Application Of Alendronate Research Articles

Added effect of 1% topical alendronate in intra-bony and inter-radicular defects as part of step II periodontal therapy: a systematic review with meta-analysis and trial sequential analysis

BackgroundThis systematic review and meta-analysis aimed to investigate the role of alendronate combined with step 2 of periodontal therapy in reducing probing pocket depth, improving clinical attachment level, and reducing bone defect depth in intra-bony and inter-radicular defects.MethodsRCTs with more than 6 months follow-up were included in this study. Risk of bias assessment was performed using the Cochrane collaboration tool. In addition, meta-analysis and trial sequential analysis were used to aggregate the available evidence.ResultsSeven studies met the inclusion criteria and were included in the systematic review. Topical application of alendronate during second step of periodontal therapy significantly improved PD and CAL.ConclusionLocal application of alendronate may confer a beneficial effect when applied during step II of periodontal therapy even if long term studies are needed to confirm these results.Clinical relevanceConsidering the emerging role of host-inflammatory response in treatment of periodontitis and the antiresorptive and osteostimulative properties of bisphosphonates, several studies are focusing on the role of alendronate as an addition to non-surgical periodontal therapy.

Effects of local application of alendronate on early healing of extraction socket in dogs.

The aim of the present study was to assess the effects of alendronate (ALN) on bone remodeling following tooth extraction in a dog model. For the study, fifteen male Beagles dogs of approximately 12months of age were used. Mesial roots of four mandibular premolars were endodontically treated, and the distal roots were removed. ALN concentrations of 0.5, 1, and 2mg/mL were topically applied for 15min, while a sterile saline was used as a negative control. After the healing period of 1, 2, and 8weeks, the samples were analyzed by micro-CT and histology. Treatment with ALN increased vertical distance between the lingual and the buccal crestal bones. While the ALN-treated sockets had preserved more lingual bone areas, control sockets showed better preservation of the buccal bone areas. ALN treatment resulted in more osteoid formation within the extraction sockets compared with the control. Higher bone volume was found in ALN groups than in the control at 2-week and 8-week healing periods, reaching the significant difference only for the extraction sockets pooled for the ALN treatment. Although ALN treatment could not prevent buccal bone resorption following tooth extraction in dogs, it proved beneficial for the preservation of the lingual bone and formation of new bone within the socket. There was no clear relation between the ALN dosages and the alterations within the extraction sockets. ALN affects bone remodeling of the extraction socket. The optimal concentration remains to be determined in future studies.

Efficient Transdermal Delivery of Alendronate, a Nitrogen-Containing Bisphosphonate, Using Tip-Loaded Self-Dissolving Microneedle Arrays for the Treatment of Osteoporosis.

To improve the transdermal bioavailability and safety of alendronate (ALN), a nitrogen-containing bisphosphonate, we developed self-dissolving microneedle arrays (MNs), in which ALN is loaded only at the tip portion of micron-scale needles by a dip-coating method (ALN(TIP)–MN). We observed micron-scale pores in rat skin just after application of ALN(TIP)–MN, indicating that transdermal pathways for ALN were created by MN. ALN was rapidly released from the tip of MNs as observed in an in vitro release study. The tip portions of MNs completely dissolved in the rat skin within 5 min after application in vivo. After application of ALN(TIP)–MN in mice, the plasma concentration of ALN rapidly increased, and the bioavailability of ALN was approximately 96%. In addition, the decrease in growth plate was effectively suppressed by this efficient delivery of ALN in a rat model of osteoporosis. Furthermore, no skin irritation was observed after application of ALN(TIP)–MN and subcutaneous injection of ALN, while mild skin irritation was induced by whole-ALN-loaded MN (ALN–MN)—in which ALN is contained in the whole of the micron-scale needles fabricated from hyaluronic acid—and intradermal injection of ALN. These findings indicate that ALN(TIP)–MN is a promising transdermal formulation for the treatment of osteoporosis without skin irritation.

Effects of Alendronate on Osteoclast Formation and Activity In Vitro

IntroductionRoot resorption is a common complication after replantation following traumatic dental avulsion. Endodontic therapy combined with local and intracanal medications aims to avoid osteoclastic activity. In such cases, the application of alendronate (ALN), a bisphosphonate widely used for the treatment of bone disorders, could be of clinical relevance. This study evaluated alendronate biocompatibility on periodontal ligament cells as well as its effects on an in vitro osteoclastogenesis model. MethodsAlendronate cytotoxicity (10−3 to 10−9 mol/L) in human periodontal ligament fibroblasts, human osteogenic sarcoma cells, and murine osteoclastic precursors (RAW 264.7) was analyzed using cell number determination, cell viability, and proliferation assays. ALN (10−6 to 10−12 mol/L) effects on RANKL-induced osteoclastogenesis of RAW cells were assessed by tartrate-resistant acid phosphatase (TRAP) staining and activity and real-time polymerase chain reaction. ResultsALN at higher concentrations was cytotoxic for all cell types, inhibiting significantly the proliferation of human osteogenic sarcoma cells and human periodontal ligament fibroblasts (≥10−5 mol/L). TRAP activity and expression of the osteoclast markers TRAP and cathepsin K by RAW-derived osteoclasts decreased significantly with ALN at low concentrations, reaching the maximum effect at 10−10 mol/L. ConclusionsWe showed that ALN at very low concentrations is an effective inhibitor of RANKL-generated osteoclasts, without causing cytotoxic effects on their precursors or periapical cells. ALN at such concentrations might be useful to prevent replacement resorption in avulsed teeth.

Application of Alendronate in Breast Cancer Patient with Letrozole Treatment

Application of Alendronate in Breast Cancer Patient with Letrozole Treatment

Effects of alendronate on the markers of bone metabolic activity in postmenopausal women with osteoporosis

Bisphosphonates are synthetic compounds used in treatment of osteoporosis and inhibition of bone resorption. The research included a group of 30 postmenopausal women with osteoporosis, treated with alendronate (70 mg per week--Fosamax tablets in combination with calcium and active vitamin D--Alpha D3 0.25mcg). The control group included 20 women with osteoporosis treated with hormone substitution therapy (HST), calcitonin and deca duraboline. Bone metabolic activity, was evaluated using osteocalcin for bone formation and cross-laps for bone resorption. Blood samples were taken before therapy and 6-8 weeks after. The serum levels of osteocalcin and cross-laps during application of alendronate were statistically significantly lower comparing to those in pre-therapy. The serum levels of osteocalcin and cross-laps during the therapy applied in the control group were statistically insignificantly lower than values in pre-therapy. Osteocalcin has a tendency of decreasing in both groups, and it was slightly more evident in alendronate group. Cross-laps demontrated the same tendency of decreasing in both groups, and it was more evident in alendronate group. Our results have shown the efficacy of alendronate in preventing bone loss, which was highly statistically significant. They have also shown its suppressive effect on bone formation and resorption, but the effects were statistically less significant. Alendronate significantly reduces the level of bone resorption in postmenopausal women with osteoporosis. Its effects on bone formation are less expressed Alendronate's effects on bone metabolism become evident not later than 6-8 weeks after therapy application. Parameters of bone metabolic activity are very useful diagnostic means in evaluation of alendronate effect on bone metabolic activity and in the prognosis of bone mass loss.