Thirteen cases of jaw osteonecrosis in patients on bisphosphonate therapy. Related Articles Thirteen cases of jaw osteonecrosis in patients on bisphosphonate therapy. Joint Bone Spine. 2007 Aug 31; Authors: Vieillard MH, Maes JM, Penel G, Facon T, Magro L, Bonneterre J, Cortet B INTRODUCTION: We report on our experience with 13 cases of jaw osteonecrosis in patients treated with amino-bisphosphonates. METHOD: Data were collected by a regional observatory for jaw osteonecrosis in northern France via letters sent to all physicians likely to manage patients with this condition. All study patients were evaluated at a multidisciplinary jaw osteonecrosis clinic between June and December 2005. RESULTS: We identified 13 cases, in 12 women and 1 man, with a mean age of 62.6 years. Intravenous amino-bisphosphonate therapy was given for metastatic bone disease from breast cancer in 7 patients and multiple myeloma in 5 patients; the remaining patient was on oral alendronate for osteoporosis. Mean treatment duration was 24 months. A history of dental extraction was found in 11 (84.6%) patients. The mandible was involved in all 13 patients and the maxillary in 3 (23%) patients. Amino-bisphosphonate therapy was discontinued in all 13 patients. We suggest a classification scheme for the clinical and computed-tomography patterns seen in our patients. CONCLUSION: Jaw osteonecrosis is a severe complication of amino-bisphosphonate therapy. In addition to the application of published guidelines, we propose discontinuing bisphosphonate therapy whenever possible. We are evaluating our classification scheme to identify early diagnostic criteria and/or clinical and computed-tomography outcome criteria that would improve the management of patients with jaw osteonecrosis. PMID: 17981488 [PubMed - as supplied by publisher] A review of the literature on osteonecrosis of the jaw in patients with osteo... Related Articles A review of the literature on osteonecrosis of the jaw in patients with osteoporosis treated with oral bisphosphonates: prevalence, risk factors, and clinical characteristics. Clin Ther. 2007 Aug;29(8):1548-58 Authors: Pazianas M, Miller P, Blumentals WA, Bernal M, Kothawala P OBJECTIVE: This literature review was performed to elucidate the relationship between bisphosphonate use and development of osteonecrosis of the jaw (ONJ) in patients receiving oral bisphosphonates for the treatment of osteoporosis. METHODS: MEDLINE, the Cochrane Database of Systematic Reviews, the Cochrane Central Register of Controlled Trials, and EMBASE were searched for English-language articles published from 1966 to September 2006 whose titles included the term osteonecrosis of the jaw in conjunction with bisphosphonates, alendronate, risedronate, ibandronate, etidronate, clodronate, zoledronic acid, or pamidronate. Articles were included in the review if the population consisted of adults with ONJ; patients received bisphosphonates for the treatment of osteoporosis only; the reported data included baseline characteristics of the study population (age; sex; comorbidities; concomitant medications; history of dental surgery, trauma, or infection), characteristics of bisphosphonate treatment (specific bisphosphonate, dose, duration of treatment, mode of administration), clinical features of ONJ (signs, symptoms, site), the treatment protocol used to manage ONJ, or the prevalence of ONJ in patients with osteoporosis treated with bisphosphonates; and the publication involved a case report, case series, or observational study. RESULTS: After application of the search strategy and the inclusion/exclusion criteria, 11 publications reporting 26 cases of ONJ in patients receiving bisphosphonates for the treatment of osteoporosis were included in the review. The most commonly affected site was the mandible (16 patients), followed by the maxilla (6 patients). Among the 23 patients whose age was reported, 18 (78%) were aged >or=60 years. Among the 23 patients whose sex was reported, only 3 (13%) were men. Of 15 patients with a history of invasive dental treatment, 12 (80%) had undergone dental surgery or experienced dental trauma at the site of ONJ. Among the 10 patients for whom the duration of bisphosphonate treatment was reported, no clear relationship between the duration of bisphosphonate treatment and the development of ONJ was observed. CONCLUSIONS: Considering that millions of patients have been prescribed bisphosphonates for the treatment of osteoporosis, the relative prevalence of ONJ in these patients was low. Age >or=60 years, female sex, and previous invasive dental treatment were the most common characteristics of those who developed ONJ. However, it is not possible to draw further conclusions about the potential association between oral bisphosphonate use and ONJ in the identified studies because of incomplete reporting and the presence of confounding factors. PMID: 17919538 [PubMed - indexed for MEDLINE] Dental enamel dissolution after alendronate treatment. Related Articles Dental enamel dissolution after alendronate treatment. Am J Dent. 2007 Aug;20(4):235-40 Authors: Gandolfi MG, Nucci C, Prati C, Mongiorgi R PURPOSE: To evaluate the effect of treatment with a bisphosphonate (alendronate) on human dental enamel dissolution in vitro. METHODS: The dissolution of each enamel sample was evaluated by monitoring the calcium release in 0.1M lactic acid solution at pH 4.5 (acidic solution) during dissolution tests, after topical alendronate treatment with 0.1M alendronate solutions at pH 5.0, pH 7.4 and pH 9.0. RESULTS: Data showed that alendronate treatment, both at pH 5.0 and pH 7.4, obtained a statistically significant reduction of enamel demineralization during dissolution test reaction time (45 minutes). The protective effect was not present after treatment at pH 9. PMID: 17907486 [PubMed - indexed for MEDLINE] Effects of alendronate on tooth eruption and molar root formation in young gr... Related Articles Effects of alendronate on tooth eruption and molar root formation in young growing rats. Cell Tissue Res. 2007 Dec;330(3):475-85 Authors: Bradaschia-Correa V, Massa LF, Arana-Chavez VE Tooth eruption consists of the movement of teeth from the bony crypt in which they initiate their development to the occlusal plane in the oral cavity. Interactions between the tooth germ and its surrounding alveolar bone occur in order to offer spatial conditions for its development and eruption. This involves bone remodeling during which resoption is a key event. Bisphosphonates are a group of drugs that interfere with the resorption of mineralized tissues. With the purpose of investigating the effects of sodium alendronate (a potent bisphosphonate inhibitor of osteoclast activity) on alveolar bone during tooth development and eruption, we gave newborn rats daily doses of this drug for 4, 14, and 30 days. Samples of the maxillary alveolar process containing the tooth germs were processed for light, transmission, and scanning electron microscopy and were also submitted to tartrate-resistant acid phosphatase histochemistry and high-resolution colloidal-gold immunolabeling for osteopontin. Inhibition of osteoclast activity by sodium alendronate caused the absence of tooth eruption. The lack of alveolar bone remodeling resulted in primary bone with the presence of latent osteoclasts and abundant osteopontin at the interfibrillar regions. The developing bone trabeculae invaded the dental follicle and reached the molar tooth germs, provoking deformities in enamel surfaces. No root formation was observed. These findings suggested that alendronate effectively inhibited tooth eruption by interfering with the activation of osteoclasts, which remained in a latent stage. PMID: 17901984 [PubMed - in process] Denture-related osteonecrosis of the maxilla associated with oral bisphosphon... Related Articles Denture-related osteonecrosis of the maxilla associated with oral bisphosphonate treatment. J Am Dent Assoc. 2007 Sep;138(9):1218-20 Authors: Levin L, Laviv A, Schwartz-Arad D BACKGROUND: Bisphosphonates are a class of agents used to treat various systemic conditions. Despite the benefits of bisphosphonates, osteonecrosis of the jaws is an important complication in a subset of patients who receive this drug treatment. CASE DESCRIPTION: A 66-year-old woman was referred to an oral surgeon at a private surgical center because of a pressure wound in the margins of a removable maxillary denture. The patient reported that she had received oral alendronate sodium treatment for eight years. A clinical examination revealed a palatal ulcer with exposed necrotic gray bone at its center. The clinician performed an excisional biopsy and separated two palatal rotational flaps to enable an adequate blood supply to reach the operated-on area. CLINICAL IMPLICATIONS: This report, together with growing evidence in the literature, serves to alert treating physicians and dental practitioners about the potential complication of maxillary and mandibular bone necrosis in patients receiving bisphosphonate therapy. PMID: 17785387 [PubMed - indexed for MEDLINE] Implant placement with or without simultaneous tooth extraction in patients t... Related Articles Implant placement with or without simultaneous tooth extraction in patients taking oral bisphosphonates: postoperative healing, early follow-up, and the incidence of complications in two private practices. J Periodontol. 2007 Sep;78(9):1664-9 Authors: Fugazzotto PA, Lightfoot WS, Jaffin R, Kumar A BACKGROUND: The development of bisphosphonate-associated osteonecrosis in patients with a history of intravenous bisphosphonate therapy is a significant cause of concern in clinical periodontal practice. The role of oral bisphosphonates in the development of bisphosphonate-associated osteonecrosis is less clear. This article documents the results of treatment of patients with a history of oral bisphosphonate therapy in two private periodontal practices. The study was a retrospective analysis of case records of patients treated as part of routine periodontal and implant treatment. METHODS: Patients with a history of oral bisphosphonate therapy of various durations were treated with implant placement and restoration or tooth extraction, immediate placement, and restoration. These patients were followed for 12 to 24 months after implant placement. The incidence of hard and soft tissue complications, including the development of osteonecrosis, was noted. RESULTS: No osteonecrosis was noted immediately postoperatively or during the follow-up period in 61 patients. One patient demonstrated a small tissue dehiscence at the 1-week postoperative examination following extraction of a mandibular first molar and simultaneous implant placement in the area of a prominent torus. No other postoperative complications were noted. All implants were functioning successfully by the Albrektsson criteria 12 to 24 months post-insertion. CONCLUSIONS: A history of oral bisphosphonate use for a mean period of 3.3 years (range, 1 to 5 years) was not found to be a contributing factor to the development of osteonecrosis following implant placement in intact ridges or tooth extraction with immediate implant placement. However, there is no doubt that larger controlled studies and retrospective reports are needed. PMID: 17760533 [PubMed - indexed for MEDLINE] [Diphosphonate therapy and osteonecrosis of the jaw] Related Articles [Diphosphonate therapy and osteonecrosis of the jaw] Tidsskr Nor Laegeforen. 2007 Aug 9;127(15):1945-7 Authors: L&#xF8;kken P, Skoglund LA, Skjelbred P PMID: 17700737 [PubMed - indexed for MEDLINE] Alendronate PLGA microspheres with high loading efficiency for dental applica... Related Articles Alendronate PLGA microspheres with high loading efficiency for dental applications. J Microencapsul. 