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Doi:10.1016/j.joms.2007.09.019

J Oral Maxillofac Surg66:223-230, 2008 Outcomes of Placing Dental Implants in
Patients Taking Oral Bisphosphonates:
A Review of 115 Cases
Bao-Thy Grant, DDS,* Christopher Amenedo, DDS,† Katherine Freeman, DrPH,‡ and Richard A. Kraut, DDS§ Purpose: In recent years, numerous cases of bisphosphonate-associated osteonecrosis of the jaw have
been reported involving both intravenous and oral therapy regimens. The majority of these cases have
involved intravenous bisphosphonates. Subsequently, drug manufacturers and the US Food and Drug
Administration issued warnings about possible bisphosphonate-associated osteonecrosis of the jaw. The
American Dental Association and the American Association of Oral and Maxillofacial Surgeons assembled
expert panels to formulate treatment guidelines. Both panels differentiated between patients receiving
bisphosphonates intravenously and those receiving the drugs orally. However, the recommendations
were based on limited data, especially with regard to patients taking oral bisphosphonates. We wanted
to ascertain the extent to which bisphosphonate-associated necrosis of the jaw has occurred in our dental
implant patients. We also wanted to determine whether there was any indication that the bisphospho-
nate therapy affected the overall success of the implants as defined by Albrektsson and Zarb.
Patients and Methods: We identified 1,319 female patients over the age of 40 who had received dental
implants at Montefiore Medical Center between January 1998 and December 2006. A survey about bisphos-
phonate therapy was mailed to all 1,319 patients. Responses were received from 458 patients of whom 115
reported that they had taken oral bisphosphonates. None had received intravenous bisphosphonates. All 115
patients were contacted and informed about the risk of bisphosphonate-associated osteonecrosis of the jaw.
Seventy-two patients returned to the clinic for follow-up clinical and radiological evaluation.
Results: A total of 468 implants were placed in the 115 patients who reported that they had received
oral bisphosphonate therapy. There is no evidence of bisphosphonate-associated osteonecrosis of the
jaw in any of the patients evaluated in the clinic and those contacted by phone or e-mail reported no
symptoms. Of the 468 implants, all but 2 integrated fully and meet criteria for establishing implant
success. Implant success rates were comparable for patients receiving oral bisphosphonate therapy and
those not receiving oral bisphosphonate therapy.
Conclusions: Guidelines for treatment of dental patients receiving intravenous bisphosphonate treatments
should be different than for patients taking the oral formulations of these medications. In this study, oral
bisphosphonate therapy did not appear to significantly affect implant success. Implant surgery on patients
receiving bisphosphonate therapy did not result in bisphosphonate-associated osteonecrosis of the jaw.
Nevertheless, sufficient evidence exists to suggest that all patients undergoing implant placement should be
questioned about bisphosphonate therapy including the drug taken, the dosage, and length of treatment prior
to surgery. For patients having a history of oral bisphosphonate treatment exceeding 3 years and those having
concomitant treatment with prednisone, additional testing and alternate treatment options should be con-
sidered.
2008 American Association of Oral and Maxillofacial Surgeons
J Oral Maxillofac Surg 66:223-230, 2008
Received from Albert Einstein College of Medicine/Montefiore Address correspondence and reprint requests to Dr Kraut: Medical Center, Bronx, NY.
Montefiore Medical Center, Dentistry/Oral and Maxillofacial Sur- *Chief Resident, Department of Oral and Maxillofacial Surgery.
gery, 111 East 210th Street, Bronx, NY 10467-2460; e-mail: †Attending, Department of Oral and Maxillofacial Surgery.
‡Professor, Department of Epidemiology and Population Health.
2008 American Association of Oral and Maxillofacial Surgeons §Chairman of Department of Dentistry, Director of Oral and Maxil- lofacial Surgery, and Professor.
