Low-frequency acoustic sweep monitoring of bone integrity and osteoporosis.

We developed a noninvasive method to evaluate bone structural integrity. It is based on the measurement of the dynamic characteristics of the bone using sweeping sound excitation in the range of acoustic frequencies. The Quality Factor (a measure of material damping) has been used as an indicator of the tendency of the bone to fracture. Results of animal studies have supported this hypothesis since linear correlations were observed between bone density, quality factor, and impact strength. A vibration excitation in the form of an acoustic sweep signal is applied to a bone to measure the quality factor. Rat bones were tested, obtained from animals with osteoporosis age-dependent (tested in vitro) or ovariectomy-induced (tested in vivo), and compared with bones of healthy (control) rats. The change in damping was, on average, equal or greater to the change in density. Moreover, excellent correlation of the quality factor was obtained with bone fracture energy measured with an impact test. During a vibration cycle, the changing strain results in temperature changes due to the reciprocity of temperature and strain. Nonreversible conduction of heat due to the unequal temperature change results in entropy production that is enhanced due to the stress concentration about the voids associated with bone porosity. Damping is a measure of the production of entropy. Its measure, the quality factor, represents a potentially useful tool for monitoring bone integrity, which is deteriorating in diseases characterized by disruption of the trabecular architecture, such as osteoporosis. A computational model yielded results that are in good correlation with the experimental results.     

Protective effect of polysaccharides from morinda officinalis on bone loss in ovariectomized rats

In order to examine the effect of polysaccharides from morinda officinalis (MOP) on bone quality of osteoporosis rats. The osteoporosis in rats was induced by ovariectomy, and MOP (100 or 300mg/kg) was orally administrated once daily. The animals were assessed 30 days after the operation for bone mineral density, serum cytokines level and mineral element concentration. MOP administration in rats resulted in an increase in bone mineral density and mineral element concentration, a decrease in serum cytokines level, which indicated that MOP administration may play an important role in the development of osteoporosis.     

Treatment of osteoporosis with a modified zeolite shows beneficial effects in an osteoporotic rat model and a human clinical trial

The severity of osteoporosis in humans manifests in its high incidence and by its complications that diminish quality of life. A societal consequence of osteoporosis is the substantial burden that it inflicts upon patients and their families. Several bone-modifying drugs have been prescribed to patients with osteoporosis. However, evidence for their anti-fracture efficacy remains inconclusive. To the contrary, long-term use of anti-osteoporotic drugs such as bisphosphonates and Denosumab, an RANKL inhibitor, have resulted in adverse events. We now present an alternative and adjuvant approach for treatment of osteoporosis. The data derive from in vivo studies in an ovariectomized rat model and from a randomized double blind, placebo-controlled human clinical study. Both studies involved treatment with Panaceo Micro Activation (PMA)-zeolite-clinoptilolite, a defined cation exchange clinoptilolite, which clearly improved all bone histomorphometric parameters examined from ovariectomized animals, indicative for increased bone formation. Moreover, intervention with PMA-zeolite-clinoptilolite for one year proved safe in humans. Furthermore, patients treated with PMA-zeolite-clinoptilolite showed an increase in bone mineral density, an elevated level of markers indicative of bone formation, a significant reduction in pain, and significantly improved quality of life compared with patients in the control (placebo) group. These encouraging positive effects of PMA-zeolite-clinoptilolite on bone integrity and on osteoporosis warrant further evaluation of treatment with PMA-zeolite-clinoptilolite as a new alternative adjuvant therapy for osteoporosis.     

Bone quality assessment in individuals of different age, gender and body constitution

The concept of bone quality describes the sets of the characteristics of the osseous tissue that influence bone strength. The aim was to explore the influence of anthropometric parameters and age on the parameters of the bone architecture and bone mineral properties in the lumbar vertebral bone of men and women. Vertebral bone samples underwent bone histomorphometry, bone densitometry and atomic absorption spectrometry. Men have greater values of the bone volume and thicker bone trabeculae in relation to women, which indicates that vertebral bone architecture is better preserved in men than in women. Age is the best predictor of changes that affect bone architecture and bone mineral properties. Bone mineral density value and calcium concentration are both negatively predicted by age, but positively predicted by body mass index. Such result supports the opinion that low body mass index is associated with conditions of bone deficit such are osteopenia and osteoporosis.     

