Introduction

Dental implants have been used clinically in a routine manner to restore completely edentulous mandibles. A recent systematic review of the literature conducted by Bryant1 describes the 5-year cumulative survival rates of mandibular fixed and removable prostheses between 83% and 100%, with corresponding levels of crestal bone loss up to 1.1 mm the first year and 0.4 mm per year thereafter. The author included in his review studies using the classical two-stage surgical approach, whereby the implant is initially covered underneath the mucosa and kept unloaded for 4–6 months.2 However, over the past decade changes in dental implant design and surface configuration combined with an improved understanding of the biological and biomechanical aspects have improved the clinical outcome of implant treatments.3 These advancements have led to the one-stage surgical procedures in conjunction with earlier loading, especially in the completely edentulous mandible. Today there is evidence, although based on a small number of studies and relatively low patient numbers, that immediate loading can lead to survival rates comparable to conventionally loaded implants.4 

The ultimate goal of an immediate loading protocol is to reduce the number of surgical interventions and to decrease the timeframe between surgery and prosthetic delivery without sacrificing implant success rates. These new protocols will ultimately diminish patients' reservations and result in increased acceptance of implant therapy.

Before embracing the procedure as a routine treatment, the immediate loading technique needs to be validated with a significant number of clinical cases, extended follow-ups, and a clear definition of limitations. Because implant macrogeometry/microgeometry and the loading mode5 play a crucial role during the healing phase, it is important when documenting immediate loading cases to identify clearly the type of implant and rehabilitation used.

In two preliminary investigations, two patients treated in one of the centers of this study received both submerged and immediately loaded (IL) implants, according to a protocol adopted by Schnitman.6 The rationale for the Schnitman6 protocol was to provide the patient with a sufficient number of implants should all the IL implants fail. Both the submerged and IL implants had the hex abutment attachment placed above the bony ridge, in a so-called crestal position.7,8 These initial patients received provisional prosthesis supported by IL implants 4 hours after surgery. Following a surgical prosthetic procedure detailed in previous studies,9,10 2 submerged and 1 IL implant were retrieved after 2 months from one patient, and 2 IL implants were retrieved after 4 months from the second patient for histologic analysis. All the retrieved IL implants showed bone-to-implant contact at both timeframes, suggesting that immediate loading does not hinder implant osseointegration. Furthermore, no significant differences in crestal bone loss could be detected between the IL and submerged implants at any follow-up evaluation. As a result of these preliminary findings, we were encouraged to apply a similar protocol to a wider range of patients.

Therefore, we have set the goal of demonstrating the potential to completely rehabilitate the jaw with full-arch technique in 9 patients receiving oral bisphosphonate therapy for less than 3 years.

Jaw osteonecrosis and bisphosphonates

In 1993 Fleisch11 first cited bisphosphonates as an alternative to hormone replacement therapies for osteoporosis. More recently, it has become evident that the bisphosphonates used intravenously such as pamidronate (Aredia; Novartis Pharmaceuticals Corp., East Hanover, NJ) and zoledronate (Zometa; Novartis Pharmaceuticals Corp) and those used orally such as Risedronate (Actonel, Proctor & Gamble, Cincinnati, Ohio) and Alendronate (Fosamax, Merck, Whitehouse Station, NJ), in particular, could lead to painful refractory bone exposure (sometimes termed osteochemonecrosis or osteonecrosis) in the jaws, defined as bisphosphonate-induced osteonecrosis of the jaw (BONJ). Therefore, BONJ usually presents 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.12 Although the precipitating event that produces this complication may be spontaneous, there is little doubt that oral surgery and endosseous implants can be responsible.13 Exodontia is the main precipitant.14 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.15 Such a mechanism could presumably interfere with the healing process after implant placement.16 Although, to our knowledge, there is no evidence that bone disorders are a contraindication to implants, there is evidence that bisphosphonate therapy is a possible relative contraindication.17 

Bisphosphonates and osteoporosis

Although the exact mechanism of development of BONJ is not yet fully elucidated, there are several hypotheses. In most cases, the pathogenesis of this process is linked to a defect in the physiologic remodeling of the jaw or in the healing of the wound.13 The potent inhibition of the function of osteoclasts may decrease the normal bone turnover in both the repair processes of micro-trauma that result from normal mechanical loading and in sites where there has been a more invasive operation (such as a tooth extraction).14 That can be followed by bone necrosis. An important property of these drugs is the influence of bisphosphonates on the microcirculation: it has been shown that zoledronic acid has an inhibitory effect on the circulatory levels of vascular endothelial growth factor (an angiogenetic stimulator).18 This can have an effect on blood supply of the jaw bones. When the risk of osteonecrosis is increased, there is a greater ischemia and an altered bone metabolism with a decreased number of osteoclasts.19 

