Originally published as JCO Early Release 10.1200/JCO.2008.16.9300 on November 17 2008

This Article Abstract Full Text (PDF) Purchase Article View Shopping Cart Alert me when this article is cited Alert me if a correction is posted Services Email this article to a colleague Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Save to my personal folders Download to citation manager Rights & Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Badros, A. Articles by Dimopoulos, M. A. Search for Related Content PubMed PubMed Citation Articles by Badros, A. Articles by Dimopoulos, M. A. Social Bookmarking                            What's this?

Natural History of Osteonecrosis of the Jaw in Patients With Multiple Myeloma

Ashraf Badros, Evangelos Terpos, Eirini Katodritou, Olga Goloubeva, Efstathios Kastritis, Evgenia Verrou, Kostas Zervas, Maria R. Baer, Timothy Meiller, Meletios A. Dimopoulos

From the University of Maryland, Department of Medicine, Greenebaum Cancer Center, Baltimore, MD; Greek Myeloma Study Group; Department of Hematology and Medical Research, General Air Force Hospital; Department of Clinical Therapeutics, University of Athens School of Medicine, Athens; and the Department of Hematology, Theagenion Cancer Center, Thessaloniki, Greece

Corresponding author: Ashraf Badros, MD, University of Maryland, Greenebaum Cancer Center, 22 South Greene St, Baltimore, MD 21201; e-mail: abadros{at}umm.edu

	ABSTRACT

TOP ABSTRACT INTRODUCTION PATIENTS AND METHODS RESULTS DISCUSSION AUTHORS' DISCLOSURES OF... AUTHOR CONTRIBUTIONS REFERENCES

 
Purpose To evaluate the natural history of bisphosphonate-related osteonecrosis of the jaw (ONJ) in patients with multiple myeloma.

Patients and Methods Ninety-seven patients with myeloma from the United States (n = 37) and Greece (n = 60) were observed prospectively for a minimum 3.2 years after ONJ. Patients characteristics were similar with regard to age, bisphosphonate use, and myeloma therapy, except more autologous transplantations were performed on patients in the United States than in Greece (73% v 28%; P < .0001).

Results ONJ resolved in 60 patients (62%), resolved and recurred in 12 patients (12%), and did not heal in 25 patients (26%). Dental procedures preceded ONJ in 46 patients (47%) and were more common in those with single episodes (35 of 60, 58%) than recurrent or nonhealing (11 of 37, 30%; P = .007). Recurrent ONJ followed reinitiation of bisphosphonates in six of 12 patients. Greek patients had more bone pain than United States patients (60% v 30%, P = .001) and were less likely to restart bisphosphonates (5% v 35%, P < .0002). Myeloma relapses were more common in patients with recurrent/nonhealing than single-episode ONJ (84% v 62%; P = .02). Median overall survival from myeloma diagnosis was 10.8 years (95% CI; 9.3 years to not reached) and did not differ between patients with single, recurrent, and nonhealing ONJ (P = .2).

Conclusion ONJ healed in 75% of patients. Patients with spontaneous ONJ have a higher risk of nonhealing and recurrence. Reinitiating bisphosphonates after healing of ONJ is a reasonable option in patients experiencing relapse who are at risk of skeletal complications. Further studies of the pathogenesis and healing of ONJ are needed.

	INTRODUCTION

TOP ABSTRACT INTRODUCTION PATIENTS AND METHODS RESULTS DISCUSSION AUTHORS' DISCLOSURES OF... AUTHOR CONTRIBUTIONS REFERENCES

 
Bone disease affects 70% of patients with multiple myeloma and is associated with pain, fractures, and hypercalcemia. Monthly infusions of bisphosphonates reduce skeletal-related events in patients with multiple myeloma by inhibiting osteoclast development and activity, thereby decreasing bone resorption. The safety profile of this class of drugs has been challenged with the recent reports of osteonecrosis of the jaw (ONJ).¹ This development has led many authorities to recommend limiting the use of bisphosphonates in multiple myeloma to 2 years, especially in patients who are in remission.² Unfortunately, many patients stop bisphosphonate therapy permanently because of fear of ONJ or after an unconfirmed diagnosis of ONJ and subsequently suffer from bone pains and fractures.³

