Impact of bisphosphonate therapy on dental implant outcomes: An overview of systematic review evidence

The purpose of this overview was to assess the methods, quality, and outcomes of systematic reviews conducted to evaluate the impact of bisphosphonates on dental implants and the risk of developing bisphosphonate-related osteonecrosis of the jaw after dental implant surgery. An electronic search without date or language restriction was performed in the PubMed/MEDLINE, Cochrane CENTRAL, Web of Science, and LILACS databases (to January 2018). Eligibility criteria included systematic reviews that evaluated the impact of bisphosphonates on implant outcomes. The quality assessment of the included reviews was done using AMSTAR 2 guidelines. The protocol of this overview was registered in PROSPERO (CRD42018089617). The search and selection process yielded seven reviews, published between 2009 and 2017. None of the systematic reviews included in this study obtained the maximum score in the quality assessment. The scientific evidence available demonstrates that patients with a history of bisphosphonate use do not present a higher risk of dental implant failure or marginal bone loss compared to patients who have not used bisphosphonates. The literature also suggests that patients who undergo surgical trauma during the installation of dental implants may be more susceptible to bisphosphonate-related osteonecrosis of the jaw.     

Placing of oral implants in patients using bisphosphonates

Dentists are with increasing frequency confronted with patients who are being treated with bisphosphonates for certain bone diseases, hypercalcaemia, and bone metastases of solid malignancies. A side effect of the use of bisphosphonates is osteonecrosis of the jaw. Bisphosphonate-induced osteonecrosis of the jaw occurs mainly after treatment with intravenous bisphosphonates and to a much lesser extent after oral administration of bisphosphonates. The question remains whether oral implants can be safely placed in patients using bisphosphonates. A survey of the literature shows that the risk ofosteonecrosis of the jaw and loss of oral implants is not increased when the implants are placed within 3 years after starting treatment with oral bisphosphonates. After this period there is the possibility of a slightly increased risk of complications. The possibility of complications is higher in patients receiving the intravenous bisphosphonates, and, therefore, elective surgical treatments is not advocated.     

Dental endosseous implants in patients on bisphosphonate therapy

About a decade ago, bisphosphonates were introduced as an alternative to hormone replacement therapies for osteoporosis and to treat osteolytic tumors. More recently, it has became evident that the bisphosphonates used intravenously such as pamidronate (Aredia; Novartis Pharmaceuticals Corp., East Hanover, NJ) and zoledronate (Zometa; Novartis Pharmaceuticals Corp.), in particular, could lead to painful refractory bone exposure (sometimes termed osteochemonecrosis or osteonecrosis) in the jaws. Patients with osteonecrosis of the jaws usually present after dental treatment with oral signs and symptoms of painful, exposed, and necrotic bone, primarily of the mandible and, to a lesser extent, the maxilla. Although the precipitating event that produces this complication may be spontaneous, there is little doubt that oral surgery and endosseous implants can be responsible. Exodontia is the main precipitant. The present postulated mechanism of osteonecrosis of the jaws is that prolonged use of bisphosphonates may suppress bone turnover to the point that the repair function of physiologic microdamage of bone is abolished. Such a mechanism could presumably interfere with the healing process after implant placement. Although, to our knowledge, there is no evidence that bone disorders are a contraindication to implants, there is evidence that bisphosphonate therapy is a contraindication. Where possible, extractions should be avoided, and it is best to avoid all elective oral surgery in patients on bisphosphonates, including endosseous implant placement, or the treatment should be performed well before commencing bisphosphonates. If surgery is essential on a patient taking bisphosphonate therapy, the patient must be counseled about the risks.     

