抗骨质疏松药物应用的依据：骨生化代谢标志物及骨组织病理学

背景：目前国际上公认双能X射线吸收测定法为诊断骨质疏松症的金标准,但常由于测量部位异位骨化、骨质增生等因素使得测量结果存在误差。目的：探讨骨代谢标志物在老年骨质疏松骨折诊疗中的临床意义以及它与骨密度和骨组织形态病理学改变的相关性。方法：选取50例需行手术治疗的老年骨质疏松骨折患者,行骨生化4项检测,其中抗酒石酸酸性磷酸酶5b(TRACP 5b)检测值明显增高患者25例(标记为抗酒石酸酸性磷酸酶5b升高组),骨碱性磷酸酶(BAP)检测值明显升高患者25例(标记为骨碱性磷酸酶升高组)。术中抽取两组各8例患者骨折断端部分骨组织,苏木精-伊红染色普通光镜检查和扫描电镜检查病理学改变。术后,抗酒石酸酸性磷酸酶5b升高组患者使用鲑鱼降钙素抗骨质疏松治疗,骨碱性磷酸酶升高组患者使用骨肽注射液抗骨质疏松治疗,6个月后再次检测骨密度和骨生化4项。结果与结论：两组患者术前骨密度和骨生化4项检查结果相比较差异无显著性意义(P > 0.05)。抗酒石酸酸性磷酸酶5b升高组患者骨折断端骨组织病理检查示成骨细胞减少、破骨细胞增多;骨碱性磷酸酶升高组患者骨折断端骨组织病理检查示成骨细胞减少;两组骨小梁/骨面积比值均降低,且抗酒石酸酸性磷酸酶5b升高组较骨碱性磷酸酶升高组降低程度差异有显著性意义(P < 0.05)。扫描电镜检查示两组破骨细胞都较正常组活跃,抗酒石酸酸性磷酸酶5b升高组骨小梁较骨碱性磷酸酶升高组稀松明显,吸收空泡增大。两组于术后使用抗骨质疏松药物治疗,两组治疗前与治疗后骨密度和骨生化4项检测结果差异有显著性意义(P < 0.05)。结果显示：①骨代谢标志物检测能明确患者骨组织是以成骨细胞功能和数量减低还是以破骨细胞功能和数量增加为主,以便指导临床针对性使用抗骨质疏松药物。②骨折断端骨组织形态病理学检查能更好地反映患者骨组织内成骨细胞、破骨细胞和骨小梁等状况。骨质疏松患者针对性使用抗骨质疏松药物治疗能提高疗效、降低相关并发症。     

骨微损伤、骨重建与代谢性骨病

骨微损伤能启动骨重建,骨重建障碍而导致微损伤积累可引发骨折。扫描电镜、同步加速器射线μ-CT和高分辨磁共振显像是研究骨微损伤的新方法,骨理化构成和年龄对微损伤发生和发展有重要影响,骨细胞在微损伤修复中起重要作用,骨微损伤研究有利于代谢性骨病防治。     

骨源性外泌体miRNAs主要物理特性及在骨重建和骨代谢中的应用潜力

背景:外泌体是生物分子在骨重建微环境中发送细胞间信息的载体.在生理和病理条件下,外泌体在骨重建和骨代谢中起着重要的调控作用.目的:对骨源性外泌体miRNAs的主要物理特性进行了简要综述,分析了其在骨重建和骨代谢领域的关键作用和应用潜力.方法:应用计算机在PubMed、Web of Science和Medline等数据库...     

Frozen sections of bone biopsies in metabolic and other bone diseases

Frozen sections of bone trephine and needle biopsies can be satisfactorily cut in a standard cryostat and, when stained with haematoxylin and eosin, they enable a rapid diagnosis to be made in a wide range of metabolic bone disorders including Paget's disease, osteoporosis, osteomalacia, hyperparathyroidism and renal osteodystrophy. Neoplastic disease of bone may also be diagnosed using the same technique. A tissue diagnosis can be established within an hour of the biopsy being taken, instead of the 1-3 weeks required for resin section diagnosis, with a consequent potential saving in further costly biochemical and radiological investigations, a possible shortening of the patient's stay in hospital and earlier initiation of correct treatment. The method is quick, reliable and highly cost-effective; it is of particular value in laboratories with insufficient workload to justify the expenditure on specialized microtomes and reagents for resin embedding.     

