雌二醇对铅中毒模型大鼠骨组织及骨代谢指标不能产生影响

背景：关于铅中毒能否引起骨质疏松症及雌激素对其治疗是否有效尚无共识。 目的：观察雌二醇对去卵巢大鼠和铅中毒大鼠所致骨质疏松症的治疗效果。 方法：雌性大白鼠100只等分成正常对照组、去卵巢模型组、染铅模型组、雌二醇+去卵巢组和雌二醇+染铅模型组。建模后1周雌二醇+去卵巢组和雌二醇+染铅模型组皮下注射雌二醇(100 μg/kg),2次/1周,连续12周。 结果与结论：在去卵巢模型组和铅中毒组中骨钙、骨磷、血钙及血磷均出现降低(P < 0.01),血碱性磷酸酶升高(P < 0.01),骨组织形态呈现骨质疏松的病理改变。雌二醇+去卵巢组的骨代谢生化指标血钙、磷、和碱性磷酸酶和骨组织形态均恢复正常,而雌二醇+铅中毒组的骨代谢生化指标和骨组织形态呈现骨质疏松未出现明显改善迹象。铅中毒组和雌二醇+铅中毒组的骨铅和血铅明显高于正常对照组(P < 0.01)。说明铅中毒可引起骨质疏松的病理改变,雌二醇对去卵巢大鼠的骨质疏松症有良好治疗效果,而对铅中毒所致的骨质疏松症无明显疗效。     

Involvement of receptor-interacting protein 140 in estrogen-mediated osteoclasts differentiation,apoptosis, and bone resorption

Estrogen withdrawal following menopause results in an increase of osteoclasts formation and bone resorption, which is one of the most important mechanisms of postmenopausal osteoporosis. Recently, growing evidence has suggested that receptor-interacting protein 140 was implicated in estrogen-regulated metabolic disease, including fat metabolism and lipid metabolism. However, little is known regarding the role of receptor-interacting protein 140 in the regulation of bone metabolic by estrogen. In the present study, Western blotting disclosed that estrogen brings a significant increasing expression of receptor-interacting protein 140 in osteoclasts, but not in osteoblasts and bone marrow mesenchymal stem cells. Furthermore, analysis of TRAP staining and bone resorption assay showed that depletion of receptor-interacting protein 140 could significantly alleviate the inhibitory effects of estrogen on osteoclasts formation and bone resorption activity. Moreover, estrogen could induce osteoclasts apoptosis by increasing receptor-interacting protein 140 expression through the Fas/FasL pathway. Taken together, receptor-interacting protein 140 might be a critical player in estrogen-mediated osteoclastogenesis and bone resorption.     

运动与绝经后女性骨强度、体成分及性激素的关系

目的 探讨运动对兰州市汉族绝经后女性骨强度、体成分及性激素的影响.方法 2018年1月～2019年6月,采用随机整群抽样选取兰州市汉族绝经后女性233例(运动组110例,非运动组123例),采用超声骨密度仪、生物电阻抗分析仪及电化学发光全自动免疫分析仪,分别测量跟骨骨强度、体成分和性激素.结果 兰州市汉族绝经后运动组女...     

东乡族成年女性绝经前后骨强度和体成分特征及其相关性

目的 分析东乡族成年女性绝经前后骨强度和体成分变化并探讨体成分变化对骨强度的影响。 方法 2016年9月~2018年7月采用随机整群抽样选取甘肃省东乡族41～50岁成年女性203例（绝经前102例,绝经后101例）,采用超声骨密度仪、生物电阻抗分析仪分别测量跟骨骨强度和体成分指标。 结果 东乡族绝经后女性的骨强度、肌肉组织体成分低于绝经前（P<0.05）;脂肪组织体成分高于绝经前（P<0.01）。东乡族绝经后女性骨质疏松的患病率高于绝经前（P<0.01）。Pearson 相关分析显示,绝经前后女性的骨强度均与肌肉组织体成分正相关（P<0.01）,与脂肪组织体成分负相关（P<0.01）。多元线性逐步回归分析显示,四肢肌肉量是东乡族女性骨强度的保护性因素,皮下脂肪含量是骨强度下降的危险因素。 结论 肌肉以及脂肪组织共同决定着东乡族女性的骨强度且与体成分分布部位有关,但两者的关系不受绝经状态的影响。绝经是东乡族女性骨质疏松发生的重要影响因素,应加强绝经后女性骨质疏松的防控。加强肢体锻炼,增加四肢肌肉量,减少皮下脂肪,有助于提高东乡族绝经前、后女性骨强度,预防骨质疏松。     

