BACKGROUND AND OBJECTIVES

Giant cell tumor of bone (GCTB) is a benign aggressive tumor primarily treated with surgery. Neoadjuvant treatment with denosumab or zoledronic acid is a common adjunct given to down-stage tumors and facilitate limb sparing surgery. This study sought to determine the characteristics, outcomes, and occurrence of complications following resection (RS) or extended curettage (EC) for GCTB of the lower extremities. Correlation of neoadjuvant therapy with the occurrence of complications was also investigated.

This is an analytical cross-sectional study of 30 patients diagnosed with GCTB of the lower extremity treated between 2015 to 2022 in a single tertiary hospital. Functional outcomes were determined using the 1993 version of the Musculoskeletal Tumor Society (MSTS) score. Mean follow-up for all patients was 2.6 years (SD 1.8). Twenty-two patients (73%) underwent resection, while eight (27%) patients underwent extended curettage. Of the 30 patients, 26 (87%) patients received neoadjuvant therapy, with 21 (81%) given denosumab and five (19%) given zoledronic acid.

Functional outcomes were excellent for 23 patients (77%), with no significant difference between RS and EC groups. Nine complications occurred in the RS group, including dehiscence (n=3), superficial infection (n=2), implant failure (n=1), nonunion (n=1), palsy (n=1), and implant irritation (n=1). Five complications occurred in the EC group, four of which were noted to be recurrences, with one case of deep infection. Recurrence was noted to be significantly higher (p=0.0004) in the EC group. Separate correlation analysis showed no significant difference in incidence of complications but found that duration of surgery was significantly longer (p=0.0001), and intraoperative blood loss was significantly higher (p=0.0072) in the RS group. No significant difference (p=0.78) was noted in complication rate between patients given denosumab versus zoledronic acid.

Functional outcomes of EC and RS appear to be comparable, including the incidence of complications. However, recurrence was noted to be significantly higher in EC. There appears to be no clear advantage between denosumab or zoledronic acid for GCTB. As a neoadjuvant medication and/or to control tumor progression, zoledronic acid may be the more economic option especially for patients in developing countries.

Bacterial infection is a common finding in patients, who develop medication-related osteonecrosis of the jaw (MRONJ) by the long-term and/or high-dose use of anti-resorptive agents such as bisphosphonate (BPs). However, pathological role of bacteria in MRONJ development at the early stage remains controversial. Here, we demonstrated that commensal microbiota protects against MRONJ development in the pulp-exposed periapical periodontitis mouse model. C57/BL6 female mice were treated with intragastric broad-spectrum antibiotics for 1 week. Zoledronic acid (ZOL) through intravenous injection and antibiotics in drinking water were administered for throughout the experiment. Pulp was exposed on the left maxillary first molar, then the mice were left for 5 weeks after which bilateral maxillary first molar was extracted and mice were left for additional 3 weeks to heal. All mice were harvested, and cecum, maxilla, and femurs were collected. ONJ development was assessed using μCT and histologic analyses. When antibiotic was treated in mice, these mice had no weight changes, but developed significantly enlarged ceca compared to the control group (CTL mice). Periapical bone resorption prior to the tooth extraction was similarly prevented when treated with antibiotics, which was confirmed by decreased osteoclasts and inflammation. ZOL treatment with pulp exposure significantly increased bone necrosis as determined by empty lacunae and necrotic bone amount. Furthermore, antibiotics treatment could further exacerbate bone necrosis, with increased osteoclast number. Our findings suggest that the commensal microbiome may play protective role, rather than pathological role, in the early stages of MRONJ development.
Animals ; Bisphosphonate-Associated Osteonecrosis of the Jaw/prevention & control* ; Bone Density Conservation Agents ; Diphosphonates ; Female ; Humans ; Mice ; Microbiota ; Periapical Diseases ; Zoledronic Acid