A review of the clinical implications of bisphosphonates in dentistry

Bisphosphonates are drugs that suppress bone turnover and are commonly prescribed to prevent skeletal related events in malignancy and for benign bone diseases such as osteoporosis. Bisphosphonate associated jaw osteonecrosis (ONJ) is a potentially debilitating, yet poorly understood condition. A literature review was undertaken to review the dental clinical implications of bisphosphonates. The present paper briefly describes the postulated pathophysiology of ONJ and conditions with similar clinical presentations. The implications of bisphosphonates for implantology, periodontology, orthodontics and endodontics are reviewed. Whilst bisphosphonates have potential positive applications in some clinical settings, periodontology particularly, further clinical research is limited by the risk of ONJ. Prevention and management are reviewed, including guidelines for reducing cumulative intravenous bisphosphonate dose, cessation of bisphosphonates prior to invasive dental treatment or after ONJ development, and the use of serum beta-CTX-1 in assessing risk. In the context of substantial uncertainty, the implications of bisphosphonate use in the dental clinical setting are still being determined.     

Effect of long-term oral bisphosphonates on implant wound healing: literature review and a case report

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.     

Effect of alendronate on endosseous implant integration: an in vivo study in rabbits.

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.     

Oral bisphosphonate-related osteonecrosis of the jaws in dental implant patients: a case series

Bisphosphonates have been associated with a serious adverse reaction known as bisphosphonate-related osteonecrosis of the jaws (BRONJ). The aim of this study was to describe its clinical characteristics in patients with dental implants who were taking bisphosphonates orally. We made a retrospective multicentre study in 3 hospitals in Galicia, Spain. The medical records and clinical and radiological follow-up of the oral cavity were reviewed for those patients given bisphosphonates and diagnosed with BRONJ after the placement of dental implants within the previous 3 years. The series comprised 9 white patients (mean age 66 years). The bisphosphonates were alendronate (n = 6), ibandronate (n = 2), and risedronate (n = 1), and the most common indication was osteoporosis (n = 7). The mean interval between the initiation of treatment and the onset of BRONJ lesions was 60 months. Most of the lesions were located around the mandibular implants (n = 8). The mean interval between placement of dental implants and the onset of BRONJ was 34 (range 1–96) months. After treatment 7/9 patients recovered completely. The prevalence of BRONJ secondary to treatment with bisphosphonates taken orally after placement of dental implants may be higher than expected in a particular geographical region, but to date specific risk factors have not been identified. Clinical characteristics and the outcomes of treatment of lesions are similar to those seen in patients with BRONJ that is unrelated to placement of dental implants.     

The use of bisphosphonates in children: review of the literature and guidelines for dental management

Bisphosphonates are inhibitors of osteoclastic bone resorption with therapeutic benefit in a variety of bone disorders in both adults and children. While these agents have been routinely used in adults for the past three decades, their more recent introduction into paediatric medicine means there is a paucity of data on long‐term safety and effects on dental development. There is uncertainty regarding the dental management of children treated with bisphosphonates, particularly when invasive dental procedures, such as extractions and oral surgical procedures, are required. There are limited data with which to make recommendations about the dental management of patients treated with bisphosphonates, and there are no published recommendations that specifically address paediatric patients. This paper aims to outline paediatric uses and adverse effects of bisphosphonates and present recommendations on the dental management of children receiving bisphosphonates.     