Relation between obesity and bone mineral density and vertebral fractures in Korean postmenopausal women

Purpose

The traditional belief that obesity is protective against osteoporosis has been questioned. Recent epidemiologic studies show that body fat itself may be a risk factor for osteoporosis and bone fractures. Accumulating evidence suggests that metabolic syndrome and the individual components of metabolic syndrome such as hypertension, increased triglycerides, and reduced high-density lipoprotein cholesterol are also risk factors for low bone mineral density. Using a cross sectional study design, we evaluated the associations between obesity or metabolic syndrome and bone mineral density (BMD) or vertebral fracture.

Materials and Methods

A total of 907 postmenopausal healthy female subjects, aged 60-79 years, were recruited from woman hospitals in Seoul, South Korea. BMD, vetebral fracture, bone markers, and body composition including body weight, body mass index (BMI), percentage body fat, and waist circumference were measured.

Results

After adjusting for age, smoking status, alcohol consumption, total calcium intake, and total energy intake, waist circumference was negatively related to BMD of all sites (lumbar BMD p = 0.037, all sites of femur BMD p < 0.001) whereas body weight was still positively related to BMD of all sites (p < 0.001). Percentage body fat and waist circumference were much higher in the fracture group than the non-fracture group (p = 0.0383, 0.082 respectively). Serum glucose levels were postively correlated to lumbar BMD (p = 0.016), femoral neck BMD (p = 0.0335), and femoral trochanter BMD (p = 0.0082). Serum high density lipoprotein cholesterol (HDLC) was positively related to femoral trochanter BMD (p = 0.0366) and was lower in the control group than the fracture group (p = 0.011).

Conclusion

In contrast to the effect favorable body weight on bone mineral density, high percentage body fat and waist circumference are related to low BMD and a vertebral fracture. Some components of metabolic syndrome were related to BMD and a vertebral fracture.     

Interrelationship among muscle,fat, and bone: Connecting the dots on cellular,hormonal, and whole body levels

While sarcopenia and sarcopenic obesity have been recognized in the last decade, a combined concept to include decreased muscle mass and strength, as well as decreased bone mass with coexistence of adiposity is discussed here. We introduce a new term, osteopenic obesity, and operationalize its meaning within the context of osteopenia and obesity. Next, we consolidate osteopenic obesity with the already existing and more familiar term, sarcopenic obesity, and delineate the resulting combined condition assigning it the term osteosarcopenic obesity. Identification and possible diagnosis of each condition are discussed, as well as the interactions of muscle, fat and bone tissues on cellular level, considering their endocrine features. Special emphasis is placed on the mesenchymal stem cell commitment into osteoblastogenic, adipogenic and myogenic lineages and causes of its deregulation. Based on the presented evidence and as expounded within the text, it is reasonable to say that under certain conditions, osteoporosis and sarcopenia could be the obesity of bone and muscle, respectively, with the term osteosarcopenic obesity as an encompassment for all.     

不同运动强度干预2型糖尿病模型大鼠的骨密度变化

BACKGROUND:More than 50% of patients with diabetes are accompanied by osteoporosis. Exercise is the main method to treat diabetes, but whether it has an impact on diabetes osteoporosis is unclear. OBJECTIVE:To analyze the different exercise intensities and changes in bone mineral density in type 2 diabetic rat models. METHODS:Forty rats were randomly divided into model group and low-, medium- and high-intensity exercise groups. All rats received intraperitoneal injection of streptozotocin to establish models of type 2 diabetes. Rats in the low-, medium- and high-intensity exercise groups did treadmill training at 10, 20, 30 m/min, 1 hour per day, 6 days as a cycle. They had a rest for 1 day after each cycle, for 8 consecutive cycles. Rats in the model group did not do any exercise. RESULTS AND CONCLUSION:Compared with the model group, the weight of rats was decreased; blood glucose levels were reduced; osteocalcin and serum calcium levels and biomechanical indexes of femur increased; serum phosphorus and alkaline phosphatase decreased in the low-, medium- and high-intensity exercise groups. Bone mineral density increased in the medium- and high-intensity exercise groups. These findings confirmed that different exercise intensities have a certain influence on bone mineral density and bone metabolism in type 2 diabetic rat models. When using a method of treating movement, proper physical exercise can increase serum osteocalcin content, improve bone metabolism, prevent diabetic osteoporosis, and have a high clinical value.     