脂联素在骨质疏松性骨代谢疾病中的研究进展

正骨质疏松症(osteoporosis,OP)是一种与遗传、环境、种族、性别和年龄等多种因素相关的退行性疾病,以骨量减少,骨组织显微结构破坏为特征,导致骨的脆性增加而易于发生骨折;它对人类健康危害大,已成为全世界关注的主要疾病之一。随着分子遗传学、人类基因组学和代谢组学研究的逐步深入,骨质疏松症的病因学研究取得了很大的进展,已明确了遗传因素是骨质     

Seasonal differences in biochemical parameters of bone remodelling.

AIMS: To compare bone remodelling parameters in late autumn and early spring in 20 post-menopausal women. METHODS: The parameters measured were serum osteocalcin and its apparent degree of carboxylation (measured by hydroxyapatite binding), total and bone specific alkaline phosphatase and urinary bone resorption markers, (pyridinoline and deoxypyridinoline). RESULTS: Serum osteocalcin concentrations were lower in autumn than in spring but the degree of carboxylation was similar. Total and bone specific alkaline phosphatase activities in serum were higher in autumn than in spring. These results support previous observations. However, notable and previously unreported changes in urinary bone resorption markers were observed. Pyridinoline concentrations were lower and deoxypyridinoline higher in autumn compared with spring. The ratio of pyridinoline:deoxypyridinoline was therefore very different between the seasons. CONCLUSIONS: The results clearly demonstrate that seasonal changes in these variables of bone remodelling must be taken into consideration when designing, reporting or analysing studies of bone metabolism in vivo.     

Sensitivity of bone histomorphometry in the diagnosis of metabolic bone diseases

Diagnostic sensitivity of bone histomorphometry was assessed in different metabolic bone diseases, after fixing the specificity at 75%, 90% and 95% reference levels. Sensitivity was particularly high in cases with greatly increased osteoid and/or resorption features, as in renal osteodystrophy (ROD). All the remodeling indicators were highly sensitive toward advanced or severe forms of mixed ROD (mROD). Osteoid indicators were the most sensitive parameters in ROD with predominant osteomalacia (oROD). Osteoclastic and several osteoid indicators were very sensitive in all grades of ROD with predominant hyperparathyroidism (hROD). Sensitivity was generally low in uremic patients without bone changes (wROD) and also in patients with idiopathic osteoporosis (OP). It is our recommendation, however, that for each individual patient the definite diagnosis should be based on both morphological, clinical and metabolic parameters.     

串联质谱技术在新生儿遗传代谢病筛查中的应用

遗传代谢病是一组种类繁多,临床症状复杂的疾病,常累及神经系统等多器官,一旦发病危害严重。通过新生儿筛查技术早发现早治疗是预防遗传代谢病危害的有效途径。现对串联质谱技术在新生儿遗传代谢病筛查应用中的技术原理、实验流程、面临的挑战和问题作综述。     

Relationships between lumbar bone mineral density and biochemical parameters in phenylketonuria patients

BackgroundThe etiology of reduced bone mineral density (BMD) in phenylketonuria (PKU) is unknown. Reduced BMD may be inherent to PKU and/or secondary to its dietary treatment.Materials and methodsLumbar BMD was measured by dual-energy X-ray absorptiometry in 53 early and continuously treated PKU patients (median age 16, range 2–35 years). First, Z-scores of BMD were correlated to age group, clinical severity of PKU, mean phenylalanine (Phe) concentration and Phe variation in the year prior to DXA scanning, as well as to blood vitamin, mineral, and alkaline phosphatase concentrations. Second, parameters were compared between subjects with reduced BMD (Z-score < ? 2 SD) and subjects with normal BMD.ResultsBMD was significantly reduced in our cohort (p = 0.000). Z-scores of BMD were neither significantly correlated to age group, nor clinical severity of PKU. Both mean Phe concentration and Phe variation in the year prior to DXA scanning did not significantly correlate with Z-scores of BMD. Higher blood calcium concentrations were significantly associated with lower BMD (r² = ? 0.485, p = 0.004). Other biochemical parameters, including vitamin B12 availability markers, did not show significant correlations with Z-score of BMD. Subjects with reduced BMD had significantly higher blood phosphorus concentrations than subjects with normal BMD (p = 0.009). No other significant differences were found between both BMD groups.ConclusionReduced BMD in PKU is present from early age onward and does not progress with age. Therefore, BMD deserves attention from early age onward in PKU patients. Our findings are consistent with increased bone turnover in PKU. It remains unclear whether reduced BMD is inherent to PKU and/or secondary to its dietary treatment.     

