Should the risk of osteonecrosis of the jaw prevent consideration of Fosamax (alendronate)?

Should Osteonecrosis of the Jaw Risk Prevent Fosamax Use?

No, the risk of osteonecrosis of the jaw (ONJ) should not prevent consideration of Fosamax (alendronate) for osteoporosis treatment, as the benefits of fracture prevention substantially outweigh this rare complication in most patients.

Primary Recommendation

The American College of Physicians strongly recommends bisphosphonates, including alendronate, as first-line pharmacologic treatment for osteoporosis to reduce fracture risk 1. This recommendation is based on high-certainty evidence showing significant reductions in vertebral, hip, and nonvertebral fractures 1. The 2017 ACP guidelines similarly recommend offering alendronate to reduce hip and vertebral fractures in women with known osteoporosis 1.

Understanding the ONJ Risk in Context

Actual Incidence

• ONJ incidence with oral bisphosphonates like Fosamax is extremely low: approximately 1-2% overall 2
• More specifically, observational studies report ONJ incidence ranging from less than 1 to 28 cases per 100,000 person-years of treatment 1
• For osteoporosis treatment specifically, the incidence is 0.01% to 0.06% 1
• This risk is substantially lower than with intravenous bisphosphonates used in cancer treatment (0.7% to 12%) 3

Risk Increases with Duration

• ONJ risk correlates with treatment duration, particularly after 5 years of continuous use 4
• With alendronate specifically, ONJ typically appears after 1 year of use, increasing over time 4
• The FDA label confirms that ONJ risk may increase with duration of bisphosphonate exposure 5

Weighing Benefits Against Risks

Substantial Fracture Prevention Benefits

For secondary prevention (patients with existing osteoporosis or prior fractures), alendronate 10 mg daily provides 6:

• 45% relative risk reduction in vertebral fractures (6% absolute risk reduction)
• 53% relative risk reduction in hip fractures (1% absolute risk reduction)
• 50% relative risk reduction in wrist fractures (2% absolute risk reduction)
• 23% relative risk reduction in nonvertebral fractures (2% absolute risk reduction)

Risk-Benefit Analysis

The benefits of fracture prevention clearly outweigh the rare ONJ risk 1. High-quality evidence shows bisphosphonates and denosumab result in no differences in serious adverse events and withdrawals in randomized controlled trials 1. While observational studies show increased ONJ risk, this must be contextualized against the substantial morbidity and mortality from osteoporotic fractures.

Risk Mitigation Strategy

Before Starting Fosamax

• Complete dental evaluation and treat any active infections or high-risk dental sites before initiating bisphosphonates 2
• Ensure adequate calcium and vitamin D supplementation 2
• Correct hypocalcemia before starting therapy 5

During Treatment

• Maintain excellent oral hygiene throughout therapy 2
• Avoid invasive dental procedures when possible while on bisphosphonates 2
• Monitor for ONJ symptoms: exposed bone, non-healing tissue, loose teeth, or jaw pain 2

Treatment Duration Considerations

• Treat for 5 years initially, then reassess fracture risk and need for continuation 1
• Consider stopping bisphosphonate treatment after 5 years unless strong indication for continuation exists 1
• Current evidence suggests continuing beyond 5 years may reduce vertebral fractures but increases long-term harm risk 1

Important Caveats

ONJ Risk Factors

The FDA label identifies specific risk factors that increase ONJ likelihood 5:

• Invasive dental procedures (tooth extraction, dental implants, bone surgery)
• Cancer diagnosis
• Concomitant therapies (chemotherapy, corticosteroids, angiogenesis inhibitors)
• Poor oral hygiene
• Pre-existing dental disease, anemia, coagulopathy, infection

Not All Jaw Pain is ONJ

Rule out common dental problems before attributing jaw symptoms to ONJ 2. The National Comprehensive Cancer Network emphasizes excluding odontogenic (tooth-related) causes or mucosal inflammation that may mimic ONJ 2.

If ONJ Develops

• Conservative management with antibiotics and 0.12% chlorhexidine mouth rinses achieves pain-free status in 90.1% of patients 2
• Refer to oral surgeon for comprehensive evaluation 2
• Discontinuation of bisphosphonate therapy should be considered based on individual benefit/risk assessment 5
• Extensive dental surgery may exacerbate ONJ 5

Alternative Considerations

If ONJ develops or patient has multiple risk factors, consider 1, 2:

• Denosumab (RANK ligand inhibitor) as second-line treatment, though it also carries ONJ risk
• Raloxifene for younger postmenopausal women 1
• Teriparatide for severe osteoporosis or very high fracture risk 1

However, the 2023 ACP guidelines establish bisphosphonates as first-line therapy with the most favorable balance of benefits, harms, patient preferences, and cost 1.

Bottom Line

The extremely low incidence of ONJ (0.01-0.06%) should not deter appropriate osteoporosis treatment with Fosamax when fracture risk is significant. The substantial reductions in vertebral (45%), hip (53%), and other fractures far outweigh the rare ONJ complication 1, 6. Proper dental screening before treatment, excellent oral hygiene during therapy, and limiting duration to 5 years unless high-risk features persist effectively mitigates ONJ risk while preserving fracture prevention benefits 1, 2, 5.