Muscle and bone,two interconnected tissues

As bones are levers for skeletal muscle to exert forces, both are complementary and essential for locomotion and individual autonomy. In the past decades, the idea of a bone–muscle unit has emerged. Numerous studies have confirmed this hypothesis from in utero to aging works. Space flight, bed rest as well as osteoporosis and sarcopenia experimentations have allowed to accumulate considerable evidence. Mechanical loading is a key mechanism linking both tissues with a central promoting role of physical activity. Moreover, the skeletal muscle secretome accounts various molecules that affect bone including insulin-like growth factor-1 (IGF-1), basic fibroblast growth factor (FGF-2), interleukin-6 (IL-6), IL-15, myostatin, osteoglycin (OGN), FAM5C, Tmem119 and osteoactivin. Even though studies on the potential effects of bone on muscle metabolism are sparse, few osteokines have been identified. Prostaglandin E2 (PGE2) and Wnt3a, which are secreted by osteocytes, osteocalcin (OCN) and IGF-1, which are produced by osteoblasts and sclerostin which is secreted by both cell types, might impact skeletal muscle cells. Cartilage and adipose tissue are also likely to participate to this control loop and should not be set aside. Indeed, chondrocytes are known to secrete Dickkopf-1 (DKK-1) and Indian hedgehog (Ihh) and adipocytes produce leptin, adiponectin and IL-6, which potentially modulate bone and muscle metabolisms. The understanding of this system will enable to define new levers to prevent/treat sarcopenia and osteoporosis at the same time. These strategies might include nutritional interventions and physical exercise.     

Analysis of the tumor necrosis factor superfamily member 11 gene polymorphism with bone mineral density and bone fracture frequency in patients with postmenopausal osteoporosis

PurposeWe aimed to examine the polymorphism of the promoter and exon 5 of the TNFSF11 gene and their impact on bone mineral density (BMD) and the frequency of bone fractures. TNFSF11 encodes the receptor activator of the NF-kB ligand (RANKL), a key regulator of bone metabolism and osteoporosis drug targets. BMD is an essential measure in diagnosing osteoporosis and assessing the risk of fractures. In vivo, RANKL expression research suggests that promoter TNFSF11 variants influence BMD. Moreover, exon 5 polymorphism of a linear epitope sequence for a denosumab could be related to the effectiveness of biological therapy.Patients and methodsThe study included 114 postmenopausal osteoporosis patients. BMD was measured in the lumbar spine and the femoral neck. Genetic analysis was performed using Sanger sequencing. Genotypes data for 263 female European population group were obtained from the 1000Genomes database.ResultsWe identified six promoter polymorphisms (rs9525641, rs9533155, rs9533156, rs11839112, rs28926171, rs183599708) and one silent TNFSF11 variant in exon 5 (rs9562415). Three of the sequence variants detected (rs9525641, rs9533155, rs9533156) proved to be polymorphic, whereas the others four occurred at a frequency below 2%. The statistical analysis demonstrated no significant differences between polymorphisms and BMD, and bone fractures. However, variant rs9533156 was relevant with the lumbar spine T-score (p = 0.0273), and no association with BMD was of borderline significance (p = 0.0529).ConclusionsVariant rs9533156 may contribute to the genetic regulation of BMD in Polish postmenopausal osteoporosis, while the exon 5 sequence of the TNFSF11 gene is very conservative.     

Recent advances in the use of serological bone formation markers to monitor callus development and fracture healing

The failure of an osseous fracture to heal, or the development of a nonunion, is common; however, current diagnostic measures lack the capability of early and reliable detection of such events. Analyses of radiographic imaging and clinical examination, in combination, remain the gold standard for diagnosis; however, these methods are not reliable for early detection. Delayed diagnosis of a nonunion is costly from both the patient and treatment standpoints. In response, repeated efforts have been made to identify bone metabolic markers as diagnostic or prognostic tools for monitoring bone healing. Thus far, the evidence regarding a correlation between the kinetics of most bone metabolic markers and nonunion is very limited. With the aim of classifying the role of biological pathways of bone metabolism and of understanding bone conditions in the development of osteoporosis, advances have been made in our knowledge of the molecular basis of bone remodeling, fracture healing, and its failure. Procollagen type I amino-terminal propeptide has been shown to be a reliable bone formation marker in osteoporosis therapy and its kinetics during fracture healing has been recently described. In this article, we suggest that procollagen type I amino-terminal propeptide presents a good opportunity for early detection of nonunion. We also review the role and potential of serum PINP, as well as other markers, as indications of fracture healing.     

