Overview: animal models of osteopenia and osteoporosis

Prior to initiating a clinical trial in a post-menopausal osteoporosis study, it is reasonable to recommence the evaluation of treatment in the 9-month-old ovariectomized female rat. A female rat of this age has reached peak bone mass and can be manipulated to simulate clinical findings of post-menopausal osteoporosis. Ample time exists for experimental protocols that either prevent estrogen depletion osteopenia or restore bone loss after estrogen depletion. More time can be saved by acceleration of the development of the osteopenia by combining ovariectomized (OVX) plus immobilization (IM) models. Methods like serum biochemistry, histomorphometry and densitometry used in humans are applicable in rats. Like most animal models of osteopenia, the rat develops no fragility fractures, but mechanical testing of rat bones substitutes as a predictor of bone fragility. Recent studies have shown that the prevailing activity in cancellous and cortical bone of the sampling sites in rats is remodeling. The problems of dealing with a growing skeleton, the site specificity of the OVX and IM models, the lack of trabecular and Haversian remodeling and the slow developing cortical bone loss have been and can be overcome by adding beginning and pre-treatment controls and muscle mass measurements in all experimental designs, selecting cancellous bone sampling sites that are remodeling, concentrating the analysis of cortical bone loss to the peri-medullary bone and combining OVX and IM in a model to accelerate the development of both cancellous and cortical bone osteopenia. Not to be forgotten is the distal tibia site, an adult bone site with growth plate closure at 3 months and low trabecular bone turnover and architecture similar to human spongiosa. This site would be most challenging to the action of bone anabolic agents. Data about estrogen-deplete mice are encouraging, but the ovariectomized rat model suggests that developing an ovariectomized mouse model as an alternative is not urgent. Nevertheless, the mouse model has a place in drug development and skeletal research. In dealing with drug development, it could be a useful model because it is a much smaller animal requiring fewer drugs for screening. In skeletal research mice are useful in revealing genetic markers for peak bone mass and gene manipulations that affect bone mass, structure and strength. When the exciting mouse glucocorticoid-induced bone loss model of Weinstein and Manolagas is confirmed by others, it could be a significant breakthrough for that area of research. Lastly, we find that the information generated from skeletal studies of nonhuman primates has been most disappointing and recommend that these expensive skeletal studies be curtailed unless it is required by a regulatory agency for safety studies.     

Mechanisms of bone loss in inflammatory arthritis: diagnosis and therapeutic implications

Rheumatoid arthritis represents an excellent model in which to gain insights into the local and systemic effects of joint inflammation on skeletal tissues. Three forms of bone disease have been described in rheumatoid arthritis. These include: focal bone loss affecting the immediate subchondral bone and bone at the joint margins; periarticular osteopenia adjacent to inflamed joints; and generalized osteoporosis involving the axial and appendicular skeleton. Although these three forms of bone loss have several features in common, careful histomorphometric and histopathological analysis of bone tissues from different skeletal sites, as well as the use of urinary and serum biochemical markers of bone remodeling, provide compelling evidence that different mechanisms are involved in their pathogenesis. An understanding of these distinct pathological forms of bone loss has relevance not only with respect to gaining insights into the different pathological mechanisms, but also for developing specific and effective strategies for preventing the different forms of bone loss in rheumatoid arthritis.     

Mechanisms of bone loss in inflammatory arthritis: diagnosis and therapeutic implications

Rheumatoid arthritis represents an excellent model in which to gain insights into the local and systemic effects of joint inflammation on skeletal tissues. Three forms of bone disease have been described in rheumatoid arthritis. These include: focal bone loss affecting the immediate subchondral bone and bone at the joint margins; periarticular osteopenia adjacent to inflamed joints; and generalized osteoporosis involving the axial and appendicular skeleton. Although these three forms of bone loss have several features in common, careful histomorphometric and histopathological analysis of bone tissues from different skeletal sites, as well as the use of urinary and serum biochemical markers of bone remodeling, provide compelling evidence that different mechanisms are involved in their pathogenesis. An understanding of these distinct pathological forms of bone loss has relevance not only with respect to gaining insights into the different pathological mechanisms, but also for developing specific and effective strategies for preventing the different forms of bone loss in rheumatoid arthritis.     

Overview of osteoporosis.

