Management of medication‐related osteonecrosis of jaw: Comparison between icariin and teriparatide in a rat model

Abstract

Background The aim of this study is to compare the effects of icariin and teriparatide on the treatment of medication‐related osteonecrosis of the jaw (MRONJ) using a rat model. Methods Fifty rats undergoing ovariectomy were randomly assigned to control group (n = 10) and the MRONJ model group (n = 40). Zoledronic acid (0.2 mg/kg) and dexamethasone (2 mg/kg) were injected into rats in the model group for 8 weeks while saline was applied in control group, then all rats underwent tooth extraction and bone defect. Eight weeks later, rats diagnosed with MRONJ (n = 33) were randomly distributed to icariin (n = 11), teriparatide (n = 11), and the untreated (n = 11) group, and rats received daily 150 mg/kg icariin, 20 µg/kg teriparatide, and no intervention, respectively, for 8 weeks. Then, mandibulars were dissected for later examination. Results Rats diagnosed with MRONJ (33/40) demonstrated significantly larger area of soft tissue wound and necrotic bone with higher ratio of empty bone lacuna. Area of soft tissue wound and ratio of empty bone lacuna were significantly decreased in the icariin group compared with the untreated group, while teriparatide group revealed significantly higher ratio of receptor activator of NF‐kB ligand (RANKL)‐positive osteocytes, smaller area of necrotic bone and lower ratio of empty lacuna. The two agents were related to higher expression of BMP‐2 in osteocytes but were not statistically significant. Conclusions Icariin benefits MRONJ in terms of the area of soft tissue wound and ratio of empty lacuna. Teriparatide activates expression of RANKL and reduces the area of bone necrosis and ratio of empty lacuna in a MRONJ lesion. The data suggest possible healing improvement in patients with MRONJ and further studies to prove the efficacy of icariin.

Establishment and assessment of rodent models of medication-related osteonecrosis of the jaw (MRONJ)

“… Bone exposure 30 , 44 , 45 , 47 , 62 , 64 , 67 , 72 , 93 – 96 Indicated by the area, time of bone exposure. Histopathological assessments Healing conditions 59 , 60 , 63 , 98 Histological sections show the soft tissue healing with the distance between the edges of the epithelia, and bone defects with the length of the necrotic bone exposed towards the oral cavity. Necrotic bone 49 , 57 – 59 , 64 , 69 , 72 , 96 , 100 The presence of necrotic bone represents the occurrence of MRONJ.…”

“…The definition of necrotic bone depends on the number of confluent empty or karyolytic osteocytic lacunae. Empty bone lacunae 30 , 45 , 95 , 96 , 98 The proportion or the number of empty bone lacunae in a certain area indicates the degree of osteocyte loss, which present the bone necrosis. TRAP + osteoclast 44 , 49 , 57 , 58 , 64 , 67 , 69 , 72 , 93 , 95 – 101 The TRAP + osteoclasts present the bone resorption, commonly used indicators including numbers of osteoclast per area or per bone line.…”

“… Inflammation 49 , 67 , 99 The extent of inflammation is assessed by the number of polymorphonuclear cells under fixed area, as well as the infiltration and bone sequestra. Serological assessments VEGF 67 , 98 , 103 Serum VEGF presents the angiogenic ability of MRONJ. GluOC 64 /CTX-1 98 /TRAcP-5b 64 /P1NP 64 Bone metabolism markers of MRONJ under further exploration.…”

“… Serological assessments VEGF 67 , 98 , 103 Serum VEGF presents the angiogenic ability of MRONJ. GluOC 64 /CTX-1 98 /TRAcP-5b 64 /P1NP 64 Bone metabolism markers of MRONJ under further exploration. Radiographic assessments μCT To present bone healing conditions, bone sequestra formation of MRONJ, with parameters of bone volume/tissue volume 30 , 48 , 59 , 60 , 69 , 95 – 98 , 100 , 101 , 103 , 104 , trabecular separation 69 , 96 , 98 , 100 , 104 , trabecular thickness, trabecular number and bone volume/tissue volume representing bone morphological markers related to the early stage of MRONJ.…”

Parathyroid Hormone 1 Receptor Signaling in Dental Mesenchymal Stem Cells: Basic and Clinical Implications

“…An animal model showed that in addition to BRONJ treatment, PTH also has potential to prevent the development of jaw necrotic lesions by maintaining osteocyte survival ( Kuroshima et al, 2014a ). The administration of teriparatide led to a higher ratio of RANKL-positive osteocytes ( Liu J. et al, 2020 ). Another study that applied different doses of teriparatide suggested that its therapeutic effect may not be dose dependent ( Yu and Su, 2020 ).…”