2007 Sep;24(6):525-38 Authors: Nafea EH, El-Massik MA, El-Khordagui LK, Marei MK, Khalafallah NM PURPOSE: Alendronate sodium, used systemically as a bone protective agent, proved to also be effective locally in various dental bone applications. Development of alendronate-loaded microspheres with high loading efficiency for such applications would be greatly challenged by the hydrophilicity and low MW of the drug. The aim of this study was to incorporate alendronate sodium, into poly (lactide-co-glycolide) (PLGA) microspheres (MS) with high loading efficiency. METHODS: Three multiple emulsion methods: water-in-oil-in-water (W/O/W), water-in-oil-in-oil (W/O(1)/O(2)) and solid-in-oil-in-oil (S/O(1)/O(2)) were tested. In addition to entrapment efficiency, MS were characterized for surface morphology, particle size, in vitro drug release and in vitro degradation of the polymer matrix. Alendronate microspheres with maximum drug loading and good overall in vitro performance were obtained using the W/O(1)/O(2) emulsion technique. RESULTS: Drug release from the microspheres exhibited a triphasic release pattern over a period of 13 days, the last fast release phase being associated with more rapid degradation of the PLGA matrix. CONCLUSIONS: Biocompatible, biodegradable PLGA microspheres incorporating alendronate sodium with high loading efficiency obtained in this study may offer promise as a delivery system for bisphosphonates in dental and probably other clinical applications. PMID: 17654173 [PubMed - in process] Effect of 17beta-estradiol and alendronate on the removal torque of osseointe... Related Articles Effect of 17beta-estradiol and alendronate on the removal torque of osseointegrated titanium implants in ovariectomized rats. J Periodontol. 2007 Jul;78(7):1316-21 Authors: Giro G, Sakakura CE, Gon&#xE7;alves D, Pereira RM, Marcantonio E, Orrico SR BACKGROUND: This study investigated the influence of estrogen deficiency and its treatment with estrogen and alendronate on the removal torque of osseointegrated titanium implants. METHODS: Fifty-eight female Wistar rats received a titanium implant in the tibia metaphysis. After 60 days, which was needed for implant osseointegration, the animals were randomly divided into five groups: control (CTLE; N = 10), sham surgery (SHAM; N = 12), ovariectomy (OVX; N = 12), ovariectomy followed by hormone replacement (EST; N = 12), and ovariectomy followed by treatment with alendronate (ALE; N = 12). The CTLE group was sacrificed to confirm osseointegration, whereas the remaining groups were submitted to sham surgery or ovariectomy according to their designations. After 90 days, these animals were also sacrificed. Densitometry of femur and lumbar vertebrae was performed by dual-energy x-ray absorptiometry (DXA) to confirm systemic impairment of the animals. All implants were subjected to removal torque. RESULTS: Densitometric analysis of the femur and lumbar vertebrae confirmed a systemic impairment of the animals, disclosing lower values of bone mineral density for OVX. Analysis of the removal torque of the implants showed statistically lower values (P <0.05) for the OVX group in relation to the other groups. However, the group treated with alendronate (ALE group) presented significantly higher torque values compared to the others. CONCLUSION: According to this study, estrogen deficiency was observed to have a negative influence on the removal torque of osseointegrated implants, whereas treatment with alendronate increased the torque needed to remove the implants. PMID: 17608587 [PubMed - indexed for MEDLINE] Bisphosphonates and osteonecrosis of the jaw: a retrospective study. Related Articles Bisphosphonates and osteonecrosis of the jaw: a retrospective study. Endocr Pract. 2007 May-Jun;13(3):232-8 Authors: Murad OM, Arora S, Farag AF, Guber HA OBJECTIVE: To assess the prevalence of osteonecrosis of the jaw (ONJ) in patients receiving bisphosphonate therapy and in those who were bisphosphonate na&#xEF;ve. METHODS: We undertook a retrospective review of medical records of patients at the New York Harbor Health Care System from 1999 through 2004. Charts were selected for review if patients had a Current Procedural Terminology (CPT) code suggestive of ONJ or if they had ever received bisphosphonate therapy. RESULTS: Among 1,951 medical records reviewed, we identified 2 patients with ONJ who had received bisphosphonates and 2 patients with ONJ who were bisphosphonate naïve. Both patients treated with bisphosphonates had multiple myeloma and were receiving monthly infusions. They had initially received pamidronate before treatment was changed to zoledronic acid. In each case, ONJ was precipitated by a routine dental extraction. The prevalence of ONJ in our patient population receiving intravenously administered bisphosphonates was 1 in 71.5. Of the 2 cases of ONJ in bisphosphonate-naïve patients, osteoradionecrosis was clearly incriminated in 1 patient and potentially the causative factor in the other patient as well. No patients receiving orally administered bisphosphonates had ONJ, nor did this complication occur in any patients receiving parenteral bisphosphonate therapy for disorders such as osteoporosis or Paget's disease of bone. CONCLUSION: Bisphosphonates remain an important option for management of metabolic bone disease and complications of malignant disease. The overall prevalence of ONJ in patients receiving bisphosphonates seems to be very low; however, patients receiving intense parenteral therapy for an underlying malignant condition appear to have a uniquely elevated risk for the development of this complication. A causal relationship between bisphosphonates and ONJ remains to be proved and merits further investigation. PMID: 17599853 [PubMed - indexed for MEDLINE] Osteonecrosis of the jaw induced by orally administered bisphosphonates: inci... Related Articles Osteonecrosis of the jaw induced by orally administered bisphosphonates: incidence, clinical features, predisposing factors and treatment outcome. Osteoporos Int. 2007 Oct;18(10):1363-70 Authors: Yarom N, Yahalom R, Shoshani Y, Hamed W, Regev E, Elad S SUMMARY: Osteonecrosis of the jaw (ONJ) is a well-known devastating side effect of bisphosphonate therapy for cancer. Several ONJ cases of patients using oral bisphosphonates have been reported in the literature. The present study analyzed the clinical features, predisposing factors, and treatment outcome of 11 patients with oral bisphosphonates-related ONJ. INTRODUCTION AND HYPOTHESIS: Osteonecrosis of the jaw (ONJ) is a well-known side effect of parenteral bisphosphonates therapy. Although ONJ has been reported in patients using oral bisphosphonates, documentation of this entity is sparse. It was hypothesized that the clinical features, predisposing factors, and treatment outcome of this population are different from those of oncologic patients. METHODS: This retrospective bi-central study involved 98 ONJ patients, 13 of whom were treated with oral bisphosphonates. Two patients were excluded because of previous use of intravenous bisphosphonates. The profiles of 11 patients were analyzed. RESULTS: The mean duration of alendronate use before developing ONJ was 4.1 years. ONJ was triggered by dental surgery in 9 patients and by ill-fitted dentures in 2. Heavy smokers were the most recalcitrant subjects. Among the nine patients with at least 6 months of follow-up, ONJ healed completely in three, partially in four, and not at all in two. CONCLUSIONS: ONJ is a rare devastating side effect of oral bisphosphonates associated with patient morbidity and high financial burden. Clinicians must be aware of this entity and inform patients of the risks of dental surgery. The synergistic effect of smoking in the pathogenesis of ONJ should be further investigated. PMID: 17598065 [PubMed - in process] Effect of long-term oral bisphosphonates on implant wound healing: literature... Related Articles Effect of long-term oral bisphosphonates on implant wound healing: literature review and a case report. J Periodontol. 2007 Mar;78(3):584-94 Authors: Wang HL, Weber D, McCauley LK BACKGROUND: Bisphosphonates suppress osteoclast activity, and their intravenous use has been reported in hundreds of cases to be associated with osteonecrosis in the jaw. Little is known of the risks associated with long-term use of oral bisphosphonates despite their use for >10 years by an oral mode of delivery for the treatment of osteopenia, osteoporosis, and Paget's disease of bone. The purpose of this report is to review the literature associated with bisphosphonate use that could impact bone healing and to report a case of bone necrosis in a patient on long-term oral bisphosphonates. METHODS: A Medline search was carried out to find relevant articles from both medical and dental literature between 1960 and 2006. A patient, who had been taking an oral bisphosphonate for >10 years, developed unexplained clinical signs of bone necrosis after routine dental implant placement. This case was followed, documented, and the treatment of the osteonecrosis described. RESULTS: A summary of how bisphosphonates may play a role in wound healing is presented. The compromised healing noted in a patient, who was under long-term oral bisphosphonate use, was successfully treated with systemic antibiotics, local microbial mouthrinse, and aggressive defect management (detoxification and mixture of bone graft and tetracycline). CONCLUSIONS: This case suggests that patients under long-term oral bisphosphonate use should be treated with caution. Well-controlled, prospective clinical trials on the effect of oral bisphosphonates on bone are warranted to determine which patients may be at risk for such complications. PMID: 17335384 [PubMed - indexed for MEDLINE] Nature and frequency of bisphosphonate-associated osteonecrosis of the jaws i... Related Articles Nature and frequency of bisphosphonate-associated osteonecrosis of the jaws in Australia. J Oral Maxillofac Surg. 2007 Mar;65(3):415-23 Authors: Mavrokokki T, Cheng A, Stein B, Goss A PURPOSE: The purpose of this study is to estimate the frequency and describe the clinical characteristics of patients diagnosed with bisphosphonate-associated osteonecrosis of the jaws (ONJ) in Australia. MATERIALS AND METHODS: Cases of ONJ were identified in 2004 and 2005 primarily by a postal survey of Australian Oral and Maxillofacial Surgeons (OMS) with additional cases from other dental specialists and the Commonwealth of Australia Adverse Drug Reaction Committee (ADRAC). The clinical characteristics were recorded. The frequency of ONJ cases was estimated from prescription and dental extraction data. Univariate and bivariate statistics were calculated. RESULTS: One hundred fifty-eight cases of ONJ were identified. These were primarily in patients with bone malignancy (72%) and the main trigger was dental extraction (73%). The reported number of cases varied between different Australian States with the highest frequency being reported in the States with the best integrated health systems. The frequency of ONJ in osteoporotic patients, mainly on weekly oral alendronate was 1 in 2,260 to 8,470 (0.01% to 0.04%) patients. If extractions were carried out, the calculated frequency was 1 in 296 to 1,130 cases (0.09% to 0.34%). The total dose of oral alendronate at the onset of ONJ was 9,060 (+/-7,269) mg. The frequency of ONJ for Paget's disease cases was 1 in 56 to 380 (0.26% to 1.8%). If extractions were carried out, the calculated frequency of ONJ was 1 in 7.4 to 48 (2.1% to 13.5%). The frequency of ONJ in bone malignancy cases, treated with mainly intravenous zoledronate or pamidronate was 1 in 87 to 114 (0.88% to 1.15%). If extractions were carried out, the calculated frequency of ONJ was 1 in 11 to 15 (6.67% to 9.1%) The total dose of pamidronate was 3,285 (+/-2,530) mg and zoledronate 62 (+/-54.28) mg at the onset of ONJ. The median time to onset of ONJ was 12 months for zoledronate, 24 months for pamidronate, and 24 months alendronate. CONCLUSIONS: Before the prescription of bisphosphonates for bone disease the patient should be made dentally fit so that the need for subsequent dental extractions is minimized. Appropriate informed consent for the risk of ONJ for different bisphosphonates, for osteoporosis, and malignancy both in general and in particular for dental extractions can be provided using this data. PMID: 17307586 [PubMed - indexed for MEDLINE] Osteonecrosis of the jaws associated with use of risedronate: report of 2 new... Related Articles Osteonecrosis of the jaws associated with use of risedronate: report of 2 new cases. Oral Surg Oral Med Oral Pathol Oral Radiol Endod. 