• RANK/RANKL signaling
• alveolar bone homeostasis
• osteoblasts
• osteoclasts
• periodontal therapy
• periodontitis

• Humans
• Periodontitis/therapy
• Signal Transduction
• Alveolar Bone Loss/therapy
• Osteoclasts
• Osteoblasts

• R56DE033249 NIDCR/NIH
• R01EY033622 NEI/NIH
• DE021052 NIDCR/NIH
• DE031737 NIDCR/NIH
• R01DE027980 NIDCR/NIH
• The Brodie Endowment Fund
• R01 EY033622 NEI NIH HHS

• cone‐beam computed tomography
• diabetes mellitus, type 2
• diphosphonates
• periodontitis
• root planing
• zoledronic acid

• Humans
• Male
• Female
• Diabetes Mellitus, Type 2/complications
• Diabetes Mellitus, Type 2/drug therapy
• Alveolar Bone Loss/diagnostic imaging
• Alveolar Bone Loss/drug therapy
• Alveolar Bone Loss/pathology
• Middle Aged
• Adult
• Gels
• Zoledronic Acid/administration & dosage
• Zoledronic Acid/therapeutic use
• Periodontitis/drug therapy
• Periodontitis/diagnostic imaging
• Periodontitis/pathology
• Periodontitis/therapy
• Drug Delivery Systems/methods
• Treatment Outcome
• Bone Density Conservation Agents/administration & dosage
• Bone Density Conservation Agents/therapeutic use
• Imidazoles/administration & dosage
• Imidazoles/therapeutic use
• Dental Scaling
• Cone-Beam Computed Tomography
• Diphosphonates/administration & dosage
• Diphosphonates/therapeutic use
• Root Planing
• Periodontal Index
• Dental Plaque Index

• Alendronate
• intra bony defect
• simvastatin

• BMD
• association
• inflammation
• osteoporosis
• oxidative stress
• periodontitis

• Alendronate
• Diphosphonates
• Periodontal therapy
• Periodontitis

Osteoporosis is a common skeletal disorder affecting postmenopausal women. Data suggest that postmenopausal women are at increased risk of periodontal diseases. Amino bisphosphonates are potent inhibitors of bone resorption and effectively used in the treatment of osteoporosis. Preliminary data indicate that there is a potential role for bisphosphonates in the management of periodontitis. Hence, this randomized placebo-controlled trial was designed to investigate the clinical efficacy of amino bisphosphonate on periodontal disease status among postmenopausal women.

Thirty patients were randomly allocated to two treatment groups: Group A, which received scaling and root debridement and 70 mg weekly single oral dose of alendronate drug, and Group B, which received scaling and root debridement and placebo drug for 6 months. Clinical periodontal measurements were carried out for all patients at the baseline and 6 months later. Mandibular bone mineral density (BMD) was measured using a dual energy X-ray absorptiometer at the beginning of the study and the end of 6 months.

A weekly single oral dose of 70 mg alendronate was well-tolerated. The intragroup comparison showed significant improvement in periodontal parameters in both groups. The intergroup comparison showed a significant increase in BMD after 6 months in Group A when compared with Group B (P = 0.0179).

Single oral dose of 70 mg alendronate per week is well-tolerable, gastro-intestinally safe, and improves the clinical outcome of nonsurgical periodontal therapy.

• Bisphosphonates
• bone mineral density
• osteoporosis
• periodontitis

Although several studies assessed the effect of bisphosphonate (BIS) administration on alveolar bone loss, this relationship has not been fully investigated using longitudinal analysis. The aim of the this article is to predict annual alveolar bone loss in a subpopulation of older adults patients who were taking oral bisphosphonate (BIS), adjusting for systemic diseases and associated risk factors.

This is a retrospective cohort study. We identified all subjects who reported receiving oral bisphosphonate from 2008 to 2015 (N = 30) using the electronic health records of each patient to identify suitable radiographs for analysis. For the longitudinal data analysis, 26 subjects were eligible for inclusion, having at least two exposures of the complete mouth set or repeated bitewing radiographs at least a one-year interval; they were then matched on age and sex to another 26 patients who did not report receiving bisphosphonate at any point of their life.

Mild periodontitis was higher in the BIS group compared to the no BIS group; however, moderate periodontitis was higher in the no BIS group. For those who did not take oral BIS, change over time was not significant after the two-year period. However, the BIS group had experienced 0.088 mm more bone loss compared to the no BIS group (95% CI: 0.001, 0.176. P-value = 0.048), adjusting for all other variables included in the model.