IMPLANTS AND ORAL BISPHOSPHONATES: 115 CASES Table 1. ORAL AND INTRAVENOUS BISPHOSPHONATE MEDICATIONS AVAILABLE IN THE UNITED STATES
Roche Pharmaceutical Aredia (intravenous) Bonefos (intravenous) Zometa (intravenous) Adapted with permission from American Dental Association Council on Scientific Affairs: Dental management of patients receiving oral bisphosphonate therapy: Expert panel recommendations. J Am Dent Assoc 137:1144, 2006.
Grant et al. Implants and Oral Bisphosphonates: 115 Cases. J Oral Maxillofac Surg 2008. According to the American Society of Clinical Oncol- thors noted that during the 3 years covered by the ogy, the use of intravenous bisphosphonates for the study, the number of patients presenting at the med- reduction of bone pain, hypercalcemia of malignancy, ical center with necrotic lesions of the jaw had dra- and skeletal complications in patients with multiple matically increased. The necrosis was typical of that myeloma, lung, breast and other cancers is the cur- seen in patients receiving radiation therapy. How- rent standard of The 2 drugs associated with ever, these patients were not being treated with radi- these treatments are pamidronate (Aredia; Novartis ation; rather they were receiving bisphosphonate Pharmaceuticals Corp, East Hanover, NJ) and zoledronic acid (Zometa; Novartis Pharmaceuticals Soon after publication of the Ruggerio article, in Oral bisphosphonates are used to treat osteoporo- September 2004, Novartis, manufacturer of Aredia sis, Paget's disease, and osteogenesis and Zometa, notified health care professionals of the They are most widely used for treatment of osteopo- possible relationship between intravenous bisphos- rosis; in the United States, some 22 million prescrip- phonate therapy and necrosis of the jaws. Thereafter tions were written for Fosamax (Merck Co, West the US Food and Drug Administration issued an alert Point, VA) between May 2003 and April It is that included not only the intravenous bisphospho- estimated that the number of hip fractures in the nate formulations but the oral ones as United States will triple by 2020 and that 1 of every 2 Additional articles and case studies have been pub- women will sustain an osteoporosis fracture in her lished though all have limited sample sizes and all are Twenty-four percent of the women who retrospective studies. Incidence of bisphosphonate- fracture a hip will die within a As the pop- associated osteonecrosis of the jaw is estimated to ulation ages, the number of people receiving bisphos- range from 0.8% to 12% for patients receiving intra- phonate therapy is likely to rise. In addition, many of venous For patients taking oral those treated will receive medication for an extended medication, the incidence is estimated to be 0.7 per number of years. Oral and intravenous bisphospho- 100,000 person years of Nationwide, nate medications available in the United States are there have been over 200 reported cases of possible bisphosphonate-associated osteonecrosis of the jaw In a letter to the editor of the Journal of Oral and in patients taking Fosamax or Actonel (Procter and Maxillofacial Surgery published in September 2003, Gamble, Cincinnati, OH). So far there are no docu- Marx alerted the dental community to the possible mented cases for patients taking Boniva (Hoffman- relationship between intravenous bisphosphonate LaRoche, Nutley, NY) although there are some anec- therapy and necrosis of the He reported on 36 dotal Results for patients taking other oral cases of bone exposure that were not responsive to bisphosphonates are expected to be comparable.
surgical or medical treatments. All 36 patients were Risks associated with intravenous therapy appear to receiving intravenous bisphosphonate in the form of be substantially higher than for the oral medications.
