Jaw Osteonecrosis Risk Increases With More Bisphosphonate Infusions

CHICAGO — The risk of jaw osteonecrosis increases with the number of bisphosphonate infusions, according to studies presented at the annual meeting of the American Society of Clinical Oncology.

Osteonecrosis of the jaw (ONJ) is a rare but serious side effect of bisphosphonates that has popped up in a number of case reports in the literature. Three groups of researchers conducted retrospective analyses to understand the natural history, incidence, and risk factors of this side effect.

In one study, Dr. Tracey L. O'Connor of Roswell Park Cancer Institute in Buffalo, N.Y., and colleagues identified 354 patients with metastatic cancer involving bones on intravenous bisphosphonates between 2002 and 2006 at the Institute. Using dental records, they identified 25 patients (7%) with ONJ. Most (80%) had breast cancer, and 27% had a medical comorbidity such as diabetes mellitus, hypertension, or chronic anticoagulation therapy for deep vein thrombosis or pulmonary embolism. In general, patients who developed ONJ had more bisphosphonate infusions—an average of 11—versus patients without ONJ (an average of 7 infusions). Most ONJ patients (52%) had stage 1 disease (exposed necrotic cortical bone); 36% had stage 2 (localized involvement of the mandible); and 12% had stage 3 (diffuse involvement of the mandible). Most (84%) were managed with antibiotics; 16% had debridement and alveoplasty. “If detected early, ONJ can be conservatively managed,” the authors wrote.

To see if scintigraphy could predict ONJ, planar whole body scans were performed 3 hours after injection of Tc-99m methylene diphosphonate using anterior and posterior perspectives. Jaw uptake was graded relative to normal posterior uptake within the ileum (grade 1), sacrum (grade 2), and sacroiliac joints (grade 3). In ONJ patients, 14 had bone scans, and 13 showed grade 3 uptake. In comparison, 183 controls had bone scans; of these, 128 (70%) had grade 3 uptake. “Uptake on bone scans is not a reliable predictor of ONJ,” the authors wrote.

In another study, Dr. Matthew R. Stumpe, an otolaryngology resident at the University of Tennessee, Memphis, and colleagues performed a retrospective review of 638 patients treated with intravenous bisphosphonate therapy for cancer. The most common malignancies were prostate, lung, breast, and multiple myeloma. Most patients were treated with pamidronate (53%), followed by zoledronic acid (26%). The rest were treated with both drugs.

“Patients who developed osteonecrosis underwent a greater number of bisphosphonate infusions and greater total infusion hours, suggesting a positive correlation between osteonecrosis and drug dose,” the authors wrote. In all, six patients had ONJ, or 0.94%. Patients with ONJ had a significantly greater number of infusions (21), versus controls (11) and a significantly greater mean number of hours of infusion time (43 vs. 18). All ONJ patients presented with exposed bone. In four, ONJ occurred after dental treatment. The mandible was affected in five patients; the maxilla in one. Bisphosphonates were discontinued in five patients after ONJ diagnosis. The patient who did not stop had a small area of exposed bone covered surgically using viable mucosa. Another patient recovered from ONJ and resumed bisphosphonates.

Dr. Mimi I. Hu of the department of endocrine neoplasia and hormonal disorders at the University of Texas M.D. Anderson Cancer Center in Houston, and colleagues performed a retrospective analysis of patients treated with intravenous bisphosphonates between 1996 and 2004. They identified 4,025 patients; 35 had ONJ. Fourteen were followed for over 6 months at a dental clinic. Patients were evenly split between having breast cancer or multiple myeloma. The average length of exposed bone at the initial evaluation was 11 mm. Most (10) were treated with pamidronate followed by zoledronic acid. Four were treated with zoledronic acid alone. The median cumulative dose was 1,710 mg for pamidronate and 72 mg for zoledronic acid. The median duration of follow-up from initial diagnosis was 17 months.

The researchers focused on the natural course of ONJ. ONJ resolved in 21% of long-term follow-up patients. On the basis of the change in the lesion from baseline to last noted size, seven patients had progression. Two were stable, one regressed, one had recurrences at different sites over 67 months, and three had resolution for over a year. Modification of therapy doesn't appear linked to resolution, the researchers noted. In some patients, persistent ONJ was seen whether therapy was discontinued, decreased in frequency, or continued at the same dose and frequency. In others, resolution occurred if intravenous bisphosphonate therapy was discontinued, decreased in frequency, and replaced by weekly oral alendronate.