The group that reported receiving oral bisphosphonates showed no improvement in maintaining alveolar bone level, and the use of oral BIS may not be effective in reducing annual alveolar bone loss; however, emerging evidence is promising for the use of bisphosphonate as an adjunctive local delivery medication for the management of periodontal diseases.

• Annual bone loss
• Bisphosphonate
• Periodontal disease
• Predict

• Bone resorption
• diabetes mellitus
• diphosphonates
• periodontitis

• Alendronate
• Bone regeneration
• Chronic periodontitis
• Smokers

• CDX2
• GATA
• FokI
• chronic periodontitis
• vitamin D receptor

• Biomarker
• Bisphosphonate
• Diabetes
• Osteoporosis
• Postmenopausal
• Selective estrogen receptor modulator

• alveolar bone loss
• dental implant
• diabetes mellitus
• gingival bleeding
• probing depth

Alendronate has been proposed as a local and systemic drug treatment used as an adjunct to scaling and root planing (SRP) for the treatment of periodontitis. However, its effectiveness has yet to be conclusively established. The purpose of the present meta-analysis was to assess the effectiveness of SRP with alendronate on periodontitis compared to SRP alone.

Five electronic databases were used by 2 independent reviewers to identify relevant articles from the earliest records up to September 2016. Randomized controlled trials (RCTs) comparing SRP with alendronate to SRP with placebo in the treatment of periodontitis were included. The outcome measures were changes in bone defect fill, probing depth (PD), and clinical attachment level (CAL) from baseline to 6 months. A fixed-effect or random-effect model was used to pool the extracted data, as appropriate. Mean differences (MDs) with 95% confidence intervals (CIs) were calculated. Heterogeneity was assessed using the Cochrane χ² and I² tests.

After the selection process, 8 articles were included in the meta-analysis. Compared with SRP alone, the adjunctive mean benefits of locally delivered alendronate were 38.25% for bone defect fill increase (95% CI=33.05–43.45; P<0.001; I²=94.0%), 2.29 mm for PD reduction (95% CI=2.07–2.52 mm; P<0.001; I²=0.0%) and 1.92 mm for CAL gain (95% CI=1.55–2.30 mm; P<0.001; I²=66.0%). In addition, systemically administered alendronate with SRP significantly reduced PD by 0.36 mm (95% CI=0.18–0.55 mm; P<0.001; I²=0.0%) and increased CAL by 0.39 mm (95% CI=0.11–0.68 mm; P=0.006; I²=6.0%).

The collective evidence regarding the adjunctive use of alendronate locally and systemically with SRP indicates that the combined treatment can improve the efficacy of non-surgical periodontal therapy on increasing CAL and bone defect fill and reducing PD. However, precautions must be exercised in interpreting these results, and multicenter studies evaluating this specific application should be carried out.

• Alendronate
• Meta-analysis
• Periodontitis
• Root planing

• Bone
• Estrogen
• Inflammation
• Mechanism
• Osteoporosis
• Periodontitis
• Risk factor

• Age Factors
• Bone Remodeling
• Calcium/deficiency
• Disease Management
• Estrogens/metabolism
• Humans
• Hydrocortisone/metabolism
• Inflammation
• Osteoporosis/epidemiology
• Osteoporosis/metabolism
• Osteoporosis/therapy
• Parathyroid Hormone/metabolism
• Patient Care Team
• Periodontitis/epidemiology
• Periodontitis/metabolism
• Periodontitis/therapy
• Risk Factors
• Smoking/epidemiology
• Testosterone/metabolism
• Thyroid Hormones/metabolism
• Vitamin D Deficiency/epidemiology

• R01 DE022327 NIDCR NIH HHS
• R01 DK053904 NIDDK NIH HHS
• R56 DK053904 NIDDK NIH HHS

• Bisphosphonates
• periodontal disease
• scaling and root planning
• systematic review

• Alveolar crestal resorption
• Bone formation
• Drug delivery vehicle

The present study aims to compare the peri-implant bone status around immediately loaded dental implants treated with aminobisphosphonate solution and untreated control implants in terms of clinical and radiographical parameters.

A total of 24 patients were randomly divided equally into two groups. This study was conducted in accordance to the Helsinki's declaration of 1975, revised in 2000, and with the approval of the institutional ethical committee. In the control group after preparation, osteotomy sites were irrigated with normal saline solution, whereas in the test group osteotomy sites were irrigated with modified bisphosphonate solution and then TRX-OP, Hi-Tec dental implants were inserted. Clinical parameters, such as modified plaque and gingival index, probing depth, mobility, and radiographic parameters were recorded at baseline (0), 3, 6, and 9 months. Data analysis was performed using the Statistical Package for the Social Sciences version 17 for windows, and the statistical techniques employed were repeated measures analysis of variance, independent sample t-test, and paired sample t-test.