Osteoporosis and osteopenia: implications for periodontal and implant therapy

How does low bone mineral density alter treatment decisions? Osteoporosis and osteopenia are major health care issues that may impact on periodontal and implant therapy. Because of the prevalence of osteoporosis, understanding its etiology and the current treatment regimens for patients with low bone mineral density is essential for dental professionals. Millions of patients are now taking medications for the treatment of osteoporosis, and periodontists should be aware of the many medication options that are prescribed. The most frequently prescribed drugs are the bisphosphonates. It is important to be aware that bisphosphonates are not all the same, and patient responses to treatment may vary depending on which bisphosphonates they are taking. Due to recent concerns about bisphosphonate‐induced osteonecrosis of the jaw, this paper provides guidance to help the clinician regarding decision‐making about preventive and interventional dental treatment when their patient has been prescribed a bisphosphonate. An understanding of current bisphosphonates, their uses, their structural differences and their intended actions helps to improve clinical decision‐making. Current knowledge regarding the effects of osteoporosis/osteopenia on periodontal diseases and alveolar bone loss is inconclusive. It is certainly clear that bisphosphonates are not indicated as an adjunctive treatment as part of periodontal therapy because of the risk of osteonecrosis. Regarding implant placement, there are no convincing data that dental implant placement is contraindicated in the osteoporotic patient. However, patients should understand the small risk of compromised bone healing following implant placement if the patient has been taking bisphosphonates. Due to the risks of osteonecrosis, dental clinicians should work closely with their medical colleagues prior to the physician prescribing oral bisphosphonates. Ideally, optimal periodontal and dental health should be established before the patient commences bisphosphonate therapy.     

Longevity of dental implants in type IV bone: a systematic review

Bone quality and quantity are important factors with regard to the survival rate of dental implants. The aim of this study was to conduct a systematic review of dental implants inserted in low-density bone and to determine the survival rate of dental implants with surface treatments over time. A systematic review of the literature was undertaken by two independent individuals; the Medline/PubMed database was searched for the period July 1975 to March 2013. Relevant reports on bone quality and osseointegration of dental implants were selected. The search retrieved 1018 references, and after inclusion and exclusion criteria were applied, 19 studies were selected for review. A total of 3937 patients, who had received a total of 12,465 dental implants, were analyzed. The survival rates of dental implants according to the bone density were: type I, 97.6%; type II, 96.2%; type III, 96.5%; and type IV, 88.8%. The survival rate of treated surface implants inserted in low-density bone was higher (97.1%) than that of machined surface implants (91.6%). Surface-treated dental implants inserted in low-density bone have a high survival rate and may be indicated for oral rehabilitation. However, more randomized studies are required to better evaluate this issue.     

Osteonekrose der Kiefer unter Bisphosphonat-Langzeittherapie

For several decades bisphosphonates have been used to reduce skeletal related events in patients with both osteoporosis or bone metastases. Under long term application, besides the known therapy side effects, a new clinical picture has been described within the last few years. This is osteonecrosis of the jaws, which is characterized by its difficulty in treatment. Besides exposed jaw bone, the start of the disease usually lacks any symptoms. The typical clinical symptoms then are foetor ex ore, swelling, exsudation, loosening of teeth, pain or paresthesia. Later oro-antral/nasal or oro-cutaneous fistula can develop. The X-ray shows persisting tooth sockets after extractions and later cloudy radio-lucency, sequestra or fractures. The patient exposed to bisphosphonate can be grouped according to the risk for osteonecrosis: high risk patients with intravenous bisphosphonate therapy and additional chemo-, radiation or corticoid therapy – predominantly patients with a malignant underlying disease and bone metastases low risk patients with an oral bisphosphonate therapy without additional chemo-, radiation or corticoid therapy – preferably patients with non-corticoid-induced osteoporosis Before starting a bisphosphonate therapy possible causes of infection should be treated and risk of injuries to the mucosa should be reduced according to the individual risk profile. This is supplemented by information of the patient about the risk of necrosis and the possibilities for prevention. Regular dental recall under bisphophonate therapy is emphasised for early recognition of possible problems. Prophylaxis is recommended for the prevention of periodontal infection combined with a follow up of removable denture for possible ulcera. Generally, conservative treatment measures are preferred to surgical ones. Inevitable operations are carried out non- traumatically using broad spectrum antibiotic prophylaxis until the day of suture removal (not before day 10). Long term follow up examinations are recommended. Patients with dental implants inserted before a bisphophonate therapy should be subject to intensive recall examinations. For patients undergoing or following a bisphosphonate therapy the indication for dental implants should be as strict as for patients following head and neck radiation therapy. In the present for patients with osteonecrosis, even after healing, dental implants are regarded as contra-indication. Therapy of the necrosis often requires general anaesthesia, hospitalisation, naso-gastral feeding tube and intravenous, systemic antiinfective treatment. The necrosis is removed completely and a tension free wound closure with vascularised tissue is intended. A literature review shows the metabolic effect of biphosphonates, the known pathogenesis of the bisphosphonate-induced jaw necrosis. It is essential to develop interdisciplinary communication, aiming at a joint care for this group of concerned patients and involving not only those medical disciplines, which order and use bisphosphonates, but especially dentists and maxillofacial surgeons.     

