The relationship between psychological conditions and recurrence of benign paroxysmal positional vertigo: a retrospective cohort study.

BACKGROUND: Psychological conditions have been found to be associated with an increased risk of incident benign paroxysmal positional vertigo (BPPV). However, much less is known on whether and how psychological conditions such as anxiety, insomnia and obsessive-compulsive disorder (OCD) affect the recurrence of BPPV. METHODS: A retrospective cohort study of 2,612 outpatients and inpatients diagnosed with BPPV between September 2012 and August 2020. BPPV recurrence was followed up until February 2021. The Cox proportional hazard regression was used to analyze the association between psychological conditions and the risk of the first recurrence. Poisson regression was applied to analyze the association between psychological conditions and the number of recurrences in patients with at least one relapse. RESULTS: During the follow-up, 391 patients had at least one BPPV recurrence. Female BPPV patients were more likely than male patients to experience relapses than male patients, but the characteristics of BPPV recurrence (number of recurrences and duration between recurrences) did not differ between men and women. After adjustment for sex, age and comorbidities, a heightened risk of first BPPV recurrence was found to be associated with anxiety (hazard ratio [HR]: 1.30, 95% confidence interval [CI]: 1.01, 1.68) and OCD (HR: 2.15, 95% CI: 1.31, 3.52). An increased risk of first BPPV recurrence associated with insomnia was only observed in male patients (HR: 2.22, 95% CI: 1.24, 3.98) but not in female patients (HR: 0.91, 95% CI: 0.63, 1.31). None of these psychological conditions were associated with the number of recurrences in patients who experienced recurrence. CONCLUSIONS: The presence of anxiety and OCD increased the risk of first BPPV recurrence, as well as insomnia for male patients. These psychological conditions were not associated with the number of BPPV recurrences. Diagnosis and treatment of these psychological conditions could be a useful strategy to prevent the recurrence of BPPV.

Osteoblast-specific inactivation of p53 results in locally increased bone formation.

Inactivation of the tumor suppressor p53 (encoded by the Trp53 gene) is relevant for development and growth of different cancers, including osteosarcoma, a primary bone tumor mostly affecting children and young adolescents. We have previously shown that deficiency of the ribosomal S6 kinase 2 (Rsk2) limits osteosarcoma growth in a transgenic mouse model overexpressing the proto-oncogene c-Fos. Our initial aim for the present study was to address the question, if Rsk2 deficiency would also influence osteosarcoma growth in another mouse model. For that purpose, we took advantage of Trp53fl/fl mice, which were crossed with Runx2Cre transgenic mice in order to inactivate p53 specifically in osteoblast lineage cells. However, since we unexpectedly identified Runx2Cre-mediated recombination also in the thymus, the majority of 6-month-old Trp53fl/fl;Runx2-Cre (thereafter termed Trp53Cre) animals displayed thymic lymphomas, similar to what has been described for Trp53-deficient mice. Since we did not detect osteosarcoma formation at that age, we could not follow our initial aim, but we studied the skeletal phenotype of Trp53Cre mice, with or without additional Rsk2 deficiency. Here we unexpectedly observed that Trp53Cre mice display a unique accumulation of trabecular bone in the midshaft region of the femur and the humerus, consistent with its previously established role as a negative regulator of osteoblastogenesis. Since this local bone mass increase in Trp53Cre mice was significantly reduced by Rsk2 deficiency, we isolated bone marrow cells from the different groups of mice and analyzed their behavior ex vivo. Here we observed a remarkable increase of colony formation, osteogenic differentiation and proliferation in Trp53Cre cultures, which was unaffected by Rsk2 deficiency. Our data thereby confirm a critical and tumorigenesis-independent function of p53 as a key regulator of mesenchymal cell differentiation.

Wnt1 is an Lrp5-independent bone-anabolic Wnt ligand.

WNT1 mutations in humans are associated with a new form of osteogenesis imperfecta and with early-onset osteoporosis, suggesting a key role of WNT1 in bone mass regulation. However, the general mode of action and the therapeutic potential of Wnt1 in clinically relevant situations such as aging remain to be established. Here, we report the high prevalence of heterozygous WNT1 mutations in patients with early-onset osteoporosis. We show that inactivation of Wnt1 in osteoblasts causes severe osteoporosis and spontaneous bone fractures in mice. In contrast, conditional Wnt1 expression in osteoblasts promoted rapid bone mass increase in developing young, adult, and aged mice by rapidly increasing osteoblast numbers and function. Contrary to current mechanistic models, loss of Lrp5, the co-receptor thought to transmit extracellular WNT signals during bone mass regulation, did not reduce the bone-anabolic effect of Wnt1, providing direct evidence that Wnt1 function does not require the LRP5 co-receptor. The identification of Wnt1 as a regulator of bone formation and remodeling provides the basis for development of Wnt1-targeting drugs for the treatment of osteoporosis.