The influence of partial gastrectomy on biochemical parameters of bone metabolism and bone density

Summary Since it has been suggested that gastric resections are followed by changes in bone metabolism, the aim of our study was to determine the biochemical parameters of bone metabolism and radial and lumbar bone density in 15 male ulcus patients treated by partial gastrectomy (Billroth II). Comparing the data with those of a corresponding control group, the lumbar bone density measured by quantitative computed tomography was statistically significantly lower (P < 0.04) in the patient group, whereas the peripheral bone mass of the distal part of the nondominant forearm measured by single-photon absorptiometry showed no statistically significant difference. In addition, a marked increase in alkaline phosphatase (P < 0.002) and urinary excretion of hydroxyproline (P < 0.003) was found in the gastrectomy group, whereas the 25-hydroxy-vitamin D levels were found to be significantly decreased (P < 0.04). Osteocalcin, a biochemical marker for osteoblast activity, and the carboxy-terminal propeptide of type I procollagen (PICP), a marker of collagen formation, were slightly but not significantly higher in gastrectomy-treated patients. The serum parathyroid hormone levels were similar in both groups. As none of the patients had any radiologic evidence of osteopenia, the changes in biochemical parameters of bone metabolism and bone mass in patients who had undergone partial gastrectomy could be a marker of latent bone loss.Abbreviations DPA/SPA dual/single-photon absorptiometry - BMD bone mineral density - QCT quantitative computed tomography - PICP carboxy-terminal propeptide of type I procollagen - 250HD₃ 25-hydroxy-vitamin D - iPTH parathyroid hormone - OC osteocalcin - BMC bone mineral content     

Bone mass,bone strength,muscle-bone interactions,osteopenias and osteoporoses

Densitometrically, the skeleton is currently conceived as 'a systemically regulated mass of mineralized material that is born, grows, reaches a more or less high peak, and then declines faster or slower as to develop a correspondingly high or low fracture risk'. Alternatively, from a biomechanical point of view, the skeleton can be conceived as 'a biomechanically-regulated structure that can be systemically disturbed (in the cybernetic sense), the strength of which depends on the intrinsic stiffness (material properties) and the spatial distribution (architectural properties) of the mineralized tissue'. The biomechanical feedback system involved (bone 'mechanostat') would not control bone mass to optimize bone strength; it would rather control bone material quality and architecture (through a modulation of bone modeling and remodeling) in order to optimize bone stiffness. The natural stimuli for the bone mechanostat would be the customary strains of bone tissue (sensed by osteocytes) that are induced by gravitational forces and, more importantly, the contractions of regional muscles. According to this view, the development of any bone-weakening disease should be related to either (1) an intrinsic illness of the system (primary disturbances of bone cells), (2) a lack of mechanical stimulation (disuse-induced bone losses), or (3) a systemically-induced shift of the system's setpoint (systemic or secondary bone diseases). This short review aims to conciliate those views: (1) taking profit of the diagnostic possibilities provided by densitometric bone 'mass' determinations; (2) proposing other resources to assess bone mechanical properties; and (3) analyzing the muscle-bone interactions. These are crucial for achieving a differential diagnosis between disuse and primary or secondary bone disturbances, based either (1) on the densitometric determination of bone and muscle masses that would provide an anthropometric diagnosis of osteopenia (not osteoporosis because no extrapolations to bone strength can be made this way) or (2) on the cross-sectional analyses of bone structure or strength and muscle strength provided by bone tomography, magnetic resonance or other techniques that could afford a diagnosis of osteoporosis according to biomechanical criteria.     

Bone marrow manifestations of infections and systemic diseases observed in bone marrow trephine biopsy review

Bone marrow modifications resulting from infections and systemic diseases can be studied by analysis of morphology and aetiology. Two types of lesions or modifications can be observed, those occurring in the connective tissue comprising inflammatory processes, acute and chronic, as well as immune reactions, and those involving the normal haematopoietic cell lines, with possible hyperplastic or aplastic changes in one or more cell lines. The main lesions are described (oedema, haemorrhage, necrosis, suppuration, granulomas, lymphoid nodules and hyperplasia, immunoblastic or plasmacytic hyperplasia), as well as the main aetiologies. In association, the three main haematopoietic cell lines show hyperplasia, hypoplasia, aplasia of one or all of the cell lines, sometimes with dysmyelopoiesis. The stroma and vessel reactions comprise myelofibrosis, gelatinous transformation or amyloid deposits. The methods for identifying aetiological agents are emphasized. It should also be stressed that malignant neoplasias of different types involving the bone marrow can be responsible for such inflammatory or immune reactions.     

