阿仑膦酸钠对兔破骨细胞功能的影响

用骨陷窝形成分析法观察阿仑膦酸钠对体外培养破骨细胞功能的影响，探讨可能的作用机制。在建立兔破骨细胞培养方法的基础上，用不同浓度的阿仑膦酸钠分别与骨片或成骨细胞提前作用，然后再将骨片或成骨细胞分别与破骨细胞共同培养。结果发现当阿仑膦酸钠（10^-11,10^-9,10^-7mol/L)与骨片预处理后，破骨细胞在骨片上形成的骨吸收陷窝数目减少，其抑制率分别为19．5％（P＜0．05）、49．0％（P＜0．01）和74．5％（P＜0．01）。用阿仑膦酸钠（10^-9,10^-7,10^-5mol/L)预处理成骨细胞后，仅在高浓度（10^-5mol/L）时可见破骨细胞骨吸收陷窝的数目明显减少，其抑制率为62．8％（P＜0．01）。结果表明阿仑膦酸钠能直接或通过成骨细胞间接抑制破骨细胞的骨吸收活性。     

Effects of Alendronate and Calcitonin on Bone Mineral Density in Postmenopausal Osteoporotic Women. An Observational Study

Objective: Alendronate and calcitonin are antiresorptive drugs that were used for the treatment of postmenopausal osteoporosis and were shown to increase bone mineral density (BMD). However, the effect of both drugs in daily clinical practice may differ from that observed in clinical trials.Method: About 50 postmenopausal osteoporotic women were observed during their first year of treatment. Among them, 32 patients used alendronate and 18 used calcitonin. Lumbar spine and femoral neck BMD were measured by dual energy X-ray absorptiometry (DXA) at baseline and after 1 year of therapy. Biochemical markers (B-ALP – bone-specific alkaline phosphatase, OTC – osteocalcin and DPD/UCr – deoxypyridinoline/creatinine ratio) of bone metabolism were measured at baseline and 6 months later. Patient compliance was assumed by tablet counting and verified at interview. Each patient was further questioned about her attitude towards the treatment, as well as her dairy product intake, physical activity, use of other medications, smoking and social status.Main outcome measure: (1) Annual percent change in BMD in lumbar spine and femoral neck after the one-year treatment with either alendronate or calcitonin. (2) The change in biochemical markers of bone turnover.Results: The lumbar spine BMD significantly increased by 7.0% (P < 0.001), the femoral neck BMD by 4.3% (P < 0.01). OTC, B-ALP and DPD/UCr decreased significantly during the therapy with alendronate. Compliance with therapy was 79% (95% CI 68–90%). In the calcitonin-treated group, the lumbar spine BMD significantly increased by 3.1 % (P < 0.05), while the femoral neck BMD remained unchanged. OTC, B-ALP and DPD/UCr did not change significantly during the treatment with calcitonin. Compliance with calcitonin therapy was 87% (95% CI 63–110%). The annual change of BMD in both treatment groups was independent on all questioned factors.Conclusion: In daily practice, alendronate enhanced significantly BMD both in lumbar spine and femoral neck. Calcitonin showed increase only in the lumbar spine BMD.     

Improvement in spine bone density and reduction in risk of vertebral fractures during treatment with antiresorptive drugs

PURPOSE: To estimate how much the improvement in bone mass accounts for the reduction in risk of vertebral fracture that has been observed in randomized trials of antiresorptive treatments for osteoporosis. METHODS: After a systematic search, we conducted a meta-analysis of 12 trials to describe the relation between improvement in spine bone mineral density and reduction in risk of vertebral fracture in postmenopausal women. We also used logistic models to estimate the proportion of the reduction in risk of vertebral fracture observed with alendronate in the Fracture Intervention Trial that was due to improvement in bone mineral density. RESULTS: Across the 12 trials, a 1% improvement in spine bone mineral density was associated with a 0.03 decrease (95% confidence interval [CI]: 0.02 to 0.05) in the relative risk (RR) of vertebral fracture. The reductions in risk were greater than predicted from improvement in bone mineral density; for example, the model estimated that treatments predicted to reduce fracture risk by 20% (RR = 0.80), based on improvement in bone mineral density, actually reduce the risk of fracture by about 45% (RR = 0.55). In the Fracture Intervention Trial, improvement in spine bone mineral density explained 16% (95% CI: 11% to 27%) of the reduction in the risk of vertebral fracture with alendronate. CONCLUSION: Improvement in spine bone mineral density during treatment with antiresorptive drugs accounts for a predictable but small part of the observed reduction in the risk of vertebral fracture.     

