Bisphosphonates Tied to High Jaw Necrosis Risk

SAN FRANCISCO — The prevalence of osteonecrosis of the jaw appears to be about 1 in 1,700 for adults taking long-term oral bisphosphonate therapy, according to an initial analysis of a group of Kaiser Permanente Northern California members.

Dr. Joan Lo surveyed 13,946 members who'd been taking oral bisphosphonates for at least 1 year and had no known exposure to intravenous bisphosphonate. The researchers received 8,568 responses to the mailed survey, which included questions about dental symptoms, said Dr. Lo, an endocrinologist at the Kaiser Permanente Division of Research, at the annual meeting of the Endocrine Society. Respondents who reported a diagnosis of osteonecrosis, or who reported exposed bone, periodontal disease, delayed bone healing, complications after invasive dental procedures, or persistent symptoms of concern were offered a dental exam by dentists on the PROBE study team. Cases of suspected osteonecrosis of the jaw (ONJ)—defined as exposed bone for greater than 8 weeks in the maxillofacial region, absent prior radiation—were referred for further examination by an oral surgeon. Dental records were reviewed in cases where patients declined a dental exam. Pharmacy records were also reviewed for all patients.

Of those who responded, about 6,402 patients did not have any symptoms of concern. A little more than 2,000 had symptoms of concern; 1,000 of those patients were examined by a dentist.

Dr. Lo said the team had identified eight cases of ONJ so far, for a prevalence of 0.09%, or 1 in 1,100. Three were localized to the palatal torus, and one in the mandible. The remaining four had bone exposure in the mandible following extraction. The confirmed cases had variable areas of bone exposure, variable locations, and various predisposing factors, she said.

In addition, the researchers identified an additional nine patients who had ONJ-like features but did not meet the classic definition of bisphosphonate-related ONJ. Three patients had signs of osteomyelitis of the mandible; an additional four had transient exposure, and another had a small area of bone exposure that persisted up to 1 year but eventually healed after a tooth extraction. The ninth patient had spontaneous tooth loss. Five had evidence of radiographic abnormalities, said Dr. Lo.

With these additional ONJ-like cases, the prevalence increased to 0.2%. Extrapolated to the entire cohort of patients taking bisphosphonates, the prevalence was 1 in 1,729, said Dr. Lo.

The current definition of bisphosphonate-related ONJ may not cover the spectrum of jaw complications seen in patients with long-term exposure, and may underestimate ONJ's prevalence, said Dr. Lo.

Such complications include nonhealing extraction sites and osteomyelitis or osteoporosis without exposed bone. The Kaiser researchers will continue to compile dental records to come up with a more accurate estimate of prevalence, she said.

Dr. Lo disclosed no conflicts of interest related to the study.

SAN FRANCISCO — The prevalence of osteonecrosis of the jaw appears to be about 1 in 1,700 for adults taking long-term oral bisphosphonate therapy, according to an initial analysis of a group of Kaiser Permanente Northern California members.

Dr. Joan Lo surveyed 13,946 members who'd been taking oral bisphosphonates for at least 1 year and had no known exposure to intravenous bisphosphonate. The researchers received 8,568 responses to the mailed survey, which included questions about dental symptoms, said Dr. Lo, an endocrinologist at the Kaiser Permanente Division of Research, at the annual meeting of the Endocrine Society. Respondents who reported a diagnosis of osteonecrosis, or who reported exposed bone, periodontal disease, delayed bone healing, complications after invasive dental procedures, or persistent symptoms of concern were offered a dental exam by dentists on the PROBE study team. Cases of suspected osteonecrosis of the jaw (ONJ)—defined as exposed bone for greater than 8 weeks in the maxillofacial region, absent prior radiation—were referred for further examination by an oral surgeon. Dental records were reviewed in cases where patients declined a dental exam. Pharmacy records were also reviewed for all patients.

Of those who responded, about 6,402 patients did not have any symptoms of concern. A little more than 2,000 had symptoms of concern; 1,000 of those patients were examined by a dentist.

