Dental implants in a patient with Paget disease underbisphosphonate treatment: A case reportJesús Torres, DDS, PhD,a Faleh Tamimi, DDS, PhD,b Ignacio Garcia, MD,a

Alicia Herrero, DDS,a Begoña Rivera, DDS, PhD,a Jose Andrés Sobrino, MD, DDS, PhD,a andGonzalo Hernández, MD, DDS, PhD,c Madrid, Spain; and Montreal, CanadaREY JUAN CARLOS UNIVERSITY, McGILL UNIVERSITY, AND COMPLUTENSE UNIVERSITY

Paget disease (PD) is an idiopathic disorder characterized by progressive enlargement and deformity of bones,resulting in structural weakness that may be unfavorable for the placement of osseointegrated dental implants.Currently, bisphosphonates are administered for the treatment of PD. However, the use of bisphosphonates has beenassociated with the onset of osteonecrosis of the jaws. This report deals with a case of a 64-year-old caucasian womandiagnosed with polyostotic PD 17 years earlier who had been treated with bisphosphonates for 7 years. The patientwas referred for implant treatment, and after initial placement of 6 fixtures, the postoperative course was uneventfuland no complications were registered during a follow-up period of 4 years. Within the limitations of this case, wereport that dental implants can be successfully placed and loaded in patients suffering from PD without discontinuingthe treatment with bisphosphonates, as long as the patient is not complaining from any additional unfavorableconditions. To the best of our knowledge, this is a unique case describing the successful placement of dental implantsin a patient with PD treated with bisphosphonates. Nevertheless, more studies would be needed to optimize theclinical guidelines for the treatment of these patients. (Oral Surg Oral Med Oral Pathol Oral Radiol Endod 2009;107:

387-392)

The use of osseointegrated implants shows high long-term success rates when used for rehabilitation of fullyedentulous, partially edentulous, and single tooth re-placement.1-3 Success of osseointegration dependsmainly on the state of the host bone bed (quality andquantity) and its healing capacity. The influence of thebone quality on the outcome of dental implant treat-ment has been discussed in several studies, and a higherfailure rate has been found in patients with soft bonequality, sometimes together with small inadequate bonevolumes.4-7 Moreover, systemic factors may affect thebone healing around dental implants.8-10 However, de-spite a reduced success rate, unfavorable systemic con-ditions are not always absolute contraindications forbone augmentation and dental implant placement.11

First described in 1876 by Sir James Paget, Pagetdisease (PD) of bone, or “osteitis deformans,” is char-

Supported by DGI, Spanish Science and Education Ministry, contractgrant no. MAT2006-13646-C03-01, FECYT MEC-Fulbright, and theCAM-UCM Program (CCG06-UCM/SEM).aDepartment of Health Sciences III, Faculty of Health Sciences, ReyJuan Carlos University.bDepartment of Dentistry, McGill University.cDepartment of Oral Medicine and Surgery, Faculty of Dentistry,Complutense University, Madrid.Received for publication Sep 1, 2008; returned for revision Nov 17,2008; accepted for publication Nov 17, 2008.1079-2104/$ - see front matter© 2009 Mosby, Inc. All rights reserved.

doi:10.1016/j.tripleo.2008.11.024

acterized by a disruption of the normal bone remodel-ing process resulting in a softer and weaker bone.12-14

Paget disease displays important geographical varia-tions, showing a high prevalence in the United King-dom (5%),15 Australia (3.6%),16 and North America(3.9%)17 and a lower prevalence (0.5%-1.1%) in Scan-dinavia, Spain, and Italy.18 The disease usually occursafter the age of 40 years and is more prevalent in menthan in women (3:1).15 Its etiology is still unknown;however, the presence of virus-like inclusions in oste-oclast nuclei has led to the development of a viralhypothesis.19,20 Paget disease may affect any bone andcan be present in one or multiple bones. The structureof pagetic bone is chaotic and consists of irregularwoven anarchic trabeculae or osteons. The pagetic wo-ven bone is less resistant but more elastic than normallamellar bone, and, as a result, affected bones are largeand dense but weak and brittle, and may suffer de-formities according to applied mechanical forces.13

Accordingly, these patients have been traditionally con-sidered to be unsuitable for treatment with osseointe-grated implants.

