Which parathyroid hormone (PTH) receptor agonists are appropriate for patients with medication‑related osteonecrosis of the jaw (ONJ)?

Teriparatide as Adjunctive Therapy for MRONJ

Teriparatide (recombinant PTH 1-34) is the only PTH receptor agonist with evidence supporting its use as adjunctive therapy in patients with medication-related osteonecrosis of the jaw (MRONJ), though it is not included in current major guidelines and should be considered an off-label adjunctive treatment option rather than standard care.

Current Guideline Position

The ASCO/MASCC/ISOO 2019 guidelines 1 do not address PTH receptor agonists in their recommendations for MRONJ management. The guidelines focus on conservative measures as the initial approach, with ongoing collaboration between dental specialists and oncologists. This absence from guidelines reflects the limited evidence base at the time of publication, though emerging research suggests potential benefit.

Evidence for Teriparatide

Efficacy Data

The most compelling evidence comes from a 2026 systematic review and meta-analysis 2 that demonstrates:

• Pooled hazard ratio of 5.35 (95% CI: 3.14-9.13, p<0.0001) favoring teriparatide when used as adjunctive therapy
• Subgroup analysis by dosing regimen showed consistent effects:
  • Daily dosing: HR = 12.52 (95% CI: 5.75-27.23)
  • Weekly dosing: HR = 8.09 (95% CI: 3.59-18.26)
• At 6-month healing endpoint: pooled OR = 14.26 (95% CI: 2.83-71.77)

Clinical Outcomes

A 2025 study 3 of 76 MRONJ patients revealed that teriparatide-treated surgical patients experienced:

• Shorter treatment duration compared to non-TPTD patients
• Fewer surgical procedures required
• Significant increases in bone turnover markers (CTX, osteocalcin, 25(OH)D)
• Significant improvements in T-scores (lumbar spine and femur neck)

Treatment Protocol

Based on case reports 4, 5, successful teriparatide protocols include:

• Subcutaneous administration for 16-60 weeks (duration varies by case severity)
• Combined with surgical intervention (sequestrectomy, decortication, saucerization)
• Enhanced when combined with:
  • Bone morphogenetic protein
  • Platelet-rich fibrin
  • Antibiotic therapy

Alternative PTH Receptor Agonists

Abaloparatide and Romosozumab

A 2026 real-world study 6 compared romosozumab (which has dual antiresorptive/anabolic effects) to PTH analogs (teriparatide/abaloparatide):

• No increased MRONJ risk with romosozumab compared to PTH analogs (HR 0.89,95% CI: 0.39-2.01)
• Absolute event rates were very low in both groups (0.070% vs 0.076%)
• This suggests PTH analogs including abaloparatide do not increase MRONJ risk, but evidence for therapeutic benefit is limited to teriparatide

Clinical Algorithm for PTH Agonist Use in MRONJ

When to Consider Teriparatide:

1. Stage 2-3 MRONJ requiring surgical intervention
2. Refractory cases not responding to conservative management
3. Patients with osteoporosis as primary disease (dual indication)
4. No contraindications to PTH therapy (see below)

Contraindications to Screen For:

• Prior radiation therapy to skeleton
• Paget's disease of bone
• Unexplained elevated alkaline phosphatase
• Open epiphyses
• Bone metastases or skeletal malignancies
• Hypercalcemia

Dosing Approach:

• 20 mcg subcutaneous daily is the standard FDA-approved dose for osteoporosis
• Duration: Minimum 16 weeks, up to 60 weeks based on healing response
• Must coordinate with endocrinology/bone health specialist for prescription and monitoring

Monitoring Requirements:

• Baseline and periodic serum calcium levels
• Clinical assessment of MRONJ staging every 4-8 weeks
• Radiographic evaluation to assess bone healing

Important Caveats

Off-Label Use

Teriparatide use for MRONJ is off-label and not included in current ASCO/MASCC guidelines 1. The evidence base, while promising, consists primarily of case series and small cohort studies rather than large randomized controlled trials.

Not Monotherapy

Teriparatide should never be used as monotherapy for MRONJ. It functions as adjunctive therapy alongside:

• Conservative debridement/surgical management
• Antimicrobial therapy
• Optimization of oral hygiene
• Management of underlying risk factors

Serum Markers

A 2026 case-control study 7 found no significant differences in baseline PTH, vitamin D, or calcium levels between MRONJ patients and controls. This suggests these markers are not predictive of MRONJ development, though adequate vitamin D and calcium supplementation remains important for bone health.

Cost and Access Considerations

Teriparatide is expensive and requires daily subcutaneous injections, which may limit patient acceptance and access. Insurance coverage for off-label MRONJ indication varies.

Bottom Line

For patients with established MRONJ requiring surgical intervention, teriparatide represents the best-studied PTH receptor agonist option with evidence supporting accelerated healing and reduced surgical burden, but it must be used as adjunctive therapy in coordination with dental specialists and endocrinologists 2, 3. Other PTH analogs (abaloparatide) lack specific evidence for MRONJ treatment, though they appear safe in this population 6.