Osteoporosis is a common age-related disorder manifested clinically by skeletal fractures, especially fractures of the vertebrae, hip, and distal forearm. The major cause of these fractures is low bone mass, although an increase in trauma due to falls in the elderly also contributes. There are multiple causes for the low bone mass which, in any given individual, may contribute differently to the development of the osteopenia. The most important groups of causes are failure to achieve adequate peak bone mass, slow bone loss due to processes relating to aging, the menopause in women, and a variety of sporadic behavioral, nutritional, and environmental factors that affect bone mass in some but not in other individuals. The most important approach is prevention. Drugs and behavioral factors known to cause bone loss should be eliminated and perimenopausal women should be evaluated for possible preventive administration of estrogen. For patients with fractures due to established osteoporosis, the only drugs approved by the Food and Drug Administration are the antiresorptive agents calcium, estrogen, and calcitonin. Formation-stimulating regimens, however, are being developed and may be available for clinical use in the foreseeable future. These regimens may be capable of increasing bone mass to above the fracture threshold, thereby resulting in a clinical cure of the osteoporosis.     

Osteoporosis: the current status of mesenchymal stem cell-based therapy

Osteoporosis, or bone loss, is a progressive, systemic skeletal disease that affects millions of people worldwide. Osteoporosis is generally age related, and it is underdiagnosed because it remains asymptomatic for several years until the development of fractures that confine daily life activities, particularly in elderly people. Most patients with osteoporotic fractures become bedridden and are in a life-threatening state. The consequences of fracture can be devastating, leading to substantial morbidity and mortality of the patients. The normal physiologic process of bone remodeling involves a balance between bone resorption and bone formation during early adulthood. In osteoporosis, this process becomes imbalanced, resulting in gradual losses of bone mass and density due to enhanced bone resorption and/or inadequate bone formation. Several growth factors underlying age-related osteoporosis and their signaling pathways have been identified, such as osteoprotegerin (OPG)/receptor activator of nuclear factor B (RANK)/RANK ligand (RANKL), bone morphogenetic protein (BMP), wingless-type MMTV integration site family (Wnt) proteins and signaling through parathyroid hormone receptors. In addition, the pathogenesis of osteoporosis has been connected to genetics. The current treatment of osteoporosis predominantly consists of antiresorptive and anabolic agents; however, the serious adverse effects of using these drugs are of concern. Cell-based replacement therapy via the use of mesenchymal stem cells (MSCs) may become one of the strategies for osteoporosis treatment in the future.     

Comparison of mandibular bone mineral density in osteoporotic, osteopenic and normal elderly edentulous subjects measured by the dual-energy X-ray absorptiometry technique

doi: 10.1111/j.1741‐2358.2012.00625.x Comparison of mandibular bone mineral density in osteoporotic, osteopenic and normal elderly edentulous subjects measured by the dual‐energy X‐ray absorptiometry technique Objective: The aim of this study was to compare the mandibular body bone mineral density according to bone mineral density status of spine and femur measured by dual‐energy X‐ray absorptiometry (DXA) technique in elderly edentulous individuals. Background: One of the factors that affect the survival rate of implants is bone mineral density (BMD) of the jaws. Materials and methods: Fifty edentulous elderly patients’ (27 women and 23 men) spine, femur and the mandibular body BMDs were measured using DXA technique. BMD scans of the AP lumbar spine (L2–L3) and femur were classified using World Health Organisation criteria for bone mass. Results: There was a statistically significant difference between the normal femur group’s–osteoporosis group’s mandibular body BMD (p = 0.001) and femoral osteopaenia group’s–osteoporosis group’s mandibular body BMD (p < 0.001). The femoral osteoporosis group’s mandibular body BMDs were lower than those of both the normal femoral and the femoral osteopaenia group subjects’. Conclusion: Classification of edentulous mandibles according to low and high bone mineral densities is a problem in implant dentistry. The results of this study demonstrated that femoral bone mineral density status may be used to provide preliminary information about the bone mineral density of the mandibular body region in elderly edentulous subjects.     

