Bisphosphonate Withdrawal: Effects on Bone Formation and Bone Resorption in Maturing Male Mice

Bisphosphonates are being increasingly used to treat pediatric patients with skeletal disorders. However, the effects of long‐term bisphosphonate therapy and cessation of therapy during growth are unclear. Thus, studies were undertaken to determine the effects of alendronate discontinuation after treatment of C57Bl/6 mice during the period of rapid skeletal growth. Compared with vehicle‐treated mice, 16 weeks of alendronate treatment starting at age 18 days resulted in a 3.7‐fold increase in trabecular bone in the setting of suppressed bone formation. Alendronate therapy for 8 weeks followed by 8 weeks of vehicle treatment resulted in a more pronounced increase in trabecular bone compared with mice treated with alendronate for 16 weeks (1.7‐fold) and to vehicle‐treated controls (6.5‐fold). Mice that received alendronate for 8 weeks followed by 8 weeks of vehicle exhibited increased osteoblast surface (2.5‐fold), mineralizing surface (5.7‐fold), and bone formation rate (5.1‐fold) compared with mice treated continuously with alendronate. However, these parameters were not restored to the levels observed in the vehicle‐treated mice. Thus, partial resumption of bone formation upon cessation of bisphosphonate therapy leads to a greater increase in trabecular bone than that found when bisphosphonates are administered continuously to growing mice. These data suggest that intermittent administration of bisphosphonates may optimize their beneficial effects on the growing skeleton. © 2017 American Society for Bone and Mineral Research.     

隐匿性甲状腺癌淋巴结及血行转移因素分析

目的　探讨隐匿性甲状腺癌淋巴结及血行转移特点,为手术治疗提供依据。方法　对６４ 例隐匿性甲状腺癌临床资料进行回顾性分析。结果　颈淋巴结转移３９ 例,转移率６０．９ ％ ;血行转移３ 例,转移率４．６ ％ 。转移与病理类型及肿瘤局部浸润程度有关,与原发灶大小无关。结论　隐匿性甲状腺癌转移特点与其同型的显性甲状腺癌相一致,治疗应遵循同类型显性癌的治疗原则。     

重症急性胰腺炎的非手术治疗

目的评估重症急性胰腺炎的非手术适应证。方法对１９９２年３月～１９９７年１０月我院１１２例急性胰腺炎非手术治疗病例进行了前瞻性研究。男４４例,女６８例,年龄２６～９１岁（平均５１９±１４３岁）,其中重症急性胰腺炎１００例。结果本组仅５例死亡,４例中转手术。大多数重症急性胰腺炎,包括有严重并发症者、老龄患者、伴发有其他系统疾病者可通过非手术治疗而治愈。结论重症急性胰腺炎非手术治疗适应于除胰周脓肿外的所有急性胰腺炎患者。     

Glucocorticoids Decrease Longitudinal Bone Growth in Pediatric Kidney Transplant Recipients by Stimulating the FGF23/FGFR3 Signaling Pathway

Renal transplantation (RTx) is an effective therapy to improve clinical outcomes in pediatric patients with terminal chronic kidney disease. However, chronic immunosuppression with glucocorticoids (GCs) reduces bone growth and BMD. The mechanisms causing GC-induced growth impairment have not been fully clarified. Fibroblast growth factor 23 (FGF23) is a peptide hormone that regulates phosphate homeostasis and bone growth. In pathological conditions, FGF23 excess or abnormal FGF receptors (FGFR) activity leads to bone growth impairment. Experimental data indicate that FGF23 expression is induced by chronic GC exposure. Therefore, we hypothesize that GCs impair bone growth by increasing FGF23 expression, which has direct effects on bone growth plate. In a post hoc analysis of a multicentric randomized clinical trial of prepubertal RTx children treated with early GC withdrawal or chronic GC treatment, we observed that GC withdrawal was associated with improvement in longitudinal growth and BMD, and lower plasma FGF23 levels as compared with a chronic GC group. In prepubertal rats, GC-induced bone growth retardation correlated with increased plasma FGF23 and bone FGF23 expression. Additionally, GC treatment decreased FGFR1 expression whereas it increased FGFR3 expression in mouse tibia explants. The GC-induced bone growth impairment in tibiae explants was prevented by blockade of FGF23 receptors using either a pan-FGFR antagonist (PD173074), a C-terminal FGF23 peptide (FGF23180-205) which blocks the binding of FGF23 to the FGFR-Klotho complex or a specific FGFR3 antagonist (P3). Finally, local administration of PD173074 into the tibia growth plate ameliorated cartilage growth impairment in GC-treated rats. These results show that GC treatment partially reduces longitudinal bone growth via upregulation of FGF23 and FGFR3 expression, thus suggesting that the FGF23/Klotho/FGFR3 axis at the growth plate could be a potential therapeutic target for the management of GC-induced growth impairment in children.     

