Pulsed electromagnetic fields prevent osteoporosis in an ovariectomized female rat model: a prostaglandin E2-associated process

With the use of Helmholtz coils and pulsed electromagnetic field (PEMF) stimulators to generate uniform time varying electromagnetic fields, the effects of extremely low frequency electromagnetic fields on osteoporosis and serum prostaglandin E(2) (PGE(2)) concentration were investigated in bilaterally ovariectomized rats. Thirty-five 3 month old female Sprague-Dawley rats were randomly divided into five different groups: intact (INT), ovariectomy (OVX), aspirin treated (ASP), PEMF stimulation (PEMF + OVX), and PEMF stimulation with aspirin (PEMF + ASP) groups. All rats were subjected to bilateral ovariectomy except those in INT group. Histomorphometric analyses showed that PEMF stimulation augmented and restored proximal tibial metaphyseal trabecular bone mass (increased hard tissue percentage, bone volume percentage, and trabecular number) and architecture (increased trabecular perimeter, trabecular thickness, and decreased trabecular separation) in both PEMF + OVX and PEMF + ASP. Trabecular bone mass of PEMF + OVX rats after PEMF stimulation for 30 days was restored to levels of age matched INT rats. PEMF exposure also attenuated the higher serum PGE(2) concentrations of OVX rats and restored it to levels of INT rats. These experiments demonstrated that extremely low intensity, low frequency, single pulse electromagnetic fields significantly suppressed the trabecular bone loss and restored the trabecular bone structure in bilateral ovariectomized rats. We, therefore, conclude that PEMF may be useful in the prevention of osteoporosis resulting from ovariectomy and that PGE(2) might relate to these preventive effects.     

Body Anthropometry and the Risk of Hip and Wrist Fractures in Men: Results from a Prospective Study

Available epidemiological information on the associations between body anthropometry and the incidence of fractures in men is limited. We therefore prospectively investigated the association between body anthropometry and the incidence of hip and wrist fractures from low and moderate trauma among 43,053 men who were 40 years to 75 years of age in 1986 when they first enrolled in the Health Professionals Follow-Up Study. After 8 years of follow-up, 201 wrist fracture cases and 56 hip fracture cases were reported. Greater height was associated with significant elevations in both hip and wrist fractures, whereas nonsignificant inverse associations were observed with weight and body mass index. Men in the highest quintile of waist circumference had a relative risk (RR) of 2.57 (95% confidence interval [CI] 0.64 to 10.3) for hip fracture and 2.05 (95% CI 1.06 to 3.96) for wrist fracture when compared with men in the lowest quintile. Waist-to-hip ratio was also positively related to fracture incidence; comparing highest with lowest quintile, the RRs were 3.92 (95% CI 1.07 to 14.3) for hip fracture and 1.50 (95% CI 0.85 to 2.66) for wrist fracture. These anthropometric indicators, in particular waist-to-hip ratio, may be useful for the prediction of hip fracture in adult men.     

Biochemical markers in preclinical models of osteoporosis

Although several treatments for osteoporosis exist, further understanding of the mode of action of current treatments, as well as development of novel treatments, are of interest. Thus, preclinical models of osteoporosis are very useful, as they provide the possibility for gaining knowledge about the cellular mechanisms underlying the disease and for studying pharmaceutical prevention or intervention of the disease in simple and strictly controlled systems. In this review, we present a comprehensive collection of studies using biochemical markers of bone turnover for investigation of preclinical models of osteoporosis. These range from pure and simple in vitro systems, such as osteoclast cultures, to ex vivo models, such as cultures of embryonic murine tibiae and, finally, to in vivo models, such as ovariectomy and orchidectomy of rats. We discuss the relevance of the markers in the individual models, and compare their responses to those observed using 'golden standard' methods.     

