.6% +/- 4.9% and 1.14% +/- 6.0% with placebo (P < 0.05). Blood Ca, P, ALP, BGP and Urine Pyd/C were no significant difference between before and after therapy. There were usually mild and transient side-effect, such as gastrointestinal symptoms.

CONCLUSIONAlendronate is an efficacy and safety drug in treatment of osteoporosis.

Absorptiometry, Photon ; Aged ; Alanine Transaminase ; blood ; Alendronate ; pharmacology ; therapeutic use ; Bone Density ; drug effects ; Calcium ; blood ; Case-Control Studies ; Double-Blind Method ; Female ; Hip Fractures ; complications ; Humans ; Male ; Middle Aged ; Osteoporosis ; blood ; complications ; drug therapy ; Treatment Outcome