either Aredia or Zometa. His letter prompted others to A conclusive cause and effect relationship between review patient records and to make reports of similar bisphosphonate therapy and osteonecrosis of the jaw has not been established. But evidence suggests that The following year, Ruggerio et al published a re- such a link may in fact exist. Unfortunately there is view of 56 cases of osteonecrosis associated with the limited data to aid in the identification of other risk use of intravenous bisphosphonate The au- factors for development of the disease. Some evi- dence suggests that those risk factors may include the If dental implants are to be placed, the panel sug- potency of the drug used, the duration of therapy, gests contacting the physician who prescribed the being Caucasian, being older than 65, having chronic oral bisphosphonate prior to surgery to suggest an periodontitis, ongoing corticosteroid therapy, having alternate dosing schedule, a drug holiday, or an alter- diabetes, smoking, and the use of native to bisphosphonate therapy. These recommen- It appears important to make a distinction between dations were made by 2 of the Task Force members osteonecrosis of the jaw induced by oral bisphospho- based on their clinical experience with 50 such pa- nates versus that induced by intravenous bisphospho- nates. Oral bisphosphonate-induced necrosis appears For years dentists have routinely performed surgi- to be less frequent, less severe, more responsive to cal procedures and placed implants in patients receiv- discontinuation of the drug, and curable with surgical ing bisphosphonate therapy. Prior to widespread debridement. Marx states that osteonecrosis from oral awareness of the risk of bisphosphonate-associated bisphosphonates differs significantly from intrave- osteonecrosis and publication of treatment guidelines, nous bisphosphonate-associated osteonecrosis in 3 these patients were treated without modification of stan- major ways: Patients taking oral bisphosphonates 1) dard treatment procedures. Additional research is re- require a longer period of drug therapy before bone is quired to determine if additional diagnostic testing or exposed, 2) manifest less bone exposure and symp- treatment modifications are actually necessary. Because toms are less severe, and 3) have a chance of symp- implant surgery is a major part of our practice, we toms improving or exposed bone healing after taking wanted to determine the necessity of making wholesale a drug holiday.
modifications in our treatment of patients receiving oral Nevertheless, the Council of Scientific Affairs of the bisphosphonate therapy based on our past clinical ex- American Dental Association assembled a panel of perience. Specifically we wanted to determine whether experts to provide dentists with guidelines for treat- any patients had developed osteonecrosis of the jaw and ing patients who are receiving bisphosphonate ther- whether there was any indication that bisphosphonate apy. The American Association of Oral and Maxillofa- therapy affected the overall success of the implants as cial Surgeons convened an expert Task Force with defined by Albrektsson and similar goals. The resulting guidelines suggested avery cautious approach to implant surgery and extrac-tions for patients receiving bisphosphonate therapy Patients and Methods
either intravenously or The American Dental Association Expert Panel rec- We identified 1,319 female patients over the age of 40 ommends that patients taking oral bisphosphonates be who had implant surgery in the Department of Oral and informed about the risks and benefits. They further Maxillofacial Surgery at Montefiore Medical Center be- recommend that nonsurgical and less invasive treatment tween January 1998 and December 2006. A survey alternatives be used when possible. The panel cautions asking about current and past oral bisphosphonate that patients may be at increased risk when extensive therapy was mailed to those patients. Thirty-five percent implant placement or guided bone regeneration is nec- (458) of the surveys were returned. Of those, 115 pa- essary. When the treatment plan involves the medullary tients reported taking oral bisphosphonates before or bone and/or periosteum in multiple sextants, the panel after implant surgery. None reported receiving intrave- recommends treating 1 sextant or tooth at a time. They nous bisphosphonate. A total of 468 implants had been recommend treatment with an antimicrobial mouth placed in these patients.
rinse and a 2-month disease-free follow-up before other The patients who responded to our survey that sextants are treated.
reported a history of bisphosphonate use were com- The Task Force appointed by the American Associ- pared with a random sample of nonresponders with ation of Oral and Maxillofacial Surgeons also recom- regard to age and number of implants. The difference mends that patients taking oral bisphosphonates be between the groups with regard to number of im- informed of the small risk of compromised bone heal- plants was not significant, whereas there was a signif- The Task Force states that elective dentoalveo- icant difference in age between the groups. In addi- lar surgery does not appear to be contraindicated in tion, 115 of the 458 responders, whereas only 5 patients without known risk factors who have been among 100 nonresponders, had a history of bisphos- taking oral bisphosphonates for less than 3 years. A phonate use (P ⬍ .0001).
drug holiday of at least 3 months prior to surgery is The remaining 343 patients indicated that they had suggested for patients who have taken an oral not received bisphosphonate therapy. A total of 1,450 bisphosphonate for more than 3 years and those that implants had been placed in these patients; 1,436 have taken corticosteroids concomitantly.
implants integrated successfully.