BMP-9与骨代谢及糖代谢关系研究进展

骨形成蛋白-9(BMP-9)是从胚胎鼠的肝脏c DNA文库中克隆得到的新型细胞因子,属于转化生长因子β超家族的成员,由肝脏非实质细胞合成分泌,在体内以类激素的形式发挥广泛的生物学作用。BMP-9不仅具有强烈的骨诱导活性,促进成骨细胞分化,还可通过调控糖代谢过程中关键酶的表达、促进胰岛素合成及分泌、增加胰岛素敏感性等方式调节体内葡萄糖平衡。本文主要对BMP-9与骨代谢及糖代谢的关系进行综述,为深入认识糖尿病、代谢性骨病及糖尿病性骨质疏松的发生机理提供理论依据,为糖尿病和骨骼疾病的防治提供新的思路。     

综合干预对原发性骨质疏松治疗依从性及生活质量的影响

目的:探讨骨质疏松防治综合干预对特需门诊原发性骨质疏松(POP)患者治疗依从性及生活质量的影响。方法:以2010年5月~2013年5月期间四川大学华西医院国际医疗中心收治的112例POP患者为研究对象,分为干预组和对照组,在药物治疗的同时给予不同的护理措施,6个月后比较两组干预前后POP知识掌握程度(OKT评分)、疼痛(VAS评分)、骨密度(BMD)以及生活质量(OQOLS评分)改善情况;随访1年后评价两组治疗依从性以及骨折发生率。结果:经过6个月的干预,干预组OKT评分、VAS评分以及BMD和治疗前比较差异均有统计学意义(P0.001),和对照组比较差异也均有统计学意义(P0.001)。干预组OQOLS评分的5个维度以及生活质量总评分和干预前比较差异均有统计学意义(P0.001),和对照组比较差异也均有统计学意义(P0.001),对照组心理维度和社会维度和干预前比较差异不大(P0.05)。两组随访1年,干预组完全依存比例明显高于对照组,不依从比例低于对照组(P0.001);干预组病理性骨折发生率低于对照组(P0.05)。结论:对特需门诊收治的原发性骨质疏松患者在药物治疗的基础上实施综合护理干预,能够明显提高患者的治疗依从性,提高骨密度增加比例,减少疼痛,降低骨折发生率,改善患者生活质量。     

唑来膦酸联合钙尔奇D治疗糖尿病性骨质疏松的临床疗效研究

目的:观察唑来膦酸联合钙尔奇D治疗糖尿病性骨质疏松症的临床疗效。方法:将120例糖尿病性骨质疏松患者随机分为实验组和对照组,实验组60例予唑来膦酸联合钙尔奇D治疗,对照组60例予钙尔奇D治疗。连续治疗12个月后,比较两组患者的骨密度、疼痛评分及不良反应的发生情况。结果:治疗12个月后,实验组患者的股骨颈、股骨粗隆和腰椎正位的骨密度均较对照组明显升高,差异有统计学意义(P0.05);VAS疼痛评分较对照组显著降低(P0.05)。治疗过程中,两组均无严重的不良反应发生。结论:唑来膦酸联合钙尔奇D治疗糖尿病性骨质疏松临床效果优于钙尔奇D单药治疗。     

Pulsed electromagnetic fields stimulation affects BMD and local factor production of rats with disuse osteoporosis

Pulsed electromagnetic fields (PEMF) have been used widely to treat nonunion fractures and related problems in bone healing, as a biological and physical method. With the use of Helmholtz coils and PEMF stimulators to generate uniform time‐varying electromagnetic fields, the effects of extremely low frequency electromagnetic fields on bone mineral density (BMD) and local factor production in disuse osteoporosis (DOP) rats were investigated. Eighty 4‐month‐old female Sprague Dawley (SD) rats were randomly divided into intact (INT) group, DOP group, calcitonin‐treated (CT) group, and PEMF stimulation group. The right hindlimbs of all the rats were immobilized by tibia‐tail fixation except for those rats in the INT group. Rats in the CT group were injected with calcitonin (2 IU/kg, i.p., once a day) and rats in the PEMF group were irradiated with PEMF immediately postoperative. The BMD, serum transforming growth factor‐beta 1 (TGF‐β1), and interleukin‐6 (IL‐6) concentration of the proximal femur were measured 1, 2, 4, and 8 weeks after treatment. Compared with the CT and DOP groups, the BMD and serum TGF‐β1 concentration in the PEMF group increased significantly after 8 weeks. The IL‐6 concentration in the DOP group was elevated significantly after operation. The PEMF group showed significantly lower IL‐6 level than the DOP group. The results found demonstrate that PEMF stimulation can efficiently suppress bone mass loss. We, therefore, conclude that PEMF may affect bone remodeling process through promoting TGF‐β1 secretion and inhibiting IL‐6 expression. Bioelectromagnetics 31:113–119, 2010. © 2009 Wiley‐Liss, Inc.     