The criteria used to diagnose ONJ in the published cases have been inconsistent.⁴ The typical clinical presentation of ONJ includes exposed bone and no healing of the soft tissue, mucosal covering after 6 to 8 weeks of follow-up. Other symptoms include pain, soft-tissue swelling and infection, loosening of teeth, or drainage.⁵ These lesions may occur spontaneously or, more commonly, at the site of previous tooth extraction or after a dental procedure. Patients may also present with pain, feelings of numbness, or heaviness of the jaw. However, ONJ may remain asymptomatic for weeks or months, and diagnosis may be established after finding an exposed bone in the jaw.⁶ Pathologically, the lesions are characterized by necrotic and acellular bone, usually with quiescent bone surface and absence of osteoblasts and osteoclasts.⁷ In many cases, foci of mixed inflammatory cellular infiltration are seen in the vicinity of acellular bone, suggesting that infection may play a role in ONJ and justifying the empiric use of systemic and oral antimicrobials.⁸

The incidence of ONJ in multiple myeloma is unclear. At the University of Maryland, we reported 3% incidence of ONJ (11 of 340 patients) 2 years ago, and the incidence remains stable in the most recent follow-up analysis of our patients.⁷ ONJ clinical presentations were confirmed by independent dental evaluation and pathologic confirmation in all our patients. Using matched case-controls, we found that the risk factors predictive of developing ONJ were dental extraction (P = .009), sequential treatment with pamidronate followed by zoledronic acid (P = .009), longer follow-up time based on longer survival (P = .03), and older age at diagnosis of multiple myeloma (P = .006). We recommended conservative management, as surgical intervention with debridement and sequestrectomy was associated with increased risk of major complications, including nonhealing. In a subsequent study, we found no association between ONJ and serum levels of 25-hydroxy vitamin D, parathyroid hormone, bone-specific alkaline phosphatase, C-terminal telopeptide, calcium and phosphorus, and urinary N-terminal cross-linking telopeptide of collagen type-I, indicating that systemic effects of bisphosphonates and changes in bone turnover markers may not be pertinent to the local environment in the oral cavity.⁹ Other studies have correlated changes in bone formation and suppression biomarkers with ONJ.^10,11

The Greek Multiple Myeloma Study Group has published three reports on ONJ. The incidence of ONJ was 9.9% (11 of 111 patients) in the first study.¹² The risk increased with the duration of exposure to bisphosphonates from 1.5% among patients treated for 4 to 12 months to 7.7% in those treated for 37 to 48 months. The cumulative hazard was significantly higher with zoledronic acid compared with pamidronate alone or pamidronate and zoledronic acid sequentially (P < .001). The second study reported an incidence of 11% (28 of 254 patients).¹³ Again, zoledronic acid was associated with a 9.5-fold greater risk for developing ONJ than pamidronate alone (P = .042) and a 4.5-fold greater risk than sequential use of pamidronate and zoledronic acid (P = .018). The use of thalidomide was reported to increase the risk for ONJ 2.4-fold (P = .043). In the third study, an incidence of 7.4% (15 of 222 patients) was reported.¹⁴ Again, the risk was higher after longer exposure to bisphosphonates (39 v 28 months, P = .048) and in the zoledronic acid–treated patients.

These studies from the University of Maryland and the Greek Multiple Myeloma Study Group have focused on the problem of ONJ in patients with multiple myeloma and compared their characteristics to matched controls who received similar therapy. There are differences between the two populations with regard to disease presentation, initial and salvage multiple myeloma therapy, and frequency of bisphosphonate use after ONJ diagnosis. We have combined our databases to better define the natural history of patients with multiple myeloma who develop ONJ. This study focused on ONJ long-term outcome with regard to healing or nonhealing and recurrence, bone complications after bisphosphonate interruptions, and multiple myeloma outcome and survival.