Reduction in mean radiographic bone levels (height) was observed on the mesial and distal aspect of the control group in comparison to its baseline at all intervals. In the test group, there was reduction in mean radiographic bone levels on mesial and distal aspect of the implant site in comparison to its baseline till 6-month follow up, however, at 9 month, there was gain in bone level on both mesial and distal aspect of implant. This represents the effectiveness of sodium alendronate in enhancing the bone formation. On comparison, between both groups on mesial and distal aspect of implants, statistically significant differences were observed at 3 and 9 months on mesial and distal aspect, respectively, without any clinical evidence of mobility in the test group.

Implant site treated with aminobisphosphonate solution represents greater efficacy in enhancing bone formation when used as an irrigant; thus, it is considered beneficial in implant dentistry.

• Aminobisphosphonate
• bisphosphonates
• bone resorption
• immediately loaded implants
• sodium alendronate

• alendronate
• bone regeneration
• dental implant
• osteoblast differentiation
• ultraviolet photofunctionalization

• Diabetes
• Hemoglobin A1c
• Medications
• Monitoring
• Periodontal therapy

• Diabetes
• glycated haemoglobin
• periodontal treatment
• periodontitis
• systematic review

• Diabetes Complications/therapy
• Diabetes Mellitus, Type 2/blood
• Diabetes Mellitus, Type 2/prevention & control
• Female
• Glycated Hemoglobin/analysis
• Humans
• Male
• Periodontitis/therapy

• Host response
• Omega-3 fatty acids
• Periodontitis

• Dental Scaling
• Diabetes Mellitus, Type 1/blood
• Diabetes Mellitus, Type 2/blood
• Glycated Hemoglobin/metabolism
• Humans
• Hyperglycemia/blood
• Hyperglycemia/therapy
• Oral Hygiene
• Periodontal Diseases/blood
• Periodontal Diseases/therapy
• Randomized Controlled Trials as Topic
• Root Planing
• Time Factors

• alveolar bone
• osteoimmunology
• osteoporosis
• periodontitis

Periodontal disease is an inflammatory condition that involves a complex interaction between pathogenic bacteria, environmental and acquired factors and host related factors. Till recently periodontal treatment was directed primarily towards reduction of bacterial load by subgingival debridement of root surfaces and modification of environmental risk factors. The current paradigm of periodontal disease stresses greater role of host-mediated inflammatory response in tissue destruction characteristic of periodontal disease. Various therapeutic modalities have been developed adjuvant to mechanical periodontal therapy. The use of laser and photodynamic therapy show great promise but their effectiveness has still not been conclusively proven. Chemotherapeutic agents, either systemic and local antimicrobials or host modulating drugs, played pivotal role in better and more predictable management of periodontal disease. The present review focuses on the best available evidence, for the current management of the chronic periodontal patients, gathered from systematic reviews and meta-analysis of mechanical non surgical periodontal therapy (NSPT) (subgingival debridement, laser therapy and photodynamic therapy) and the adjunctive chemotherapeutic approaches such as systematic and local antibiotics and antiseptics, subgingival pocket irrigation and host modulation therapies. The review also attempts to briefly introduce future developments in some of these modalities. At the end, the review summarizes the analysis of the current evidence that suggests that thorough subgingival debridement remains the mainstay of NSPT and that adjunct use of chemotherapeutic agents may offer better management of clinical parameters in periodontitis patients.

• Systematic reviews
• Mechanical nonsurgical periodontal therapy
• chemotherapeutic approaches
• Host modulation therapy
• Laser

• Diabetes mellitus
• Glycemic control
• Periodontal disease
• Periodontal treatment

• Aging/physiology
• Alveolar Bone Loss/prevention & control
• Bone Density/physiology
• Bone Density Conservation Agents/therapeutic use
• Bone Remodeling/physiology
• Fractures, Bone/etiology
• Humans
• Osteoporosis/complications
• Osteoporosis/physiopathology
• Osteoporosis/therapy
• Periodontal Diseases/prevention & control
• Risk Factors

• Diabetes
• Metabolic control
• Periodontal diseases

• Diabetes Mellitus, Type 1/complications
• Diabetes Mellitus, Type 2/complications
• Humans
• Hyperglycemia/therapy
• Models, Biological
• Periodontal Diseases/etiology
• Periodontal Diseases/therapy
• Risk Factors