Inhibition of fatty acid biosynthesis prevents adipocyte lipotoxicity on human osteoblasts in vitro

Although increased bone marrow fat in age‐related bone loss has been associated with lower trabecular mass, the underlying mechanism responsible remains unknown. We hypothesized that marrow adipocytes exert a lipotoxic effect on osteoblast function and survival through the reversible biosynthesis of fatty acids (FA) into the bone marrow microenvironment. We have used a two‐chamber system to co‐culture normal human osteoblasts (NHOst) with differentiating pre‐adipocytes in the absence or presence of an inhibitor of FA synthase (cerulenin) and separated by an insert that allowed unidirectional trafficking of soluble factors only and prevented direct cell–cell contact. Supernatants were assayed for the presence of FA using mass spectophotometry. After 3 weeks in co‐culture, NHOst showed significantly lower levels of differentiation and function based on lower mineralization and expression of alkaline phosphatase, osterix, osteocalcin and Runx2. In addition, NHOst survival was affected by the presence of adipocytes as determined by MTS‐formazan and TUNEL assays as well as higher activation of caspases 3/7. These toxic effects were inhibited by addition of cerulenin. Furthermore, culture of NHOst with either adipocyte‐conditioned media alone in the absence of adipocytes themselves or with the addition of the most predominant FA (stearate or palmitate) produced similar toxic results. Finally, Runx2 nuclear binding was affected by addition of either adipocyte conditioned media or FA into the osteogenic media. We conclude that the presence of FA within the marrow milieu can contribute to the age‐related changes in bone mass and can be prevented by the inhibition of FA synthase.     

Understanding of stem cells in bone biology and translation into clinical applications

Developments of stem cell biology provide new approaches for understanding the mechanisms of a number of diseases, including osteoporosis. In this minireview, we highlight two areas that related to stem cells in bone biology. Recent discovery of the role of osteoclast and their stem cells leads to developing a new approach for treatment of osteoporosis with the initial stimulation of cells in osteoclast lineage and followed by sequentially enhanced bone formation. Stimulation on both sides in bone remodeling is expected to achieve a long term effect on bone formation. For bone regeneration, multiple disciplinary collaborations among bone biologists, stem cell biologists and biomaterial scientists are necessary to successfully develop an integrated stem cell therapy that should include stem cells, suitable scaffolds and bioactive factors/small molecular compounds.     

A QTL for osteoporosis detected in an F2 population derived from White Leghorn chicken lines divergently selected for bone index

Osteoporosis, resulting from progressive loss of structural bone during the period of egg-laying in hens, is associated with an increased susceptibility to bone breakage. To study the genetic basis of bone strength, an F(2) cross was produced from lines of hens that had been divergently selected for bone index from a commercial pedigreed White Leghorn population. Quantitative trait loci (QTL) affecting the bone index and component traits of the index (tibiotarsal and humeral strength and keel radiographic density) were mapped using phenotypic data from 372 F(2) individuals in 32 F(1) families. Genotypes for 136 microsatellite markers in 27 linkage groups covering approximately 80% of the genome were analysed for association with phenotypes using within-family regression analyses. There was one significant QTL on chromosome 1 for bone index and the component traits of tibiotarsal and humeral breaking strength. Additive effects for tibiotarsal breaking strength represented 34% of the trait standard deviation and 7.6% of the phenotypic variance of the trait. These QTL for bone quality in poultry are directly relevant to commercial populations.