	PATIENTS AND METHODS

TOP ABSTRACT INTRODUCTION PATIENTS AND METHODS RESULTS DISCUSSION AUTHORS' DISCLOSURES OF... AUTHOR CONTRIBUTIONS REFERENCES

 
The study included patients with multiple myeloma diagnosed with ONJ at the University of Maryland Greenebaum Cancer Center and at three major medical centers in Greece, including the University of Athens Medical School and General Air Force Hospital in Athens and Theagenion Cancer Center in Thessaloniki. The institutional review boards of the corresponding institutions approved the study. We defined ONJ strictly as an exposed bone that occurred spontaneously or after a dental procedure and had no evidence of healing of the mucosal covering for at least 8 weeks. A nonhealing ONJ lesion was defined as a lesion that did not heal during 9 months of follow-up, the shortest time of follow-up we have for nonhealing patients. Nonhealing lesions were classified as chronic nonprogressive if they remained stable or progressive if the lesion site increased in size or if complications developed such as fistula, infection and submandibular lymph adenopathy. ONJ recurrence was defined as development of new lesions, either at the same site or in a different location, after complete healing of the initial lesion.

Pain assessment was inconsistent in the four centers involved in the study. In general, patients reported new onset of pain or when pain was poorly controlled. In the United States, patients’ pain scores (0 to 10) were recorded at each clinic visit. Most patients underwent radiologic evaluation if symptoms persisted. Multiple myeloma responses were assessed using Bladé criteria.¹⁵

Statistics
The General Linear Models approach was used to estimate differences in continuous variables between patient subgroups. Associations between independent categoric variables and country of origin were assessed with the Fisher's exact test for 2 x 2 tables and with the Fisher-Freeman-Halton test for rxc contingency tables. Overall survival was estimated using the Kaplan-Meier method. Survival was compared across patient subgroups using the log-rank test. Testing was performed at the two-sided .05 significance level.

	RESULTS

TOP ABSTRACT INTRODUCTION PATIENTS AND METHODS RESULTS DISCUSSION AUTHORS' DISCLOSURES OF... AUTHOR CONTRIBUTIONS REFERENCES

 
Patient Characteristics
The study population included 97 patients with multiple myeloma from the United States (n = 37) and Greece (n = 60). Patient characteristics in the two groups are summarized in Table 1. The median age at multiple myeloma diagnosis, the median time from diagnosis of multiple myeloma to ONJ, and median follow-up times were similar in both groups. All of the Greek patients were white, whereas 10 of 37 patients in the United States were African American. Primary therapy of multiple myeloma included autologous stem-cell transplantation in 73% of the United States patients but only 28% of patients in the Greek group (P < .0001). More patients in the United States had relapsed disease at the time of their first ONJ episode, as compared with the Greek patients (51% v 23%; P = .008) and more were receiving multiple myeloma salvage therapy with novel agents (70% v 23%; P = .0001). Additionally, United States patients more frequently had diabetes mellitus (24% v 8%; P = .0002) and renal insufficiency (P = .002) at diagnosis of ONJ. Dental extraction preceded ONJ in 46 (47%) of 97 patients, with similar frequencies in both groups. Surgical interventions for ONJ were performed more often in patients in the United States than in Greece (17 [45%] of 37 patients v 19 [32%] of 60 patients.

Bisphosphonate Interruptions and Skeletal-Related Events
United States and Greek patients did not differ in their incidence of lytic bone disease and use of bisphosphonates at multiple myeloma diagnosis. However, more skeletal-related events were reported in the Greek compared with the United States patients after ONJ diagnosis and discontinuation of bisphosphonates, including more bone pain (60% v 30%; P = .001; Table 1). United States patients’ pain was secondary to new lytic lesions and fractures of long bones (n = 3), ribs (n = 2), and vertebrae (n = 6), all occurring in the context of progressive multiple myeloma. The cause of bone pain in the Greek patients was not evaluated radiologically consistently. Additionally, avascular necrosis of the hip developed in six patients and was more common in United States than Greek patients (14% v 2%; P = .03), probably not related to bisphosphonate interruption but rather to dexamethasone use in patients with myeloma.

