Survival of Dental Implants Among Post-Menopausal Female Dental School Patients Taking Oral Bisphosphonates: A Retrospective Study

Pouran Famili, DMD, MDS, MPH, PhD; Sean Quigley; and Timothy Mosher, DMD

Osteoporosis is a common bone-resorptive, host-dependent, multifactorial systemic skeletal disease generally affecting older adults. Characterized by reduced bone strength, decreased bone mineral density, and altered bone morphology, the disease results in increased risk of bone fracture. Because dental implants are a viable treatment option for an increasingly older population, investigators have focused on implant success and longevity in people with diagnosed osteoporosis or osteopenia. Endosseous dental implants have high long-term success rates when used for replacing fully, partially, or single-tooth edentulous spaces in the oral cavity, and successful outcomes can be expected when implants are placed in bone of sufficient quality and quantity and good surgical technique is used. Individuals with osteoporosis may have decreased alveolar bone height and greater tooth loss compared with a population that does not have osteoporosis. Osteoporosis may be a risk factor for implant loss or, conversely, implant placement may protect against alveolar bone resorption by stimulating continuous bony remodeling and, thus, may protect against oral bone loss. However, more research and knowledge are needed to confirm this statement.¹ Added to the clinical dilemma are mixed reviews regarding the oral safety implications of bisphosphonates, which have been used for years to treat resorptive bone diseases such as osteoporosis and suppress bone resorption and bone turnover.

Ninety-nine percent of body calcium is stored in bone. In sustained negative calcium balance, the body will resorb bone-supporting structures to the point of spontaneous failure. When a tooth is lost, that part of the jawbone becomes no longer functional, the nature of the jawbone changes, and the jaw falls into atrophy. On the cellular level, bone resorption is initiated by the inflammatory process that accompanies tooth loss. Proinflammatory cytokines (IL-1, IL-6, TNF-α) incite preosteoclasts into the area of bone resorption, where they differentiate into active osteoclasts. Osteoclasts take possession of the ruffled membrane and clear zone to ensure that resorption remains localized, maintaining the pH-regulated proton pump in the bone resorptive microenvironment. Basal bone in jaws and the alveolar process is highly subject to metabolically driven bone atrophy.²

Insertion of one endosteal implant within the residual alveolar ridge calls forth the formation of substantial new bone in response to function.³ This is clearly seen on a standard dental radiograph. New trabeculation surrounds the inserted implant in function, and there is a lack of trabeculation in areas further away from the implant. It is this reorganized bone following healing and early function that will support the implant long-term.

European researchers⁴ use the concept biocybernetic feedback circuit of the masticatory system to explain the interaction of the trabeculae realigning themselves in direct response to the direction, magnitude, character, and duration of the forces created by implant placement. Simply put, an implant helps to restore the system that has been interrupted by tooth loss, which changes the structure of the jawbone.

Bone morphology⁵ describes functional mechanical forces. The mandible is subject to vertical atrophy and oral aspect resorption, with bone collapsing and disintegrating along the vertical plane. Mandibular bone destruction mostly occurs where bone holds the teeth and gingiva in the front lower jaw. The maxilla is subject to horizontal atrophy, and resorption is to the vestibular aspect, or toward the mouth cavity outside the teeth and gingiva. Biologically, the mandible is more compact bone, while the maxilla is spongier.

Several investigators^1,6-13 have used dual-emission X-ray absorptiometry (DXA) imaging techniques to investigate osteoporosis in the jaw and have concluded that quality and mass of mandibular bone is mostly correlated with retained dentition. Mandibular cortical erosion seen even visually on a panoramic radiograph can be a diagnostic tool for general dental practitioners to gauge undetected low skeletal bone mineral density,^11-13 and computer-aided systems¹¹ may generalize results. General mineral status in postmenopausal women affects both cortical and trabecular bone. Mandibular cortical bone correlates with the third lumbar vertebrae in long-term postmenopausal women.⁹

Some practitioners theorize it is important to replace missing teeth with implants to ensure function by duplicating loading, thus ensuring bone density.^1,14,15 The implant prosthesis is not contraindicated for people with osteoporosis, provided the general systemic condition is controlled, bone manifestation is monitored, and the pharmacotherapy for the condition is accurately administered.¹⁴ This clinical opinion seems to be shared by the majority of dental practitioners and is upheld in seminal research.^16,17

Nevertheless, the subject of dental implants in individuals with osteoporosis—and even more compellingly, among individuals, particularly the elderly and frail, on long-term high-dose intravenous bisphosphonate treatment—remains under scrutiny by the US federal government, dental practitioners, and the drug-development industry. In this retrospective review of the dental implant-placement electronic health records (EHRs) at the University of Pittsburgh School of Dental Medicine, the authors hypothesized that osteoporotic patients who take oral bisphosphonates have a higher chance of developing osteonecrosis of the jaw if they receive dental implants.