火针对实验性小鼠膝骨关节炎关节软骨病理改变的影响

【目的】观察火针对实验性小鼠膝骨关节炎关节软骨病理改变的影响。【方法】将64只NIH小鼠随机分成火针组、电针组、模型组和正常组,采用谢氏法复制膝骨关节炎模型,火针组和电针组分别给予火针、电针治疗2周。【结果】火针组和电针组的小鼠右后膝关节活动角度增大,与模型组比较差异具有显著性意义（P〈0．01）;且火针组增大较电针组显著（P〈0．01）;火针组和电针组的小鼠右后膝关节软骨病变积分与模型组比较具有显著性差异（P〈O．01）。【结论】火针能抑制实验性小鼠膝骨关节炎关节软骨的病变发展,并能较好地改善膝关节的活动角度。     

Crose氏改良根治术治疗乳癌

目的 探讨Crose氏改良根治术治疗乳癌的疗效。方法 对采用Crose氏改良根治术114例（C组）,Halsted根治术205例（H组）的乳癌患者的临床资料进行回顾性分析和对比。结果 319例中,278例获随访（C组98例,H组180例）,随访3－14年。随访3年以上278例（C组98例,H组180例）,5年以上216例（C组56例,H组160例）,10年以上69例（C组31例,H组38例）。C组和H组,3,5,10年生存率分别为100％,85．71％,70．97％和95．6％,83．13％,71．05％;3,5,10年局部复发率为4．08％,7．1％,6．45％和3．98％,6．88％,5．26％,3,5,10年远处转移率分别为6．1％,12．5％,12．9％和6．67％,11．25％,15．79％,两组各指标均无显著差异（P＞0．05）。而C组患者上肢活动功能较H组明显为佳（P＜0．01）。结论 Crose氏改良根治术治疗乳癌,其根治性疗效同Halsted根治术,而患侧上肢功能好,并发症少,是一种有效、满意的方法。     

Violence Prevention in a Small-scale Psychiatric Unit: Program Planning and Evaluation

Abstract

Aggression against nurses and ancillary personnel is a major—overall under-reported—occupational problem in sociomedical facilities for psychiatric and demented patients. The frequency of violent incidents against workers in a residential rehabilitation unit was assessed during medical examinations in the workplace between 1996 and 2009. The majority of the workers had been subjected to physical aggression over time. A violence prevention program that included educational, organizational, and medical measures was implemented in 2002. Interrupted time series analysis showed that the aggression trend prior to intervention was flat (β₁ = –0.004; SD = 0.003; P = 0.241), while there was a significant drop in aggressions after the intervention (β₂ = –0.149; SD = 0.018; P < 0.0001). No late increase in trend was observed in the post-intervention period (β₃ = –0.006; SD = 0.004; P = 0.175). The program contributed to reducing violence in the workplace.     

低频脉冲超声波促进骨折愈合的实验研究与临床观察

对超声波的促进骨折愈合作用进行了动物实验和临床初步观察。Ｘ线检查显示实验侧骨缺损处新生骨痂各阶段普遍比对照侧出现早且多；组织学观察显示实验侧骨折修复较对照例明显加快；生物力学测试显示实验侧最大扭矩、最大刚度、最大能量吸收平均高于对照例４２．３～４８．９％，转角８°时各指标平均高于对照例５５．３～６６．２％。临床观察结果显示该法能较快消除肿胀、疼痛，加速骨痂形成，缩短临床愈合过程。上述结果表明低频脉冲超声波具有穿透力强、不产生热效应、治疗时间短、使用方便、无不良反应，及适用于采用不同固定方法的甚或有创面、有感染的各种各部位的新鲜或陈旧性骨折等优点。应用广泛，疗效可靠，为治疗骨折提供了一种新方法，开辟了一个新途径。     