Use of bisphosphonate

The current widespread use of bisphosphonates as an inhibitor of bone resorption is directly attributable to their efficacy in improving the quality of life for patients with metastatic bone cancer, osteoporosis, and Paget's disease.15 

Bone metastasis to the axial skeleton, pelvis, femora, and ribs is a common occurrence for many malignancies.20 In a study on 1000 consecutive autopsies of people who died with metastatic diseases, 272 (27.2%) had metastatic osteolytic bone diseases. The most common tumors associated with bone metastasis are breast (73% of 167 patients), lung (32% of 160 patients), and renal (24% of 34 patients).21 

Myeloma-related lytic disease is now understood to be secondary to increased osteoclastic activity and impaired osteoblastic activity.22 Myeloma cells are known to be secret stimulators of both osteoclast activation, such as receptor activator of nuclear-kB ligand, and soluble molecules, such as Dickkopf-1 that inhibit osteoblastic activity.23 Bisphosphonates inhibit osteoclast function and therefore block the formation of “punched out” lytic bony lesions and consequent manifestations of lytic bony disease.24 In patients with osteolytic metastases, oral bisphosphonate therapy is as efficacious as the intravenous forms in preventing skeletal complications, and therefore both therapies can be used without distinction.25 

Osteopenia and osteoporosis are diseases that result from an unbalanced level of bone remodeling.26 The function and activity of osteoblasts and osteocytes are modulated by sex hormones, a variety of cytokines, and physiologic mechanical stress.27 Age-related changes in physical activity and sex hormones levels result in an increase in the number of osteoclasts and bone resorption sites.28 The final result is an overall decrease in bone mass and bone strength.

Osteoporosis is a great clinical problem worldwide, and it is responsible for over 1.5 million fractures in postmenopausal women each year in the United States.29 It is estimated that 35% of postmenopausal white American women have some degree of osteoporosis in the hip, spine, or forearm, and that 40% of these women will experience some type of osteoporotic fracture. This is in contrast to men over the age of 50: only 13% of them are estimated to have an osteoporotic disease.

In a case series, the long term use of steroids in conjunction with bisphosphonates has also been identified as a potential risk factor.30 The duration of bisphosphonate therapy also appears to be related to the likelihood of an individual's developing necrosis, with longer treatment regimens associated with a greater risk of developing disease.31 

In addition, the more potent intravenous bisphosphonates, such as pamidronate and especially zoledronic acid, appear to be significantly more problematic as compared with the oral bisphosphonate medications.32 In fact, patients who develop BONJ after receiving an oral surgical treatment, have been exposed to these agents for a long period of time (greater than 3 years), or were exposed to bisphosphonates and steroids at the same time.33 

Implants and bisphosphonates

The literature shows a benefit of bisphosphonates on the integration of dental implants in conjunction with a reduction of alveolar bone resorption and peri-implantitis.34 Studies on animals show an increase in mineralization of bone and the amount of contact surface bone-implant bone integration in cases treated with bisphosphonates, in particular alendronate or pamidronate, compared with untreated cases.3537 

We must consider that the first case of bone complications in the maxillofacial area that occurred during bisphosphonate therapy and described in the literature dates back to 1995 and concerns the failure of 5 implants, already osteointegrated and loaded some years earlier, due to a massive osteolysis in a patient treated for 6 months with alendronate.38 The case itself is of particular value for historical reference, as the presence of other important cofactors (prosthetic solution, occlusal loading, timing operational follow-up, exposure time, and type of bisphosphonate) establishes the cause-effect relationship between drug intake and the loss of the implant.

The aim of this paper was to show how a full-arch immediate loading rehabilitation in the mandible was possible in patients taking bisphosphonates.

Materials and Methods

Nine adult patients (8 women and 1 man) aged 45 to 68 years presented for rehabilitation of the mandible with a fixed prosthesis. All patients were nonsmokers with noncontributory medical histories. None of the patients had received chemotherapy or radiation. None of the patients were taking concomitant glucocorticosteroid therapy. All patients had confirmed osteoporotic disease (t-scan < 2.5), and they were being treated with oral bisphosphonates (Risedronate, 5 patients; Alendronate, 4 patients) for less than 3 years. Furthermore, all patients had residual teeth with severe periodontal disease. The study was conducted from January 2005 to June 2006 in accordance with the Helsinki Declaration of 1975, as revised in 2000. Subjects provided informed consent to participate in the study. A complete examination of oral hard and soft tissues was conducted for each patient. Panoramic radiographs (Figure 1) were taken of all patients, as were formatted computerized tomography scans when they were deemed clinically necessary. Diagnostic casts, wax-ups, and surgical template were also used as needed. The presence or absence of periodontal or periapical pathology had no bearing on patient selection.