2007 Jun;103(6):780-6 Authors: Brooks JK, Gilson AJ, Sindler AJ, Ashman SG, Schwartz KG, Nikitakis NG Use of various bisphosphonates has been associated with the development of osteonecrosis of the jaws (ONJ). At least 865 cases of ONJ attributed to these agents have been reported in the English-language literature. Approximately 96% of these published cases were seen with administration of the intravenous agents pamidronate and zoledronate, whereas only 26 cases have been associated with oral bisphosphonates, 25 of them with alendronate. Only a single case of ONJ associated with the oral bisphosphonate risedronate has been previously cited. We report 2 cases of ONJ attributed to risedronate administration. The patients developed osteonecrosis 15 and 24 months after treatment for osteopenia. A regimen of antibiotics and chlorhexidine mouthrinse resolved the osseous defect in the mandible caused by complete exfoliation of a lingual torus in 1 patient. The other patient required sequestrectomy, repeated courses of antibiotics, surgical debridement, and steroids to promote closure of an oroantral fistula and management of sinusitis after bone grafting and implant placement in the posterior maxilla. A demographic profile of reported oral bisphosphonate users affected by ONJ is also provided. With the millions of patients receiving various oral bisphosphonates for osteopenia and osteoporosis, health care practitioners should be aware of the potential for the onset of osteonecrosis and familiar with its management. PMID: 17223592 [PubMed - indexed for MEDLINE] Matrix metalloproteinases, tissue inhibitor of matrix metalloproteinase-1, an... Related Articles Matrix metalloproteinases, tissue inhibitor of matrix metalloproteinase-1, and laminin-5 gamma2 chain immunolocalization in gingival tissue of endotoxin-induced periodontitis in rats: effects of low-dose doxycycline and alendronate. J Periodontol. 2007 Jan;78(1):127-34 Authors: Buduneli E, Vardar-Seng&#xFC;l S, Buduneli N, Atilla G, Wahlgren J, Sorsa T BACKGROUND: Matrix metalloproteinases (MMPs) play important roles in tissue destruction mechanisms of periodontitis. MMP-8 and -13 are the major collagenases that act in extracellular matrix degradation in periodontal tissues. MMP-14 is a membrane-type MMP, and laminin (Ln)-5 is a basal membrane component. The aim of the present study was to evaluate the effects of doxycycline and alendronate on gingival tissue expression of MMP-8, -13, and -14; tissue inhibitors of MMP (TIMP)-1; and Ln-5 gamma2 chain in experimental periodontitis induced by Escherichia coli endotoxin (LPS) in rats. METHODS: Experimental periodontitis was induced by repeated injection of LPS. Forty-four adult male Sprague-Dawley rats were divided into five study groups: saline control, LPS, LPS + doxycycline, LPS + alendronate, and LPS + doxycycline + alendronate. Doxycycline and alendronate were given as a single agent or as combination therapy during the 7 days of the experimental study period. On day 7, the rats were sacrificed, and the gingival tissues were analyzed immunohistochemically for expression of MMP-8, -13, and -14, Ln-5 gamma2 chain, and TIMP-1. Alveolar bone loss was evaluated morphometrically under a stereomicroscope. Data were tested statistically by Kruskal-Wallis and Mann-Whitney tests and Spearman correlation analysis. RESULTS: Alveolar bone loss was significantly higher in the LPS, doxycycline, alendronate, and combination groups than in the saline control group (all P <0.01). MMP-8 expression was significantly higher in the LPS group than in the saline control group (P = 0.001). Individual administration of doxycycline or alendronate significantly decreased the expression of MMP-8 compared to LPS (P = 0.01). Combined drug administration reduced MMP-14 significantly compared to doxycycline (P = 0.004). No significant differences in Ln-5 gamma2 chain expression were found between the study groups (P >0.05). MMP-14 significantly correlated with the Ln-5 gamma2 chain in the LPS + alendronate group (P = 0.04) and with the amount of alveolar bone loss in the LPS + doxycycline + alendronate group (P = 0.03). CONCLUSIONS: Our findings suggest that alendronate and/or doxycycline may inhibit MMP-8 expression significantly; particularly, their combined administration may provide beneficial effects in periodontal treatment. Moreover, individual administration of alendronate and doxycycline results in significant increases in TIMP-1 expression in gingiva. However, these effects of combined low-dose doxycycline and alendronate on MMPs and TIMP should be verified by clinical human trials before these agents are used in dental practice. PMID: 17199549 [PubMed - indexed for MEDLINE] Effects of osteoporosis medications on bone quality. Related Articles Effects of osteoporosis medications on bone quality. Joint Bone Spine. 2007 Jan;74(1):39-47 Authors: Benhamou CL In clinical practice, the quantitative evaluation of bone tissue relies on dual-energy X-ray absorptiometry (DXA) measurements of bone mineral density (BMD) values, which are closely associated with the risk of osteoporotic fracture. However, only a small fraction of the antifracture effect of bone resorption inhibitors is ascribable to BMD gains (4% with raloxifene and 16-28% with alendronate and risedronate). Bone quality encompasses a number of bone tissue properties that govern mechanical resistance, such as bone geometry, cortical properties, trabecular microarchitecture, bone tissue mineralization, quality of collagen and bone apatite crystal, and presence of microcracks. All these properties are dependent on bone turnover and its variations. In populations, the decreases in bone resorption markers achieved with resorption inhibitors may predict in part the decrease in fracture risk. At the spine, however, this correlation exists down to a 40% fall in bone resorption markers; larger drops did not provide further protection against fractures in patients taking risedronate in one evaluation of this relationship. Osteoporosis medications can exert favorable effects on bone size and cortical thickness. Such effects have been documented with teriparatide (PTH 1-34), which is the unique purely anabolic treatment for osteoporosis available to date. More surprising are the favorable effects on bone size seen with some of the bone resorption inhibitors such as neridronate in adults with osteogenesis imperfecta. Similarly, estrogens and alendronate can increase femoral neck size in postmenopausal women. Preservation of the trabecular microarchitecture was demonstrated first with risedronate and subsequently with alendronate. In placebo-controlled studies, a deterioration in trabecular microarchitecture occurred within 1 to 3 years in the placebo groups but not in the bisphosphonate groups. Teriparatide, in contrast, improves trabecular microarchitecture, in particular by increasing connectivity and improving the plate-rod distribution. The minerals within trabecular or cortical bone can be evaluated using microradiography or synchrotron micro-computed tomography. Marked or prolonged secondary mineralization may result in poor bone quality. Increased bone mineralization is among the key effects of bone resorption inhibitors, most notably bisphosphonates. Prolonged use of the most potent bisphosphonates may lead to unwanted effects related to excessive mineralization. Microcracks may play a physiological role; however, a large number of microcracks may be deleterious via an effect on osteocytes. Excessive mineralization may promote the development of multiple microcracks. Studies of bone crystal and collagen properties with several bone resorption inhibitors, including risedronate and raloxifene, showed no harmful effects. An increasing number (several hundreds) of mandibular osteonecrosis associated with bisphosphonate therapy has been reported. The typical patient was receiving injectable bisphosphonate therapy for bone cancer and had undergone dental work shortly before bisphosphonate administration. The mechanism of this adverse effect is poorly understood. PMID: 17196423 [PubMed - indexed for MEDLINE] Cytotoxicity evaluation of sodium alendronate on cultured human periodontal l... Related Articles Cytotoxicity evaluation of sodium alendronate on cultured human periodontal ligament fibroblasts. Dent Traumatol. 2006 Dec;22(6):312-7 Authors: Correia Vde F, Caldeira CL, Marques MM External root resorption processes are usually associated with dental trauma, mainly avulsion and intrusion. In such cases endodontic therapy aims to prevent this process by using medications that can inhibit osteoclastic activity, such as bisphosphonates. However, these drugs must be biocompatible to the periapical tissues. The aim of this study was to analyze the cytotoxicity of a bisphosphonate (sodium alendronate) on human periodontal ligament fibroblasts (PDL cells). Cells were plated in a density of 1 x 10(3) cells per dish. The experimental groups were GI (control) no sodium alendronate, and GII, GIII, and GIV with sodium alendronate at the concentrations of 10(-5), 10(-6), and 10(-7) M, respectively. The experimental times were 1, 6, 12, and 24 h (short-term) for viability and 2, 4, 6, and 8 days (long-term) for cell survival. Data in triplicate were statistically analyzed. Cultures treated with the highest alendronate concentration (GII) showed cell viability percentages significantly lower (P < 0.01) than those of the other groups (GI, GIII, and GIV), at 12 and 24 h. Cell growth on GII and GIII groups was similar. GII presented smaller growth than the other groups (P < 0.05). We concluded that sodium alendronate, on direct contact with human periodontal ligament fibroblasts, is cytotoxic in concentrations higher than of 10(-6) M. PMID: 17073923 [PubMed - indexed for MEDLINE] Bisphosphonates and osteonecrosis of the jaw: cause and effect or a post hoc ... Related Articles Bisphosphonates and osteonecrosis of the jaw: cause and effect or a post hoc fallacy? Ann Oncol. 2006 Aug;17(8):1197-204 Authors: Van den Wyngaert T, Huizing MT, Vermorken JB BACKGROUND: An increasing amount of reports are being published suggesting a relationship between the use of bisphosphonates (BPs) and the development of osteonecrosis of the jaw (ONJ). We reviewed the currently available evidence and explore the potential mechanisms of action based on the known effects of the concerned BP. DESIGN: The MEDLine, Current Contents and Science Citation Index Expanded databases were queried and the results augmented by analyzing cited references and recent congress proceedings. RESULTS: 22 papers were included detailing 225 patients, all based on retrospective chart review without control groups. The prevalence of ONJ was estimated at 1.5%. The involved BPs were pamidronate, zoledronic acid, alendronate and risedronate, all potent nitrogen-containing agents. The most common symptom was pain (81.7%), although 12.2% of cases were asymptomatic. In 69.3% of patients ONJ was preceded by a dental extraction. At the time of diagnosis, 74.5% of patients were receiving chemotherapy and in 38.2% of cases corticosteroids were administered. Although various conservative and surgical treatment modalities were reported, residual sites of ONJ persisted in 72.5% of cases. CONCLUSION: Although not enough evidence is available to prove a causal link, it seems that under specific circumstances local defenses can become overwhelmed resulting in ONJ. PMID: 16873439 [PubMed - indexed for MEDLINE] Osteonecrosis of the jaw and oral bisphosphonate treatment. Related Articles Osteonecrosis of the jaw and oral bisphosphonate treatment. J Am Dent Assoc. 