Paget disease is often asymptomatic, and only �5%of affected patients present the main clinical features ofbone pain, deformity, and fractures.13 When PD affectsthe jaws, the most frequent complications are associ-ated with dental extractions.21 The presence of hyperce-mentosis and ankylosis often requires surgical extrac-

tion of teeth which may be complicated by excessive

387

OOOOE388 Tamimi et al. March 2009

bleeding in the vascular lytic phase of the disease, orpostoperatively by poor healing and infection in theavascular phase.22

Bisphosphonates are used for successful treatment ofpatients with osteoporosis and PD, especially in caseswith elevated disease activity. Nevertheless, the use ofbisphosphonates has been associated with the outbreakof osteonecrosis of the jaws (ONJ) after surgical pro-cedures in the oral cavity.23-25 Therefore, even thoughlong-term treatments with oral bisphosphonates haveappeared to have no effect on ONJ onset after implantplacement procedures, patients taking bisphosphonateshave been a cause of special concern in the dentalclinic. 26

Herein we describe a case of active PD treated withoral bisphosphonates where dental implants were suc-cessfully placed. To our knowledge, no other caseshave been reported describing the placement of dentalimplant in patients presenting both systemic unfavor-able conditions.

CASE REPORTA 64-year-old nonsmoking white woman was referred in

May 2003 to the Department of Health Sciences III, Rey JuanCarlos University, for implant treatment. Her past medicalhistory was significant. In 1986 she was diagnosed withpolyostotic PD. Her initial symptoms included diffuse painsin the cervical bones and moderate level of hearing loss.Radiologic exams showed the involvement of several bones,including cranial and facial bones, and blood analysis re-vealed augmented alkaline phosphatase levels in serum (192mg/dL; normal range 32-92 mg/dL). The serum calcium was3.5 mg/dL (normal range 4.0-5.5 mg/dL), the phosphoruslevel was 3.9 mg/dL (normal range 2.5-4.6 mg/dL), and urinehydroxyproline was 35 mg/g (normal range �20 mg/g). Otherparameters were within normal limits.

In June 1986, initial treatment with calcitonin ampules (100UI/day; Miacalcic; Novartis Pharmaceuticals, Basel, Switzer-land) was started, but it was replaced with sodium risedronatetablets (35 mg/week; Actonel; MS&D Pharmaceuticals,Whitehouse Station, NJ) in February 1996, which was main-tained until present. No other drugs or hormones had beenadministered, and she did not present with any other systemicdisorder or history of tobacco use. During the precedingdecade, the patient had received regular medical examina-tions, and the disease was currently stable.

An intraoral examination revealed the presence of a bilat-eral edentulous upper posterior alveolar ridge with an over-lying healthy mucosa. The patient was wearing a partialdental prosthesis. The panoramic radiograph and computer-ized tomographic images revealed several low bone densityareas in the posterior maxilla and a favorable bone dimensionof 4 mm width and 10-13 mm length (Figs. 1 and 2).

The treatment plan included the placement of 6 fixtures(Biomet 3i, Palmbeach Gardens, FL), 3 in the right and 3 inthe left posterior maxilla, to support a fixed prosthesis. After

local anesthesia, ridge incisions with vertical releasing inci-

sions were carefully performed, and the fixtures were placedfollowing the routine surgical protocol. During the surgicalprocedure, bone density was observed to be soft and severalbone cavities were noticed. A bone biopsy from the leftsecond molar region (on the same spot the implant was to beplaced), was taken using a trephine bur (2.0 mm diameter �10.0 mm length), and sent for histopathologic examination.After insertion, all implants presented good primary stability.Continuous sutures were used to close the flap, and antibioticswere prescribed (amoxicillin 750 mg, 3 times a day; Clam-oxyl; GlaxoSmithKline, Middlesex, U.K.). After 7 days thesutures were removed, and the antibiotics were maintained for3 more days. The patient recovered without postoperativesigns of infection and showed no impairment in the wound-healing process. Subsequent appointments showed normalhealing of soft and hard tissues. Microscopic examinationrevealed the replacement of marrow spaces by fibrovasculartissues, and irregular bony trabeculae surrounded by numer-ous osteoblasts and osteoclasts, indicating increased activity(Fig. 3). These microscopic findings were consistent with PD.