• citrullination
• geriatrics
• host response
• periodontitis
• rheumatoid arthritis

Osteoporosis and periodontal disease (PD) are frequently associated in the elderly, both concurring to the loss of jaw alveolar bone and finally of teeth. Bisphosphonates improve alveolar bone loss but have also been associated with osteonecrosis of the jaw (ONJ), particularly using oncological doses of zoledronate. The effects and therapeutic margin of zoledronate on jaw bone therefore remain uncertain. We reappraised the efficacy and safety of Zoledronate (Zol) in ovariectomized (OVX) periostin (Postn)-deficient mice, a unique genetic model of systemic and jaw osteopenia. Compared to vehicle, Zol 1M (100 µg/kg/month) and Zol 1W (100 µg/kg/week) for 3 months both significantly improved femur BMD, trabecular bone volume on tissue volume (BV/TV) and cortical bone volume in both OVX Postn^+/+ and Postn^−/− (all p<0.01). Zol 1M and Zol 1W also improved jaw alveolar and basal BV/TV, although the highest dose (Zol 1W) was less efficient, particularly in Postn^−/−. Zol decreased osteoclast number and bone formation indices, i.e. MAR, MPm/BPm and BFR, independently in Postn^−/− and Postn^+/+, both in the long bones and in deep jaw alveolar bone, without differences between Zol doses. Zol 1M and Zol 1W did not reactivate inflammation nor increase fibrous tissue in the bone marrow of the jaw, whereas the distance between the root and the enamel of the incisor (DRI) remained high in Postn^−/− vs Postn^+/+ confirming latent inflammation and lack of crestal alveolar bone. Zol 1W and Zol 1M decreased osteocyte numbers in Postn^−/− and Postn^+/+ mandible, and Zol 1W increased the number of empty lacunae in Postn^−/−, however no areas of necrotic bone were observed. These results demonstrate that zoledronate improves jaw osteopenia and suggest that in Postn^−/− mice, zoledronate is not sufficient to induce bone necrosis.

• Animals
• Bone Density/drug effects
• Bone Density Conservation Agents/administration & dosage
• Bone Diseases, Metabolic/diagnosis
• Bone Diseases, Metabolic/drug therapy
• Bone Remodeling/drug effects
• Bone Resorption/drug therapy
• Bone Resorption/pathology
• Bone and Bones/diagnostic imaging
• Bone and Bones/drug effects
• Bone and Bones/pathology
• Cell Adhesion Molecules/deficiency
• Diphosphonates/administration & dosage
• Female
• Imidazoles/administration & dosage
• Jaw/pathology
• Mice
• Mice, Knockout
• Ovariectomy
• Tomography, X-Ray Computed
• Zoledronic Acid

• Alendronate/therapeutic use
• Animals
• Biomechanical Phenomena
• Bone Density Conservation Agents/therapeutic use
• Bone and Bones/drug effects
• Female
• Hypoglycemic Agents/adverse effects
• Hypoglycemic Agents/therapeutic use
• Insulin Resistance
• Osteoporosis/drug therapy
• Rats
• Rosiglitazone
• Thiazolidinediones/adverse effects
• Thiazolidinediones/therapeutic use

• Canadian Institutes of Health Research

Alendronate, an aminobisphosphonate, is capable of inhibiting periodontitis associated osteoclastic activity and hence is effective in protecting the alveolar bone in periodontitis. In the present study, we explored the efficacy of local delivery of alendronate on the alveolar bone following mucoperiosteal flap surgery. This is the first study to use polymer impregnated gel based delivery of alendronate.

A total of 15 patients with chronic periodontitis in the age group of 35 - 55 years, of both sexes, with pocket depth of ≥ 5mm and radiographic evidence of identical osseous defects in the mandibular molar region bilaterally were included in this prospective study. A gel based drug delivery system of Alendronate was formulated. Following surgical flap debridement, 0.1 ml alendronate gel and 0.1 ml placebo gel was placed at the experimental and control sites respectively. Clinical and radiographic parameters were recorded at baseline, three months and six months post surgery.

Alendronate was more effective in improving clinical and radiographic parameters compared to placebo.

Alendronate is effective in the management of periodontitis associated bone loss. Gel based local delivery of the drug addresses the critical concern of exposing the patient to adverse effects of systemic administration.

• Alendronate/therapeutic use
• alveolar bone loss
• bisphosphonates/therapeutic use
• bone resorption
• osteoclasts
• surgical flaps