Complication Of Bisphosphonate Therapy Research Articles

Tooth Extraction Socket Healing in Pediatric Patients Treated with Intravenous Pamidronate

Osteonecrosis of the jaw (ONJ) has been described as a complication of bisphosphonate therapy in adults. In the present study, we did not find a case of ONJ among 278 pediatric patients who had received intravenous pamidronate during childhood or adolescence.

Osteonecrosis of the Jaw Related to Bisphosphonates Therapy in Multiple Myeloma and Metastatic Prostate Cancer Patients. A Latin American Report: An Adverse Event To Look For!!.

Background: Association between osteonecrosis of the jaw (ONJ) and aminobisphosphonate treatment in patients (pts.) with multiple myeloma, breast cancer and prostate cancer has been increasingly reported in the literature. Risk factors for this complication include presence of infection, recent dental extraction and any oral surgical procedure with bone exposure.Patients and Methods: All patients with myeloma multiple or prostate cancer diagnosis treated at two institutions from Lima with either IV zoledronic acid or pamidronate from 2005–2007 were evaluated using outpatient records. Patients with ONJ were identified and their characteristics were compared to all patients receiving bisphosphonate therapy.Results: One hundred eighty three patients were evaluated. One hundred three had metastatic prostate cancer, and eighty myeloma multiple. All patients with myeloma multiple received pamidronate and all patients with prostate cancer received zoledronic acid. Six patients developed ONJ (3.2%). Five pts. were male and one female; a median age of 62 (range 50–74) and 5 had metastatic prostate cancer and 1 myeloma multiple. Zoledronic acid and pamidronate were involved in 5 and 1 cases respectively. The median number of bisphosphonate infusions prior to the development of ONJ was 16 (range 12–20). No patient had dental extraction or oral surgical procedure before ONJ. Bone exposition occurred in four cases. Treatment was antibiotics in all cases and surgery in two.Conclusions: ONJ is a serious complication of bisphosphonate therapy and it affected a significant proportion of our Latino american patients.

Dental care and tooth extraction as a risk factor for developing osteonecrosis of the jaw after long-term bisphosphonate therapy in patients with metastatic breast cancer

1076 Background: Association between osteonecrosis of the jaw (ONJ) and bisphosphonate treatment in patients (pts.)with Multiple Myeloma, breast cancer and prostate cancer has been increasingly reported in the literature. Risk factor for this complication include presence of infection, recent dental extraction and any oral surgical procedure with bone exposure. Methods: This is a retrospective review of our experience with patients diagnosed with bone metastasis secondary to breast cancer, who developed ONJ while treated with bisphosphonates, between January 2002 and December 2006. Presentation, age, dental status, and outcome were reviewed. Logistic Regression was used to test for statistical significance. Results: 100 pts. with bone metastasis secondary to breast cancer, median age 63 years, treated with bisphosphonates were reviewed. ONJ developed in 5 (5%) pts. Age did not impact occurrence of ONJ. All 5 patients developed ONJ after a minimum of 100mg of Zoledronic Acid and 2700mg of Pamidronate. All pts. had a history of previous tooth extraction and inadequate dental care. Three pts. were treated with debridement and antibiotics and their lesions healed. Two pts. ended up suffering from a chronically exposed bone. Conclusions: ONJ is a serious complication of bisphosphonate therapy and it affected a significant proportion of our patients. Our data suggests a strong association between dental care, tooth extraction, and the development of ONJ. No significant financial relationships to disclose.

Bisphosphonates and osteonecrosis of the jaws: Science and rationale

Bisphosphonates as a group of drugs were introduced for the management of various conditions such as osteoporosis, Paget's disease, multiple myeloma, hypercalcemia of malignancy, breast cancer, prostate cancer, and other tumors. This group of drugs has improved the quality of life in many patients with proven efficacy in limiting pain and skeletal-related events. The controversy of osteonecrosis of the jaws and bisphosphonates is a recent and growing problem. Osteonecrosis of the jaws is recognized as a serious complication of bisphosphonate therapy, more commonly with the intravenous form of the drugs. However, there is limited scientific understanding about the association between osteonecrosis of the jaws and bisphosphonates. In the present article we discuss various mechanisms of action of bisphosphonates, the rationale for occurrence of osteonecrosis in the jaws, and treatment guidelines for the condition.

Race as a risk factor for developing osteonecrosis of the jaw after long term bisphosphonate therapy in patients with metastatic breast cancer

596 Background: Association between osteonecrosis of the jaw (ONJ) and bisphosphonate treatment has been increasingly reported in the literature. Methods: This is a retrospective review of a single institution’s experience with patients diagnosed with bone metastasis secondary to breast cancer, who developed ONJ while treated with bisphosphonates (Zoledronic acid - Zometa; Pamidronate - Aredia), between 1.1.2001 and 10.30.2005. Presentation, age, race, and outcome were reviewed. Logistic Regression was used to test for statistical significance. Results: 161 patients with bone metastasis secondary to breast cancer treated with bisphosphonates were reviewed (82 African American, 29 Caucasians, 26 Hispanic, 15 Asian and 9 others.). ONJ developed in 6 (3.7%) patients, 5 of which were Caucasians. Logistic regression adjusting for dose shows that the odds ratio for developing ONJ comparing Caucasians with non-Caucasians is 45.7 (p=0.016). Age did not impact occurrence of ONJ. All 6 patients developed ONJ after a minimum of 31 months of treatment. Two patients had a history of previous tooth extraction. In four other patients, ONJ appeared spontaneously. One patient, who presented with an abscess, developed sepsis which resulted in the patient’s death. Two patients were treated with debridement and antibiotics and their lesions healed. Three other patients ended up suffering from a chronically exposed bone. Conclusion: ONJ is a serious complication of bisphosphonate therapy and it affected a significant proportion of our patients. Our data suggests that Caucasians may be more susceptible. Since sample size is small, determining if race is a risk factor for the development of ONJ, while on bisphosphonate therapy, will require further investigation. No significant financial relationships to disclose.