2006 Aug;137(8):1115-9; quiz 1169-70 Authors: Nase JB, Suzuki JB BACKGROUND: Bisphosphonates are becoming recognized increasingly as having a significant impact on dental therapies. This case report describes adverse clinical sequelae and successful treatment following periodontal surgery in a dental patient receiving bisphosphonate treatment. CASE DESCRIPTION: A 78-year-old woman experienced a nonhealing interproximal wound subsequent to a minor periodontal procedure performed to facilitate restoration of an adjacent tooth. Her medical history revealed that she had been taking an oral bisphosphonate every day for the previous five years for treatment of osteoporosis. After three months of periodic d&#xE9;bridement and meticulous oral home care, one of the authors recovered a large piece of necrotic bone. The wound healed after the author performed surgery at the site. CLINICAL IMPLICATIONS: Dentists should exercise caution when considering surgical procedures for patients with a history of oral bisphosphonate use. Thorough treatment of nonhealing wounds in these patients can lead to favorable outcomes. PMID: 16873327 [PubMed - indexed for MEDLINE] Safety of oral bisphosphonates: controlled studies on alveolar bone. Related Articles Safety of oral bisphosphonates: controlled studies on alveolar bone. Int J Oral Maxillofac Implants. 2006 May-Jun;21(3):349-53 Authors: Jeffcoat MK PURPOSE: Osteoporosis and osteopenia are characterized by reductions in bone mass and may lead to skeletal fragility and fracture. The latest generation of oral bisphosphonate drugs, including alendronate and risendronate, has been approved for the prevention and treatment of osteoporosis. These medications are chemically absorbed into bone, decreasing osteoclast number and activity and thereby decreasing bone resorption. The purpose of this report is to present safety data from 2 controlled studies in patients receiving oral bisphosphonates. MATERIALS AND METHODS: Study 1 tested the effect of alendronate, an inhibitor of bone resorption, on alveolar bone. A total of 335 patients (162 men and 173 women, aged 30 to 79 years) with moderate or severe periodontal disease were randomized to either placebo or 70 mg alendronate once weekly. Alveolar bone height and safety were assessed over a 2-year period. Study 2 was a longitudinal single-blind controlled design comparing implant success in 50 consecutive patients (210 implants), 25 patients who received bisphosphonate therapy and 25 age-matched control subjects. Implant success and safety, including incidence of osteonecrosis of the jaws (ONJ), was blindly assessed for at least 3 years. RESULTS: In study 1, no cases of ONJ were observed in either treatment group. Furthermore, a trend toward lower incidences of infection and tooth loss was observed in the alendronate group. In study 2, no cases of ONJ were observed in either group, and implant success was greater than 99% in both groups. CONCLUSION: On the basis of 2 controlled clinical studies, oral bisphosphonate usage was not associated with occurrence of ONJ. PMID: 16796276 [PubMed - indexed for MEDLINE] Jaw osteonecrosis associated with use of bisphosphonates and chemotherapy: pa... Related Articles Jaw osteonecrosis associated with use of bisphosphonates and chemotherapy: paradoxical complication of treatment of bone lesions in multiple myeloma patients. Int J Hematol. 2006 Jun;83(5):439-42 Authors: Capalbo S, Delia M, Diomede D, Dargenio M, Chiefa A, Favia G, Liso V It has been demonstrated that bisphosphonate-based supportive therapy (pamidronate or zoledronate) reduces skeletal events (onset or progression of osteolytic lesions) both in patients with multiple myeloma (MM) and in cancer patients with bone metastasis. Bisphosphonates (eg, alendronate) are also indicated in the treatment of osteoporosis. Nevertheless, osteonecrosis of the jaw (ONJ) has been reported in some patients being treated with bisphosphonates. We present a series of 9 MM patients who developed ONJ after treatment with bisphosphonates and chemotherapy. All the patients in this case series had undergone tooth extraction for recurrent dental abscesses while taking bisphosphonates. We also review the diagnostic and therapeutic implications of this paradoxical complication associated with treatment of bone lesions in MM. PMID: 16787865 [PubMed - indexed for MEDLINE] Effect of alendronate on endosseous implant integration: an in vivo study in ... Related Articles Effect of alendronate on endosseous implant integration: an in vivo study in rabbits. J Oral Maxillofac Surg. 2006 Jul;64(7):1005-9 Authors: Chacon GE, Stine EA, Larsen PE, Beck FM, McGlumphy EA PURPOSE: Alendronate sodium (Fosamax; Merck, Whitehouse Station, NJ) is a second-generation bisphosphonate used widely in osteopenic individuals for decreasing bone resorption and increasing bone density. The ability of alendronate to affect systemic bone remodeling raises natural questions about the drug's influence on dental implant osseointegration. Current knowledge regarding the effect of systemic bisphosphonates, specifically alendronate, on all 3 phrases of osseointegration is incomplete and only a few studies have started to investigate peri-implant bone responses to alendronate-coated implants. The purpose of this study was to determine the effect of systemic alendronate therapy on osseointegration of dental implants based on torque-removal values in rabbits. MATERIALS AND METHODS: Identical titanium dental implants were placed using a standardized surgical protocol in the bilateral distal femur and proximal tibia of 20 New Zealand white rabbits (79 implants total). One week before implant placement, 10 rabbits were given doses of alendronate and continued on weekly dosing for 5 weeks until euthanized. The other 10 rabbits were untreated controls. Torque-removal values were determined using a Tohinichi 15-BTG torque wrench (Tohinichi Mfg Co, Ltd, Tokyo, Japan) for all implants. RESULTS: Analysis of torque data showed no statistical differences between the alendronate and control groups in both femur and tibia sites. A statistically significant difference, however, was noted in torque removal values between femur and tibia sites regardless of drug or non-drug groups. CONCLUSIONS: In summary, orally dosed alendronate administration in rabbits had no significant effect on dental implant torque-removal values 6 weeks after endosseous placement in femur and tibia. PMID: 16781331 [PubMed - indexed for MEDLINE] Narrative [corrected] review: bisphosphonates and osteonecrosis of the jaws. Related Articles Narrative [corrected] review: bisphosphonates and osteonecrosis of the jaws. Ann Intern Med. 2006 May 16;144(10):753-61 Authors: Woo SB, Hellstein JW, Kalmar JR Osteonecrosis of the jaws is a recently described adverse side effect of bisphosphonate therapy. Patients with multiple myeloma and metastatic carcinoma to the skeleton who are receiving intravenous, nitrogen-containing bisphosphonates are at greatest risk for osteonecrosis of the jaws; these patients represent 94% of published cases. The mandible is more commonly affected than the maxilla (2:1 ratio), and 60% of cases are preceded by a dental surgical procedure. Oversuppression of bone turnover is probably the primary mechanism for the development of this condition, although there may be contributing comorbid factors. All sites of potential jaw infection should be eliminated before bisphosphonate therapy is initiated in these patients to reduce the necessity of subsequent dentoalveolar surgery. Conservative d&#xE9;bridement of necrotic bone, pain control, infection management, use of antimicrobial oral rinses, and withdrawal of bisphosphonates are preferable to aggressive surgical measures for treating this condition. The degree of risk for osteonecrosis in patients taking oral bisphosphonates, such as alendronate, for osteoporosis is uncertain and warrants careful monitoring. PMID: 16702591 [PubMed - indexed for MEDLINE] Formulation and in vitro evaluation of bisphosphonate loaded microspheres for... Related Articles Formulation and in vitro evaluation of bisphosphonate loaded microspheres for implantation in osteolysis. Drug Dev Ind Pharm. 2006 Apr;32(4):473-81 Authors: Samdancioglu S, Calis S, Sumnu M, Atilla Hincal A Chitosan and poly(lactide-co-glycolide) acid (PLGA) microspheres loaded with alendronate sodium (AS) were prepared for orthopedic as well as dental applications. In orthopedics the aim was to make the total joint prostheses stay in the body for a long time without causing bone tissue loss, while in dentistry it was aimed to treat the alveolar bone resorption caused by periodontitis and also to make the dental treatment using implants easier by reducing the bone loss in patients with osteoporosis. Solvent evaporation method was used to prepare AS loaded PLGA microspheres and emulsion polimerization method was used to prepare AS loaded chitosan microspheres. Particle size, loading efficacy, surface characteristics, and in vitro release characteristics were examined on prepared formulations. After the examination of the scanning electron microscopy photographs of microspheres, chitosan microspheres were observed to have spherical structure and smooth surface characteristics while PLGA microspheres were observed to have spherical porous surface structure. Loading efficacy was found to be 3.30% for chitosan microspheres and 7.70% for PLGA microspheres. It was observed that 85% of AS had been released at the end of the third day from chitosan microspheres whereas 58% was released at the end of the fifth day from PLGA microspheres. It was found that chitosan microspheres gave first order release while PLGA microspheres gave zero order release. PMID: 16638686 [PubMed - indexed for MEDLINE] Relationship between periodontal disease and systemic diseases. Related Articles Relationship between periodontal disease and systemic diseases. Tex Dent J. 2006 Feb;123(2):139; author reply 139 Authors: Alexander RE PMID: 16579501 [PubMed - indexed for MEDLINE] Osteonecrosis of the mandible or maxilla associated with the use of new gener... Related Articles Osteonecrosis of the mandible or maxilla associated with the use of new generation bisphosphonates. Laryngoscope. 2006 Jan;116(1):115-20 Authors: Farrugia MC, Summerlin DJ, Krowiak E, Huntley T, Freeman S, Borrowdale R, Tomich C OBJECTIVE: The use of bisphosphonates is well established for the treatment of patients with metastatic bone disease, osteoporosis, and Paget's disease. Osteonecrosis of the mandible or maxilla associated with the use of bisphosphonates is a newly described entity never before discussed in the otolaryngology literature. In this paper, we review a series of patients diagnosed with osteonecrosis, all treated with new generation bisphosphonates. Our objective is to inform and educate others, particularly otolaryngologists/head and neck surgeons, about this drug induced entity, a condition that should be recognized early to avoid potential devastating consequences. STUDY DESIGN: Retrospective chart review of a series of patients from a tertiary referral center. METHODS: Pathology reports of specimens submitted from either the mandible or maxilla were reviewed from the previous 12 months. Any patient diagnosed with osteonecrosis without evidence of metastatic disease at that site was included; those with a previous history of radiation therapy were excluded. Each patient's medical history and profile were reviewed. RESULTS: Twenty-three patients were identified with osteonecrosis of the mandible or maxilla. All of these were associated with the use of new generation bisphosphonates: zolendronate (Zometa, Novartis), pamidronate (Aredia, Novartis), and alendronate (Fosamax, Merck). Eighteen patients with known bone metastases had been treated with the intravenous form, whereas five patients with either osteoporosis or Paget's disease were using oral therapy. Patients typically presented with a nonhealing lesion, often times the result of previous dental intervention. Although the majority of these patients were treated with conservative surgical debridement, we present a case requiring a near total maxillectomy. CONCLUSIONS: Drug induced osteonecrosis of the mandible or maxilla has been recently recognized as a sequelae of treatment with the new generation of bisphosphonates. Most patients can be treated with conservative surgical debridement and cessation of bisphosphonate therapy, whereas a few may require radical surgical intervention. Other