4q22.1 Contributes to Bone Mineral Density and Osteoporosis Susceptibility in Postmenopausal Women of Chinese Han Population

Osteoporosis is a multifactorial disease in which genetic determinants are modulated by hormonal, environmental and nutritional factors. An important clinical risk factor in the pathogenesis of osteoporosis is the presence of genetics polymorphism in/around susceptibility genes/regions. This study explored whether the region of 4q22.1, which confers risk of developing osteoporosis in some populations, associated with bone mineral density and osteoporosis susceptibility in postmenopausal women of Han Chinese. We investigated 32 SNPs with minor allele frequencies ≥0.05 between 20 kb upstream and 20 kb downstream (40 kb window) of rs6532023, mapping in the 4q22.1 region, which was reported to be significantly associated with osteoporosis in previous studies. We found that rs6532023 was significantly associated with bone mineral density and osteoporosis (corrected p = 0.015) in our sample, including 440 cases and 640 controls, and allele G was supposed as a risk factor while T worked as a protective factor. Further genotype association analyses suggested a similar pattern (corrected p = 0.040). Additionally, analyses by haplotypes indicated that a haplotype block rs7683315-rs6532023-rs1471400-rs1471403 in the region associated with bone mineral density and osteoporosis (global p = 0.032), and risk haplotype A-G-G-C had almost 1.5-fold increased in the cases. To our knowledge, this is the first report to examine 4q22.1 region polymorphisms and osteoporosis in Han Chinese. Our results provide further evidence for an effect of the region of 4q22.1 on the etiology of osteoporosis and suggest that 4q22.1 may be a genetic risk factor for bone mineral density and osteoporosis.     

Conjugated linoleic acid protects against age-associated bone loss in C57BL/6 female mice

Osteoporosis is one of the major causes of morbidity in the elderly. Inflammation exerts a significant influence on bone turnover, inducing the chronic form of osteoporosis. Dietary nutrition has the capacity to modulate inflammatory response. Therefore, nutritional strategies and lifestyle changes may prevent age-related osteoporosis, thereby improving the quality of life of the elderly population. Conjugated linoleic acid (CLA) has been shown to positively influence calcium and bone metabolism. Hence, this study was undertaken to examine the effect of CLA on bone mineral density (BMD) in middle-aged C57BL/6 female mice. After 10 weeks on diet, CLA-fed mice (14 months) maintained a higher BMD in different bone regions than corn oil (CO)-fed mice. The increased BMD was accompanied by a decreased activity of proinflammatory cytokines (such as tumor necrosis factor alpha, interleukin-6 and the receptor activator of NF-kappaB ligand) and decreased osteoclast function. Furthermore, a significant decrease in fat mass and an increase in muscle mass were also observed in CLA-fed mice compared to CO-fed mice. In conclusion, these findings suggest that CLA may prevent the loss of bone and muscle mass by modulating markers of inflammation and osteoclastogenic factors.     

The role of anorexia nervosa in secondary osteoporosis development with the risk for low energy fractures

Anorexia nervosa (AN) has in recent years become considerably more common. The disease primarily affects girls and young women, also boys and young men. AN is a risk factor for secondary osteoporosis. AN-related metabolic disturbances lead to diminished bone quality and increased risk of fractures. The consequences of low energy fractures are the main causes of death in women with AN. Hormonal disturbances (e.g. hypoestrogenism, increased levels of ghrelin and Y peptide, changes in leptin and endocannabinoid levels), as well as the mechanisms involved in bone resorption (RANK/RANKL/OPG system), are considered to be of great importance for anorectic bone quality. The risk for osteoporotic, non-vertebral fractures in AN patients is significantly higher than in healthy women. Improvement of bone mineral density is possible after substantial body mass increase. Weight loss, in conjunction with a well-balanced, controlled diet, is the key to correct peak bone mass levels, and diminishes the risk for osteoporosis with its consequence of low energy bone fractures.     