IMPLANTS AND ORAL BISPHOSPHONATES: 115 CASES FIGURE 1. Patient survey.
Grant et al. Implants and Oral Bisphosphonates: 115 Cases. J Oral Maxillofac Surg 2008. We used the criteria developed by Albrektsson and The mean duration of oral bisphosphonate therapy Zarb to determine implant success. Those criteria are was 38 months. Twenty-six patients started oral bisphosphonate therapy after implant surgery andsubsequent healing. The remaining 89 patients started bisphosphonate therapy before implant placement.
Sixty-six patients reported taking Fosamax prior to The 115 patients who reported having bisphospho- implant placement; 21 patients were taking Actonel; nate therapy were contacted and informed that there and 2 patients were taking Boniva. Out of the 89 was a slight risk of bisphosphonate-associated osteone- patients taking oral bisphosphonates prior to surgery, crosis of the jaw. All 115 patients had been treated using 33 patients reported taking an oral bisphosphonate standard implant surgery techniques without modifica- for more than 3 years prior to surgery: 27 patients tion due to the bisphosphonate therapy. Sixty-three per- reported taking Fosamax, 5 patients reported taking cent of the patients (72 out of 115) were seen for a Actonel, and 1 patient reported taking Boniva. The follow-up clinical and radiographic examination.
remaining 56 patients reported taking oral bisphos- teonecrosis, then the upper bound of a 1-sided confi- Table 2. CRITERIA FOR IMPLANT SUCCESS
dence interval for 0 events for N ⫽ 115 is 0.026. Thus, An individual, unattached implant is immobile when we would not expect that the rate of osteonecrosis is tested clinically.
greater than 2.6%. However, none of the 72 patients A radiograph does not show any evidence of peri-implant who were examined in the clinic after reporting a his- tory of bisphosphonate therapy had evidence of osteo- Vertical bone loss is less than 0.2 mm annually after the implant's first year of service.
necrosis. We have no reports of osteonecrosis from any Individual implant performance is characterized by an of the 861 patients who did not return the survey. Nor absence of persistent and/or irreversible signs and do we have reports of osteonecrosis from any of the symptoms such as pain, infection, neuropathies, referring restorative dentists. We cannot say definitively paresthesia, or violation of the mandibular canal.
that none of these patients has developed bisphospho- To be considered successful, the dental implant should provide functional service for 5 years in 75% of the nate-associated necrosis. However, it is our experience that we hear rather quickly from implant patients whohave problems such as losing an implant or develop- Adapted with permission from Albrektsson et ment of oral lesions.
Grant et al. Implants and Oral Bisphosphonates: 115 Cases. J Oral Patients taking bisphosphonates who reported to Maxillofac Surg 2008. the clinic or who contacted us by phone or e-mailwere asked about known risk factors such as age over phonates for less than 3 years prior to dental implant 65, having diabetes or taking prednisone concomitantly with bisphosphonate therapy. The mean age of the A total of 468 dental implants were placed in pa- patients who had bisphosphonate therapy was 67.4 tients receiving bisphosphonate therapy. Four hun- years; 51 of the 115 were over the age of 65. Three of dred sixty-six implants are in function and are suc- the patients reported taking prednisone concomitantly cessful according to criteria for success defined by with bisphosphonate therapy; 2 patients had diabetes.
