What is the annual incidence of bisphosphonate-related osteonecrosis of the jaw (BRONJ) in patients undergoing bisphosphonate treatment?

Annual Incidence of Bisphosphonate-Related Osteonecrosis of the Jaw

The annual incidence of bisphosphonate-related osteonecrosis of the jaw (BRONJ) ranges from less than 1 to 28 cases per 100,000 person-years for patients taking bisphosphonates for osteoporosis, with oral formulations having the lowest risk (0% to 0.5%) and intravenous bisphosphonates for cancer treatment having dramatically higher rates (1% to 12% at 36 months). 1

Incidence Stratified by Route and Indication

Oral Bisphosphonates for Osteoporosis (Lowest Risk)

• The incidence is less than 1 case per 100,000 person-years according to ASCO guidelines, with some estimates as low as 0% to 0.5% 1
• The American Society for Bone and Mineral Research estimates the risk between 1 in 10,000 to less than 1 in 100,000 patient-treatment years 2
• A systematic review confirmed the incidence is less than 1 case per 100,000 person-years of exposure in osteoporosis patients 3

Intravenous Bisphosphonates for Osteoporosis (Intermediate Risk)

• When administered every 6 months for osteoporosis prevention or treatment, the incidence is 0% to 1% 1
• This represents a substantially lower risk than monthly IV dosing used in oncology 1

Intravenous Bisphosphonates for Cancer (Highest Risk)

• The incidence ranges from 1% to 12% at 36 months of exposure in oncology patients receiving high-dose monthly IV bisphosphonates 3
• ASCO guidelines report 6.7% to 11% incidence in multiple myeloma patients receiving monthly high-dose IV bisphosphonates 4
• The risk is clearly 1 to 10 per 100 patients depending on duration of therapy 2

Critical Risk Modifiers

Duration and Dosing Schedule

• The incidence increases with extended durations of monthly IV bisphosphonates, especially exceeding 2 years 1
• Risk escalates with cumulative dose and frequency of administration 1
• The schedule of dosing profoundly influences incidence—monthly IV schedules carry far higher risk than every-6-month osteoporosis schedules 1

Dental Surgery as Primary Trigger

• At least 60% of BRONJ cases occur after dentoalveolar surgery, particularly tooth extractions 4
• Recent dental surgery or extraction is the most consistent risk factor for developing BRONJ 1, 4
• The risk of BRONJ increases dramatically when invasive dental procedures are performed during bisphosphonate therapy 4

Clinical Context and Interpretation

Absolute Risk Perspective

• For patients taking oral bisphosphonates like alendronate or risedronate for osteoporosis, BRONJ is exceedingly rare with an estimated incidence of approximately 0.7 cases per 100,000 person-years 5
• In the general oncology population receiving IV bisphosphonates, approximately 1 in 10,000 treated patients develop BRONJ 5
• The true incidence may be higher than initially reported as recognition and reporting have evolved 2

Route-Specific Risk Gradient

• Oral bisphosphonates carry the lowest risk (0% to 0.5%), followed by IV bisphosphonates for osteoporosis at 6-month intervals (0% to 1%), with monthly IV bisphosphonates for cancer having the highest risk (1% to 12% at 36 months) 1, 3
• This 10- to 100-fold difference in incidence between osteoporosis and cancer treatment regimens is critical for risk counseling 4

Important Caveats

• The incidence data are rapidly evolving, and prospective studies evaluating etiologic factors remain very limited 2, 3
• Current estimates are based on spontaneous reporting systems and retrospective reviews, which may underestimate true incidence 2
• The incidence in the general population (not receiving bisphosphonates) is not well established, making it difficult to determine the attributable risk 3