OBJECTIVE: To explore the clinical effect of zoledronic acid combined with vitamin K2 regimen in percutaneous vertebroplasty for multi-segment osteoporotic vertebral compression fractures(OVCFs). METHODS: This study was a retrospective control study. A total of 364 patients with OVCFs who were admitted to our spinal surgery department from January 2014 to January 2017 were selected as the study subjects. According to whether zoledronic acid combined with vitamin K2 was used to treat osteoporosis after surgery, the patients were divided into control group and experimental group. Among them, 257 patients in the control group were treated with calcium carbonate and vitamin D regimen, while 107 patients in the experimental group were treated with zoledronic acid combined with vitamin K2 regimen on the basis of the control group. Visual analogue scale (VAS) score and Oswestry Disability Index (ODI) were used to evaluate the clinical effect. Pre- and post-operative bone mineral density of lumbar spine and proximal femur, vertebral height ratio of responsible vertebral body and Cobb angle of vertebral body were observed by image data. Serological indicators related to bone metabolism were detected by laboratory. The complications such as fever, dizziness, osteoarthritis, muscular and soft tissue pain and adjacent vertebral re-fracture were compared between two groups. RESULTS: There was no significant difference in general data between the two groups (<0.05). There was no significant difference in VAS score between experimental group and control group before and 24 hours after operation (>0.05);VAS score in the experimental group was significantly lower than that in the control group 1 month, 3 months and 1 year after operation(<0.05). There was no significant difference in ODI between two groups before operation(>0.05), and at the 24 hours, 3 months, 1 year after operation, the experimental group was significantly lower than the control group (<0.05). There was no significant difference in the vertebral height ratio of the responsible vertebral body and the Cobb angle before operation between two groups (>0.05). The vertebral height ratio of the responsible vertebral body in experimental group was significantly higher than that in control group and Cobb angle in experimental group was significantly lower than that in control group at 3 months and 1 year after operation (<0.05). There was no significant difference in preoperative bone mineral density of lumbar spine and proximal femur between two groups (>0.05), but at 3 months and 1 year after operation, the bone mineral density of lumbar spine and proximal femur in experimental group was significantly lower than that in control group (< 0.05). There was no significant difference in preoperative bone metabolic markers such as total type I collagen amino-terminal elongation peptide, β-collagen degradation products and 25-hydroxyvitamin D between two groups (>0.05). At 1 year after operation the total type I collagen amino-terminal elongation peptide and β-collagen degradation products in experimental group was significantly lower than that in the control group (<0.05), but the 25-hydroxyvitamin D operation in experimental group was significantly higher than that in control group(<0.05). The incidence of postoperative complications such as fever, dizziness, osteoarthritis, muscle and soft tissue pain and adjacent vertebral re-fracture in experimental group was significantly lower than that in control group (<0.05). CONCLUSION Zoledronic acid injection combined with vitamin K2 regimen can be used for anti-osteoporosis treatment of OVCFs vertebroplasty. It has a definite curative effect and a high safety factor. It is worth popularizing.
Bone Cements ; Fractures, Compression ; Humans ; Kyphoplasty ; Osteoporotic Fractures ; Retrospective Studies ; Spinal Fractures ; Treatment Outcome ; Vertebroplasty ; Vitamin K 2 ; Zoledronic Acid

OBJECTIVE: To investigate the clinical efficacy of vertebral body stent (VBS) system and percutanous kyphoplasty (PKP) combined with zoledronic acid for the treatment of severely osteoporotic compression vertebral fractures (OVCFs). METHODS: The clinical data of 48 patients with osteoporotic thoracolumbar fractures treated from December 2017 to December 2018 were retrospectively analyzed, including 13 males and 35 females, aged 55 to 92 years old with an average (71.2±10.5) years. All patients were treated with VBS system PKP surgery, and zoledronic acid injection was used for anti-osteoporosis treatment after operation. The VAS scores ODI, the height of diseasedvertebral lost were compared before operation, 3 d and half a year after operation, and whether there was re-fracture of diseased or adjacent vertevrae after operation was observed. RESULTS: Before operation, 3 d and half a year after operation, VAS scores were 7.60±0.12, 3.00±0.46, 1.20±0.23, ODI were(82.00±0.32)%, (30.00±1.50) %, (18.00±0.16) %, the height of diseased vertebral lost were (12.00±0.43) mm, (3.00± 0.15) mm, (3.60±0.51) mm respectively. Postoperative VAS score, ODI, the height of diseased vertebral lost were obviously improved (<0.05), and there was no significant difference between 3 d and half a year after operation (>0.05). All the 48 patients were followed up with an average time of (6.6±0.5) months. All the incisions healed at grade A after operation, and no re-fracture of diseased vertebrae or adjacent vertebrae was found at the final follow-up. CONCLUSION VBS system and PKP combined with zoledronic acid in the treatment of OVCFs not only may effectively relieve the pain in the thoracolumbar back, improve the mobility of the thoracolumbar, but also can restore the height of the vertebral body to the maximum extent, and prevent the re-fracture of the affected vertebrae and adjacent vertebrae, which is worthy to spread in clinic.
Aged ; Aged, 80 and over ; Bone Cements ; Female ; Fractures, Compression ; Humans ; Kyphoplasty ; Male ; Middle Aged ; Osteoporotic Fractures ; Retrospective Studies ; Spinal Fractures ; Stents ; Treatment Outcome ; Zoledronic Acid

OBJECTIVE: To investigate the effect of zoledronate (ZOL) on osteoclast differentiation and bone resorption under high glucose, and the regulation mechanism of p38 mitogen activated kinase (p38 MAPK) signaling pathway in this process. METHODS: RAW264.7 cells were divided into four groups: low group, high group, low+ZOL group and high+ZOL group after induced into osteoclasts. Cell proliferation activity was determined by MTT assay. The migration of RAW264.7 cells were examined Optical microscopy. Immunofluorescence microscopy was used to observe the cytoskeleton and sealing zones of osteoclasts. After adding group 5: high + ZOL + SB203580 group, trap staining was used to identify the number of positive osteoclasts in each group. The number and area of resorption lacunae were observed by SEM. The mRNA and protein expression of osteoclast related factors were detected by real-time PCR and Western blotting. RESULTS: The cells in the 5 groups showed similar proliferative activity. High glucose promoted the migration of RAW264.7 cells ( CONCLUSIONS High glucose inhibits osteoclast differentiation and bone resorption. ZOL inhibits osteoclast differentiation and bone resorption in high-glucose conditions by regulating p38 MAPK pathway, which can be a new pathway for ZOL to regulate diabetic osteoporosis.
Animals ; Bone Resorption ; Cell Differentiation ; Glucose ; MAP Kinase Signaling System ; Mice ; NFATC Transcription Factors ; Osteoclasts ; RANK Ligand ; Zoledronic Acid/pharmacology* ; p38 Mitogen-Activated Protein Kinases