Albrektsson and Zarb. Two implants failed. In the first More invasive surgical procedures have been iden- case, the patient had 2 implants placed in the maxilla tified as risk factors for developing bisphosphonate- to restore the upper left first and second molars, and associated osteonecrosis. In the group of 115 pa- a simultaneous sinus lift. In the next year, an addi- tients, 32 had maxillary sinus augmentation. Six of the tional 2 implants were placed to restore the upper left 32 were taking an oral bisphosphonate for at least 3 first and second bicuspids. The following year the years prior to sinus augmentation.
implant in the area of the upper left second bicuspid The ADA panel recommended that surgical treat- failed to integrate. This was discovered prior to res- ments be limited to a single sextant with a substan- toration. The implant was subsequently removed and tial interval for healing before proceeding to treat- replaced several months later. This implant success- ment of another sextant.4 At Montefiore, single fully integrated and was definitively restored 6 session, multiple sextant surgery was performed on months later. The patient did report taking oral 29 patients who had been taking oral bisphospho- bisphosphonates for 3 years prior to implant place- nates prior to surgery.
ment. The patient was no longer taking the oral The most interesting of these patients is a 67-year- bisphosphonate at the time of implant placement or old female who had been taking Actonel for more thereafter. To date, all implants are successful and than 5 years prior to dental implant placement. Two have been in function for more than 4 years.
implants were placed into the upper right quadrant In the second case, the patient started taking oral with a simultaneous maxillary bone graft. The follow- bisphosphonates more than 4 years prior to implant ing year, 5 additional implants were placed in the placement. The patient had 6 implants placed in the right and left mandible. To date, the patient is still maxilla. Two months later, 7 implants were placed in taking Actonel. All 7 dental implants are in function the mandible. The most posterior implant replacing and show no evidence of osteonecrosis the lower left second molar did not integrate and wasremoved 1 month later. That implant was not re- placed and the area healed uneventfully. All 12 im-plants are integrated and in function. The patient Ruggerio's study that included 7 patients taking remains on oral bisphosphonates and reports over 8 oral bisphosphonates for treatment of osteoporosis consecutive years of oral bisphosphonate therapy.
contains the single most compelling evidence of a link None of the 458 patients who responded to the sur- between oral bisphosphonate treatment and osteone- vey reported symptoms of bisphosphonate-associated None of the 7 patients had a history of malig- osteonecrosis of the jaw. If it is assumed that none of the nant disease or chemotherapy. He did not report on 115 responders treated with bisphosphonates had os- the duration of the bisphosphonate therapy. The re-

IMPLANTS AND ORAL BISPHOSPHONATES: 115 CASES FIGURE 2. Preoperative panoramic x-ray taken in September 2005.
Grant et al. Implants and Oral Bisphosphonates: 115 Cases. J Oral Maxillofac Surg 2008. maining 56 patients in the study were all taking intra- the jaw. Marx speculates that Didronel does not cause venous bisphosphonate in conjunction with treat- osteonecrosis because it contains no nitrogen and ment for multiple myeloma, breast cancer, or some therapy is not constant; patients are treated with a other form of malignant disease.
cycle of on-off doses.
Despite the widespread use of oral bisphospho- According to the case report, 5 implants were nates, a review of the literature found only 1 case of placed and successfully integrated in the anterior dental implant failure associated specifically with oral mandible. The patient was restored and had an bisphosphonate use. A case report from 1995 sug- uneventful postoperative course. The patient began gested that failure of 5 implants was caused by etidronate disodium (Didronel) therapy 28 months bisphosphonate therapy.The drug discussed in this after implant placement. This drug can be adminis- case report was etidronate disodium (Didronel; Procter tered intravenously or orally; however, the route of and Gamble), a non-nitrogen containing bisphospho- drug administration for the patient was not speci- nate that is not the drug of choice for treatment of fied by the authors. After taking the drug for 4 osteoporosis. Didronel is 1,000 times less potent than months, the patient presented with pain in the alendronate (Fosamax) and is used to treat fibrous mandible. A panoramic radiograph revealed exten- dysplasia and Paget's disease.Didronel does not sive osteolysis around all implants and all 5 im- contain nitrogen. Other than this report, only nitro- plants were removed 1 month later. The bisphos- gen containing bisphosphonates have been found to phonate treatment was discontinued. The authors produce bisphosphonate-associated osteonecrosis of make no mention of poor or delayed healing fol- FIGURE 3. Postoperative panoramic x-ray after 2 dental implants were placed in the upper right quadrant with a simultaneous maxillary sinus lift
in October 2005.