Effect of parity on bone mineral density in female rhesus macaques from Cayo Santiago

This cross-sectional study investigates the relationship between parity, bone mineral density, and spontaneous osteopenia/osteoporosis in a large skeletal population of female rhesus macaques (Macaca mulatta) from the free-ranging colony of Cayo Santiago, Puerto Rico. The sample consists of 119 mature female monkeys aged 4.0-22.2 years at time of death. The data consist of measurements of bone mineral content (BMC) and bone mineral density (BMD), obtained from dual-energy X-ray absorptiometry (DEXA) of the last lumbar vertebra. After controlling for age, there is a significant increase in BMD of the spine with increasing parity (P = 0.0006), up to a parity of 7 offspring. Thus, high parity initially has a positive effect on BMD in female rhesus monkeys, but this positive effect disappears with parities that are greater than 7 offspring. After controlling for parity, however, age has a negative (P = 0.015) effect on BMD, beginning several years after the attainment of peak BMD (age 9.5 years). Thus, it appears that parity initially mitigates the effects of aging, but the positive effect of parity on BMD is eventually overwhelmed by the aging process. Mean BMC and BMD values are higher in parous females compared to nulliparous females in the same age range. Similarly, females with low parity have significantly lower mean BMD values than do age-matched high-parity controls, and the frequency of osteopenia and osteoporosis is greater in low-parity females. Forty-three percent (43%) of the osteopenic/osteoporotic females in the sample are members of the low-parity group, even though it composes only 13% (16/119) of the entire sample. This study demonstrates that the free-ranging female rhesus monkeys from Cayo Santiago are a good nonhuman primate model for the study of bone mineral density, parity, osteopenia, and osteoporosis.     

Age-associated Iron Accumulation in Bone: Implications for Postmenopausal Osteoporosis and a New Target for Prevention and Treatment by Chelation

Iron accumulation in tissues is believed to be a characteristic of aged humans and a risk factor for some chronic diseases. However, it is not known whether age-associated iron accumulation is part of the pathogenesis of postmenopausal osteoporosis that affects approximately one out three women worldwide. Here, we confirmed that this accumulation of iron was associated with osteopenia in ovariectomized (OVX) rats (a model of peri- and postmenopausal osteoporosis due to estrogen deficiency). To further investigate whether the increased iron level plays a causal role in the onset of bone loss, we treated OVX rats with an orally active and bone targeted chelator that prevented iron accumulation in their skeletal tissues. The results showed that this treatment mitigated the loss of bone mass and the deterioration of bone micro-architecture. We also found that one possible mechanism of the protective action of iron chelation was to significantly reduce bone resorption. Thus, these findings provide a novel target and a potentially useful therapeutic strategy for the prevention and treatment of postmenopausal osteoporosis and perhaps other age-related diseases.     

Systemically administered rhBMP-2 promotes MSC activity and reverses bone and cartilage loss in osteopenic mice

Osteoporosis is a disease manifested in drastic bone loss resulting in osteopenia and high risk for fractures. This disease is generally divided into two subtypes. The first, post-menopausal (type I) osteoporosis, is primarily related to estrogen deficiency. The second, senile (type II) osteoporosis, is mostly related to aging. Decreased bone formation, as well as increased bone resorption and turnover, are thought to play roles in the pathophysiology of both types of osteoporosis. In this study, we demonstrate in murine models for both type I (estrogen deficiency) and type II (senile) osteopenia/osteoporosis that reduced bone formation is related to a decrease in adult mesenchymal stem cell (AMSC) number, osteogenic activity, and proliferation. Decreased proliferation is coupled with increased apoptosis in AMSC cultures obtained from osteopenic mice. Recombinant human bone morphogenetic protein (rhBMP-2) is a highly osteoinductive protein, promoting osteogenic differentiation of AMSCs. Systemic intra-peritoneal (i.p.) injections of rhBMP-2 into osteopenic mice were able to reverse this phenotype in the bones of these animals. Moreover, this change in bone mass was coupled to an increase in AMSCs numbers, osteogenic activity, and proliferation as well as a decrease in apoptosis. Bone formation activity was increased as well. However, the magnitude of this response to rhBMP-2 varied among different stains of mice. In old osteopenic BALB/c male mice (type II osteoporosis model), rhBMP-2 systemic treatment also restored both articular and epiphyseal cartilage width to the levels seen in young mice. In summary, our study shows that AMSCs are a good target for systemically active anabolic compounds like rhBMP-2.     