Figures 1–4.

Figure 1. Start panoramic radiograph. Figure 2. (a,b) Intra-oral viewed. Figure 3. Implant placement. Figure 4 . Impression taken immediately after implant placement.

Figures 1–4.

Figure 1. Start panoramic radiograph. Figure 2. (a,b) Intra-oral viewed. Figure 3. Implant placement. Figure 4 . Impression taken immediately after implant placement.

Success criteria

The following success criteria were applied in evaluating each implant: (1) no clinically detectable mobility when tested with opposing instrument pressure; (2) no evidence of peri-implant radiolucency on periapical radiographs; (3) no recurrent or persistent peri-implant infection; (4) no complaint of pain at the site of treatment; (5) no complaint of neuropathies or paraesthesia; (6) no soft tissue swellings; and (7) no osteonecrotic lesions.

Clinical procedure

Preoperative management included: (1) suspension of bisphosphonate therapy 1 month before the surgery; (2) antibiotic prophylaxis before surgery (1 g amoxicillin 2 times a day to start the day before the surgery); (3) oral rinse with chlorhexidine 0.20% (3 times a day to start 1 week before the surgery).

Regarding surgical and prosthesis management, all patients received tapered screw-shaped Way implants (Geass, Pozzuolo del Friuli, Italy) with a Syntegra surface.

The surgical protocol treatment followed in our procedure was the one described in the literature for crestal implant placement.7,8 All clinicians followed the implant manufacturer's instructions for implant site preparation and implant insertion procedure. The initial primary stability was assessed by setting the insertion torque of the surgical unit and recorded according to the following classifications: “tight” when torque was ≥32 Ncm, “firm” torque was between 25 and 32 Ncm, or “loose” when torque was <25 Ncm.9 The length and the diameter of the individual implants could vary from subject to subject, depending upon bone quality and quantity at each surgical site.

The treatment objective involved delivery of the full-arch prosthesis within 48 hours of implant placement, by utilizing the prosthetic procedure that best suited the clinical case.

The design of the prosthesis was determined by a collaborative effort between the surgeon, the restorative doctor, and the patient, as long as the outcome was consistent with the study's objectives.

Surgical steps included: (1) local anesthesia (Scandonest 3% mepivacaine hydrochloride 54 mg); (2) atraumatic extraction of the teeth and careful debridement of the socket to remove any granulation tissue and any periapical lesion that was evident; and (3) placement of no. 6 fixtures for patients (it was possible if you used the flapless technique) (Figures 2a,b and 3).

Prosthetic steps included: (1) impressions taken immediately after implant placement (Figure 4); (2) placement of healing cuppings on the implants and sutures around them; (3) trying of the metal structure of the full-arch 24 hours after implant placement (Figure 5); and (4) placement of the definitive full-arch 48 hours after implant placement (Figures 6 through 8). The occlusal contacts were evenly distributed on all teeth including the teeth on the cantilevers, which were maximal one-tooth-long to minimize the risk for fractures. Within 48 hours after finalizing the surgery, the full-arch bridges were screwed into place and finger tightened. Minor adjustments were needed in order to achieve maximal occlusal contacts and bilaterally balanced group function in articulation.

Figures 5–7.

Figure 5. The metal structure of full-arch was tried after 24 hours of implant placement. Figures 6 and 7. The definitive full-arch was placed after 48 hours.

Figures 5–7.

Figure 5. The metal structure of full-arch was tried after 24 hours of implant placement. Figures 6 and 7. The definitive full-arch was placed after 48 hours.

Figures 8–10.

Figure 8. Postoperative panoramic radiograph. Figure 9. One-year follow-up panoramic radiograph. Figure 10. Two-year follow-up panoramic radiograph.

Figures 8–10.

Figure 8. Postoperative panoramic radiograph. Figure 9. One-year follow-up panoramic radiograph. Figure 10. Two-year follow-up panoramic radiograph.

Postoperative management included (1) suspension of bisphosphonate therapy 1 month after the surgery; (2) antibiotic therapy after the surgery (1 g amoxicillin 2 times a day for 1 week); (3) chlorhexidine 0.20% rinses (3 times a day for 1 week after the surgery); (4) ibuprofen 600 mg or paracetamol 500 mg for pain relief at the patient's own discretion; and (5) removal of the sutures after 1 week.