Long-term exposure to lifelong therapies

Three categories of highly active antiretroviral therapy (HAART)-associated major toxic effects have been identified: nucleoside-related toxic effects (e.g., neuropathy, myopathy, pancreatitis, hepatic steatosis, lactic acidosis, and possibly lipoatrophy), metabolic complications (e.g., fat redistribution, insulin resistance, and hyperlipidemia), and bone disease (e.g., osteopenia and/or osteoporosis). The toxic effects caused by nucleosides are hypothesized to be a result of mitochondrial injury and include myopathy, pancreatitis, liver failure, and lactic acidosis. Alterations in lactic acid metabolism range from common instances of asymptomatic lactic acidemia to rare occurrences of life-threatening lactic acidosis with hepatic steatosis. A metabolic syndrome consisting of lipodystrophy (i.e., fat redistribution), hyperlipidemia and insulin resistance has been observed, particularly with protease inhibitor treatment. Some additive interaction between protease inhibitors and nucleosides has also been described. The potential relationship of these metabolic abnormalities to increased risk of cardiovascular disease and diabetes has broad implications on long-term patient management. Lipodystrophy associated with HAART is generally accompanied by potentially serious abnormalities, including dyslipidemia (i.e., hypercholesterolemia and hypertriglyceridemia) and altered glucose metabolism (i.e., insulin resistance). Regimens of HAART may have adverse effects on bone metabolism, as indicated by emerging reports of osteopenia, osteoporosis, and avascular necrosis.     

淫羊藿苷去蛋白无机牛骨复合材料与去蛋白无机牛骨材料修复下颌骨缺损

文题释义：去蛋白无机牛骨：是采用化学提纯法从牛骨中提取的碳酸磷灰石晶体，去除了蛋白及其他的有机成分，而保留了多孔天然骨的无机机构，与人体骨的结构相似，目前已被广泛应用于口腔临床骨再生手术。 淫羊藿苷：是一种具有补肾壮阳、祛风除湿功效的中药，临床多用于免疫力低下、性功能障碍与抗衰老食疗等。淫羊藿苷是淫羊藿的有效药理成分，近年来的研究发现其具有防治骨质疏松，并且其可促进间充质干细胞、成骨细胞的成骨分化与成血管因子的表达。 背景：去蛋白无机牛骨与人体骨的结构相似，目前已被广泛应用于口腔临床骨再生手术，但其缺乏成骨诱导能力。近年来的研究发现淫羊藿具有防治骨质疏松的作用。 目的：观察淫羊藿苷去蛋白无机牛骨复合材料修复下颌骨缺损的效果。 方法：将小鼠成骨细胞MC3T3-E1分别接种于淫羊藿苷去蛋白无机牛骨复合材料(观察组)与去蛋白无机牛骨材料(对照组)上，培养7 d后，活死染色观察材料表面细胞的存活，扫描电镜观察材料表面细胞的黏附；培养5，10 d后，检测细胞分泌碱性磷酸酶情况。在30只新西兰大白兔双侧下颌骨制作13 mm×6 mm×4 mm的全层骨缺损，右侧植入淫羊藿苷去蛋白无机牛骨复合材料(实验侧)，左侧植入去蛋白无机牛骨材料(对照侧)，术后4，8，12周获取双侧下颌骨组织，分别进行锥形束CT检测、组织学观察与改良Gomori染色观察。实验获得牡丹江医学院实验动物中心伦理委员会批准。结果与结论：①活死染色显示，两组材料表面的成骨细胞生长状态良好；②扫描电镜显示，成骨细胞可在两种材料表面黏附，在观察组材料表面的黏附数量更多、分布更加均匀；③观察组培养10 d的细胞碱性磷酸酶活性高于对照组(P < 0.05)；④锥形束CT显示，实验侧骨缺损至术后12周时基本愈合，对照侧术后12周时仍可见骨缺损；⑤术后12周组织学观察显示，实验侧缺损区可见大量成熟骨组织，仅见少量残余材料，可见少量脂肪组织；对照侧虽然材料部分降解，可见较多的新生骨组织，骨成熟度低于实验侧；⑥术后12周改良Gomori染色显示，实验侧可见大量成熟度较高的新生骨组织，对照侧也可见较多成熟度较高的骨组织，但骨量与骨成熟度均不及实验侧；⑦结果表明相对于去蛋白无机牛骨材料，淫羊藿苷去蛋白无机牛骨复合材料可促进下颌骨缺损的修复。ORCID: 0000-0001-5823-7228(董文杰)中国组织工程研究杂志出版内容重点：生物材料；骨生物材料; 口腔生物材料; 纳米材料; 缓释材料; 材料相容性；组织工程     