CHICAGO — The risk of jaw osteonecrosis increases with the number of bisphosphonate infusions, according to studies presented at the annual meeting of the American Society of Clinical Oncology.

Osteonecrosis of the jaw (ONJ) is a rare but serious side effect of bisphosphonates that has popped up in a number of case reports in the literature. Three groups of researchers conducted retrospective analyses to understand the natural history, incidence, and risk factors of this side effect.

In one study, Dr. Tracey L. O'Connor of Roswell Park Cancer Institute in Buffalo, N.Y., and colleagues identified 354 patients with metastatic cancer involving bones on intravenous bisphosphonates between 2002 and 2006 at the Institute. Using dental records, they identified 25 patients (7%) with ONJ. Most (80%) had breast cancer, and 27% had a medical comorbidity such as diabetes mellitus, hypertension, or chronic anticoagulation therapy for deep vein thrombosis or pulmonary embolism. In general, patients who developed ONJ had more bisphosphonate infusions—an average of 11—versus patients without ONJ (an average of 7 infusions). Most ONJ patients (52%) had stage 1 disease (exposed necrotic cortical bone); 36% had stage 2 (localized involvement of the mandible); and 12% had stage 3 (diffuse involvement of the mandible). Most (84%) were managed with antibiotics; 16% had debridement and alveoplasty. “If detected early, ONJ can be conservatively managed,” the authors wrote.

To see if scintigraphy could predict ONJ, planar whole body scans were performed 3 hours after injection of Tc-99m methylene diphosphonate using anterior and posterior perspectives. Jaw uptake was graded relative to normal posterior uptake within the ileum (grade 1), sacrum (grade 2), and sacroiliac joints (grade 3). In ONJ patients, 14 had bone scans, and 13 showed grade 3 uptake. In comparison, 183 controls had bone scans; of these, 128 (70%) had grade 3 uptake. “Uptake on bone scans is not a reliable predictor of ONJ,” the authors wrote.

In another study, Dr. Matthew R. Stumpe, an otolaryngology resident at the University of Tennessee, Memphis, and colleagues performed a retrospective review of 638 patients treated with intravenous bisphosphonate therapy for cancer. The most common malignancies were prostate, lung, breast, and multiple myeloma. Most patients were treated with pamidronate (53%), followed by zoledronic acid (26%). The rest were treated with both drugs.

“Patients who developed osteonecrosis underwent a greater number of bisphosphonate infusions and greater total infusion hours, suggesting a positive correlation between osteonecrosis and drug dose,” the authors wrote. In all, six patients had ONJ, or 0.94%. Patients with ONJ had a significantly greater number of infusions (21), versus controls (11) and a significantly greater mean number of hours of infusion time (43 vs. 18). All ONJ patients presented with exposed bone. In four, ONJ occurred after dental treatment. The mandible was affected in five patients; the maxilla in one. Bisphosphonates were discontinued in five patients after ONJ diagnosis. The patient who did not stop had a small area of exposed bone covered surgically using viable mucosa. Another patient recovered from ONJ and resumed bisphosphonates.

Dr. Mimi I. Hu of the department of endocrine neoplasia and hormonal disorders at the University of Texas M.D. Anderson Cancer Center in Houston, and colleagues performed a retrospective analysis of patients treated with intravenous bisphosphonates between 1996 and 2004. They identified 4,025 patients; 35 had ONJ. Fourteen were followed for over 6 months at a dental clinic. Patients were evenly split between having breast cancer or multiple myeloma. The average length of exposed bone at the initial evaluation was 11 mm. Most (10) were treated with pamidronate followed by zoledronic acid. Four were treated with zoledronic acid alone. The median cumulative dose was 1,710 mg for pamidronate and 72 mg for zoledronic acid. The median duration of follow-up from initial diagnosis was 17 months.

The researchers focused on the natural course of ONJ. ONJ resolved in 21% of long-term follow-up patients. On the basis of the change in the lesion from baseline to last noted size, seven patients had progression. Two were stable, one regressed, one had recurrences at different sites over 67 months, and three had resolution for over a year. Modification of therapy doesn't appear linked to resolution, the researchers noted. In some patients, persistent ONJ was seen whether therapy was discontinued, decreased in frequency, or continued at the same dose and frequency. In others, resolution occurred if intravenous bisphosphonate therapy was discontinued, decreased in frequency, and replaced by weekly oral alendronate.