果糖与代谢性疾病

<正>随着社会经济的发展,肥胖、糖尿病、脂肪肝、高血脂和痛风等代谢性疾病的患病率在全球呈现快速上升趋势。这些代谢性疾病可进一步发展为动脉粥样硬化、高血压和冠心病等心血管疾病或肾脏疾病,严重危害人们的身心健康和社会发展。因此,代谢性疾病及其相关心血管疾病已经成为我国公共卫生领域的重大挑战。     

Bone mass regulation by leptin: a hypothalamic control of bone formation

Bone mass is maintained constant between puberty and menopause by the balance between osteoblasts and osteoclasts activity. The existence of a hormonal control of osteoblast activity has been speculated for years by analogy to osteoclast biology. Through the search for such humoral signal(s) regulating bone formation, leptin has been identified as a powerful inhibitor of bone formation. Furthermore, by means of intracerebroventricular infusion of leptin, it has been shown that the effect of this adipocyte-derived hormone on bone is mediated via a brain relay, like all its other functions. Subsequent studies have led to the identification of hypothalamic neurons involved in leptin's antiosteogenic function. In addition, it has been shown that those neurons or neuronal pathways are distinct from neurons responsible for the regulation of energy metabolism. Finally, the peripheral mediator of leptin's antiosteogenic function has been identified as being the sympathetic nervous system. Catecholamine-deficient mice have a high bone mass and sympathomimetics administered to mice decreased bone formation and bone mass. Conversely, beta-blockers increased bone formation and bone mass and blunt the bone loss induced by ovariectomy.     

Correlation between biochemical tests, parameters of drug elimination and hepatic enzyme induction in chronic liver diseases

The biochemical liver function tests form an integral part of diagnostic practice in hepatology. In this study the parameters suited for the estimation of drug elimination and of the induced state of the liver, thus the excretion of D-glucaric acid, of menthol glucuronide and the parameters of antipyrine and sulphadimidine kinetics were correlated with the results of biochemical laboratory tests in patients with chronic liver disease. The aim was to establish universally valid quantitative correlations between the above results. Multiple relationships were revealed, but generally valid correlations for the group of liver diseases occurred only in special relationships (serum albumin level and antipyrine T1/2; serum bilirubin level and sulphadimidine T1/2). The results have been evaluated from the methodological aspect to work out an appropriate dosage regime in liver diseases.     

骨的结构与表征参数

阐述了骨的微米结构、纳米结构、表征参数与测量方法、及研究进展。     

Bone mineral density,bone turnover markers,lean mass,and fat mass in Egyptian children with congenital adrenal hyperplasia

Introduction

Aim of this paper is to assess bone mineral density (BMD) and body composition, by dual energy X-ray absorptiometry (DXA), and various markers of bone growth, in a group of children with congenital adrenal hyperplasia (CAH) on long-term glucocorticoid therapy.

Material and methods

A case-control study included thirty patients with CAH with different states of metabolic control. Their mean age was 7.5 ±4.2 years. All patients are subjected to BMD using DXA at the neck of the femur and lumbar spine. A blood sample was taken for assessment of osteocalcin, osteoprotegerin, and procollagen type 1, as markers of bone formation, as well as RANKL and urinary deoxypyridinoline (DPD), as markers of bone resorption.

Results

We found no difference in BMD in patients and control subjects; however, patients showed significantly lower serum osteocalcin (p = 0.008) and osteoprotegerin (p = 0.0001) and significantly higher serum RANKL levels (p = 0.0001). Our results show that patients had significantly lower lean body mass (p = 0.005) and fat/lean ratio (p = 0.008) compared to matched controls. The duration of treatment showed a significant negative correlation with procollagen type 1 (r = –0.49, p = 0.02) and lean mass % (r = –0.43, p = 0.04); however, it showed a significant positive correlation with total fat mass % (r = 0.6, p = 0.0006), and fat/lean ratio (r = 0.43, p = 0.04). Dose of steroid had a significant positive correlation with BMI SDS (r = 0.4, p = 0.02).

Conclusions

Bone mineral density is normal but bone turnover is low in patients with CAH. There is an increase in fat/lean mass in patients with CAH.