In an Australian study reported in the Journal of Clinical Oncology, Sim et al found that the osteoanabolic agent teriparatide improved the rate of resolution of medication-related osteonecrosis of the jaw lesions vs placebo in a population of patients who had previous exposure to either bisphosphonate therapy or denosumab, primarily for malignant bone disease.
As noted by the investigators, medication-related osteonecrosis of the jaw is an infrequent but potentially serious condition associated with antiresorptive and antiangiogenic therapies. Teriparatide (recombinant human parathyroid hormone 1–34) is an osteoanabolic agent used to treat osteoporosis.
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Study Details
In the double-blind trial, 34 patients with established medication-related osteonecrosis of the jaw and a total of 47 distinct necrotic lesions were randomly assigned to receive 8 weeks of daily subcutaneous teriparatide at 20 µg (n =15) or placebo injections (n = 19) in addition to calcium and vitamin D supplementation and standard clinical care. Five patients in each group had two or more medication-related osteonecrosis of the jaw lesions.
The indication for antiresorptive therapy was treatment of malignant bone disease in 79% of patients. The primary outcome measure was clinical and radiologic resolution of medication-related osteonecrosis of the jaw lesions over 1 year. Study visits occurred at 0, 4, 8, 12, 24, 36, and 52 weeks.
Key Findings
Medication-related osteonecrosis of the jaw lesions progressively resolved in both groups, with resolution of 45.4% (odds ratio [OR] for resolution at each visit = 0.15, P < .001) in the teriparatide group and 33.3% (OR = 0.40, P = .003) in the placebo group at 52 weeks. The rate of resolution was significantly greater in the teriparatide group (P = .013).
The proportion of patients with at least one unresolved lesion at 52 weeks was 73.3% in the teriparatide group vs 72.2% in the placebo group (OR = 0.95, P > .999). The proportion of resolved lesions was nonsignificantly higher in the teriparatide group (OR = 1.67, P = .478). Reduction in bony defect size was observed in 80.0% of the teriparatide group vs 31.3% of the placebo group at 52 weeks (OR = 8.1, P = .017).
The most common adverse events of any grade in the teriparatide group were nausea/vomiting (33% vs 21% in placebo group), abdominal discomfort (20% vs 11%), and injection site reaction (20% vs 5%). Serious adverse events occurred in 20% vs 16%.
The investigators concluded, “Teriparatide improves the rate of resolution of medication-related osteonecrosis of the jaw lesions and represents an efficacious and safe treatment for it.”
Peter R. Ebeling, MBBS, MD, of the Department of Medicine, Monash University, Victoria, is the corresponding author for the Journal of Clinical Oncology article.
Disclosure: The study was supported by the Australian National Health and Medical Research Council. For full disclosures of the study authors, visit ascopubs.org.