After these events were noted and after complete healing of the first episode of ONJ, bisphosphonates were restarted in 16 patients, including more United States than Greek patients (35% v 5%, P = .0002). Bisphosphonate infusions were not complicated in 10 patients, including eight patients in the healed and two patients in the nonhealed group. However, of the 12 patients with recurrent ONJ, six patients had their recurrences 1 to 2 months after restarting bisphosphonates. Several of them were subsequently restarted on bisphosphonates because of bone pain and development of new lytic lesions; again, all had more ONJ lesion recurrences. Two patients in the nonhealing group restarted bisphosphonate therapy because of significant bone complications, and ONJ lesions had not progressed in either one, at 12 and 16 months of follow-up.

Multiple Myeloma Outcome
The rate of multiple myeloma relapse was higher in patients with recurrent and nonhealing ONJ, as compared with patients with a single ONJ episode (84% v 62%; P = .02). The median survival time from diagnosis of multiple myeloma was 10.8 years (95% CI; 9.3 years to not reached) and did not differ between patients with single-episode, recurrent, and nonhealing ONJ (P = .7). After diagnosis of ONJ, 29 patients remained in continuous remission and 68 patients had experienced relapse, of whom 28 patients had died and 40 of whom are undergoing salvage therapy.

	DISCUSSION

TOP ABSTRACT INTRODUCTION PATIENTS AND METHODS RESULTS DISCUSSION AUTHORS' DISCLOSURES OF... AUTHOR CONTRIBUTIONS REFERENCES

 
The literature to date includes many reports of ONJ, but this report is, to our knowledge, the first prospective analysis of the course of the condition. Although the study included heterogeneous populations of patients with myeloma from four institutions in two different countries, several observations were noted. Patients in whom ONJ was precipitated by dental procedures were less likely to have recurrent or nonhealing lesions as compared with those who developed spontaneous ONJ lesions. Nonhealing ONJ lesions could be chronic and remain stable over time, without extensive intervention. ONJ recurrence was linked to bisphosphonate rechallenge, mostly in the setting of relapsed multiple myeloma.

Although ONJ is seen in patients with prostate and breast cancer as well as in those with osteoporosis receiving oral bisphosphonates, it is clearly more common in multiple myeloma.¹⁶ However, our data suggest no correlation between multiple myeloma stage or status (active disease or remission) and ONJ. In addition, ONJ developed in few patients without lytic bone disease, and half of the patients developed first episodes of ONJ while their multiple myeloma was in remission. In contrast, nonhealing and recurrent/ONJ was seen more in patients with relapsed myeloma. The extended survival of patients with myeloma seen in the current study is a consequence of the introduction of novel agents that have changed the outcome of the disease.^17,18 We have no comparative group to establish that patients with ONJ have an improved survival. However, we can speculate that prolonged exposure to various drugs in addition to improving survival is a major risk for developing drug side effects and toxicities such as ONJ. As in other reports, more than half of the patients in this study developed ONJ after a dental procedure, usually an extraction; one patient developed ONJ after a surgical placement of an implant prosthesis and one patient developed ONJ after a soft tissue surgery to reduce redundant tissue adjacent to a tooth.