Six months after the surgery, all implants were loaded with2 bridges of 4 units each (Fig. 4), and the patient wasfollowed for a period of 4 years. No clinical mobility or signsof looseness were observed, and the implants were success-fully functional after 4 years. Normal marginal bone resorp-tion (i.e., 0.5 mm) was found radiographically (Fig. 5), andsoft peri-implant tissues showed no signs of inflammation.

DISCUSSIONBone and soft tissue response after implant place-

ment is modulated by intrinsic factors (i.e., wound-healing factors, biomechanics, and mineral metabo-lism) which can be modified by several systemicconditions.10 Numerous studies have reported the sig-nificance of systemic disorders as contraindications fordental endosseous implant treatments. Absolute contra-indications for implant rehabilitation include recentmyocardial infarction, cerebral-vascular accidents, val-vular prosthesis surgery, immunosuppression, bleeding

Fig. 1. Panoramic radiograph before the treatment revealsirregular areas where altered amounts of bone with radiolu-cency and radiopacity areas can be noted.

issues, active treatment of malignancy, drug abuse,

affected bone.

�20).

OOOOEVolume 107, Number 3 Tamimi et al. 389

psychiatric illness, and intravenous bisphosphonate up-take.27,28 On the other hand, relative contraindicationsinclude adolescence, advanced age, smoking, diabetes,

lar resorption cavities with an increased radiolucency of the

Fig. 4. Panoramic radiograph 1 year after treatment, showingsuccessful osteointegration of the implants.

Fig. 2. Dental scan tomography images at the first visit show irregu

Fig. 3. Microscopic appearance of the patient’s pagetic bone,showing the typical mosaic pattern (original magnification

positive interleukin-1 genotype, human immunodefi-

OOOOE390 Tamimi et al. March 2009

ciency virus positivity, cardiovascular disease, and hy-pothyroidism.27-32 Systemic conditions that affect thequality of maxillary bones, such as osteoporosis andPD, are also considered to be relative contraindicationsfor dental implant placement that must be taken intoconsideration in the treatment planning.8-10

So far, only 1 case has been reported describing theplacement of dental implants in patients with PD inremission,33 but none in patients with PD treated withbisphosphonates and in the intermediate stage of thedisease, when osteolytic and osteoblastic features cometogether.33 Accordingly, the combination of these 2factors deserves particular consideration in the presentcase report: 1) the unfavorable bone quality due to PD;and 2) the use of bisphosphonates, which are known tobe implicated in serious complications after oral bonesurgery. Nevertheless, the patient did not suffer fromany additional relative or absolute contraindication fordental implants. Therefore, the results observed in thiscase should be interpreted with respect to patients wholack other conditions besides PD and bisphosphonateuse.

Paget disease is characterized by an abnormal bonestructure, featuring an extremely anarchic bone remod-

Fig. 5. Dental scan tomography images 4 years after treatmpagetic bone throughout. The radiolucent regions approximatiwas not disrupted.

eling caused by pathologic osteoclast activity that cre-

ates multiple profound resorption cavities in the bonematrix during its initial osteolytic stage.14 Accordingly,delayed healing has been observed in PD patients aftertooth extractions,34-36 and bone deformities have beenobserved, mainly in long bones.13

Primary implant stability plays a major role in suc-cessful osseointegration, and it depends largely on localbone quality and quantity as well as on an appropriatedental implant and surgical technique.30 In the presentcase, the poor quality of the maxillary bone caused bysevere PD may have been a serious problem for implantstability and osteointegration. However, similarly toosteoporosis, another, more frequent, disease affectingbone quality,31,32 a delicate noninvasive surgical tech-nique and an adequate dental implant helped to achieveprimary stability in the abnormal pagetic bone. It ap-peared to be that the continuous remodeling process ofthe pagetic bone, may have provided the bone supportneeded for long-term implant stability.