Grant et al. Implants and Oral Bisphosphonates: 115 Cases. J Oral Maxillofac Surg 2008.

FIGURE 4. Panoramic x-ray after mandibular dental implants were placed in May 2006.
Grant et al. Implants and Oral Bisphosphonates: 115 Cases. J Oral Maxillofac Surg 2008. lowing removal of the implants as might be ex- that the implant failure and osteolysis were caused pected with bisphosphonate-induced necrosis.
by the Didronel They recommend that The authors reported that the patient developed patients who have previously undergone implant a parafunctional clenching habit subsequent to im- placement forego bisphosphonate therapy. They plant placement and loading. It is possible that further recommend that dentists avoid implant increased physiologic loads were the cause of im- placement in patients who require bisphosphonate plant failure. Nevertheless, the authors concluded FIGURE 5. Clinical photos show no evidence of biphosphonate-associated osteonecrosis.
Grant et al. Implants and Oral Bisphosphonates: 115 Cases. J Oral Maxillofac Surg 2008. IMPLANTS AND ORAL BISPHOSPHONATES: 115 CASES In 2006, Jeffcoat reported the results of a single- 2. Hillner BE, Ingle JN, Berenson JR, et al: American Society of blind controlled study of 50 postmenopausal female Clinical Oncology guideline on the role of bisphosphonates inbreast cancer. J Clin Oncol 18:1378, 2000 dental implant patients, all of whom had bone mineral 3. Berenson JR, Hillner BE, Kyle RA, et al: American Society of density scores indicative of Twenty- Clinical Oncology clinical practice guidelines: The role of five patients had taken oral bisphosphonates (alen- bisphosphonates in multiple myeloma. J Clin Oncol 20:3719,2002 dronate or risendronate) for 1 to 4 years prior to in- 4. Migliorati CA. Bisphosphonates and oral cavity avascular bone clusion in the study. The mean duration of bisphos- necrosis. J Clin Oncol 21:4253, 2003 phonate therapy prior to the study was 3 years. The 5. Marx RE. Pamidromate (Aredia) and zoledronate (Zometa) in- duced avascular necrosis of the jaws: A growing epidemic.
other 25 patients did not take oral bisphosphonates J Oral Maxillofac Surg 61:1115, 2003 prior to or during the study. One patient in each 6. Glorieux FH, Bishop NJ, Plotkin H, et al: Cyclic administration group smoked. A total of 102 implants were placed in of pamidronate in children with severe osteogenesis imper- the group taking bisphosphonates; 108 dental im- fecta. N Engl J Med 339:947, 1998 7. Marx RE: Oral and Intravenous Bisphosphonate-Induced Osteo- plants were placed in the nonbisphosphonate group.
necrosis of the Jaws. Hanover Park, IL, Quintessence, 2007 After 3 years, there was a 100% success rate with no 8. American Dental Association Council on Scientific Affairs: Den- clinical evidence of infection, pain, or necrosis in the tal management of patients receiving oral bisphosphonate ther-apy: Expert panel recommendations. J Am Dent Assoc 137: patients who received oral bisphosphonates. There was a 99.2% success rate in the group who did not 9. US Department of Health and Human Services. Bone health and receive oral bisphosphonates.