Sex steroids and bone: current perspectives

Although the process of bone remodelling or its control has not yet been fully elucidated there is, at present, sufficient information available to conclude that ovarian steroids (estrogens, androgens, progesterone) play an essential role in skeletal homeostasis. The mechanism of action of sex steroids on the skeleton is still not entirely clear, but it has traditionally included indirect effects on systemic hormones that regulate calcium balance and a direct receptor-mediated action. More recently, changes in cytokine production within the bone marrow, as well as pro-apoptotic and anti-apoptotic effects in the osteoblastic cells, have been proposed as new perspectives on the cellular and molecular mechanisms by which sex steroids influence adult bone homeostasis. Mechanical loading, when combined with estrogens or androgens, results in a greater osteogenic response than either condition separately. Women are especially at risk for osteoporosis if they have had a premature or surgical menopause and have not received hormone replacement therapy (HRT). Other reproductive factors that can help to identify women with osteopenia and emphasize the role of sex steroids in preserving bone mass in premenopausal women include: age at menarche, menstrual history and irregularities (including those associated with excessive exercise), age at menopause, previous hysterectomy, hyperprolactinaemia, anorexia nervosa, scoliosis, ovarian dysgenesis, pregnancy and lactation, and pharmacological ovarian suppression. The prevention of osteoporosis starts with the onset of the menarche. A combination of exercise, appropriate nutrition and a healthy lifestyle all maximize bone mineral accrual and result in optimal peak bone mass; normal ovarian function is essential to this process. Unfortunately, many women actually become aware of the need for osteoporosis prevention much later in life, usually after they have already become menopausal. HRT, however, has important limitations for prevention of fractures in post-menopausal women. Future perspectives for treatment of osteoporosis include androgen therapy and anabolic agents. Specifically, synthetic ligands of the estrogen receptor that can evoke the non-genotrophic but not the genotrophic signal of the receptor may be bone anabolic agents, as opposed to natural estrogens or selective estrogen receptor modulators that are anti-resorptive agents. The same ligands may circumvent the side effects associated with conventional HRT.     

Integrative Physiology: Defined Novel Metabolic Roles of Osteocalcin

The prevailing model of osteology is that bones constantly undergo a remodeling process, and that the differentiation and functions of osteoblasts are partially regulated by leptin through different central hypothalamic pathways. The finding that bone remodeling is regulated by leptin suggested possible endocrinal effects of bones on energy metabolism. Recently, a reciprocal relationship between bones and energy metabolism was determined whereby leptin influences osteoblast functions and, in turn, the osteoblast-derived protein osteocalcin influences energy metabolism. The metabolic effects of bones are caused by the release of osteocalcin into the circulation in an uncarboxylated form due to incomplete γ-carboxylation. In this regard, the Esp gene encoding osteotesticular protein tyrosine phosphatase is particularly interesting because it may regulate γ-carboxylation of osteocalcin. Novel metabolic roles of osteocalcin have been identified, including increased insulin secretion and sensitivity, increased energy expenditure, fat mass reduction, and mitochondrial proliferation and functional enhancement. To date, only a positive correlation between osteocalcin and energy metabolism in humans has been detected, leaving causal effects unresolved. Further research topics include: identification of the osteocalcin receptor; the nature of osteocalcin regulation in other pathways regulating metabolism; crosstalk between nutrition, osteocalcin, and energy metabolism; and potential applications in the treatment of metabolic diseases.     