Regarding “Recommendations for Zoledronic Acid Treatment of Patients with Bone Metastases”

The Oncologist 2005;10:304–305 www.TheOncologist.com As a cancer patient and advocate who has been receiving zoledronic acid for bone metastases since August 2002, I read Dr. James R. Berenson’s recent article, “Recommendations for Zoledronic Acid Treatment of Patients with Bone Metastases,” in The Oncologist [1] with concern regarding its failure to mention the association of osteonecrosis of the jaw (ONJ) with intravenous bisphosphonates. Since September 2003 when Marx first reported a 36-case series in the Journal of Oral and Maxillofacial Surgery [2], there has been an increasing number of published articles and research investigations into this serious condition found in some patients receiving intravenous bisphosphonates engendering awareness, debate, and study of the ONJ issue in the multiple myeloma medical and advocacy communities. Patient safety concerns prompted a post-marketing addition to the FDA-approved label for Zometa (zoledronic acid) Injection in August 2004 [3], and a related “Dear Doctor” letter from Novartis in September 2004 [4], that specifically warned of cases of osteonecrosis of the jaw in patients receiving bisphosphonates, most commonly in association with a dental procedure. Given the immediate implications for patient care and the stated CME objective of educating readers regarding “the types of adverse events associated with intravenous bisphosphonate therapy,” it is difficult to imagine how this potentially devastating complication was left out of Dr. Berenson’s article. Unfortunately, given Dr. Berenson’s financial relationships with Novartis (per disclosure, Dr. Berenson is a member of Novartis advisory board and a recipient of grants and honoraria from Novartis), the appearance of conflict of interest raises itself. The challenging issue of commercial bias in CME content is a timely one with a recent “perspective” piece by Robert Steinbrook, M.D., in the February 10, 2005, issue of the New England Journal of Medicine that discusses the updated ACCME standards for CME commercial conflictsof-interest [5, 6]. In seeking to provide unbiased CME content, I question the choice of a sole author, such as Dr. Berenson, who has financial ties to the manufacturer of the commercial product he is reviewing. Furthermore, the financial relationships of the members of the Monterey Zoledronic Acid Advisory Board (whom Dr. Berenson thanks for their “insight and input”) but who are not co-authors, and the Institute for Myeloma and Bone Cancer Research, of which Dr. Berenson is CEO and President, are not disclosed. Thus, a reader is left without information to mitigate conflict of interest as a possible explanation for Dr. Berenson’s omission of critical information from his CME review. Interestingly enough, the ONJ-bisphosphonate association was discussed in an article on the safety of intravenous and oral bisphosphonates published in the September 2004 supplement to The Oncologist. In my opinion, the absence of any information on the ONJ issue in Dr. Berenson’s review of zoledronic acid published in January 2005 points out a serious editorial inadequacy. I hope Dr. Berenson and the editors of The Oncologist will update The Oncologst’s CME exercise to include pertinent information that allows patients to take steps to reduce their risk of a potentially horrific complication of bisphosphonate therapy. It is heartening to see that The Oncologist has suspended CME activity and provided links to relevant information for its online readers. However, it is important that the author and editors take time to consider why a patient advocate, and someone potentially at-risk for bisphosphonate-related ONJ, finds the occurrence of this error of omission distressing and unacceptable—and why they should, too. The Oncologist Letter to the Editor

Renal Safety of Intravenous Ibandronic Acid in Breast Cancer Patients with Metastatic Bone Disease

Renal adverse events are a troublesome complication of bisphosphonate therapy. This study investigated the effect of intravenous ibandronic acid (ibandronate) treatment on renal function in breast cancer patients with metastatic bone disease. 74 patients were randomised to double-blind (but not dose-blind) treatment with bolus injections of ibandronic acid 2mg (n = 23), 1-hour infusions of ibandronic acid 6mg (n = 28), or placebo injections or infusions (n = 23). According to randomisation, patients received either three injections or three infusions over the 3-month period, one at the start and two subsequent doses at 4-weekly intervals. Measurements of urinary excretion of total protein, albumin, alpha(1)-microglobulin, N-acetyl-beta-D-glucosaminidase, haematuria and serum creatinine were performed before, during and after treatment. Treatment with ibandronic acid was not associated with impairment of renal function; the renal safety profiles of ibandronic acid 2 and 6mg were similar to that of placebo. Assessments of proteinuria, haematuria, enzymuria and serum creatinine indicated that there were no statistically significant changes between pre- and post-treatment levels in patients receiving ibandronic acid 2 or 6mg or between patients receiving ibandronic acid or placebo. Urine parameters varied during treatment in the same range with approximately similar frequency in the ibandronic acid and placebo groups. Short-term administration of intravenous ibandronic acid did not impair renal function in breast cancer patients with metastatic bone disease. Because tolerability profiles vary between bisphosphonates, the lack of renal toxicity with ibandronic acid makes the drug an attractive treatment option for metastatic bone disease.