Diagnosis of a first episode of ONJ carries significant consequences for the patient and should therefore be confirmed by an oral surgeon who is experienced in ONJ. Many cases of presumed ONJ may simply represent delayed healing after dental procedures, which is quite common in older patients with multiple myeloma. For that reason, close monitoring for 8 weeks is crucial in establishing the diagnosis. Of note, at least 30% of the patients referred to the University of Maryland with diagnosis of ONJ were found to have other common dental diseases that involve the bone and supporting structures of the teeth rather than ONJ. These include periodontal diseases with inflammation of the soft tissues, gingivitis and/or inflammation of the bone and ligaments supporting the teeth, and periodontitis. These conditions are quite common and may affect up to 20% of the population.¹⁹ Patients may also have mucosal ulceration after chemotherapy, which may become chronically infected. These conditions seldom result in exposed bone and need to be considered in every patient suspected of having ONJ.

In contrast to patients with ONJ after dental procedures, patients with spontaneous, unprovoked ONJ fared poorly and were at increased risk of nonhealing and of recurrent lesions. ONJ recurrence was clearly linked to bisphosphonate rechallenge in 50% of those with recurrent lesions, usually in the setting of relapsed myeloma and development of new skeletal-related events. The recurrence rate was higher in the United States than in the Greek patients, in whom bisphosphonates were rarely restarted after their first episode of ONJ. However, of note, the presence of bone pain in 60% of the Greek patients may be secondary to stopping bisphosphonates after the first episode of ONJ. Nonhealing ONJ lesions were the most challenging. They were seen in 25% of our patients, though we believe that they may be less common in the general population and that the high percentage in our series is a reflection of our referral patterns as tertiary centers.

Several medications, such thalidomide, a known inhibitor of osteoclasts, have been linked to ONJ.¹³ In this study, the use of immunomodulatory drugs (thalidomide and lenalidomide) did not seem to impact the incidence or outcome of ONJ lesions. Similarly, many patients developed ONJ while being treated with bortezomib. Whether the activation of osteoblasts by bortezomib may contribute to ONJ healing remains speculative, as the cause of ONJ remains unknown.²⁰

There is a need to change the old paradigms with regard to frequency and duration of bisphosphonate therapy; several studies are underway to address these questions.²¹ The American Society of Clinical Oncology recently changed the recommendation for indefinite use of bisphosphonates in patients with myeloma in favor of a more conservative approach, in which therapy is stopped after 2 years if the disease is in remission and is restarted at relapse.² There are no prospective studies to support this recommendation. The current study did not address the common practice of discontinuing bisphosphonates until ONJ heals; however, all patients on the study had stopped therapy once ONJ was diagnosed. The decision to restart bisphosphonates should be individualized until prospective long-term studies are available. However, permanent discontinuation of bisphosphonate infusions after one episode of ONJ may have adverse consequences, such as the fractures seen in the United States patients and the bone pain seen in the Greek patients. Observations in our study suggest that patients who develop ONJ after dental procedures can restart bisphosphonate therapy if skeletal-related events develop. However, patients with no predisposing cause for the first ONJ episode are at increased risk of recurrence after initial healing and permanent interruption of bisphosphonate therapy may be justified, but should be weighed against the risk of skeletal-related events and symptoms. The decision to restarting bisphosphonates in patients with nonhealing ONJ should be discussed with the patient and the decision should be individualized after consultation with an oral surgeon experienced in ONJ until prospective trials establish its safety and efficacy.

	AUTHORS’ DISCLOSURES OF POTENTIAL CONFLICTS OF INTEREST

TOP ABSTRACT INTRODUCTION PATIENTS AND METHODS RESULTS DISCUSSION AUTHORS' DISCLOSURES OF... AUTHOR CONTRIBUTIONS REFERENCES

 
The author(s) indicated no potential conflicts of interest.