Materials and Methods

A retrospective review of the online dental–medical patient EHRs, focusing on survival, complications, and oral bone quality among women with osteoporosis receiving dental implants at the University of Pittsburgh, was approved in August 2009 by the University of Pittsburgh Institutional Review Board.

Among a total of 211 women receiving 592 dental implants in the University of Pittsburgh's Multidisciplinary Implant Center during the study period January 2008 through June 2010, 120 of the patients were identified as over the age of 50, receiving 347 implants. The medical records of all women over age 50 who had received dental implants were searched for notation of clinical evidence of osteonecrosis of the jaw. None of the women had ever received intravenous bisphosphonate treatment for their bone quality condition at any point in time.

Datapoints regarding patient-level and implant-level indices were extracted from the combined online dental and medical records at the University of Pittsburgh School of Dental Medicine using axiUm™ dental management software (Exan Academic, www.exanacademic.com). Patient-level data collected were: 1) age of patient; 2) diagnosis of osteoporosis or osteopenia; 3) history of bisphosphonate use; 4) smoking status; 5) diagnosis of diabetes; and 6) history of other medication. Implant-level data collected were: 1) number of implants placed; 2) type of implants; 3) location of implants; 4) size or diameter of implants; 5) length of implants; and 6) survival or time to failure of the implant device.

Over 50 years of age was recognized as arbitrary criterion for status of postmenopause. Survival of each implant was documented by its presence or absence in the oral cavity. Implant failure was recognized upon subsequent placement of a second implant in a location previously implanted. For each implant, the duration of follow-up was calculated from the time of placement to the date of failure or date of last follow-up in the specified time period.

Initial descriptive analyses included bisphosphonate users' demographic and medication characteristics. Mean, standard deviations (SD), and percentages were used as descriptive statistics. Logistic regressions were used to compare implant patients with and without osteopenia/osteoporosis and also with and without bisphosphonate therapy. Regression-adjusted models included variables (age, race, smoking, weight, dietary calcium intake) known to influence bone density, as well as the set of variables already being controlled.

Results

Only women taking oral bisphosphonates were included in the research. Among the total 211 patients, 120 were over the age of 50, receiving 347 implants. Twenty-two of those women reported taking oral bisphosphonates as treatment for osteoporosis; one individual reported taking oral bisphosphonates as treatment for osteoarthritis. Five additional women reported taking alternative medications instead of bisphosphonates as treatment for diagnosed osteoporosis. Seventy-five implants were placed in the 22 women who self-reported osteoporosis and oral bisphosphonate treatment, and seven implants were placed in osteoporotic women who did not self-report oral bisphosphonate treatment. There was no evidence of osteonecrosis of the jaw in the follow-up medical records among either set of patients. Of the 82 implants placed in osteoporotic patients, only one implant did not osseointegrate and was replaced within 1 year. This 98.7% success rate is consistent with standard implant success rates.

Time-length of exposure to bisphosphonates/treatment with bisphosphonate therapy was:

• >/< 6 months up to 1 year: six patients
• 1 year or more: nine patients
• more than 5 years: five patients (one record not listing length of treatment)

Fosamax™ was the most frequently prescribed bisphosphonate (15 occurrences); Boniva™, Fosamax™ to Boniva,™ and vice versa had one occurrence each; and Actonel™ had four occurrences.

Among the 82 implants placed in osteoporotic patients, only one, which was placed in a woman who reported a history of bisphosphonate use, failed to osseointegrate. At placement in 2008, this implant that ultimately failed was reported to reach primary stability during the first part of a standard two-stage implant placement procedure. Postoperative examination revealed healing within normal limits, and it was not until the abutment insertion stage that failure to osseointegrate was identified. One year later an implant of the same manufacturer, size, and diameter (narrow-platform 3.5 mm) was placed in the same location in the maxilla as the failed implant, and, according to the patient's medical record, has remained stable without failure or contraindication.