Oral hygiene was reinstructed with the soft manual toothbrush and additionally with appropriate-sized interdental brushes.

With regard to clinical and radiographic follow up, no specific diet was recommended to the patients. The patients were on a strict recall program during the first 6 months: every week during the first month, and every month between the second and sixth months. Patients were followed thereafter at 12 and 18 months postloading, and then on a yearly basis.

Orthopantograms and periapical radiographs were obtained for image analysis at implant insertion. Panoramic radiographs were also performed subsequently, after 2, 6, and 12 months of occlusal loading (Figures 9 and 10), and yearly thereafter.

Results

In total, 54 implants were installed (19 in fresh extractive sockets) (Table 1); 9 of 15 mm length, 26 of 13 mm length, and 19 of 10 mm length. The implant diameter was 4.5 mm in 34 implants and 3.8 mm in 20 implants (Tables 2 and 3). All implants were mechanically and manually installed with the applicable insertion torque.

Table 1

Missing teeth (X) and extracted teeth (E)*

Missing teeth (X) and extracted teeth (E)*
Missing teeth (X) and extracted teeth (E)*
Table 2

Number of implants and length

Number of implants and length
Number of implants and length
Table 3

Number of implants and diameter

Number of implants and diameter
Number of implants and diameter

Thirty-two implants (59.3%) were placed in the interforaminal area that scored dense or normal bone quality, utilizing an insertion torque ≥32 Ncm (tight). Twenty-two additional implants (40.7%) were inserted into areas distal to the foramen that scored soft bone, utilizing a torque between 25 and 32 Ncm (firm) (Tables 4 and 5). No deviations from the protocol were reported. Patients' subjective assessments in relation to the type of treatment received were favorable overall. No subjective complaints were reported throughout the follow-up period. After 2 years of loading, all implants were checked and all were found to be clinically stable without signs of infection. The clinical survival rate is 100% in this interval. In the same period no soft tissue swellings and no osteonecrotic lesions were noted.

Table 4

Number of implants and site of placement

Number of implants and site of placement
Number of implants and site of placement
Table 5

Type of implants and site of placement

Type of implants and site of placement
Type of implants and site of placement

Discussion

There are 3 considerations to be taken into account. First, there is a tendency in medicine to reduce the treatment time and simplify the treatment in order to increase patient acceptance and reduce the risk of complications. Treatment simplification for implant dentistry might be obtained either by early9,10,3941 or by immediate loading procedures.4247 The key difference between the two approaches is that early loading can be applied on a routine basis and is also suitable for the treatment of unilateral cases. Early loading has been made possible by using textured surfaces that promote osseointegration.9,4852 By contrast, immediate occlusal loading procedures can be successful only when the amount of micro-motion at the bone-implant interface is kept beneath a certain threshold during the healing phase.5 Several studies have reported higher failure rates for IL implants when compared with delay-loaded ones.41,42,46,47 This shows that this procedure, although predictable, is technique-sensitive and should be applied cautiously.

Secondly, for patients taking oral bisphosphonates, the factor that significantly increases their risk of developing osteonecrosis of the jaws is the duration of continuous oral bisphosphonate therapy: treatment of 3 years or more is associated with progressively increased risk.

The first risk factor is concerning because oral bisphosphonates are intended for ongoing use over several decades. Since 2000, the use of oral bisphosphonates has increased steadily, particularly in otherwise healthy postmenopausal women. Many individuals in this population have already exceeded the 3-year threshold and will likely continue on oral bisphosphonates for many more years. Moreover, patients who took an oral bisphosphonate for 7 years or longer had greater amounts of exposed bone and more severe symptoms.

A source of information for bone turnover marker is the serum test C-terminal cross linking telopeptide that measures the rate of bone turnover.53,54 This test does not give values of predictability regarding BONJ in an individual patient, but can identify the area of greatest risk where we can demonstrate this phenomenon. Normal or minimal risk values (ie, ≥150 pg/mL) are seen in patients taking an oral bisphosphonate for a period of less than 3 years, while values associated with higher risk (<100 pg/mL) begin to register in patients taking an oral bisphosphonate regularly for more than 3 years.

Conclusion

Rehabilitation of the edentulous mandible in patients with osteoporosis who are receiving oral bisphosphonate therapy by an immediate occlusally loaded full-arch prosthesis, supported by 6 Way Syntegra implants, is a viable alternative treatment to the classical delayed protocols.

Abbreviations

     
  • BONJ

    bisphosphonate-induced osteonecrosis of the jaw

  •  
  • IL

    immediately loaded

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