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.

AB0891 BARE TO THE BONE - AN AUDIT OF RENAL BONE DISEASE AGAINST KDIGO GUIDELINES

Background:Chronic kidney disease-mineral and bone disorder (CKD-MBD) is complex and management can be difficult. We aimed to compare management of our CKD patients to 2018 KDIGO guidelines. The guidelines suggest checking calcium and phosphate (Ca/PO4) within 12 mths in CKD 3a and 3b, within 6 mths for CKD 4, and within 3 mths for CKD 5. Parathyroid hormone (PTH) should be checked at baseline in CKD 3a-b, within 12 mths in CKD 4 and within 6mths in CKD 5. Alkaline phosphatase (ALP) should be measured within 12 mths in CKD 4 and 5. 25-(OH)D levels ‘might’ be measured at baseline in CKD 3a to 5D. BMD scanning is suggested if the result will impact treatment decisions. Lateral abdominal X ray is recommended as an alternative to CT for detection of vascular calcification. Calcitriol and vitamin D analogues are no longer routinely advised in CKD 3a-5; 25-(OH)D insufficiency should be corrected as in the normal population.Objectives:To compare management of our CKD patients to 2018 KDIGO guidelinesMethods:We randomly selected 70 patients in whom data was available from renal clinics between May and September 2019.Results:Mean age was 67.3 yrs. 41 male, 29 female. 33 patients had CKD 3a-b; 31 had CKD 4; 6 had CKD 5. Mean duration of CKD was 10.6 yrs. 10 patients were taking activated vitamin D analogues; 13 were taking 25-(OH)D analogues. 25-(OH)D levels ranged from 24-158 nmol/L (mean 65nmol/L). PTH levels ranged from 2- 69pmol/L (mean 23pmol/L). 3 patients were taking bisphosphonates. 44 had previous lumbar spinal imaging; vertebral fractures were evident in 4 (9%). 12 patients had had DXA scans; lowest T score was -2.5. Table 1 - tests within suggested time frames:CKD 3a-3bCKD 4CKD 5Ca/ PO433 (100%)29 (93%)6 (100%)ALP33 (100%)31 (100%)6 (100%)PTH14 (42%) (ever)8 (26%)3 (50%)25-(OH)D8 (24%) (ever)8 (26%) (ever)1 (14%)(ever)Conclusion:Optimum PTH levels in CKD patients are not known, and therapeutic options in CKD-MBD often limited. Nevertheless, our results suggest that bone biochemistry could be checked more consistently in CKD patients. Although detection of vascular calcification may not alter renal management, abdominal imaging provides an opportunity to screen for vertebral fracture, present in a significant number of our patients. The KDIGO guidelines offer a framework to work with our renal colleagues, as many patients will be jointly managed.References:[1]Diagnosis, Evaluation, Prevention, and Treatment of Chronic Kidney[2]Disease–Mineral and Bone Disorder: Synopsis of the Kidney Disease:[3]Improving Global Outcomes 2017 Clinical Practice Guideline Update. Ann Int Med 2018Disclosure of Interests:NATALIA CERNOVSCHI: None declared, SHABEENA ZEB: None declared, TRACEY SALTER: None declared, MARK LLOYD Speakers bureau: £700 into department fund