recommendations include regimented prophylactic care with an assessment of dental status before the administration of bisphosphonates, avoidance of dental procedures, and close monitoring of oral hygiene. PMID: 16481822 [PubMed - indexed for MEDLINE] Effects of alendronate and hormone replacement therapy, alone and in combinat... Related Articles Effects of alendronate and hormone replacement therapy, alone and in combination, on saliva, periodontal conditions and gingival crevicular fluid matrix metalloproteinase-8 levels in women with osteoporosis. Oral Dis. 2006 Mar;12(2):187-93 Authors: Evi&#xF6; S, Tarkkila L, Sorsa T, Furuholm J, Välimäki MJ, Ylikorkala O, Tiitinen A, Meurman JH OBJECTIVE: To compare the effects of hormone replacement therapy (HRT), alendronate and their combination on oral health of elderly postmenopausal women with osteoporosis. MATERIALS AND METHODS: Sixty patients, aged 65-80 years (mean 71 years), with a T-score of bone mineral density of -2.5 s.d. or less at either the lumbar spine or the femoral neck, were randomized to receive 2 mg of estradiol plus 1 mg norethisterone acetate (HRT) (n = 20), 10 mg of alendronate (n = 18), or their combination (n = 22) for 2 years. Periodontal and oral status and mouth symptoms were recorded, and salivary analyses made at the beginning and at the end of the study. Gingival crevicular fluid (GCF) matrix metalloproteinase (MMP-8) levels were determined to address destructive events in periodontal tissue. RESULTS: Resting salivary flow rate decreased by 19% (P < 0.05), and GCF MMP-8 tended to increase in the alendronate group. None of the regimens affected subjective feelings of dry or burning mouth. There were no significant changes in dental or periodontal status, stimulated flow rate or composition of saliva during the study. CONCLUSIONS: Alendronate decreased resting salivary flow rate but otherwise HRT or alendronate separately or in combination had no effect on oral health in elderly women with osteoporosis. PMID: 16476042 [PubMed - indexed for MEDLINE] Immunocytochemical study of amelogenin deposition during the early odontogene... Related Articles Immunocytochemical study of amelogenin deposition during the early odontogenesis of molars in alendronate-treated newborn rats. J Histochem Cytochem. 2006 Jun;54(6):713-25 Authors: Massa LF, Bradaschia-Correa V, Arana-Chavez VE Newborn rats were treated with sodium alendronate to study how enamel is formed and the effect of alendronate during early odontogenesis. Ultrastructural analysis combined with high-resolution immunocytochemistry for amelogenin was carried out. Twelve rats were subjected to daily SC injections of sodium alendronate (2.5 mg/kg/day) for 3 days on their dorsal region, whereas three rats were daily injected with saline solution as a control. Molar tooth germs from 3-day-old rats were fixed under microwave irradiation in 0.1% glutaraldehyde + 4% formaldehyde buffered at pH 7.2 with 0.1 M sodium cacodylate. The specimens were left undecalcified, postfixed with osmium tetroxide, dehydrated, and embedded in LR White resin. Ultrathin sections were incubated with a chicken anti-24-kDa rat amelogenin antibody, a secondary antibody, and finally with a protein A-gold complex. Large patches of amelogenin were present over the unmineralized mantle dentin and at early secretory ameloblasts. At more advanced stages, they were also detected at the enamel matrix, as well as in the mineralized dentin, at the periodontoblastic space of the dentinal tubules, and at the predentin. It is likely that the main effect of alendronate at early stages of odontogenesis is the increase of synthesis/secretion of amelogenin, promoting its deposition within the forming dentin and enamel. PMID: 16461365 [PubMed - indexed for MEDLINE] Evaluation of the topical effect of alendronate on the root surface of extrac... Related Articles Evaluation of the topical effect of alendronate on the root surface of extracted and replanted teeth. Microscopic analysis on rats' teeth. Dent Traumatol. 2006 Feb;22(1):30-5 Authors: Lustosa-Pereira A, Garcia RB, de Moraes IG, Bernardineli N, Bramante CM, Bortoluzzi EA The treatment of choice for tooth avulsion is replantation. The ideal replantation should be realized as quickly as possible, or at least, the avulsed tooth should be kept in an adequate solution to preserve the periodontal ligament attached to the root. If that is not possible, treatment of the radicular surface should be done in order to prevent radicular resorption. The purpose of this study was to test sodium alendronate as a substance for topical treatment of the radicular surface of avulsed teeth in an attempt to prevent the occurrence of dental resorptions. Fifty-four rat maxillary right central incisors were extracted and replanted. Group I--extra-alveolar dry period of 15 min, intracanal dressing with calcium hydroxide (CALEN, S.S. White, Artigos Dent&#xE1;rios LTDA, Rio de Janeiro, Brazil) and replantation; Groups II and III - extra-alveolar dry periods of 30 and 60 min, respectively, immersion in 1% sodium hypochlorite for 30 min for removal of the periodontal ligament, washing in saline solution for 5 min, and treatment of the radicular surface with 3.2 mg/l sodium alendronate solution for 10 min. Intracanal dressing with calcium hydroxide and replantation followed. At 15, 60, and 90 days post-reimplantation, the animals were killed and the samples obtained and processed for microscopic analysis. The results indicated that sodium alendronate was able to reduce the incidence of radicular resorption, but not of dental ankylosis. No significant differences were observed regarding variations in the extra-alveolar periods among the groups. PMID: 16422756 [PubMed - indexed for MEDLINE] The dental implications of bisphosphonates and bone disease. Related Articles The dental implications of bisphosphonates and bone disease. Aust Dent J. 2005 Dec;50(4 Suppl 2):S4-13 Authors: Cheng A, Mavrokokki A, Carter G, Stein B, Fazzalari NL, Wilson DF, Goss AN In 2002/2003 a number of patients presented to the South Australian Oral and Maxillofacial Surgery Unit with unusual non-healing extraction wounds of the jaws. All were middle-aged to elderly, medically compromised and on bisphosphonates for bone pathology. Review of the literature showed similar cases being reported in the North American oral and maxillofacial surgery literature. This paper reviews the role of bisphosphonates in the management of bone disease. There were 2.3 million prescriptions for bisphosphonates in Australia in 2003. This group of drugs is very useful in controlling bone pain and preventing pathologic fractures. However, in a small number of patients on bisphosphonates, intractable, painful, non-healing exposed bone occurs following dental extractions or denture irritation. Affected patients are usually, but not always, over 55 years, medically compromised and on the potent nitrogen containing bisphosphonates pamidronate (Aredia/Pamisol), alendronate (Fosamax) and zolendronate (Zometa) for non-osteoporotic bone disease. Currently, there is no simple, effective treatment and the painful exposed bone may persist for years. The main complications are marked weight loss from difficulty in eating and severe jaw and neck infections. Possible preventive and therapeutic strategies are presented although at this time there is no evidence of their effectiveness. Dentists must ask about bisphosphonate usage for bone disease when recording medical histories and take appropriate actions to avoid the development of this debilitating condition in their patients. PMID: 16416712 [PubMed - indexed for MEDLINE] Cytotoxicity analysis of alendronate on cultured endothelial cells and subcut... Related Articles Cytotoxicity analysis of alendronate on cultured endothelial cells and subcutaneous tissue. a pilot study. Dent Traumatol. 2005 Dec;21(6):329-35 Authors: Moreira MS, Katayama E, Bombana AC, Marques MM The use of alendronate, a bisphosphonate which is able to inhibit bone resorption, in order to prevent dental root resorption after tooth replantation would be of clinical relevance. However, this drug must be biocompatible to the periapical tissues. The aim of this study was to analyze the effect of an alendronate paste in polyethyleneglycol (2 g ml(-1)) on endothelial cells in culture (in vitro) and on rat subcutaneous tissue (in vivo). For the in vitro study the paste was applied on round glass coverslips that were immersed into confluent cell cultures (clone Cips). The cell viability percentages of these cultures were obtained 0, 6 and 12 h after contact with the substance. As control, cultures that received plain coverslips were used. This analysis was carried out in triplicate using the Trypan blue dye exclusion assay. For the in vivo study the paste was introduced into polyethylene tubes that were placed into the rat subcutaneous tissue. The rats were killed 7 and 14 days later; then, the tissue sections stained with hematoxylin-eosin were analyzed. In vitro, the alendronate caused a significant decrease in the cell viability in 6 h (P < 0.05) and 12 h (P < 0.01), when compared with the control cultures. In vivo the tissue response was exuberant and similar at the two experimental times. There was a necrosis in a comprehensive area in contact with the open end of the tube. Presence of micro-abscesses and intense inflammatory infiltrate in the hypoderm permeating the muscle fibers and fat lobules were observed. In conclusion, the alendronate paste in polyethylene glycol as used showed to be highly cytotoxic in vitro as well as in vivo. PMID: 16262618 [PubMed - indexed for MEDLINE] Bisphosphonate-induced exposed bone (osteonecrosis/osteopetrosis) of the jaws... Related Articles Bisphosphonate-induced exposed bone (osteonecrosis/osteopetrosis) of the jaws: risk factors, recognition, prevention, and treatment. J Oral Maxillofac Surg. 2005 Nov;63(11):1567-75 Authors: Marx RE, Sawatari Y, Fortin M, Broumand V PURPOSE: Bisphosphonates inhibit bone resorption and thus bone renewal by suppressing the recruitment and activity of osteoclasts thus shortening their life span. Recently three bisphosphonates, Pamidronate (Aredia; Novartis Pharmaceuticals, East Haven, NJ), Zoledronate (Zometa; Novartis Pharmaceuticals), and Alendronate (Fosamax; Merck Co, West Point, VA) have been linked to painful refractory bone exposures in the jaws. MATERIALS AND METHODS: One hundred-nineteen total cases of bisphosphonate-related bone exposure were reviewed. RESULTS: Thirty-two of 119 patients (26%) received Aredia, 48 (40.3%) received Zometa, 36 (30.2%) received Aredia later changed to Zometa, and 3 (2.5%) received Fosamax. The mean induction time for clinical bone exposure and symptoms was 14.3 months for those who received Aredia, 12.1 months for those who received both, 9.4 months for those who received Zometa, and 3 years for those who received Fosamax. Sixty-two (52.1%) were treated for multiple myeloma, 50 (42%) for metastatic breast cancer, 4 (3.4%) for metastatic prostate cancer and 3 (2.5%) for osteoporosis. Presenting findings in addition to exposed bone were 37 (31.1%) asymptomatic, 82 (68.9%) with pain, 28 (23.5%) mobile teeth, and 21 (17.6%) with nonhealing fistulas. Eighty-one (68.1%) bone exposures occurred in the mandible alone, 33 (27.7%) in the maxilla, and 5 (4.2%) occurred in both jaws. Medical comorbidities included the malignancy itself 97.5%, previous and/or maintenance chemotherapy 97.5%, Dexamethasone 59.7%. Dental comorbidities included the presence of periodontitis 84%, dental caries 28.6%, abscessed teeth 13.4% root canal treatments 10.9%, and the presence of mandibular tori 9.2%. The precipitating event that produced the bone exposures were spontaneous 25.2%, tooth removals 37.8%, advanced periodontitis 28.6%, periodontal surgery 11.2%, dental implants 3.4% and root canal surgery 0.8%. CONCLUSIONS: Complete prevention of this complication in not currently possible. However, pre-therapy dental care reduces this incidence, and non-surgical dental procedures can prevent new cases. For those who present with painful exposed bone, effective control to a pain free state without resolution of the exposed bone is 90.1% effective using a regimen of antibiotics along with 0.12% chlorohexidine antiseptic mouth. PMID: 16243172 [PubMed - indexed for MEDLINE] [Avascular necrosis of the jaw bone after bisphosphonate therapy] Related Articles [Avascular necrosis of the jaw bone after bisphosphonate therapy] Harefuah. 