老年女性类风湿关节炎合并骨质疏松症的代谢特点分析

目的:探讨老年女性类风湿关节炎(RA)合并骨质疏松症的代谢特点。方法:选择老年绝经后女性RA患者共59例,检测患者血生化代谢指标如血糖、血脂、CRP等和骨代谢指标如骨钙素(OC)、β-胶原特殊序列(β-Crosslaps)甲状旁腺素(iPTH)等,并进行统计分析。结果:骨质疏松患者的绝经时间、病程长度、OC、β-Crosslaps、iPTH显著高于骨量正常和骨量减少的患者,25羟基维生素D显著低于骨量正常和骨量减少的患者(P均0.05)。RA患者的骨密度水平与是否使用激素和X线分期情况无关。结论:老年女性RA患者易发生骨质疏松,出现骨质疏松的RA女性患者绝经时间更长,可出现脂代谢紊乱及明显的维生素D缺乏,并具有高转换型骨代谢特点。     

Time Related Changes of Mineral and Collagen and Their Roles in Cortical Bone Mechanics of Ovariectomized Rabbits

As cortical bone has a hierarchical structure, the macroscopic bone strength may be affected by the alterations of mineral crystal and collagen, which are main components of cortical bone. Limited studies focused on the time related alterations of these two components in osteoporosis, and their contributions to bone mechanics at tissue level and whole-bone level. Therefore, the purpose of this study was to elucidate the time related changes of mineral and collagen in cortical bone of ovariectomized (OVX) rabbits, and to relate these changes to cortical bone nanomechanics and macromechanics. 40 Rabbits (7-month-old) were randomly allocated into two groups (OVX and sham). OVX group received bilateral ovariectomy operation. Sham group received sham-OVX operation. Cortical bone quality of five rabbits in each group were assessed by DXA, μCT, nanoindentation, Fourier transform infrared (FTIR) spectroscopy and biomechanical tests (3-point bending of femoral midshaft) at pre-OVX, 4, 6, and 8 weeks after OVX. As time increased from pre-OVX to 8 weeks, the mineral to matrix ratio decreased with time, while both collagen crosslink ratio and crystallinity increased with time in OVX group. Elastic modulus and hardness measured by nanoindentation, whole-bone strength measured by biomechanical tests all decreased in OVX group with time. Bone material properties measured by FTIR correlated well with nano or whole-bone level mechanics. However, bone mineral density (BMD), structure, tissue-level and whole-bone mechanical properties did not change with age in sham group. Our study demonstrated that OVX could affect the tissue-level mechanics and bone strength of cortical bone. And this influence was attributed to the time related alterations of mineral and collagen properties, which may help us to design earlier interventions and more effective treatment strategies on osteoporosis.     

The role of anorexia nervosa in secondary osteoporosis development with the risk for low energy fractures

Anorexia nervosa (AN) has in recent years become considerably more common. The disease primarily affects girls and young women, and also boys and young men. AN is a risk factor for secondary osteoporosis. AN-related metabolic disturbances lead to diminished bone quality and increased risk of fractures. The consequences of low energy fractures are the main causes of death in women with AN. Hormonal disturbances (e.g. hypoestrogenism, increased levels of ghrelin and Y peptide, changes in leptin and endocannabinoid levels), as well as the mechanisms involved in bone resorption (RANK/RANKL/OPG), are considered to be of great importance for anorectic bone quality. The risk of osteoporotic, non-vertebral fractures in AN patients is significantly higher than in healthy women. An improvement of bone mineral density is possible after substantial body mass increase. Weight loss, in conjunction with a well-balanced, controlled diet, is the key to correct peak bone mass levels, and diminishes the risk of osteoporosis with its consequence of low energy bone fractures. (Pol J Endocrinol 2011; 62 (1): 45-47).     