osteoporosis: A report of the Surgeon General. Rockville, MD:US Department of Health and Human Services, Office of the We found similar results in our study. Of the 115 Surgeon General, 2004 patients taking oral bisphosphonates, none show ev- 10. American Dental Association Council on Scientific Affairs: Den- idence or have symptoms of necrosis. All have had tal management of patients receiving oral bisphosphonate ther-apy: Expert panel recommendations. J Am Dent Assoc 137: successful implant restorations. Had recommenda- tions of the ADA and AAOMS panels been followed, 11. Advisory Task Force on Bisphosphonate-Related Ostenonecro- treatment for at least 30 of these patients would have sis of the Jaws, American Association of Oral and Maxillofacial been modified. Possible treatment modifications in- Surgeons: American Association of Oral and Maxillofacial Sur-geons position paper on bisphosphonate-related osteonecrosis clude a drug holiday, obtaining a C-terminal cross- of the jaws. J Oral Maxillofac Surg 65:369, 2007 linking telopeptide serum test, treating individual 12. Durie BGM, Katz M, Crowley J: Osteonecrosis of the jaws and quadrants separately, or even use of nonimplant-sup- bisphosphonates. N Engl J Med 353:99, 2005 13. Bamias A, Kastritis E, Bamia C, et al: Osteonecrosis of the jaw ported Management of patients re- in cancer after treatment with bisphosphonates: Incidence and ceiving oral bisphosphonates should be separated and risk factors. J Clin Oncol 23:8580, 2005 distinguished from the management of patients re- 14. Dimopoulos MA, Kastritis E, Anagnostopoulos A, et al: Osteo- necrosis of the jaw in patients with multiple myeloma treated ceiving intravenous bisphosphonates. All patients with bisphosphonates: Evidence of increased risk after treat- considering surgical treatments should be asked ment with zoledronic acid. Haematologica 91:968, 2006 about bisphosphonate use and should be advised of 15. Zavras AI, Zhu S: Bisphosphonates are associated with in- creased risk for jaw surgery in medical claims data; Is it osteo- possible risks. Dental records should be revised to necrosis? J Oral Maxillofac Surg 64:917, 2006 include this information. Additional research is re- 16. Marx RE, Sawatari Y, Fortin M, et al: Bisphosphonate-induced quired to guide the management of patients taking oral exposed bone (osteonecrosis/psteopetrosis) of the jaws. Risk bisphosphonates. Some evidence suggests that duration factors, recognition, prevention, and treatment. J Oral Maxillo-fac Surg 63:1567, 2005 of oral bisphosphonate therapy correlates with the de- 17. Ruggiero SL, Mehrotra B: Ten years of alendronate treatment velopment and severity of osteonecrosis. More data are for osteoporosis in postmenopausal women. N Engl J Med needed to determine at what point invasive dental treat- 18. Schwartz HC: Osteonecrosis and bisphosphonates: Correlation ment should be routinely modified. In addition, more versus causation. J Oral Maxillofac Surg 62:763, 2004 data is needed to determine whether the serum C-ter- 19. Albrektsson T, Zarb G, Worthington P, et al: The long-term effi- minal cross-linking telopeptide serum test is valid for cacy of currently used dental implants: A review and proposedcriteria of success. Int J Oral Maxillofac Implants 1:11, 1986 assessing There is insufficient evidence to suggest 20. Stark WJ, Epker BN: Failure of osteointegrated dental implants that implant placement, tooth extraction, and other sur- after diphosphonate therapy for osteoporosis: A case report.
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22. Jeffcoat MK: Safety of oral bisphosphonates: Controlled studies on alveolar bone. Int J Oral Maxillofac Implants21:349, 2006 23. Rosen HN, Moses AC, Garber J, et al: Serum CTX. A new marker of bone resorption that shows treatment effect more 1. Ruggerio SI, Mekrotra B, Engroff SL: Osteonecrosis of the jaws often than other markers because of low coefficient of variabil- associated with the use of bisphosphonates. A review of 63 ity and large changes with bisphosphonate therapy. Calcif cases. J Oral Maxillofac Surg 62:527, 2004 Tissue Int 66:100, 2000

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