Paget disease is usually treated with bisphosphonatesand calcitonin, and surgery is reserved only for com-plications related to PD-induced mechanical alterationsof bones (tumor deformation, tumor compression) andjoints (arthoplasties).22,37 However, many of the com-

eal radiolucent regions surrounding the implants and denseimplants represent osteolytic areas; however, implant stability

ent revng the

plications caused by PD described in the literature

OOOOEVolume 107, Number 3 Tamimi et al. 391

might be caused by the antiangiogenic effect of thepharmacologic treatments as well.23

Bisphosphonates are widely used in treating cancer,osteoporosis, and PD, among other systemic disorders.However, these treatments have been strongly associ-ated with ONJ. Little is known regarding the appropri-ate guidelines for dental implant therapy in patientsundergoing bisphosphonates therapy, in order to avoidONJ.9,29 Moreover, the combined effect of bisphospho-nates and PD on osteointegration and success of endos-seous dental implants, to our knowledge, has neverbeen addressed before in the literature.

The current theory suggests that bisphosphonates canreach high concentrations in the maxillofacial area ow-ing to the high metabolic activity of the jawbones.Subsequently, an outbreak of ONJ occurs due to thereduction of osteoclastic remodeling, promoting acel-lular bone formation and subsequent necrosis with theinability to heal.37-46 Moreover, the presence of Acti-nomyces colonies in the oral cavity, as found in somecases of bisphosphonate ONJ and osteoradionecrosis,has been suggested to further compromise the healingprocess.23,33,34

Although there is already strong evidence supportingthe relationship between parenteral bisphosphonatesand ONJ, the case is not as clear regarding the use oforal bisphosphonates.25,38-40 So far, only 481 patientshave been reported in the literature to be diagnosedwith bisphosphonate-related ONJ. This disease seemedto occur more frequently in patients receiving intrave-nous bisphosphonates (94.2% of the cases reported inthe literature) than in patients receiving oral bisphos-phonates (5.8%). Most of the patients who developedONJ had cancer (93.8%), and nearly one-third of thepatients had a history of glucocorticoid uptake. Theinciting event preceding the diagnosis of ONJ was atooth extraction or other surgical or invasive dentalprocedure in 68.8% of the patients, whereas only 20.7%of the patients developed ONJ spontaneously.45

Although other studies had suggested that bisphos-phonate therapy should be stopped 3 months before anysurgical placement of dental implants, we believe thataccording to the scientific evidence present in the lit-erature,45 ONJ is unlikely to occur in patients who lacka history of cancer, parenteral bisphosphonate treat-ment, or glucocorticoid uptake. Therefore, the risksassociated with stopping the bisphosphonate treatmentin these patients might be greater than the unlikelyoutbreak of ONJ.

In the present case, the patient was being treated withoral bisphosphonates, but she was not diagnosed with anyknown malignancy and she was not taking glucocorti-coids; therefore, the risk of ONJ was very low. Based on

this information, we decided to maintain the treatment

with bisphosphonates throughout the implant placement,preoperative, and postoperative periods, to avoid reactiva-tion of the PD. The treatment with dental implants wassuccessful for at least 4 years, and complications related toPD or bisphosphonate treatment were not registered.

Moreover, a minimally invasive surgical techniquealong with a careful handling and suturing of the flapsmay have helped to reduce the chances of an ONJoutbreak. Likewise, the use of antimicrobial mouthrinses and administration of antibiotics, such as amoxi-cillin and clindamycin, may have been beneficial forpatients receiving these drugs.46

Paget disease may cause pathologic fractures, poorwound healing, and osteomyelitis in the maxillarybones. In addition, bone deformity in PD patients iscontinuous, rendering the use of removable prosthesisuncomfortable owing to the lack of adjustments overtime, and dentures need to be changed more often. Forthis reason, the treatment with dental implants results ina significant improvement in the quality of life of thesepatients, as we could confirm in this study.

Although implant therapy showed an excellent out-come in the present patient, it would be of great benefitto determine the predictability of implant treatments inpatients with PD. Long-term clinical trials on the place-ment of implants in patients with PD would be requiredto establish optimal clinical guidelines for the manage-ment of this disorder.23-26,46 Furthermore, the risk ofONJ associated with the intake of bisphosphonates inPD patients should be further investigated.

The authors thank the staff of “Clinica Dental Alcala”and Mrs. Ascension Marin for their help and support.

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Reprint requests:

Jesús Torres García-DencheDepartment of Health Sciences IIIFaculty of Health SciencesRey Juan Carlos University28922 AlcorcónMadridSpain

jesus.torres@urjc.es