	AUTHOR CONTRIBUTIONS

TOP ABSTRACT INTRODUCTION PATIENTS AND METHODS RESULTS DISCUSSION AUTHORS' DISCLOSURES OF... AUTHOR CONTRIBUTIONS REFERENCES

 
Conception and design: Ashraf Badros

Administrative support: Ashraf Badros

Provision of study materials or patients: Ashraf Badros, Evangelos Terpos, Eirini Katodritou, Efstathios Kastritis, Evgenia Verrou, Kostas Zervas, Timothy Meiller, Meletios A. Dimopoulos

Collection and assembly of data: Ashraf Badros, Evangelos Terpos, Olga Goloubeva, Efstathios Kastritis, Evgenia Verrou, Kostas Zervas, Meletios A. Dimopoulos

Data analysis and interpretation: Olga Goloubeva, Maria R. Baer

Manuscript writing: Ashraf Badros

Final approval of manuscript: Ashraf Badros, Evangelos Terpos, Eirini Katodritou, Olga Goloubeva, Efstathios Kastritis, Evgenia Verrou, Kostas Zervas, Maria R. Baer, Timothy Meiller, Meletios A. Dimopoulos

	NOTES

 
published online ahead of print at www.jco.org on November 17, 2008

Authors’ disclosures of potential conflicts of interest and author contributions are found at the end of this article.

	REFERENCES

TOP ABSTRACT INTRODUCTION PATIENTS AND METHODS RESULTS DISCUSSION AUTHORS' DISCLOSURES OF... AUTHOR CONTRIBUTIONS REFERENCES

 
1. Ruggiero SL, Woo SB: Biophosphonate-related osteonecrosis of the jaws. Dent Clin North Am 52:111-128, ix, 2008[CrossRef][Medline]

2. Kyle RA, Yee GC, Somerfield MR, et al: American Society of Clinical Oncology 2007 clinical practice guideline update on the role of bisphosphonates in multiple myeloma. J Clin Oncol 25:2464-2472, 2007[Abstract/Free Full Text]

3. Barker K, Lowe D, Olujohungbe A, et al: Survey of members of myeloma UK on bisphosphonates-associated jaw osteonecrosis. Br J Haematol 139:626-628, 2007[CrossRef][Medline]

4. Marx RE, Sawatari Y, Fortin M, et al: Bisphosphonate-induced exposed bone (osteonecrosis/osteopetrosis) of the jaws: Risk factors, recognition, prevention, and treatment. J Oral Maxillofac Surg 63:1567-1575, 2005[CrossRef][Medline]

5. Boonyapakorn T, Schirmer I, Reichart PA, et al: Bisphosphonate-induced osteonecrosis of the jaws: Prospective study of 80 patients with multiple myeloma and other malignancies. Oral Oncol [epub ahead of print on February 15, 2008]

6. American Association of Oral and Maxillofacial Surgeons position paper on bisphosphonate-related osteonecrosis of the jaws. J Oral Maxillofac Surg 65:369-376, 2007[CrossRef][Medline]

7. Badros A, Weikel D, Salama A, et al: Osteonecrosis of the jaw in multiple myeloma patients: Clinical features and risk factors. J Clin Oncol 24:945-952, 2006[Abstract/Free Full Text]

8. Dental management of patients receiving oral bisphosphonate therapy: Expert panel recommendations. J Am Dent Assoc 137:1144-1150, 2006[Abstract/Free Full Text]

9. Badros A, Goloubeva O, Trepos E, et al: Prevelance and significance of vitamin D deficiency in multiple myeloma patients. Br J Haematol [epub ahead of print on May 15, 2008]

10. Marx RE, Cillo JE Jr, Ulloa JJ: Oral bisphosphonate-induced osteonecrosis: Risk factors, prediction of risk using serum CTX testing, prevention, and treatment. J Oral Maxillofac Surg 65:2397-2410, 2007[CrossRef][Medline]

11. Raje N, Woo SB, Hande K, et al: Clinical, radiographic, and biochemical characterization of multiple myeloma patients with osteonecrosis of the jaw. Clin Cancer Res 14:2387-2395, 2008[Abstract/Free Full Text]

12. Bamias A, Kastritis E, Bamia C, et al: Osteonecrosis of the jaw in cancer after treatment with bisphosphonates: Incidence and risk factors. J Clin Oncol 23:8580-8587, 2005[Abstract/Free Full Text]

