Eight weeks of daily subcutaneous injections of teriparatide, a parathyroid hormone analogue (PTH 1-34), were associated with an increased rate of resolution of medication-related osteonecrosis of the jaw (MRONJ) lesions, according to results of a small, placebo-controlled study reported in the Journal of Clinical Oncology.1
MRONJ is a relatively rare, but potentially serious adverse effect of antiresorptive therapy, including bisphosphonates and denosumab, particularly when administered at high doses for the treatment of malignant bone disease. With the current focus on prophylactic approaches for improving oral health as a means of preventing MRONJ, to date, no placebo-controlled randomized clinical trials have investigated interventions for the treatment of established MRONJ.
Based on limited data suggesting a potential benefit for teriparatide in the treatment of MRONJ, as well as the results of an 8-week study that investigated its use in the setting of chronic peritonitis, teriparatide, an agent that has been approved by the U.S. Food and Drug Administration (FDA) since 1987 for the treatment of patients with osteoporosis,2 was evaluated in a randomized, placebo-controlled trial of patients with established MRONJ.
This study (ACTRN12612000950864) enrolled 34 patients with MRONJ who were randomly assigned in a 1:1 ratio to receive 8 weeks of once-daily subcutaneous injections of either of teriparatide (20 µg/day; 19 patients) or saline (15 patients), with all patients receiving oral calcium carbonate and vitamin D, as well as standard clinical care for MRONJ.
All patients were followed for 12 months, and underwent oral examinations performed at 0, 4, 8, 12, 24, 36, and 52 weeks, conical beam computed tomography (CBCT) performed at 0, 4, 8, and 52 weeks, and 18F-fluoride positron emission tomography/computed tomography (PET/CT) imaging performed at 0 and 8 weeks.
Other assessments included quality of life using the Oral Health Impact 14 (OHIP-14) questionnaire, evaluation of bone mineral density at 0 and 52 weeks, and measurements of circulating markers of bone turnover, including procollagen type 1
N-propeptide (P1NP), at each study visit. The primary study outcome was resolution of MRONJ as measured by oral examination and CBCT imaging.
The median age of the study population was 64 years, and approximately 80% of patients had received antiresorptive therapy for malignant bone disease.
A key study finding was a higher percentage of resolution of MRONJ lesions at 52 weeks in those receiving teriparatide (45.4%) compared with placebo (33.3%), with corresponding odds ratios for MRONJ resolution of 0.15 compared with 0.40 (P =.013).
In addition, a higher proportion of patients receiving teriparatide (80.0%) showed increased bone volume and a reduction in the size of bony defects at 12 months compared with those receiving saline injections (31.3%; OR, 8.1; 95% CI, 1.36-66.20; P =.017).
Furthermore, the level of P1NP was 3 times higher at 4- and 8-week assessments for those treated with teriparatide compared with placebo (P =.001), and the former group was more likely to exhibit increased uptake on metabolic imaging compared with the latter.
“Our study shows that 8 weeks of once-per-day subcutaneous teriparatide injections improves the rate of resolution of established MRONJ lesions,” the study authors noted in conclusion. “Notwithstanding that most participants previously received high doses of potent antiresorptive therapies, teriparatide was able to elicit an osteoblastic response as demonstrated both biochemically and radiologically,” they added.
No significant differences between study groups were observed with respect to bone mineral density at any skeletal site, quality of life, or the frequency of adverse effects, including injection site reactions, gastrointestinal symptoms, and musculoskeletal pain.
While noting that these findings support “support the osteoanabolic action of teriparatide within the craniofacial region in the setting of MRONJ,” and stating that teriparatide “represents an efficacious and safe therapeutic option for MRONJ,” the study authors stressed the importance of limiting the cumulative dose of this agent given findings from preclinical studies showing an increased incidence of osteosarcoma in rats treated with teriparatide.
1. Sim J-W, Borromeo GL, Tsao C, et al. Teriparatide promotes bone healing in medication-related osteonecrosis of the jaw: a placebo-controlled, randomized trial [published July 2, 2020]. J Clin Oncol. doi: 10.1200/JCO.19.02192
2. Teraparatide (Forteo) [package insert]. Indianapolic, IN: Lilly USA, LLC; 2020.