CHICAGO — The risk of jaw osteonecrosis increases with the number of bisphosphonate infusions, according to studies presented at the annual meeting of the American Society of Clinical Oncology.

Osteonecrosis of the jaw (ONJ) is a rare but serious side effect of bisphosphonates that has popped up in a number of case reports in the literature. Three groups of researchers conducted retrospective analyses to understand the natural history, incidence, and risk factors of this side effect.

In one study, Dr. Tracey L. O'Connor of Roswell Park Cancer Institute in Buffalo, N.Y., and colleagues identified 354 patients with metastatic cancer involving bones on intravenous bisphosphonates between 2002 and 2006 at the Institute. Using dental records, they identified 25 patients (7%) with ONJ. Most (80%) had breast cancer, and 27% had a medical comorbidity such as diabetes mellitus, hypertension, or chronic anticoagulation therapy for deep vein thrombosis or pulmonary embolism. In general, patients who developed ONJ had more bisphosphonate infusions—an average of 11—versus patients without ONJ (an average of 7 infusions). Most ONJ patients (52%) had stage 1 disease (exposed necrotic cortical bone); 36% had stage 2 (localized involvement of the mandible); and 12% had stage 3 (diffuse involvement of the mandible). Most (84%) were managed with antibiotics; 16% had debridement and alveoplasty. “If detected early, ONJ can be conservatively managed,” the authors wrote.

To see if scintigraphy could predict ONJ, planar whole body scans were performed 3 hours after injection of Tc-99m methylene diphosphonate using anterior and posterior perspectives. Jaw uptake was graded relative to normal posterior uptake within the ileum (grade 1), sacrum (grade 2), and sacroiliac joints (grade 3). In ONJ patients, 14 had bone scans, and 13 showed grade 3 uptake. In comparison, 183 controls had bone scans; of these, 128 (70%) had grade 3 uptake. “Uptake on bone scans is not a reliable predictor of ONJ,” the authors wrote.

In another study, Dr. Matthew R. Stumpe, an otolaryngology resident at the University of Tennessee, Memphis, and colleagues performed a retrospective review of 638 patients treated with intravenous bisphosphonate therapy for cancer. The most common malignancies were prostate, lung, breast, and multiple myeloma. Most patients were treated with pamidronate (53%), followed by zoledronic acid (26%). The rest were treated with both drugs.

“Patients who developed osteonecrosis underwent a greater number of bisphosphonate infusions and greater total infusion hours, suggesting a positive correlation between osteonecrosis and drug dose,” the authors wrote. In all, six patients had ONJ, or 0.94%. Patients with ONJ had a significantly greater number of infusions (21), versus controls (11) and a significantly greater mean number of hours of infusion time (43 vs. 18). All ONJ patients presented with exposed bone. In four, ONJ occurred after dental treatment. The mandible was affected in five patients; the maxilla in one. Bisphosphonates were discontinued in five patients after ONJ diagnosis. The patient who did not stop had a small area of exposed bone covered surgically using viable mucosa. Another patient recovered from ONJ and resumed bisphosphonates.

Dr. Mimi I. Hu of the department of endocrine neoplasia and hormonal disorders at the University of Texas M.D. Anderson Cancer Center in Houston, and colleagues performed a retrospective analysis of patients treated with intravenous bisphosphonates between 1996 and 2004. They identified 4,025 patients; 35 had ONJ. Fourteen were followed for over 6 months at a dental clinic. Patients were evenly split between having breast cancer or multiple myeloma. The average length of exposed bone at the initial evaluation was 11 mm. Most (10) were treated with pamidronate followed by zoledronic acid. Four were treated with zoledronic acid alone. The median cumulative dose was 1,710 mg for pamidronate and 72 mg for zoledronic acid. The median duration of follow-up from initial diagnosis was 17 months.

The researchers focused on the natural course of ONJ. ONJ resolved in 21% of long-term follow-up patients. On the basis of the change in the lesion from baseline to last noted size, seven patients had progression. Two were stable, one regressed, one had recurrences at different sites over 67 months, and three had resolution for over a year. Modification of therapy doesn't appear linked to resolution, the researchers noted. In some patients, persistent ONJ was seen whether therapy was discontinued, decreased in frequency, or continued at the same dose and frequency. In others, resolution occurred if intravenous bisphosphonate therapy was discontinued, decreased in frequency, and replaced by weekly oral alendronate.