What is the most appropriate next step for a patient with osteoporosis and osteonecrosis of the jaw who has completed 2 years of Forteo (Teriparatide) treatment and still requires bone protection?

Sequential Therapy After Forteo in a Patient with Osteonecrosis of the Jaw

In a patient with osteoporosis and existing osteonecrosis of the jaw (ONJ) who has completed 2 years of Forteo (teriparatide), the most appropriate next step is to avoid all antiresorptive bone-targeted agents (bisphosphonates and denosumab) and instead continue teriparatide beyond 2 years if the patient remains at high fracture risk, or implement a drug holiday with calcium, vitamin D, and close monitoring if fracture risk has improved. 1

Rationale for Avoiding Standard Sequential Therapy

Why Bisphosphonates Are Contraindicated

• Bisphosphonates significantly increase the risk of ONJ progression and should be absolutely avoided in patients with existing ONJ. 2
• The ESMO guidelines explicitly state that patients with pre-existing ONJ should avoid invasive dental procedures during bisphosphonate therapy, and if invasive dental surgery is necessary, therapy should be deferred until complete healing. 2
• Multiple myeloma guidelines note that ONJ occurs in 1-2% of patients on bisphosphonates, and most patients who develop ONJ have pre-existing dental problems. 2
• The standard recommendation to start oral bisphosphonates (alendronate, risedronate) or IV bisphosphonates (zoledronic acid) immediately after teriparatide does not apply when ONJ is present. 3

Why Denosumab Is Also Contraindicated

• Denosumab carries similar or potentially higher risk for ONJ compared to bisphosphonates. 2, 4
• The ESMO bone health guidelines report that denosumab causes hypocalcemia more frequently than zoledronic acid (13% vs 6%) and has a 1-2% incidence of ONJ. 2
• Unlike bisphosphonates which are embedded in bone and slowly released, denosumab discontinuation causes rapid reversal of bone effects and increased fracture risk, making it particularly problematic in this clinical scenario. 4
• Denosumab should be avoided in patients with existing ONJ due to the risk of worsening the condition. 2

Alternative Management Strategy

Option 1: Extended Teriparatide Therapy (Preferred if High Fracture Risk Persists)

• The FDA label states that teriparatide use beyond 2 years should only be considered if a patient remains at or has returned to having a high risk for fracture. 1
• Emerging evidence suggests teriparatide may actually improve ONJ symptoms and promote bone healing in patients with bisphosphonate-related ONJ. 5, 6, 7
• Case reports demonstrate that teriparatide administration promotes bone formation and sequestration in ONJ patients, with clinical improvement of jaw symptoms occurring within 1-4 weeks. 5, 6, 7
• One case report showed successful treatment of denosumab-induced ONJ with teriparatide, achieving clinical benefits and CT healing within 2 months. 8
• If the patient remains at high fracture risk, continuing teriparatide beyond the standard 2-year duration is justified given the contraindication to standard antiresorptive sequential therapy. 1

Option 2: Drug Holiday with Supportive Care (If Fracture Risk Has Improved)

• If the patient's fracture risk has significantly improved after 2 years of teriparatide, implement a drug holiday with calcium (1000-1200 mg/day) and vitamin D (800 IU/day) supplementation. 2
• The EULAR/EFORT guidelines recommend adequate calcium intake of 1000-1200 mg/day together with vitamin D 800 IU/day when managing osteoporosis. 2
• Monitor bone mineral density via DEXA scan every 1-2 years to assess for bone loss. 2, 3
• Anti-fracture efficacy of teriparatide may persist for up to 18 months after discontinuation. 3

Critical Monitoring Requirements

ONJ Management During Treatment

• Maintain excellent oral hygiene and ensure regular dental/oral surgery review throughout any bone-targeted therapy. 2
• Avoid invasive dental procedures (extractions and implants) if possible. 2
• If tooth extraction cannot be avoided, use prophylactic antibiotics and suspend any bone-targeted agent until healing appears complete. 2
• The ESMO guidelines emphasize that oral hygiene, baseline dental evaluation for high-risk individuals, and avoidance of invasive dental surgery are essential to reduce ONJ risk. 2

Bone Health Monitoring

• Perform DEXA scans to assess bone mineral density response and guide treatment decisions. 3
• Monitor serum calcium levels, particularly if considering any future bone-targeted therapy. 2
• Assess biochemical markers of bone turnover if available to evaluate bone remodeling status. 3, 6
• Regular assessment of calcium and vitamin D status is recommended. 3

Common Pitfalls to Avoid

• Do not automatically transition to bisphosphonates or denosumab after completing teriparatide in a patient with existing ONJ - this represents the standard sequential therapy algorithm but is absolutely contraindicated in this clinical scenario. 3, 2
• Do not assume that the 2-year teriparatide limit is absolute - the FDA label specifically allows for extended use in patients who remain at high fracture risk, and this patient's ONJ represents a unique contraindication to standard alternatives. 1
• Do not discontinue all bone protection without a plan - even if stopping teriparatide, ensure adequate calcium and vitamin D supplementation with close monitoring. 2, 3
• Do not ignore the potential therapeutic benefit of teriparatide for ONJ itself - emerging evidence suggests teriparatide may actually help heal ONJ lesions while providing continued bone protection. 5, 6, 7, 8