In vivo vibrational wave propagation in human tibiae at different ages

Vibrational wave propagation was tested in vivo on the tibial bone of both legs of 56 female volunteers. The impact was produced by a hammer with a force strain gauge and the response was monitored by two accelerometers. The peak amplitude of the accelerations, the velocity of the acceleration wave propagation and damping were analysed for comparison among the different age groups. The results showed significant negative correlations between age and the peak amplitude of acceleration, and the velocity of acceleration wave propagation (p less than 0.01). The damping time of the acceleration wave also had a negative correlation with age. These findings suggested that age differences were related to the differences in the mechanical properties of bone. With reduction of bone mineral density, the velocity of the vibrational wave propagation would decrease, with simultaneous increase in impedance. In addition, wave absorption would be accelerated. It is suggested that this method could be used as an indicator of bone density. The method could also be developed to provide an index to monitor the progress of osteoporosis.     

Constructive effect of exogenous melatonin against osteoporosis after ovariectomy in rats

OBJECTIVE: To analyze histomorphometric, densitometric and biochemical effects of melatonin on osteoporosis in ovariectomized rats. STUDY DESIGN: Wistar rats were divided into 6 groups. Group C: control; Group I: bilateral ovariectomy (OVX); Group II: OVX + vehicle; Group III: OVX + 10 mg/kg/day melatonin (MLT); Group IV: OVX + 30 mg/kg/day MLT; Group V: sham + 10 mg/kg/day MLT. Cortex, trabecula, osteoblast and osteoclast numbers were evaluated on vertebra and femur histomorphometrically. Hydroxyproline analysis was used to determine collagen content of femur and vertebrae. Bone mineral density and bone mineral content were measured. RESULTS: Trabecular thickness and trabecular area of vertebra and femur and cortical thickness of femur showed remarkable decrease after OVX, but increased after MLT treatment in the OVX+MLT groups. Following OVX, no statistically significant difference was found in number of osteoblasts or osteoclasts, trabecular number or levels of hydroxyproline after treatment with MLT. OVX caused significant decrease in bone mineral density, but treatment with MLT was unable to reverse this effect. CONCLUSION: MLT may trigger microscopic changes in bone, and time of application is critical for clinical recovery. It can be effective in helping treat postmenopausal osteoporosis. However, it is contraindicated in women who have normal-functioning ovaries.     

不同强度的体育运动对糖尿病大鼠骨密度及骨代谢的影响

目的:探讨运动强度对糖尿病大鼠骨密度及骨代谢的影响,为糖尿病骨质疏松的预防和治疗提供实验依据。方法:采用一次性腹腔注射链服佐菌素建立糖尿病大鼠模型,随机分为糖尿病对照组、小强度运动组(10 m/min)、中强度运动组(20 m/min)和高强度运动组(30 m/min)。分别于运动前后测定各组大鼠的血糖、骨密度、血清骨钙素(BGP)、碱性磷酸化酶(AKP)、血钙(S-Ca)及血磷(S-P)含量。结果:运动组大鼠血糖均低于训练前和对照组(P0.05)。小强度运动组和高强度运动组大鼠骨密度低于对照组,中强度运动组大鼠骨密度显著高于对照组、小强度运动组和高强度运动组(P0.05);小强度运动组与高强度运动组大鼠骨密度无显著性差异(P0.05)。运动组大鼠BGP和S-P显著升高,AKP下降,差异具有统计学意义(P0.05)。小强度运动组和高强度运动组大鼠S-Ca无显著变化(P0.05);中强度运动组大鼠S-Ca显著升高,且高于小强度运动组和高强度运动组(P0.05)。结论:运动强度对骨密度和骨代谢有一定影响,采取适当的体育运动可提高血清骨钙素含量,改善骨代谢状况,有利于糖尿病骨质疏松症的预防。     

Zinc Supplementation Increased Bone Mineral Density,Improves Bone Histomorphology,and Prevents Bone Loss in Diabetic Rat

Biological Trace Element Research - Diabetic osteoporosis (DOP) is a complication of diabetes, with the characteristics of bone mineral density (BMD) reduction and bone structure destruction. Zinc...     