2005 Aug;144(8):536-9, 600, 599 Authors: Shlomi B, Levy Y, Kleinman S, Better H, Kahn A, Shtabsky A, Chaushu G Bisphosphonates have an antiosteolytic effect by the inhibition of osteoclastic action. Although the exact mode of action is not completely understood, major progress on both the cellular and molecular levels has been made in recent years. Bisphosphonates alleviate pain and reduce complications, such as pathologic fractures, or hypercalcemia. Dental and periodontal research has shown great interest in clinical applications of bisphosphonates' antiosteolytic and antiosteoclastic traits, since they can be applied to counteract bone loss in chronic periodontitis. Investigations have associated avascular necrosis events in the jawbones with bisphosphonate therapy. Maxillary and mandibular osteonecrotic foci accompanied by pain, inconvenience and purulent exudates were incidentally found in patients who were taking pamidronate (Aredia), zolendronate (Zometa) and even alendronate (Fosalan). Our institutional database search over the past year yielded ten patients who were admitted to the Oral and Maxillofacial Surgery Unit at the Tel Aviv Sourasky Medical Center, due to an osteonecrotic bone lesion coupled with a prior history of bisphosphonate therapy. All these patients also had a recent dental extraction. They were all treated according to the osteomyelitis protocol, and their response to therapy varied from several weeks to many months, with some cases requiring repeat surgical intervention (curettage or sequestrectomy). This article strives to alert on the possible linkage between drug therapy using bisphosphonates and the serious event of avascular jawbone necrosis. The important role of the oral surgeon in following up on this group of patients should not be underestimated. PMID: 16146148 [PubMed - indexed for MEDLINE] Bisphosphonate therapy improves the outcome of conventional periodontal treat... Related Articles Bisphosphonate therapy improves the outcome of conventional periodontal treatment: results of a 12-month, randomized, placebo-controlled study. J Periodontol. 2005 Jul;76(7):1113-22 Authors: Lane N, Armitage GC, Loomer P, Hsieh S, Majumdar S, Wang HY, Jeffcoat M, Munoz T BACKGROUND: Bone loss in periodontitis results from inflammatory reactions that stimulate osteoclastic bone resorption. Bisphosphonates inhibit bone resorption and increase bone mass. This study evaluated the effect of bisphosphonate therapy as an adjunct to non-surgical periodontal treatment in patients with moderate to severe chronic periodontitis. METHODS: Patients were randomized (2:1) to one of two bisphosphonate therapies or placebo for 1 year. All patients received non-surgical periodontal treatment (scaling, root planing) and periodontal maintenance therapy every 3 months. Clinical assessments at baseline and 6 and 12 months included clinical attachment level (CAL), probing depth (PD), and bleeding on probing (BOP). Periodontal bone mass was assessed by dental radiographs at baseline and 12 months using fractal analysis and digital subtraction radiography (DSR). RESULTS: Seventy patients were randomized, 43 to the bisphosphonate group and 27 to the placebo group. Bisphosphonate therapy significantly improved CAL, PD, and BOP relative to the placebo group during the 6- to 12-month period (CAL, P = 0.0002; PD, P = 0.0156; BOP, P = 0.0079). There was no difference in the change in periodontal bone mass between the bisphosphonate and placebo groups as measured by fractal analysis and DSR. CONCLUSION: These data suggest that bisphosphonate treatment improves the clinical outcome of non-surgical periodontal therapy and may be an appropriate adjunctive treatment to preserve periodontal bone mass. PMID: 16018754 [PubMed - indexed for MEDLINE] Bisphosphonate-associated osteonecrosis of mandibular and maxillary bone: an ... Related Articles Bisphosphonate-associated osteonecrosis of mandibular and maxillary bone: an emerging oral complication of supportive cancer therapy. Cancer. 2005 Jul 1;104(1):83-93 Authors: Migliorati CA, Schubert MM, Peterson DE, Seneda LM BACKGROUND: The current report presented 17 patients with cancer with bone metastases and 1 patient with osteopenia who received treatment with bisphosphonates and who subsequently developed osteonecrosis of the mandible and/or maxilla. METHODS: The authors reviewed information on 18 patients who were referred to oral medicine or oral surgery specialists for evaluation and treatment of mandibular and/or maxillary bone necrosis from June 2002 to September 2004. To be included in the current review, patients must have been treated with either pamidronate or zoledronic acid to control or prevent metastatic disease, or with alendronate for osteoporosis. All patients with cancer had received chemotherapy while receiving bisphosphonate management. RESULTS: The 17 patients with cancer were receiving active medical care for a malignancy. Cancer treatment included a variety of chemotherapeutic agents. They presented with metastatic disease to bone and were treated intravenously with the bisphosphonates pamidronate or zoledronic acid for a mean time of 25 months (range, 4-41 mos). There were 14 females and 4 males with a mean age of 62 years (range, 37-74 yrs). Malignancies included breast carcinoma (n = 10), multiple myeloma (n = 3), prostate carcinoma (n = 1), ovarian carcinoma (n = 1), prostate carcinoma/lymphoma (n = 1), and breast/ovarian carcinoma (n = 1). One female patient with osteopenia received alendronate. The most common clinical osteonecrosis presentations included infection and necrotic bone in the mandible. Associated events included dental extractions, infection, and trauma. Two patients appeared to develop disease spontaneously, without any clinical or radiographic evidence of local pathology. Despite surgical intervention, antibiotic therapy, hyperbaric oxygen therapy, and topical use of chemotherapeutic mouth rinses, most of the lesions did not respond well to therapy. Discontinuation of bisphosphonate therapy did not assure healing. However, 1 patient with cancer healed after discontinuation of bisphosphonate therapy for 4 months. CONCLUSIONS: The findings in the patient population combined with recent literature reports suggested that bisphosphonates may contribute to the pathogenesis of the oral lesions. The risk factors and precise mechanism involved in the formation of the osteonecrosis are not known. This condition represents a new oral complication in patients with cancer and can be termed bisphosphonate-associated osteonecrosis. Lesions in patients with osteoporosis are worrisome and need to be further evaluated. PMID: 15929121 [PubMed - indexed for MEDLINE] Alendronate therapy may be effective in the prevention of bone loss around ti... Related Articles Alendronate therapy may be effective in the prevention of bone loss around titanium implants inserted in estrogen-deficient rats. J Periodontol. 2005 Jan;76(1):107-14 Authors: Duarte PM, de Vasconcelos Gurgel BC, Sallum AW, Filho GR, Sallum EA, Nociti FH BACKGROUND: This study evaluated whether alendronate (ALD) influences bone healing around titanium implants inserted in ovariectomized rats and whether it provides a residual effect after its withdrawal. METHODS: Bilateral ovariectomies were performed in 87 Wistar rats and one screw-shaped titanium implant was placed in the tibiae. The animals were divided into the following groups: group SHAM (N = 15): sham surgeries; group OVX (N = 15): ovariectomy; group AT (N = 15): OVX plus alendronate administration for 80 days; group AW (N = 14): OVX plus alendronate administration for 40 days; group ET (N = 14): OVX plus 17beta estradiol administration for 80 days; or group EW (N = 14): OVX plus 17beta estradiol administration for 40 days. Bone-to-implant contact (BIC), bone area (BA) within the limits of implant threads, and bone density in a 500 microm-wide zone lateral to the implant (BD) were obtained and measured for the cortical (zone A) and cancellous (zone B) regions. RESULTS: In zone A, data analysis showed no significant differences among the groups regarding BIC and BD (P >0.05), and a slight beneficial effect of estradiol on BA when compared with the OVX, EW, and AW groups (P <0.05). In zone B, OVX negatively impacted bone healing around the implants, resulting in reduced BA and BD (P<0.05). ALD (continuous/interrupted) and estradiol (only continuous) positively affected BIC, BA, and BD, resulting in values at the same level as the control group (SHAM). CONCLUSIONS: ALD may prevent the negative influence of estrogen deficiency on bone healing around titanium implants inserted in OVX rats. This positive effect, in contrast to estradiol, is sustained following its withdrawal. PMID: 15830644 [PubMed - indexed for MEDLINE] Effects of combined systemic administration of low-dose doxycycline and alend... Related Articles Effects of combined systemic administration of low-dose doxycycline and alendronate on endotoxin-induced periodontitis in rats. J Periodontol. 2004 Nov;75(11):1516-23 Authors: Buduneli E, Vardar S, Buduneli N, Berdeli AH, T&#xFC;rkoğlu O, Başkesen A, Atilla G BACKGROUND: Doxycycline has been widely used in periodontal treatment for its antimicrobial and anti-enzymatic effects. Recently, bisphosphonates have been shown to inhibit alveolar bone resorption. The aim of the present study was to evaluate the effects of doxycycline and the bisphosphonate alendronate on the gingival tissue levels of prostaglandin E2 (PGE2), prostaglandin F2alpha (PGF2alpha), leukotriene B4 (LTB4), and platelet-activating factor (PAF) in endotoxin-induced periodontal breakdown in rats. METHODS: Experimental periodontitis was induced by repeated injection of Escherichia coli endotoxin (LPS) and 44 adult male Sprague-Dawley rats were divided into five study groups as follows: LPS, doxycycline + LPS, alendronate + LPS, doxycycline + alendronate + LPS, and saline control. Doxycycline and alendronate were given either as a single agent or as a combination therapy during the 7-day study period. At the end of the 1-week protocol, the rats were sacrificed, the gingival tissues were dissected and extracted, and the extracts were analyzed for PGE2, PGF2alpha, LTB4, and PAF levels. The defleshed jaws were analyzed morphometrically for alveolar bone loss. Data were evaluated statistically by using parametric tests. RESULTS: Alveolar bone loss measurements revealed significantly higher values in LPS, doxycycline + LPS, alendronate + LPS, and doxycycline + alendronate + LPS groups in comparison to the saline control group (P <0.05). Combined administration of doxycycline and alendronate exhibited the most prominent inhibition on gingival tissue levels of PGE2 and PGF2alpha (P<0.05). Doxycycline + alendronate + LPS group also significantly reduced LTB4 and PAF levels, although doxycycline provided the most reduction in the levels of these mediators (P <0.05). CONCLUSIONS: Alendronate and/or doxycycline may provide significant inhibition of the major inflammatory mediators of periodontal tissue destruction, and combined administration of these agents may provide beneficial effects in periodontal treatment. However, this hypothesis must be further verified by clinical human trials before introducing its use in dental practice. PMID: 15633329 [PubMed - indexed for MEDLINE] Alendronate may protect against increased periodontitis-related bone loss in ... Related Articles Alendronate may protect against increased periodontitis-related bone loss in estrogen-deficient rats. J Periodontol. 