13. Zervas K, Verrou E, Teleioudis Z, et al: Incidence, risk factors and management of osteonecrosis of the jaw in patients with multiple myeloma: A single-centre experience in 303 patients. Br J Haematol 134:620-623, 2006[CrossRef][Medline]

14. Dimopoulos MA, Kastritis E, Anagnostopoulos A, et al: Osteonecrosis of the jaw in patients with multiple myeloma treated with bisphosphonates: Evidence of increased risk after treatment with zoledronic acid. Haematologica 91:968-971, 2006[Abstract/Free Full Text]

15. Bladé J, Samson D, Reece D, et al: Criteria for evaluating disease response and progression in patients with multiple myeloma treated by high-dose therapy and haemopoietic stem cell transplantation: Myeloma Subcommittee of the EBMT—European Group for Blood and Marrow Transplant. Br J Haematol 102:1115-1123, 1998[CrossRef][Medline]

16. Wang EP, Kaban LB, Strewler GJ, et al: Incidence of osteonecrosis of the jaw in patients with multiple myeloma and breast or prostate cancer on intravenous bisphosphonate therapy. J Oral Maxillofac Surg 65:1328-1331, 2007[CrossRef][Medline]

17. San-Miguel J, Harousseau JL, Joshua D, et al: Individualizing treatment of patients with myeloma in the era of novel agents. J Clin Oncol 26:2761-2766, 2008[Abstract/Free Full Text]

18. Bensinger W: Stem-cell transplantation for multiple myeloma in the era of novel drugs. J Clin Oncol 26:480-492, 2008[Abstract/Free Full Text]

19. Pihlstrom BL, Michalowicz BS, Johnson NW: Periodontal diseases. Lancet 366:1809-1820, 2005[CrossRef][Medline]

20. Roodman GD: Bone building with bortezomib. J Clin Invest 118:462-464, 2008[Medline]

21. Corso A, Varettoni M, Zappasodi P, et al: A different schedule of zoledronic acid can reduce the risk of the osteonecrosis of the jaw in patients with multiple myeloma. Leukemia 21:1545-1548, 2007[CrossRef][Medline]

Submitted February 25, 2008; accepted July 24, 2008.

CiteULike    Complore    Connotea    Del.icio.us    Digg    Facebook    Reddit    Technorati    Twitter    What's this?

This article has been cited by other articles:

				K. Vahtsevanos, A. Kyrgidis, E. Verrou, E. Katodritou, S. Triaridis, C. G. Andreadis, I. Boukovinas, G. E. Koloutsos, Z. Teleioudis, K. Kitikidou, et al. Longitudinal Cohort Study of Risk Factors in Cancer Patients of Bisphosphonate-Related Osteonecrosis of the Jaw J. Clin. Oncol., November 10, 2009; 27(32): 5356 - 5362. [Abstract] [Full Text] [PDF]

				S. N. Gebara and H. Moubayed Risk of osteonecrosis of the jaw in cancer patients taking bisphosphonates Am. J. Health Syst. Pharm., September 1, 2009; 66(17): 1541 - 1547. [Abstract] [Full Text] [PDF]

				E. Terpos, O. Sezer, P. I. Croucher, R. Garcia-Sanz, M. Boccadoro, J. San Miguel, J. Ashcroft, J. Blade, M. Cavo, M. Delforge, et al. The use of bisphosphonates in multiple myeloma: recommendations of an expert panel on behalf of the European Myeloma Network Ann. Onc., August 1, 2009; 20(8): 1303 - 1317. [Abstract] [Full Text] [PDF]

This Article Abstract Full Text (PDF) Purchase Article View Shopping Cart Alert me when this article is cited Alert me if a correction is posted Services Email this article to a colleague Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Save to my personal folders Download to citation manager Rights & Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Badros, A. Articles by Dimopoulos, M. A. Search for Related Content PubMed PubMed Citation Articles by Badros, A. Articles by Dimopoulos, M. A. Social Bookmarking                            What's this?