Dr. Lo said the team had identified eight cases of ONJ so far, for a prevalence of 0.09%, or 1 in 1,100. Three were localized to the palatal torus, and one in the mandible. The remaining four had bone exposure in the mandible following extraction. The confirmed cases had variable areas of bone exposure, variable locations, and various predisposing factors, she said.

In addition, the researchers identified an additional nine patients who had ONJ-like features but did not meet the classic definition of bisphosphonate-related ONJ. Three patients had signs of osteomyelitis of the mandible; an additional four had transient exposure, and another had a small area of bone exposure that persisted up to 1 year but eventually healed after a tooth extraction. The ninth patient had spontaneous tooth loss. Five had evidence of radiographic abnormalities, said Dr. Lo.

With these additional ONJ-like cases, the prevalence increased to 0.2%. Extrapolated to the entire cohort of patients taking bisphosphonates, the prevalence was 1 in 1,729, said Dr. Lo.

The current definition of bisphosphonate-related ONJ may not cover the spectrum of jaw complications seen in patients with long-term exposure, and may underestimate ONJ's prevalence, said Dr. Lo.

Such complications include nonhealing extraction sites and osteomyelitis or osteoporosis without exposed bone. The Kaiser researchers will continue to compile dental records to come up with a more accurate estimate of prevalence, she said.

Dr. Lo disclosed no conflicts of interest related to the study.

SAN FRANCISCO — The prevalence of osteonecrosis of the jaw appears to be about 1 in 1,700 for adults taking long-term oral bisphosphonate therapy, according to an initial analysis of a group of Kaiser Permanente Northern California members.

Dr. Joan Lo surveyed 13,946 members who'd been taking oral bisphosphonates for at least 1 year and had no known exposure to intravenous bisphosphonate. The researchers received 8,568 responses to the mailed survey, which included questions about dental symptoms, said Dr. Lo, an endocrinologist at the Kaiser Permanente Division of Research, at the annual meeting of the Endocrine Society. Respondents who reported a diagnosis of osteonecrosis, or who reported exposed bone, periodontal disease, delayed bone healing, complications after invasive dental procedures, or persistent symptoms of concern were offered a dental exam by dentists on the PROBE study team. Cases of suspected osteonecrosis of the jaw (ONJ)—defined as exposed bone for greater than 8 weeks in the maxillofacial region, absent prior radiation—were referred for further examination by an oral surgeon. Dental records were reviewed in cases where patients declined a dental exam. Pharmacy records were also reviewed for all patients.

Of those who responded, about 6,402 patients did not have any symptoms of concern. A little more than 2,000 had symptoms of concern; 1,000 of those patients were examined by a dentist.

Dr. Lo said the team had identified eight cases of ONJ so far, for a prevalence of 0.09%, or 1 in 1,100. Three were localized to the palatal torus, and one in the mandible. The remaining four had bone exposure in the mandible following extraction. The confirmed cases had variable areas of bone exposure, variable locations, and various predisposing factors, she said.

In addition, the researchers identified an additional nine patients who had ONJ-like features but did not meet the classic definition of bisphosphonate-related ONJ. Three patients had signs of osteomyelitis of the mandible; an additional four had transient exposure, and another had a small area of bone exposure that persisted up to 1 year but eventually healed after a tooth extraction. The ninth patient had spontaneous tooth loss. Five had evidence of radiographic abnormalities, said Dr. Lo.

With these additional ONJ-like cases, the prevalence increased to 0.2%. Extrapolated to the entire cohort of patients taking bisphosphonates, the prevalence was 1 in 1,729, said Dr. Lo.

The current definition of bisphosphonate-related ONJ may not cover the spectrum of jaw complications seen in patients with long-term exposure, and may underestimate ONJ's prevalence, said Dr. Lo.

Such complications include nonhealing extraction sites and osteomyelitis or osteoporosis without exposed bone. The Kaiser researchers will continue to compile dental records to come up with a more accurate estimate of prevalence, she said.

Dr. Lo disclosed no conflicts of interest related to the study.