The effects of L-thyroxin replacement therapy on bone minerals and body composition in hypothyroid children

Introduction

Prolonged treatment with levothyroxine 4 (L-T4) is a well known risk factor for osteoporosis. Patients on L-T4 replacement occasionally have a subnormal TSH, which carries a risk of development of bone loss. Thyroid hormones directly affect bone cells, stimulating osteoclastic and osteoblastic activity with a predominance of bone resorption and decrease of bone mineral density (BMD).

Material and methods

The study included 35 hypothyroid patients with mean age 11.57 ±5.06, while 26 age- and sex-matched children served as controls. Dual energy X-ray absorptiometry (DXA) was done to detect the bone mineral density (BMD), bone mineral content (BMC) and Z score in lumbar and femur neck regions. Body composition was also studied by DXA. Calcium, phosphorus, osteocalcin as a bone formation marker, osteoprotegerin as an indicator of osteoclast activity and urinary deoxypyridinoline as a bone collagen breakdown marker were assessed.

Results

No significant differences were detected in lumbar Z score (−0.12 ±0.66) and femur Z score (−0.17 ±0.58) compared to controls (−0.33 ±0.74 and −0.21 ±0.53 respectively). Bone mineral density and BMC were not significantly different from controls. No significant difference was detected between cases and controls in body composition. A positive correlation was detected between BMD and age (r=0.857, p<0.01), and with the period of treatment (r=0.766, p<0.01). A positive correlation was found between BMD and total body fat (r=0.693, p<0.01), and with abdominal fat (r=0.667, p<0.01).

Conclusions

Levothyroxine 4 treatment in hypothyroid children does not alter bone metabolism and body composition.     

Function of matrix IGF-1 in coupling bone resorption and formation

Balancing bone resorption and formation is the quintessential component for the prevention of osteoporosis. Signals that determine the recruitment, replication, differentiation, function, and apoptosis of osteoblasts and osteoclasts direct bone remodeling and determine whether bone tissue is gained, lost, or balanced. Therefore, understanding the signaling pathways involved in the coupling process will help develop further targets for osteoporosis therapy, by blocking bone resorption or enhancing bone formation in a space- and time-dependent manner. Insulin-like growth factor type 1 (IGF-1) has long been known to play a role in bone strength. It is one of the most abundant substances in the bone matrix, circulates systemically and is secreted locally, and has a direct relationship with bone mineral density. Recent data has helped further our understanding of the direct role of IGF-1 signaling in coupling bone remodeling which will be discussed in this review. The bone marrow microenvironment plays a critical role in the fate of mesenchymal stem cells and hematopoietic stem cells and thus how IGF-1 interacts with other factors in the microenvironment are equally important. While previous clinical trials with IGF-1 administration have been unsuccessful at enhancing bone formation, advances in basic science studies have provided insight into further mechanisms that should be considered for future trials. Additional basic science studies dissecting the regulation and the function of matrix IGF-1 in modeling and remodeling will continue to provide further insight for future directions for anabolic therapies for osteoporosis.     

Quantitative ultrasound (QUS) of bone in the management of postmenopausal women

OBJECTIVES: Postmenopausal osteoporosis is becoming a major problem for healthcare institutions as it has a growing social and economic impact. The incidence of osteoporotic fractures is constantly increasing due to the increase in life expectancy. The gynaecologist plays an important role in establishing a "biological zero" in each perimenopausal patient, and controlling the rate of bone loss during postmenopausal period. RESULTS: Dual energy X-ray absorptiometry (DXA) has been widely used for the diagnosis and management of osteoporosis and represents a strong risk factor for fractures, but it presents several limitations with regards to diagnosis, treatment follow-up and differential diagnosis of secondary osteoporosis. In these last years quantitative ultrasound (QUS) technique has been introduced for the evaluation of bone status in postmenopausal women and several in vitro and clinical studies have demonstrated the reliability of the examination in terms of: reproducibility, evaluation of fracture risk, treatment follow-up, differential diagnosis. QUS has proven to be equally capable in the prediction of future osteoporosis related fractures in comparison to DXA. Large-scale cross-sectional and longitudinal studies have demonstrated the applicability of QUS in screening the female population during the climacteric period. QUS technique seems to be very efficient in identifying "fast losers", identifying subjects at risk for osteoporosis requiring second-level investigation (DXA, X-ray), diagnosing secondary osteoporosis. CONCLUSION: If QUS is used in a systematic and rational manner in clinical practice, it is a valid technique for the prevention of osteoporosis in postmenopausal women.     