Bone loss induced by ovariectomy in rats is prevented by gene transfer of parathyroid hormone or an Arg-Gly-Asp-containing peptide

Osteoporosis is a major and growing healthcare concern as the population ages. The genes of both a Arg-Gly-Asp (RGD)-containing peptide and parathyroid hormone (PTH) were used to reduce bone loss induced by ovariectomy (OVX) in rats. Plasmids with either RGD or PTH gene were delivered into the quadriceps of OVX rats. The expression of the genes was detected by RT-PCR and radioimmunoassay. Analysis of bone mineral density, bone mechanical testing and bone mineral content indicated an improvement in bone properties in both RGD-transferred and PTH-transferred rats compared to OVX rats. Gene transfer of either RGD or PTH is therefore a possible approach to prevent bone loss in OVX rats thus providing a potential method to prevent osteoporosis in clinical situations.These authors contributed equally to this work     

仙灵骨葆对骨质疏松大鼠OPG/RANK/RANKL 表达的影响

目的:观察仙灵骨葆治疗骨质疏松模型大鼠后,对大鼠体内OPG/RANKL/RANK表达的影响。方法:卵巢摘除法建立SD大鼠骨质疏松模型,设立假手术组、对照组(单纯去卵巢组)、雌激素组(给予17β-雌二醇)和治疗组(给予仙灵骨葆)。术后1周开始给药,给药12周后检测各组大鼠股骨骨密度,ELISA法检测血清中OPG/RANKL含量,RT-PCR检测骨组织中OPG/RANK/RAN-KL mRNA表达,免疫组化检测骨组织中RANK的表达。结果:对照组大鼠骨密度显著低于假手术组;治疗组和雌激素组大鼠O-PG表达显著高于对照组,RANK及RANKL的表达显著低于对照组。结论:采用卵巢摘除法成功建立大鼠骨质疏松模型;仙灵骨葆可促进骨质疏松大鼠OPG的表达,并抑制RANK及RANKL的表达,对骨质疏松模型大鼠有治疗作用。     

In vivo anti-osteoporotic activity of isotaxiresinol, a lignan from wood of Taxus yunnanensis

Isotaxiresinol, the main lignan isolated from the water extract of wood of Taxus yunnanensis, was investigated for its effect on bone loss, on serum biochemical markers for bone remodeling and on uterine tissue, using ovariectomized (OVX) rats as the model of postmenopausal osteoporosis. After oral administration of isotaxiresinol (50 and 100mg/kg/d) for 6 weeks, bone mineral content (BMC) and bone mineral density (BMD) in total and cortical bones were increased as compared to those of OVX control rats, and decreases of three bone strength indexes induced by OVX surgery were prevented. Serum biochemical markers for bone remodeling revealed that isotaxiresinol slightly increased bone formation and significantly inhibited bone resorption without side effect on uterine tissue. These results suggest that isotaxiresinol may be useful for treatment of postmenopausal osteoporosis, especially for prevention of bone fracture induced by estrogen deficiency.     

Measurement of bone mineral density (BMD) with quantitative computed tomography (QCT) in postmenopausal osteoporosis: effect of estrogen.

To determine the efficacy of the estrogen replacement therapy (ERT) on the bone mineral density (BMD) measured with quantitative computed tomography (QCT) in postmenopausal osteoporosis 16 women aged 46-72 were examined. They were divided into two groups: 8 women treated with conjugated estrogens (Group I) and 8 who did not received ERT (Group II). In all 16 patients the serum hormonal concentrations (LH, FSH and estradiol) were measured with radioimmunological methods. The bone densitometry was performed in all of them using the single-energy computed tomography (QCT) with the computer Picker 1200. Bone mineral density was measured in three lumbar vertebra (L1-L3) and expressed in milligrams K2HPO4 per ml. The bone mineral density (BMD) was statistically significantly higher in the estrogen treated group (Group I) in every vertebra compared with that of controls (Group II). The serum FSH concentration was statistically significantly lower in the ERT group (Group I) and a statistically significant correlation between FSH level and average BMD (Lmean) was present. In conclusion: 1. the ERT is very efficacious in preventing bone loss in postmenopausal women; 2. measurement of BMD in lumbar vertebra L1 or L3 may be a sufficiently reliable and accurate, cost-effective and time-saving method of screening for osteoporosis; 3. the serum FSH determination seems to be useful in monitoring of the estrogen therapy for postmenopausal osteoporosis.     