Polygenic Risk Score of Adolescent Idiopathic Scoliosis for Potential Clinical Use

Adolescent idiopathic scoliosis (AIS) is a common disease causing three-dimensional spinal deformity in as many as 3% of adolescents. Development of a method that can accurately predict the onset and progression of AIS is an immediate need for clinical practice. Because the heritability of AIS is estimated as high as 87.5% in twin studies, prediction of its onset and progression based on genetic data is a promising option. We show the usefulness of polygenic risk score (PRS) for the prediction of onset and progression of AIS. We used AIS genomewide association study (GWAS) data comprising 79,211 subjects in three cohorts and constructed a PRS based on association statistics in a discovery set including 31,999 female subjects. After calibration using a validation data set, we applied the PRS to a test data set. By integrating functional annotations showing heritability enrichment in the selection of variants, the PRS demonstrated an association with AIS susceptibility (p = 3.5 × 10⁻⁴⁰ with area under the receiver-operating characteristic [AUROC] = 0.674, sensitivity = 0.644, and specificity = 0.622). The decile with the highest PRS showed an odds ratio of as high as 3.36 (p = 1.4 × 10⁻¹⁰) to develop AIS compared with the fifth in decile. The addition of a predictive model with only a single clinical parameter (body mass index) improved predictive ability for development of AIS (AUROC = 0.722, net reclassification improvement [NRI] 0.505 ± 0.054, p = 1.6 × 10⁻⁸), potentiating clinical use of the prediction model. Furthermore, we found the Cobb angle (CA), the severity measurement of AIS, to be a polygenic trait that showed a significant genetic correlation with AIS susceptibility (rg = 0.6, p = 3.0 × 10⁻⁴). The AIS PRS demonstrated a significant association with CA. These results indicate a shared polygenic architecture between onset and progression of AIS and the potential usefulness of PRS in clinical settings as a predictor to promote early intervention of AIS and avoid invasive surgery. © 2021 American Society for Bone and Mineral Research (ASBMR).     

Higher-Impact Physical Activity Is Associated With Maintenance of Bone Mineral Density But Not Reduced Incident Falls or Fractures in Older Men: The Concord Health and Aging in Men Project

High-impact physical activities with bone strains of high magnitude and frequency may benefit bone health. This study aimed to investigate the longitudinal associations between changes in loading intensities and application rates, estimated from self-reported physical activity, with bone mineral density (BMD) changes over 5 years and also with incident falls over 2 years and long-term incident fractures in community-dwelling older men. A total of 1599 men (mean age 76.8 ± 5.4 years) from the Concord Health and Aging in Men Project (CHAMP) were assessed at baseline (2005–2007) and at 2- and 5-year follow-up. At each time point, hip and lumbar spine BMD were measured by dual-energy X-ray absorptiometry, and physical activity energy expenditure over the past week was self-reported via the Physical Activity Scale for the Elderly (PASE) questionnaire. Sum effective load ratings (ELRs) and peak force were estimated from the PASE questionnaire, reflecting the total and highest loading intensity and application rate of physical activities, respectively. Participants were contacted every 4 months over 2 years to self-report falls and over 6.0 ± 2.2 years for fractures. Hip fractures were ascertained by data linkage for 8.9 ± 3.6 years. Compared with sum ELR and PASE scores, peak force demonstrated the greatest standardized effect size for BMD maintenance at the spine (β = 9.77 mg/cm²), total hip (β = 14.14 mg/cm²), and femoral neck (β = 13.72 mg/cm²) after adjustment for covariates, including PASE components (all p < .01). Only PASE scores were significantly associated with reduced falls risk (standardized incident rate ratio = 0.90, 95% confidence interval 0.81–1.00, p = .04). All physical activity measures were significantly associated with reduced incident fractures in univariate analyses, but none remained significant after multivariable adjustments. Older men who engaged in physical activity of high and rapid impact maintained higher BMD, while higher energy expenditure was associated with reduced falls risk. Coupling traditional physical activity data with bone loading estimates may improve understanding of the relationships between physical activity and bone health. © 2020 American Society for Bone and Mineral Research (ASBMR).