Examination of osteoarthritis and subchondral bone alterations within the stifle joint of an ovariectomised ovine model

The exact relationship between osteoporosis and osteoarthritis is still a matter for debate for many. The ovariectomised ewe is frequently used as a model for osteoporosis, resulting in significant alterations in bone morphometry and turnover in both trabecular and subchondral bone after 1 year. This study examines whether ovariectomy has any impact on development of osteoarthritis within the ovine stifle joint at the same time point. In addition, we investigate whether there are any significant correlations present between articular cartilage degeneration and alterations in microstructural parameters or turnover rates in the underlying bone. Twenty‐two sheep were examined in this study; 10 of the sheep underwent ovariectomy and 12 were kept as controls. Five distinctive fluorochrome dyes were administered intravenously at 12‐week intervals to both groups, to label sites of bone turnover. All animals were then sacrificed 12 months postoperatively. Although most specimens showed some evidence of osteoarthritis, no measurable difference between the two study groups was detected. Osteoarthritis was associated with a thinning of the subchondral plate, specifically the subchondral cortical bone; however, whereas previous studies have suggested a link between trabecular thinning and osteoarthritis, this was not confirmed. No correlation was found between osteoarthritis and bone turnover rates of either the subchondral trabecular bone or bone plate. In conclusion, despite the fact that ovariectomy results in marked morphological and structural changes in the ovine stifle joint at 1‐year postoperatively, no evidence was found to suggest that it plays a direct role in the aetiology of osteoarthritis.     

Nitric oxide and bone.

Nitric oxide (NO) is a free radical which has important effects on bone cell function. The endothelial isoform of nitric oxide synthase (eNOS) is widely expressed in bone on a constitutive basis, whereas inducible NOS is only expressed in response to inflammatory stimuli. It is currently unclear whether neuronal NOS is expressed by bone cells. Pro-inflammatory cytokines such as IL-1 and TNF cause activation of the iNOS pathway in bone cells and NO derived from this pathway potentiates cytokine and inflammation induced bone loss. These actions of NO are relevant to the pathogenesis of osteoporosis in inflammatory diseases such as rheumatoid arthritis, which are characterized by increased NO production and cytokine activation. Interferon gamma is a particularly potent stimulator of NO production when combined with other cytokines, causing very high concentrations of NO to be produced. These high levels of NO inhibit bone resorption and formation and may act to suppress bone turnover in severe inflammation. The eNOS isoform seems to play a key role in regulating osteoblast activity and bone formation since eNOS knockout mice have osteoporosis due to defective bone formation. Other studies have indicated that the NO derived from the eNOS pathway acts as a mediator of the effects of oestrogen in bone. eNOS also mediates the effects of mechanical loading on the skeleton where it acts along with prostaglandins, to promote bone formation and suppress bone resorption. Pharmacological NO donors have been shown to increase bone mass in experimental animals and preliminary evidence suggests that these agents may also influence bone turnover in man. These data indicate that the L-arginine/NO pathway represents a novel target for therapeutic intervention in the prevention and treatment of bone diseases.     

Association between the SPRY1 gene polymorphism and obesity-related traits and osteoporosis in Korean women

BackgroundEmerging evidence has revealed a close relationship between obesity and osteoporosis. It was reported recently that conditional knockout of the Spry1 gene in mice adipocytes causes an increase in body fat and a decrease in bone mass, and that these phenotypes are rescued by Spry1 overexpression in adipose tissue. In this study, we investigated whether genetic variation in the human SPRY1 gene is associated with obesity-related phenotypes and/or osteoporosis in humans.MethodsWe performed a candidate gene association analysis between the four single nucleotide polymorphisms (SNPs) and 14 imputed SNPs in the SPRY1 gene and obesity-related traits and osteoporosis in a Korean women cohort (3013 subjects).ResultsAll four SPRY1 gene SNPs were significantly associated with either obesity-related traits or osteoporosis. The TGCC haplotype in the SRPY1 gene showed simultaneous association with an increased risk for obesity-related traits, percentage body fat (p = 0.0087) and percentage abdominal fat (p = 0.047), and osteoporosis (odds ratio = 1.50; p = 0.025) in the recessive genetic model.ConclusionsOur results support a previous finding in conditional Spry1 gene knockout mice and suggest that the SPRY1 gene is an important genetic factor for determining the risk of both obesity and osteoporosis in humans.