Discussion

After nearly three decades of experimentation, rates of success in dental implant placement are consistently high, routinely exceeding 95% at 5 years.¹⁸ Practicing implantologists insist that failures are rare and can be overcome by expert clinicians and motivated patients. Implant loss will cluster in a few patients, and early failures are the most common. Implants in the maxilla will fail more often, particularly if many are placed at the same time. Failing implants exhibit increased mobility and radiolucencies, and half the time show significant (> 6 mm) pocket depths.¹⁹ Twenty years ago, pioneers in the field of oral implantology had already clearly identified²⁰ the factors that lead to implant success: surgery without compromise in technique; sound bone; avoiding thin bone or implant dehiscence; keeping the implant covered during healing; balanced restoration; and adequate follow-up hygiene. Keratinized gingiva is a key indicator of maximum soft- or hard-tissue health.^21,22 Poor bone quality, chronic periodontitis, systemic disease, smoking, unresolved caries or infection, advanced age, implant location, implants that are too short, acentric loading, inadequate number of implants, and the patient's parafunctional oral habits best predict implant failure.²³ Study of a 10-year retrospective cohort¹⁷ achieved concurrent results, especially regarding smoking, age (failures increase over age 60), and systemic conditions (diabetes, postmenopause, and head and neck radiation predispose to failure), but concluded that overall dental implant failure is low and no absolute contraindications can be stated.

It is noteworthy that no evidence of bisphosphonate-associated osteonecrosis of the jaw—exposed bone for more than 8 weeks in a maxillofacial region that does not have a history of radiation therapy—appeared in the medical records of any of the 211 women receiving implants in this study. These data are encouraging to the clinician and patient confronted with the question of whether to proceed with dental implant placement even when the patient has a history of bisphosphonate use. All implants studied were placed using a surgical flap and standard surgical procedure; no osteonecrosis of the jaw was observed in any. Marx et al²⁴ has suggested that osteonecrosis of the jaw is more likely to occur in patients with a history of prolonged (> 3 years) bisphosphonate use and that placement of dental implants in such individuals is strongly discouraged. Some subjects in this research had taken prescribed oral bisphosphonates for periods of time greater than 5 years and yet this group was not found to be more susceptible to implant failure or osteonecrosis of the jaw.

Dental extraction is the most common predisposing event to trigger the development of osteonecrosis of the jaw due to bisphosphonate use. These data reveal that although the dental implant surgery was performed using a flap surgical procedure, this invasive surgical protocol did not increase the subjects' risk of implant failure or predispose the subjects to osteonecrosis of the jaw.

The possible etiology of osteonecrosis of the jaw and certainly the most often-cited rationale for this malady is reduced bone turnover. Still, understanding the risk and incidence, etiology, prevention, and management of osteonecrosis of the jaw remains unclear and requires further investigation. The space between an implant and an osteotomy site is very small and the amount of bone needed to fill in this space is much less. Gingival tissue over an implant or around a transmucosal component prevents debris and plaque from reaching the host–implant interface. At the same time, not all dental surgeries pose a risk for developing osteonecrosis of the jaw, so the chance of developing this condition after placement of dental implants is very low. The evidence of this study—that none of the implanted patients developed osteonecrosis of the jaw—supports the conclusion that "drug holidays" away from bisphosphonate treatment are unnecessary in individuals with a bisphosphonate medication history who are scheduled to receive dental implants.

Dental implant treatment and placement for edentulous spaces in the maxillary and mandibular ridges has improved substantially in 30 years of investigation. Success rates over 95% for up to 10 years post-implantation are common. Refinement in surgical technique and improvement in implants themselves will serve to keep implantology at the forefront of dentistry for years to come. Both implant surgical technique and the devices themselves continue to demand further investigation.

Conclusion

Within the limitations of the study design, the following conclusions can be upheld:

• Dental implants placed in the jawbones of postmenopausal women with a medical history of osteoporosis or a medication history of bisphosphonate use, whether for the treatment of osteoporosis or not, have an excellent survival profile.
• No evidence of osteonecrosis of the jaw was seen in the medical record of any women recipients of dental implant placement therapy at the University of Pittsburgh through the 3-year period of electronic dental-medical recordkeeping at the school. Included in this set are postmenopausal osteoporotic women receiving bisphosphonate therapy and women receiving bisphosphonate therapy for other medical conditions.
• Dental implants can be placed confidently in postmenopausal osteoporotic women receiving oral bisphosphonate therapy in treatment for osteoporosis.

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About the Authors

Pouran Famili, DMD, MDS, MPH, PhD Professor
Chair
Director of the Residency Program
Department of Periodontics and Preventive Dentistry
University of Pittsburgh School of Dental Medicine
Pittsburgh, Pennsylvania

Sean Quigley
Fourth-Year First Professional
University of Pittsburgh School of Dental Medicine
Class of 2011
Pittsburgh, Pennsylvania

Timothy Mosher, DMD
First-Year Resident
Department of Periodontics and Preventive Dentistry
University of Pittsburgh School of Dental Medicine
Pittsburgh, Pennsylvania