Outcomes of Dental Implants in Osteoporotic Patients. A Literature Review

Purpose: This article reviews available data on the outcome of dental implants in osteoporotic patients.
Materials and Methods: A search was performed in PubMed and completed in July 2007. The keywords "dental AND implants AND osteoporosis,""dental AND implants AND age,""dental AND implants AND gender," and "dental AND implants AND bone AND quality," with no limitations for language or year of publication, resulted in 82, 598, 94, and 541 articles, respectively. After abstract scanning (in case of doubt the article was read), 39 nonreview articles studying dental implant outcomes in osteoporotic/osteopenic subjects remained for our review. The bibliographies of the 39 articles were also inspected, but no additional studies were identified.
Results: Thirteen of 16 animal studies found lower osseointegration rates in osteoporotic/osteopenic bone than in normal bone. Six in nine clinical reports mention success. Eight of 12 studies in humans support the applicability of dental implants in osteoporotic patients.
Conclusions: There are no data to contraindicate the use of dental implants in osteoporotic patients; however, a proper adjustment of the surgical technique and a longer healing period may be considered in order to achieve osseointegration. Data on the use of biphosphonates in osteoporotic patients and implant outcomes are very limited, and no conclusions can be drawn. In addition, large prospective studies investigating the long-term success of dental implants in osteoporotic individuals are required.     

Immediate loading with mini dental implants in the fully edentulous mandible

The use of immediate loaded prostheses is not recommended for at least 2 weeks to prevent implants from premature loading. In addition, immediate removable prostheses are negated for at least 4 weeks at the site of guided bone regeneration or bone graft. However, patients are often not pleased with limited diets and the unaesthetic appearance during the healing period without a denture between implant placement and final prosthesis. Mini dental implants provide stable and esthetic temporary prostheses immediately after implant placement and bone grafts. The use of mini dental implants is simple and cost effective because the patient's old denture is used as a provisional prosthesis. This article shows the success of 27 mini dental implants that were placed for 11 mandibular fully edentulous patients.     

Crestal bone loss and the consequences of retained excess cement around dental implants

Crestal bone loss around dental implants has been a subject of discussion in implant dentistry since its inception. Many of the research and design developments related to dental implants have sought to limit the amount of crestal bone loss. While there are a variety of possible causes for crestal bone loss around dental implants, one iatrogenic cause that has become the subject of several articles is retained dental cement. The focus of this article will be to discuss the predisposing factors that can lead to retained cement and clinical strategies to minimize or prevent cement peri-implantitis. Case reports are presented in which retained cement resulted in significant peri-implant inflammation and bone loss around restored dental implants. Strategies for early detection to limit the damage from retained dental cement and cementing techniques are also discussed.     

Use of alveolar distraction osteogenesis for implant placement: a case report with eight‐year follow‐up

Insufficient alveolar ridge width may impede the success of dental implants. Techniques for resolving this problem include autologous bone grafts, guided bone regeneration, bone splitting and bone spreading techniques. Recently, alveolar distraction osteogenesis has become an alternative method for alveolar augmentation. We propose the use of alveolar bone distraction for insufficient alveolar ridge width. A healthy 33‐year‐old female presented with missing teeth to our clinic. Clinical and radiographic examination revealed the alveolar ridge was too narrow for placement of dental implants. Therefore, horizontal distraction osteogenesis of the posterior mandibular ridge was chosen for augmentation. Two months later, two implants were placed. No significant marginal bone resorption was seen around the implants eight years after placement. Our results indicate that horizontal alveolar distraction is recommended to increase ridge width and allow placement of standard dental implants.     