Prevalence of Periapical Lesions in Patients with Osteoporosis

IntroductionOsteoporosis is a major systemic disease that can significantly deteriorate the quality of life of the affected individuals. It is more common in women, particularly after menopause. Osteoporosis may be associated with alterations in oral health. Treatment of osteoporotic patients mainly involves the administration of bisphosphonates (BPs). Nitrogen-containing BPs are more potent therapeutically and more commonly used. The purpose of this study was to assess the prevalence of periapical lesions in patients with osteoporosis and to evaluate the difference in the prevalence of periapical lesions in patients treated with alendronate and risedronate, 2 nitrogen-containing types of BPs.MethodsIntegrated data of hospital patients were used. Data from the corresponding diagnosis codes for osteoporosis and periapical periodontitis were retrieved by searching the appropriate query in the database. The odds ratio (OR) of periapical lesions, its association with osteoporosis, and the use of 2 BP medications were calculated and analyzed statistically.ResultsOf 1,644,953 hospital patients, 8715 presented with periapical lesions. A total of 42,292 patients were diagnosed with osteoporosis. A total of 754 patients diagnosed with osteoporosis presented with periapical lesions. The prevalence of periapical lesions in patients with osteoporosis was 1.78% compared with 0.52% in the general patient population of the hospital. The OR for the prevalence of periapical lesions in patients with osteoporosis was 3.36 and was statistically significant (P < .0001). Patients with osteoporosis treated with any type of BPs showed a prevalence of periapical lesions in 1.25% of cases compared with 0.52% in the general patient population of the hospital. The difference in the OR was statistically significant (P < .0001). The OR for the presence of periapical lesions in the osteoporosis group treated with BPs was 2.35 compared with 3.52 in the osteoporosis group not treated with BP. The difference in the OR was statistically significant (P < .0001). Patients treated with alendronate showed an OR of 1.6 for the prevalence of periapical lesions, and the difference in the OR was statistically significant (P < .0001). Patients treated with risedronate showed an OR of 1.34 for the prevalence of periapical lesions, and the difference in the OR was not statistically significant (P = .3502).ConclusionsUnder the conditions of this study, it appears that the prevalence of periapical lesions is significantly higher in osteoporotic patients. Osteoporotic patients treated with BPs showed a marked reduction in the prevalence of periapical lesions, especially when risedronate was used.     

Periodontitis in Rats Induces Systemic Oxidative Stress That Is Controlled by Bone‐Targeted Antiresorptives

Background: Periodontitis is a chronic, polymicrobial inflammatory disease that degrades connective tissue and alveolar bone and results in tooth loss. Oxidative stress has been linked to the onset of periodontal tissue breakdown and systemic inflammation, and the success of antiresorptive treatments will rely on how effectively they can ameliorate periodontal disease–induced oxidative stress during oral infection. Methods: Rats were infected with polybacterial inoculum consisting of Porphyromonas gingivalis, Treponema denticola, and Tannerella forsythia, as an oral lavage every other week for 12 weeks. Daily subcutaneous injections of enoxacin, bis‐enoxacin, alendronate, or doxycycline were administered for 6 weeks after 6 weeks of polybacterial infection in rats. The serum levels of oxidative stress parameters and antioxidant enzymes, including glutathione peroxidase, superoxide dismutase, and catalase, were evaluated in each of the infected, treated, and sham‐infected rats. Results: Rats infected with the periodontal pathogens displayed a five‐fold increase in the oxidative stress index compared with controls as a result of increased levels of serum oxidants and decreases in total antioxidant activity. The overall decrease in antioxidant activity occurred despite increases in three important antioxidant enzymes, suggesting an imbalance between antioxidant macromolecules/small molecules production and antioxidant enzyme levels. Surprisingly, the bone‐targeted antiresorptives bis‐enoxacin and alendronate inhibited increases in oxidative stress caused by periodontitis. Bis‐enoxacin, which has both antiresorptive and antibiotic activities, was more effective than alendronate, which acts only as an antiresorptive. Conclusion: To the best of the authors’ knowledge, this is the first study to demonstrate that the increased oxidative stress induced by periodontal infection in rats can be ameliorated by bone‐targeted antiresorptives.     

Adjuvant Therapy With Sodium Alendronate for the Treatment of Experimental Periodontitis in Rats

Background: This study assesses the effects of topical sodium alendronate (SA) as an adjuvant to the mechanical treatment of ligature‐induced periodontitis in rats. Methods: Ninety animals were subjected to the induction of periodontitis via the installation of a ligature around the mandibular left first molar. After 7 days, the ligature was removed, and the animals were distributed into the following groups: 1) NT group (n = 30), no treatment; 2) SRP group (n = 30), scaling and root planing (SRP) and local irrigation with physiologic saline solution; and 3) SRP/SA group (n = 30), SRP and local irrigation with SA (10^?5 M). Ten animals from each group were euthanized at 7, 15, and 30 days after treatment. Histologic and histometric analyses were performed in the furcation region. The percentage of bone in the furcation (PBF) was measured. Immunohistochemical analyses for detecting the receptor activator of nuclear factor‐κB ligand (RANKL), osteoprotegerin (OPG), tartrate‐resistant acid phosphatase (TRAP), and activated caspase‐3 were performed at the furcation region. Results: Compared with the other groups, the SRP/SA group showed less local inflammation and better tissue reparation during the entire experiment. There was more PBF in the SRP/SA group than in the other groups at days 7 and 15. Stronger OPG immunolabeling and weaker RANKL immunolabeling were observed in the SRP/SA group at 15 and 30 days. There were fewer TRAP‐positive cells in the SRP/SA group than in the NT group at all of the time points. There was no difference in the number of activated caspase‐3‐positive osteocytes among groups and time points. Conclusion: It can be concluded that topical use of SA as an adjuvant to SRP is effective in the treatment of experimental periodontitis.     