2004 Sep;75(9):1196-202 Authors: Duarte PM, de Assis DR, Casati MZ, Sallum AW, Sallum EA, Nociti FH BACKGROUND: The aim of this study was to evaluate the impact of alendronate (ALD) and estrogen (EST) therapies and their withdrawal on bone loss in experimental periodontitis in ovariectomized rats. METHODS: Eighty-seven Wistar rats were divided into six groups: group 1 (N = 15): sham surgery; group 2 (N = 15): ovariectomy (OVX); group 3 (N = 15): OVX plus alendronate administration for 80 days (AT); group 4 (N = 14): OVX plus alendronate administration for 40 days (AW); group 5 (N = 14): OVX plus 17beta estradiol administration for 80 days (ET); and group 6 (N = 14): OVX plus 17beta estradiol administration for 40 days (EW). Twenty-one days after ovariectomy or sham surgery, one mandibular molar was randomly assigned to receive a ligature, while the contralateral tooth was left unligated. Sixty days later, the animals were sacrificed and the specimens processed. RESULTS: OVX presented a direct impact on alveolar bone, regardless of plaque accumulation and significantly increased bone loss resulting from periodontitis (P < 0.05). The effect of OVX on unligated sites was significantly reduced by AT, AW, and ET (P < 0.05), but not by EW (P > 0.05). In addition, alendronate administration (AT/AW) significantly reduced the impact of OVX on periodontitis-related bone loss (P < 0.05), while estradiol did not (P > 0.05). CONCLUSION: Within the limits of this study, alendronate administration, but not estrogen replacement, may protect against the impact of estrogen deficiency on alveolar bone presenting a significant residual effect after its withdrawal. PMID: 15515333 [PubMed - indexed for MEDLINE] Effects of alendronate on restoration of biomechanical properties of periodon... Related Articles Effects of alendronate on restoration of biomechanical properties of periodontium in replanted rat molars. J Periodontal Res. 2004 Dec;39(6):405-14 Authors: Shibata T, Komatsu K, Shimada A, Shimoda S, Oida S, Kawasaki K, Chiba M OBJECTIVE: We examined the effect of the pretreatment of roots with alendronate on the restoration of the support function of the healing periodontal ligament in replanted rat molars. METHODS: The left maxillary first molars were extracted, placed in 0.9% NaCl containing 1 mm alendronate (alendronate group) or 0.9% NaCl (control group) for 5 min, and were replanted into their sockets. Groups of animals were killed at 7, 14, and 21 days after replantation. Normal control rats were also killed on the same days. The force required to extract the replanted or normal tooth from its socket was measured, and a load-deformation curve was developed and analyzed. Micro-computed tomography and histologic analyses were also made. RESULTS: The mechanical properties of the healing periodontal ligament in the alendronate group were gradually restored from 7 to 21 days. However, fractures of the roots and bones during mechanical testing occurred in most of the replanted teeth in the control group at 21 days. The rates of restoration of the mechanical strength, extensibility, stiffness, and toughness for the alendronate group at 21 days were 67, 98, 74, and 68% of the normal controls, respectively. Micro-computed tomography and histologic observations revealed that bone-like structures within the pulp and ankylosis between the roots and socket bones occurred commonly in the control group, but were uncommon in the alendronate group. CONCLUSIONS: Our findings suggest that the pretreatment with alendronate inhibits the formation of abnormal mineralized tissues and results in better restoration of the support function of the healing periodontal ligament in replanted teeth. PMID: 15491345 [PubMed - indexed for MEDLINE] The effect of alendronate on resorption of the alveolar bone following tooth ... Related Articles The effect of alendronate on resorption of the alveolar bone following tooth extraction. Int J Oral Maxillofac Surg. 2004 Apr;33(3):286-93 Authors: Altundal H, G&#xFC;vener O Maintenance of alveolar bone width and height following tooth loss is essential with regard to the restoration of missing teeth with endosseous dental implants or prosthodontics approaches. A various amount of alveolar ridge resorption is likely to occur after tooth extraction at the buccal and lingual alveolar bone plates. Bisphosphonates, alendronate, is well known for its potent inhibition of osteoclast-mediated bone resorption. The objective of this study was to examine the inhibitory effect of alendronate on alveolar bone resorption following tooth extraction in rats. Male Wistar Albino rats were divided into three groups: baseline group, saline-treated group and alendronate-treated group. The saline-treated group was administered with daily saline solution for 2 and 4 weeks respectively while the alendronate-treated group was given a daily amount of 0.25 mg/kg alendronate subcutaneously for the same periods. The level of urinary calcium, creatinine, and serum calcium, alkaline phosphatase and phosphate were measured. Serum alkaline phosphatase level was measured as a marker of osteoblastic activity. Histopathological sections of 4 microm thickness were obtained from the right first mandibular molar region in a bucco-lingual direction. The number of osteoclasts, osteoblasts, and haversian canals, the number and size of resorptive lacunae, and osteoid formation were evaluated histopathologically. The mean thickness of buccal and lingual alveolar bone was measured. In the alendronate-treated group, both buccal and lingual alveolar bone volume reduction was significantly less than the saline treated group. Significant reduction in serum and urinary calcium levels and the number of osteoclasts revealed the pronounced suppression of bone resorption in the alendronate-treated group. PMID: 15287313 [PubMed - indexed for MEDLINE] A histopathological investigation on the effect of systemic administration of... Related Articles A histopathological investigation on the effect of systemic administration of the bisphosphonate alendronate on resorptive phase following mucoperiosteal flap surgery in the rat mandible. J Periodontol. 2003 Sep;74(9):1348-54 Authors: Kaynak D, Meffert R, Bostanci H, Günhan O, Ozkaya OG BACKGROUND: The present study was designed to assess histopathologically whether the systemic administration of aminobisphosphonate (alendronate), 0.5 mg/kg body weight, is effective in preventing alveolar bone resorption following mucoperiosteal flap surgery, and whether alendronate modulates tissue factors. METHODS: The effect of alendronate on bone resorption was evaluated in mucoperiosteal flaps used as a resorptive model. The animals were given subcutaneous injections of either saline (control group) or 0.5 mg/kg of alendronate (experimental group). The alendronate or saline was administered subcutaneously 1 week prior to surgery, immediately prior to surgery, and 1 week after surgery. The parameters determined with a semiquantitative subjective method for histopathological evaluation were as follows: inflammatory cell infiltration (ICI) of adjacent periodontal tissue, degree of fibrosis and collagen bundle formation, number and morphology of osteoclasts of the alveolar bone and interdental septum, resorption lacunae (osteoclast surfaces), and osteoblastic activity (forming surfaces). RESULTS: There were no statistically significant differences between the saline and alendronate groups with regard to inflammatory cell infiltration, number of osteoclasts, and osteoblastic activity. Fibrosis and collagen bundle formation, osteoclast morphologies, and resorption lacunae formation were significantly different between the two groups, in favor of the alendronate group. CONCLUSIONS: The systemic administration of 0.5 mg/kg alendronate was effective in preventing alveolar bone loss and in modulating tissue factors. These findings indicate that alendronate would be a valuable addition to the therapeutic armamentarium available for the treatment of periodontal diseases, either alone or in combination with regenerative components such as anti-inflammatory drugs, bone graft materials, and guided tissue regeneration techniques, and even with dental implants. PMID: 14584869 [PubMed - indexed for MEDLINE] [Influence of biphosphonates on the integration process of endosseous implant... Related Articles [Influence of biphosphonates on the integration process of endosseous implants evaluated using single photon emission computerized tomography (SPECT)] Minerva Stomatol. 2003 Jun;52(6):331-8 Authors: Bambini F, De Stefano CA, Giannotti L, Memè L, Pellecchia M Biphosphonates are a large class of drugs which inhibits the resorbing activity of osteoclasts. The aim of this study was to evaluate the influence of topical application of the biphosphonate alendronate on the integration process of endosseus implants placed in a partially edentulous patient. After incision and elevation of a mucoperiosteal flap and carrying out the osteotomy, 2 SLA implants 10 mm long and 3.5 mm wide were inserted in the area of # 4.5 and 4.6. Before placement of # 4.5, a paste made of grinded tablets of alendronate and Rifocin was applied in the osteotomy. Fifteen days after stage I, an evaluation of the osteoblastic peri-implant activity was carried out using single photon emission computerized tomography. Healing was within normal limits. Four months after stage I, the 2 implants were uncovered and considered clinically and radiographically integrated. The osteoblastic activity was judged similar bet-ween the 2 implants in terms of quality of biological response. Osseous scintigraphy and the achievement of implant osseointegration demonstrate the lack of toxicity of the topical application of the biphosphonate alendronate during the initial osseous healing. However, new experimental studies and clinical trials are necessary to confirm the results obtained. PMID: 12874537 [PubMed - indexed for MEDLINE] Effects of alendronate on the removal torque of implants in rats with induced... Related Articles Effects of alendronate on the removal torque of implants in rats with induced osteoporosis. Int J Oral Maxillofac Implants. 2003 Mar-Apr;18(2):218-23 Authors: Narai S, Nagahata S PURPOSE: In this study, the removal torques of commercially pure titanium Implants that had been implanted simultaneously with the start of treatment for osteoporosis were compared to those of a group without treatment and a healthy group. MATERIALS AND METHODS: Rats treated by ovariectomy or sham surgery at the age of 12 weeks were used. Twenty-eight days after surgery, the rats treated by ovariectomy were divided into an alendronate-treated group and an untreated (ovariectomy-control) group. At the start of administration of alendronate, a titanium implant was placed in the distal metaphysis of the femur. After 1 month of administration of alendronate and a vehicle, removal torque, the percentage of bone-implant contact (BIC), and parameters of treatment using alendronate were measured. RESULTS: The removal torque values were 10.1 +/- 1.6 Ncm for the group of osteoporotic rats that had been administered alendronate and 6.4 +/- 1.0 Ncm for the group of osteoporotic rats that did not receive alendronate, indicating that the removal torque was significantly higher in the former group than in the latter group. However, there was no significant difference between the alendronate-treated group and the healthy control group (ie, sham surgery) (9.3 +/- 1.3 Ncm). DISCUSSION and CONCLUSION: These results suggested that implant placement together with treatment of osteoporosis is possible in the ovariectomized rat model. PMID: 12705299 [PubMed - indexed for MEDLINE] The effect of alendronate sodium on alveolar bone loss in periodontitis (clin... Related Articles The effect of alendronate sodium on alveolar bone loss in periodontitis (clinical trial). J Int Acad Periodontol. 