[Changes of TGF-ß1 expression during orthodontic tooth movement in rats with osteoporosis].

PURPOSES: To observe the expression and distribution of TGF-ß1 in periodontal tissue under intervention of Strontium ranelate and Qianggu capsule during orthodontic tooth movement in rats, and explore the efficacy of the 2 drugs. METHODS: Seventy male SD rats of 3 months old were selected in the study, and randomly divided into control group, model control group, Strontium ranelate group, Qianggu capsule group, each group had 15 animals. Retinoic acid was given by gavage to animals in the control group, Strontium ranelate group, Qianggu capsule group for 2 weeks, and bone density was detected to determine successful establishment of osteoporosis model. All rats were installed orthodontic device, and were sacrificed at 7 days, 14 days and 21 days, respectively. The tissue blocks of the first maxillary molar and adjacent alveolar bone were taken for H-E staining, immunohistochemical staining and semi-quantitative analysis was used to detect TGF-ß1 expression in periodontal tissues. The data were statistically analyzed by SPSS 17.0 software package. RESULTS: TGF- beta 1 expression was significantly increased in Strontium ranelate group and Qianggu capsule group compared with control group (P<0.05); TGF- beta 1 expression in Strontium ranelate group was significantly stronger than that of Qianggu capsule group (P<0.05). CONCLUSIONS: Strontium ranelate and Qianggu capsule could enhance the expression of TGF- beta 1 and promote bone metabolism in osteoporosis rats, which is helpful to the movement of healthy teeth; the effect of Strontium ranelate is stronger than Qianggu capsule.

Early healing of hydroxyapatite-coated implants in grafted bone of zoledronic acid-treated osteoporotic rabbits.

BACKGROUND: Resorption of grafted bone and delayed osseointegration of implants are main problems associated with alveolar bone augmentation in dental implantology, especially for patients with osteoporosis. The aim of this study is to investigate the early healing response of implants to systemic treatment of zoledronic acid (ZA) in autogenous grafted iliac bone of osteoporotic rabbits. METHODS: Ovariectomy (OVX) or sham operation was performed in 46 rabbits, and osteoporotic changes were verified in animals receiving OVX 3 months later. The remaining animals were divided into three groups (n = 12): sham, OVX, and OVX with ZA treatment (ZA group). Autogenous iliac bone grafting was performed in bilateral tibiae, and hydroxyapatite-coated titanium implants were simultaneously placed into the grafted bone. The animals were sacrificed 2 and 8 weeks later for examination. RESULTS: At both time points, systemic treatment of ZA efficiently promoted bone healing of implants in grafted bone, and all histologic and microcomputed tomography bone indices, including mineralized bone volume, implant-bone contact ratio, connectivity density, trabecular thickness, and trabecular number, were significantly increased in the ZA group compared with the OVX-only group (P <0.01); implant-bone contact rates in the ZA group were even restored to levels similar to those of sham-operated animals (P >0.05). Furthermore, biomechanical testing demonstrated that removal torque of implants was significantly increased in the ZA group compared with the OVX group (P <0.01). CONCLUSION: Systemic treatment with ZA could efficiently promote early bone healing of implants in autogenous grafted bone of osteoporotic rabbits by increasing early osseointegration and fixation of implants.

[Effect of alendronate on expressions of osteoprotegerin and receptor activator of nuclear factor κB ligand in mouse osteoblasts].

OBJECTIVE: To investigate the effect of alendronate on the expressions of osteoprotegerin (OPG) and receptor activator of nuclear factor-κB ligand (RANKL) in mouse osteoblasts. METHODS: Mouse calvarial osteoblasts cultured in vitro were identified by alkaline phosphatase (ALP) staining and immunofluorescence assay of OPG and RANKL expressions. The second passage of the osteoblasts were treated with different concentrations of alendronate (10(-4) to 10(-7) mol/L) for 48 h, and the changes in OPG and RANKL mRNA and protein expressions were examined using real-time PCR and Western blotting, respectively. RESULTS: The isolated osteoblasts were positive for ALP and expressed OPG and RANKL. Real-time PCR and Western blotting showed that at the concentration of 1×10(-4) mol/L, alendronate caused an obvious down-regulation of OPG and RANKL expressions in the cells, whereas at lower concentrations, alendronate increased the expressions of both genes with the highest expressions occurring after treatment with 1×10(-5) mol/L. CONCLUSION: High concentrations of alendronate (>1×10(-4) mol/L) decrease the expressions of OPG and RANKL, whereas low concentrations (1×10(-5) to 1×10(-7) mol/L) increase their expressions in mouse osteoblasts cultured in vitro.