Bone mineral density, osteopenia, and osteoporosis in the rhesus macaques of Cayo Santiago

This cross-sectional study investigates metabolic bone disease and the relationship between age and bone mineral density (BMD) in males and females of a large, well-documented skeletal population of free-ranging rhesus monkeys (Macaca mulatta), from the Caribbean Primate Research Center Museum collection from Cayo Santiago, Puerto Rico. The sample consists of 254 individuals aged 1.0-20+ years. The data consist of measurements of bone mineral content and bone mineral density, obtained from dual-energy X-ray absorptiometry (DEXA), of the last lumbar vertebra from each monkey. The pattern of BMD differs between male and female rhesus macaques. Females exhibit an initial increase in BMD with age, with peak bone density occurring around age 9.5 years, and remaining constant until 17.2 years, after which there is a steady decline in BMD. Males acquire bone mass at a faster rate, and attain a higher peak BMD at an earlier age than do females, at around 7 years of age, and BMD remains relatively constant between ages 7-18.5 years. After age 7 there is no apparent effect of age on BMD in the males of this sample; males older than 18.5 years were excluded due to the presence of vertebral osteophytosis, which interferes with DEXA. The combined frequency of osteopenia and osteoporosis in this population is 12.4%. BMD values of monkeys with vertebral wedge fractures are generally higher than those of virtually all of the nonfractured osteopenic/osteoporotic individuals, thus supporting the view that BMD as measured by DEXA is a useful but imperfect predictor of fracture risk, and that low BMD may not always precede fractures in vertebral bones. Other factors such as bone quality (i.e., trabecular connectivity) should also be considered. The skeletal integrity of a vertebra may be compromised by the loss of key trabeculae, resulting in structural failure, but the spine may still show a BMD value within normal limits, or within the range of osteopenia.     

Bone quality and healing in a swine vascularized bone allotransplantation model using cyclosporine-based immunosuppression therapy

Although vascularized bone and joint allotransplantation is a promising new treatment option for reconstructing large bone defects, the need for immunosuppressive agents to prevent rejection in these procedures poses a major problem. This problem stems from the fact that several of these agents can cause harmful side effects, such as alterations in bone quality and healing. Therefore, the purpose of this study was to determine what effect the commonly used immunosuppressant regimen cyclosporine A-based combination therapy has on bone quality and healing. In 10 pigs, vascularized bone allografts with skin and muscle components (osteomyocutaneous free flaps) were transplanted from size-matched donor animals. Recipient animals received oral cyclosporine A/mycophenolate mofetil/prednisone therapy for 90 days. Bone quality was studied before and after transplantation by measuring the bone's acoustic velocity and density and calculating the bone's elastic coefficient. Bone healing was assessed using radiographic analysis. Four animals were lost as a result of graft rejection or immunosuppression-related complications before the 90-day endpoint of the study. Although bone specimens taken from the six animals that completed the 90-day protocol had histological signs of rejection, they all seemed to have normal bone healing. Posttransplant bone density values were significantly decreased (p < 0.05) (1544.7 +/- 47.5 kg/m3) as compared with pretransplant values (1722.7 +/- 44.1 kg/m3). Results of the acoustic velocity and elastic coefficients measurements showed a significant decrease (p < 0.05) in posttransplant values (from 3503.0 +/- 165.1 meters/sec to 2963.0 +/- 54.6 meters/sec and from 21.6 +/- 2.2 GPa to 13.6 +/- 0.5 GPa, respectively), indicating diminished bone quality. The findings indicate that cyclosporine A/mycophenolate mofetil/prednisone combination therapy is ineffective in preventing bone rejection, that it decreases bone quality, and that it is associated with systemic toxicity, suggesting that this immunosuppressive regimen at the doses used in this study is not ideal for vascularized bone allotransplantation procedures.