Immunolocalization of Smad-4 in developing molar roots of alendronate-treated rats

Introduction

During root formation, Smad-4 plays a key role during the epithelial–mesenchymal interactions and the Hertwig's epithelial root sheath (HERS) apical proliferation. The root formation and eruption of rat molars is impeded by alendronate treatment due to the inhibition of bone resortion by this drug. The present study aimed to examine the structures affected in the developing root and immunodetect the presence of Smad-4 in rats treated with alendronate.

Methods

Newborn Wistar rats were daily injected 2.5 mg/kg alendronate (ALN) during 9, 12 and 30 days. The controls (CON) were injected with saline. The maxillae were fixed and embedded in paraffin or Spurr resin. Paraffin sections were incubated in Smad-4 antibody that was labelled with DAB. The ultrathin sections were examined in a transmission electron microscope.

Results

In ALN, a short portion of root dentine was formed; the epithelial diaphragm (ED) and the dental follicle (DF) were disorganized by the contact of bone trabeculae. The (CON) molar roots developed normally. Smad-4 labelling was detected in the cytoplasm of fibroblasts and cementoblasts adjacent to the cementum in CON; in ALN group, few ED cells presented weak immunolabelling. Ultrastructurally, the ED and DF appeared disrupted due to the presence of thin bone trabeculae between its cells. It resulted in the lack of apical proliferation of HERS and, consequently, arrest of root formation.

Conclusion

The immunodetection of Smad-4 in the DF cells of ALN specimens indicates that the signalling for the differentiation of these cells into cementum-forming fibroblasts and cementoblasts occurs, despite the impairment of root elongation.     

阿仑膦酸钠与鲑鱼降钙素对腰椎后路椎间融合术后疗效的比较研究

【摘要】目的 探讨阿仑膦酸钠与鲑鱼降钙素对椎间融合临床疗效的差异。方法 回顾性分析我科自2010年9月~2012年8月间治疗168例腰椎管狭窄合并腰椎间盘突出症患者资料,所有患者均行椎弓根螺钉固定、后路椎间融合术。依照PLIF术后用药的不同将患者机分为阿仑膦酸钠组(A组,n=51),鲑鱼降钙素组(B组,n=52)和对照组(C组,n=65,不使用任何抗骨质疏松及补钙药物)。比较患者的基本情况、临床效果和影像学结果(融合率和手术节段椎间隙高度的变化)。结果 术后随访半年~2年1个月,平均18个月。A、B、C组三组的优良率分别为88.2%、88.5%、61.5%,A、B组优良率均较对照组明显提高,但A、B组间优良率差异无显著性意义;A组和B组在手术时间、失血量以及住院时间上差异也无显著性。术后1年随访时融合率A组为84.3%,B组84.6%,C组53.8%,A、B组均高于C组,A、B组间比较差异无显著性意义。三组患者术后椎间隙高度均有不同程度的丢失,A组1.1 (0.6~1.9)mm、B组1.1 (0.8~2.1) mm,两组间比较差异无显著性意义,但A、B组椎间隙高度丢失程度均较对照组C组4.0 (1.9~4.9) mm明显降低。结论 腰椎后路椎间融合术(PLIF)术后规范使用阿仑膦酸钠或鲑鱼降钙素能够获得令人满意的临床效果,具有较高的椎间植骨融合率及较少的椎间隙高度丢失。     

阿仑膦酸钠与阿法骨化醇治疗老年性骨质疏松症的疗效比较

目的比较阿仑膦酸钠片、阿法骨化醇胶囊治疗老年性骨质疏松症的临床疗效及安全性。方法将56例老年性骨质疏松症患者,采取随机法分成2组。观察组给予口服阿仑膦酸钠片70 mg,每周1次;对照组给予口服阿法骨化醇胶囊0.5μg,每日1次;同时2组患者每天均服用钙剂600 mg,连续治疗6个月。测定治疗前后骨密度(BMD)、生化指标,采取VAS法评价治疗前后疼痛改善情况等。结果治疗后观察组的L2、L3、L4、股骨颈的骨密度值分别增加了3.61%、4.76%、3.66%和5.06%;观察组的骨密度值分别增加了3.57%、4.71%、3.61%和5.0%,2组间差异无统计学意义(p>0.05)。治疗后观察组改善疼痛症状优于对照组(p<0.05)。结论两种药物治疗老年性骨质疏松症具有良好的临床疗效,能显著增加患者骨密度,缓解疼痛程度;但阿仑膦酸钠片服药方便,患者顺从性较好,较适宜在临床推广应用。