Rehabilitation of a patient with cleft lip and palate with an extremely edentulous atrophied posterior maxilla using zygomatic implants: case report.

OBJECTIVE: This case report describes the clinical and surgical management of a patient with a unilateral alveolar cleft and associated extremely atrophied totally edentulous maxilla. METHOD: Two zygomatic implants and four endosseous oral implants were placed under general anesthesia in a compromised maxilla to rehabilitate a 33-year-old patient with cleft lip and palate. The two specially designed zygomatic implants were utilized to avoid the need for bone grafting in the patient. The final prosthetic rehabilitation was an esthetic and functional maxillary overdenture prosthesis supported by implants. RESULTS: Preliminary results have shown how dental prostheses supported by endosseous implants in grafted alveolar cleft are a reliable possibility in the dental rehabilitation of this malformation. CONCLUSION: The use of zygomatic implants may be considered a reliable alternative to more resource-demanding techniques such as bone grafting in patients with cleft palate.     

Osteonecrosis of the jaws: a secondary effect of bisphosphonates

When treated with intravenous bisphosphonates to prevent bone resorption, 4-10% of the patients may develop osteonecrosis of the jaws a side effect. The osteonecrosis is usually preceded by an invasive dental procedure such as the removal of a tooth. Treatment of the osteonecrosis should be conservative using aseptic mouth rinses, oral antibiotics and small debridement. It seems advisable to have a dental check-up before starting using intravenous bisphosphonates, since a potential dental infections can be treated before the bone healing capacity is reduced by the bisphosphonates.     

Oral bisphosphonate therapy and osteonecrosis of the jaw: what to tell the concerned patient

Bisphosphonate-associated osteonecrosis of the jaw (BONJ) is encountered predominantly in cancer populations being treated with high-dose intravenous bisphosphonates for skeletal complications such as bone metastases and secondary fracture risk. A minority of BONJ lesions have been observed in patients receiving oral bisphosphonates for management of osteoporosis or osteopenia. In this paper, the current knowledge pertaining to the incidence, definition, and signs and symptoms of BONJ is presented, followed by a discussion of the incidence and consequences of osteoporotic skeletal fracture and the use of oral bisphosphonates to mitigate fracture. The risk of BONJ appears to be very small in patients taking oral bisphosphonates. In addition, the consequences of osteoporotic fracture likely have significantly greater mortality and morbidity than BONJ. Within this context, management concepts and guidelines are presented to help the dental clinician allay concerns about BONJ expressed by patients receiving oral bisphosphonate therapy.     

引导骨组织再生技术应用于牙种植的临床观察

目的:临床观察引导骨组织再生技术在牙种植应用中的疗效。方法:对16例22枚牙种植区域的骨量不足及植入后的骨穿孔和骨缺损,采用人工骨、自体骨混合移植及生物胶原膜覆盖技术,促进和引导其骨形成从而完成牙种植术。结果:16例22枚牙种植体,全部成功,临床成功率为100%。结论:引导骨组织再生术的正确应用在牙种植方面是可靠而有效的。     

Bisphosphonate therapy for bone loss in patients with osteoporosis and periodontal disease: clinical perspectives and review of the literature.

As the baby boomer generation in the United States ages, more patients are using bisphosphonates for systemic bone diseases like osteoporosis. Because of their ability to inhibit bone resorption and osteoclastic activity, bisphosphonates may also be beneficial in modulating host response for periodontal disease management. This literature review examines the mechanism of action for bisphosphonates and their uses in treating periodontal disease. The dental profession should continue to evaluate this class of drugs and to closely monitor patients who are on bisphosphonate therapy.