2003 Jan;5(1):5-10 Authors: El-Shinnawi UM, El-Tantawy SI Alendronate sodium is a potent inhibitor of bone resorption which has been effectively used to control osteolysis, and to treat Paget's disease and osteoporosis. The objective of this study was to investigate the effect of alendronate sodium, systemically induced in the treatment of patients with periodontitis. Twenty-four adult periodontitis patients were included in the study (for six months) and were divided into two groups. Group I, included twelve patients who received one tablet of fosamax (alendronate sodium, MSD) every morning for six months. Group II, also included twelve patients who received no drug during the study period. All patients received initial periodontal therapy. Bone mineral density (BMD) of the maxilla and mandible was measured for all subjects using a dual energy absorptiometer (DEXA) at the beginning of the study and at the end of six months using DPX. MD Scanner. Clinical periodontal measurements were carried out for all patients at the initial appointment and six months later in the form of pocket depth, attachment level and gingival index. A statistically significant difference in bone density (P < 0.001) was observed favouring the alendronate group (Group I). Alendronate sodium had no effect on the clinical parameters and could play an important role as an adjunct to conventional periodontal therapy in management of periodontal diseases. PMID: 12666950 [PubMed - indexed for MEDLINE] The accuracy of tooth loss data collected by nurses. Related Articles The accuracy of tooth loss data collected by nurses. Spec Care Dentist. 1999 Mar-Apr;19(2):75-8 Authors: Warren JJ, Levy SM, Hand JS This paper reports on the accuracy of tooth counts conducted in 22 subjects by 10 trained nurses as part of a large longitudinal study of a pharmacological agent. These nurses participated in a training course consisting of seminars, discussion, demonstrations, and practice examinations. Each of the nurses then counted the teeth of 22 subjects and recorded their findings independently. The counts of the nurses were compared with those of the dentists to assess the accuracy of the nurses' counts. We found that nurses and dentists were in perfect agreement for 86% of the patient counts conducted. Individual nurses' levels of agreement with dentists ranged from 73% to 100%, with pairwise kappa statistic values ranging from 0.70 to 1.00. In addition, both Pearson correlation and interclass correlation measures exceeded 0.98 for every comparison of dentist and nurse counts. The results of this study suggest that training nondental health care workers may be an accurate and low-cost way of obtaining tooth loss data and other oral health measures, particularly when oral health data are collected as part of larger, multi-disciplinary studies. PMID: 11833110 [PubMed - indexed for MEDLINE] [The treatment of osteoporosis and bone resorption of alveoli with alendronat... Related Articles [The treatment of osteoporosis and bone resorption of alveoli with alendronate in rat model] Zhonghua Kou Qiang Yi Xue Za Zhi. 2001 May;36(3):193-6 Authors: Wang X, Yang Z, Yu S OBJECTIVE: To evaluate the anti-osteoporosis effect of alendronate on bone in rat model. METHODS: The osteoporosis and alveolar bone resorption animal model were established in rats. The experimental groups were given alendronate in 5 mg/kg BW by subcutaneous injection after first day of ovariectomy and dental ligature, three times a week for 6 weeks. All the animals were sacrifised 12 weeks after the operation. The blood samples were collected for determination of biochemical indices. The left femora and jaw bones were processed for histomorphometry. The right femora and mendibles were prepared for determination of bone density and bone biodynamics. RESULTS: As compared with the control groups(without alendronate), the values of experimental groups (with alendronate) were all significantly improved on bone density, bone anti-flexure ability and body weight. The alkaline phosphatase, calcium in serum of ovariectomy groups(without alendronate) were obviously increased. In the experimental group, however, these indices were close to normal levels. In histomorphometry, there were little inflammation in gingiva and no obvious bone resorption in the alveolar crests of the experimental groups; but there were obvious gingivitis and alveolar crests resorption of the control groups. CONCLUSIONS: Alendronate can effectively prevent bone loss to reduce osteoporosis in ovariectomized rats and prohibit pathological alveolar bone resorption. PMID: 11812340 [PubMed - indexed for MEDLINE] Effect of topical alendronate on root resorption of dried replanted dog teeth. Related Articles Effect of topical alendronate on root resorption of dried replanted dog teeth. Dent Traumatol. 2001 Jun;17(3):120-6 Authors: Levin L, Bryson EC, Caplan D, Trope M Alendronate (ALN) is a third generation bisphosphonate with demonstrated osteoclast inhibitory activity that may slow down the resorptive process after severe traumatic injuries. Eighty-two premolar roots of five mongrel dogs were endodontically treated and restored, extracted and treated as follows: 70 roots were bench dried for either 40 or 60 min. Thirty-eight of these roots were then soaked for 5 min in a 1 mM solution of ALN in Hanks' Balanced Salt Solution (HBSS) and replanted. Thirty-two roots were soaked for 5 min in HBSS and replanted. In the remaining 12 roots which were not exposed to the bench drying procedure, a 0.5 mM deep lingual mid-root cemental defect was made. Six of these roots were soaked in a 1 mM solution of ALN in HBSS for 5 min and replanted. The other six roots were soaked for 5 min in HBSS and replanted. Historical negative and positive controls were used from similarly treated teeth in our previous studies. After 4 months the dogs were killed and the roots prepared for histological evaluation. Five-microm-thick cross-sections of the root and surrounding tissue taken every 70 microm were evaluated for healing according to the criteria of Andreasen. In the 12 roots with cemental defects, healing with cementum of the damaged root surface was evaluated. In addition, residual root mass was also measured to determine the extent of root structure loss for each soaking method. Cemental healing took place in all 12 artificially damaged roots, indicating that these soaking media did not inhibit cementogenesis. The alendronate-soaked roots had statistically significantly more healing than the roots soaked in HBSS without alendronate. This improvement in healing was seen in all dogs except one and in all teeth except the first premolar. Soaking in alendronate also resulted in significantly less loss in root mass due to resorption compared to those teeth soaked in HBSS without alendronate. PMID: 11499761 [PubMed - indexed for MEDLINE] Effect of alendronate on immature human dental root explants. Related Articles Effect of alendronate on immature human dental root explants. J Endod. 2000 Mar;26(3):133-7 Authors: Sommercorn LM, Di Fiore PM, Dixit SN, Koerber A, Lingen MW, Veis A This study investigated the use of alendronate in the formation of new dentin in vitro. Extracted human premolar and molar teeth with immature apices were grown in tissue culture medium for 60 days. Six control specimens were grown without alendronate in the medium, and 22 experimental specimens were grown with alendronate at [10(-9) M] in the medium. Newly formed dentin was stained with tetracycline and procion brilliant red at days 1 to 3, 30 to 33, and 60. Specimens were decalcified and 5-micron sections were prepared for examination using fluorescent microscopy. New dentin formation was measured in microns at the most apical region, at 125-micron from the apical measurement and at 250-micron from the apical measurement. The alendronate group had 57.15% more growth than the control group at the most apical region, and this difference was significant (p = 0.0001). The results indicate that alendronate at [10(-9) M] is effective in accelerating dentin formation in vitro. PMID: 11199704 [PubMed - indexed for MEDLINE] A histopathological investigation on the effects of the bisphosphonate alendr... Related Articles A histopathological investigation on the effects of the bisphosphonate alendronate on resorptive phase following mucoperiosteal flap surgery in the mandible of rats. J Periodontol. 2000 May;71(5):790-6 Authors: Kaynak D, Meffert R, G&#xFC;nhan M, Günhan O, Ozkaya O BACKGROUND: The present study was designed to examine histopathologically whether local delivery of aminobisphosphonate (alendronate) could be effective in preventing the alveolar bone resorption associated with mucoperiosteal flaps. METHODS: Following mucoperiosteal flap elevation in the molar region of the rat mandible, a surgical pellet soaked with aminobisphosphonate was locally applied on the exposed bone surface and covered by flap. The determined parameters with a semi-quantitative subjective method for the histopathological evaluation were as follows: existing inflammatory cell infiltration of the related periodontal tissue; fibrotic component content and bundles of collagen fibers; the number and morphology of osteoclasts of the alveolar bone and interdental septum; existing resorption lacunae (osteoclast surfaces); and existing osteoblastic activity (forming surfaces). RESULTS: The results showed that while there were no detectable statistically significant differences between the saline and alendronate-treated groups on the existing inflammatory cell infiltration (ICI), number of osteoclasts, and osteoblastic activity, the results for the fibrotic and collagen component, osteoclast morphologies, and existing resorption lacunae were statistically significant. CONCLUSIONS: These results suggest that local application of the aminobisphosphonate alendronate can be used as an adjunct in therapy for reducing bone resorption following surgery. It can also be suggested for consideration that, even for the surgical approaches in dentistry where bone graft materials and/or dental implants are needed, using bisphosphonate may achieve a new dimension in periodontal therapy in the near future. PMID: 10872961 [PubMed - indexed for MEDLINE] Qualitative analysis of peripheral peri-implant bone and influence of alendro... Related Articles Qualitative analysis of peripheral peri-implant bone and influence of alendronate sodium on early bone regeneration. J Periodontol. 1999 Oct;70(10):1228-33 Authors: Meraw SJ, Reeve CM BACKGROUND: Alendronate sodium increases alveolar bone density with systemic use. It inhibits osteoclast activity and is thought to result in a net increase in osteoblastic activity. However, little is known about local in vivo use. The purpose of this study was to evaluate the effect of local delivery of alendronate on bone regeneration within peri-implant defects. Peri-implant bone was examined histomorphometrically to evaluate the amount of supporting bone peripheral to the bone-implant interface. METHODS: Six adult hound dogs were evenly divided into 2 groups, with one group receiving alendronate-coated dental implants and the other group serving as controls. Dental implants were placed immediately after extraction of right and left second, third, and fourth mandibular premolars. Forty-eight dental implants were placed (2 types in each dog: 24 hydroxyapatite [HA]-coated and 24 titanium machine-polished [TMP]), for a total of 4 variables. A bioabsorbable collagen membrane was secured over the implants and defects, and the flaps closed primarily. The dogs were sacrificed on day 28. Specimens were sectioned, mounted, and stained with Stevenel's blue and van Gieson's picric fuchsin. The amount of bone adjacent and 1 mm peripheral to the implant surface was recorded with a computerized microscopic digitizer. RESULTS: Locally applied alendronate resulted in significantly increased amounts of bone (P<0.0002, ANOVA) in the peripheral area with both HA and TMP implants. However, the most influential factor in the amount of peripheral bone was the type of implant surface (P<0.0001). CONCLUSIONS: Local application of alendronate is useful in increasing the amount of peripheral peri-implant bone. Also, the amount of supporting bone was not related to the bone-to-implant contact but to the surface characteristics of the implant. The findings of the present study indicate that the evaluation of dental implant-supporting bone should include peripheral bone as well as bone-to-implant interface. PMID: 10534078 [PubMed - indexed for MEDLINE]

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