Osteonecrosis development by tooth extraction in zoledronate treated mice is inhibited by active vitamin D analogues, anti-inflammatory agents or antibiotics

Invasive dental treatment such as tooth extraction following treatment with strong anti-bone resorptive agents, including bisphosphonates and denosumab, reportedly promotes osteonecrosis of the jaw (ONJ) at the extraction site, but strategies to prevent ONJ remain unclear. Here we show that in mice, administration of either active vitamin D analogues, antibiotics or anti-inflammatory agents can prevent ONJ development induced by tooth extraction during treatment with the bisphosphonate zoledronate. Specifically, tooth extraction during treatment with zoledronate induced osteonecrosis in mice, but administration of either 1,25(OH)2D3 or ED71, both active vitamin D analogues, significantly antagonized osteonecrosis development, even under continuous zoledronate treatment. 1,25(OH)2D3 or ED71 administration also significantly inhibited osteocyte apoptosis induced by tooth extraction and bisphosphonate treatment. Administration of either active vitamin D analogue significantly inhibited elevation of serum inflammatory cytokine levels in mice in response to injection of lipopolysaccharide, an infection mimetic. Furthermore, administration of either anti-inflammatory or antibiotic reagents significantly blocked ONJ development following tooth extraction and zoledronate treatment. These findings suggest that administration of active vitamin D, anti-inflammatory agents or antibiotics could prevent ONJ development induced by tooth extraction in patients treated with zoledronate.

P1398EFFECTS OF CONVERTING FROM CINACALCET TO ETELCALCETIDE

Background and Aims Secondary hyperparathyroidism is a common problem in patients undergoing chronic hemodialysis and its treatment includes vitamin D analogs and calcimimetics which act upon the calcium-sensing receptor. Etelcalcetide was introduced as an intravenous calcimimetic easy to administer at the end of the hemodialysis session with improved adherence. Hypocalcemic episodes have raised some concerns although this side effect is not unanimously described. As an institutional policy most patients from 2 hemodialysis units were switched from cinacalcet to etelcalcetide between July 2017 and January 2018. We aimed at evaluating the impact of this conversion upon laboratory values and ongoing medication. Method We collected data from patients in 2 hemodialysis units including monthly serum values of calcium, phosphorus, hemoglobin and albumin, quarterly parathormone (PTH) values from 3 months previous to conversion until 3 months post-conversion as well as the calcimimetic dose during the same time frame. Descriptive statistics concerning mean and median values of the previous 3 and next 3 months following conversion were used. A paired sample t-test was performed to compare values before and after conversion. Results Of the approximately 200 patients, 22 were on cinacalcet and were switched to etelcalcetide. These had a mean age of 66.9 years and included 9 women and 8 diabetics. Mean PTH value before conversion was 728±391 (range 371-1900pg/mL) and did not differ significantly from that after conversion 717±330 (p=0.9). No significant statistical difference between values before and after conversion was found for serum calcium (9.3±0.5 vs 9.2±0.6; p=0.43), phosphorus (5.4±0.8 vs 5.1±1.0; p=0.15), albumin (4.1±0.2 vs 4.1±0.2; p=0.83) and hemoglobin (11.3±0.8 vs 11.4±0.9; p=0.50). The mean number of hypocalcemic values during the 3 months before and after conversion was identical (0.6±1 vs 0.6±0.9; p=0.86). The median cinacalcet dose on the month before conversion was 30mg/day (IQR 22.5) and the median etelcalcetide dose at conversion was 2.5mg three times per week (IQR 1.9). The conversion factor was 27mg cinacalcet: 1mg etelcalcetide, because even patients on high cinacalcet doses were initially started at low etelcalcetide doses. However, at 3 months following conversion, the median etelcalcetide dose was 8.75 (IQR 7.5). The doses of erythropoiesis-stimulating agents (ESA), vitamin D analogues and phosphorus binders were not significantly affected. Conclusion Switching from cinacalcet to etelcalcetide in all patients on hemodialysis in a particular institution did not change laboratory values or increased the number of hypocalcemic measurements. The etelcalcetide dose was adjusted up for the first 3 months and the mean PTH value did not change significantly. Treatment with ESA, vitamin D analogues and phosphorus binders remained unchanged after conversion. Secondary hyperparathyroidism is a chronic condition and etelcalcetide provides a useful means to control it with an easy administration regimen.