Association of T869C gene polymorphism of transforming growth factor-β1 with low protein levels and anthropometric indices in osteopenia/osteoporosis postmenopausal Thai women

Osteoporosis is the most common metabolic bone disease; it is an important health problem among postmenopausal women. We evaluated the association of three polymorphisms, T869C, C-509T and G915C, of the TGF-β1 gene with bone mineral density (BMD) serum TGF-β1 levels in 278 postmenopausal female osteopenia/osteoporosis subjects and 95 postmenopausal female control subjects. Serum TGF-β1 levels were significantly lower in osteopenia/osteoporosis subjects than in control subjects. Serum TGF-β1 levels of the CT+CC (T869C) genotype group were significantly lower in osteopenia/osteoporosis subjects than in control subjects (11.3 vs 15.8 ng/mL). There was a significant difference in the CT+CC (T869C) genotype frequencies between the osteopenia/osteoporosis and control subjects (74.18 vs 60.22%; OR = 1.90, 95%CI = 1.16-3.12). In the age group of more than 50 years, subjects with the TC+CC genotype of T869C polymorphism had significantly increased risk of osteopenic/ osteoporotic bones at L1 (OR = 2.36, 95%CI = 1.37-4.07), L2 (OR = 1.71, 95%CI = 1.01-2.90), L3 (OR = 2.21, 95%CI = 1.23-3.98), L4 (OR = 1.74, 95%CI = 1.00-3.03) and the femoral neck (OR = 1.80, 95%CI = 1.04-3.12). The CT+CC genotype of the T869C polymorphism of the TGF-β1 gene was found to be associated with lower serum TGF-β1 in osteopenia/osteoporosis subjects and increased risk of osteopenic and osteoporotic fracture at L1-4, femoral neck and total hip in postmenopausal Thai women. Logistic regression analysis showed that T869C polymorphism is a significant risk factor for osteopenia/ osteoporosis. We concluded that T869C polymorphism of the TGF-β1 gene has an impact on decreased serum TGF-β1 levels and influences susceptibility to osteopenia/osteoporosis in Thai women.     

Involvement of serum‐derived exosomes of elderly patients with bone loss in failure of bone remodeling via alteration of exosomal bone‐related proteins

Exosomes are secreted into the blood by various types of cells. These extracellular vesicles are involved in the contribution of exosomal proteins to osteoblastic or osteoclastic regulatory networks during the failure of bone remodeling, which results in age‐related bone loss. However, the molecular changes in serum‐derived exosomes (SDEs) from aged patients with low bone density and their functions in bone remodeling remain to be fully elucidated. We present a quantitative proteomics analysis of exosomes purified from the serum of the elderly patients with osteoporosis/osteopenia and normal volunteers; these data are available via Proteome Xchange with the identifier PXD006463. Overall, 1,371 proteins were identified with an overlap of 1,160 Gene IDs among the ExoCarta proteins. Bioinformatics analysis and in vitro studies suggested that protein changes in SDEs of osteoporosis patients are not only involved in suppressing the integrin‐mediated mechanosensation and activation of osteoblastic cells, but also trigger the differentiation and resorption of osteoclasts. In contrast, the main changes in SDEs of osteopenia patients facilitated both activation of osteoclasts and formation of new bone mass, which could result in a compensatory elevation in bone remodeling. While the SDEs from aged normal volunteers might play a protective role in bone health through facilitating adhesion of bone cells and suppressing aging‐associated oxidative stress. This information will be helpful in elucidating the pathophysiological functions of SDEs and aid in the development of senile osteoporosis diagnostics and therapeutics.     

Genetic research in osteoporosis: Where are we? Where should we go next?

Fractures resulting from low bone mass and excessive skeletal fragility (osteoporosis) are common worldwide both in males and females, particularly in later years of life. Both fractures, and the most important predictor of fractures, bone mass, are now known to be strongly heritable. This fact, plus the current growth in genetic science, has led to a surge of genetic research in osteoporosis, mostly in the search for genes and their polymorphisms that are responsible for variation in bone mass. Finding the genetic basis underlying variation in bone mass will lead us to deeper understanding of the biology of bone mass accumulation, maintenance and adaptation to load. This, plus finding the genetic basis for overall variation in fracture risk per se, will facilitate the development of interventions, both pharmaceutical and non-pharmaceutical, to prevent and/or treat osteoporosis successfully. This research has produced a rather large number of gene loci that seem to influence bone mass. The challenge now is to refine the statistical genetics and the phenotypes involved so that we can confidently identify those gene loci that truly influence bone mass, and to find ways to study the genetic basis for the most direct disease outcome of interest, fracture.     

JunD suppresses bone formation and contributes to low bone mass induced by estrogen depletion

JunD is an activator protein-1 (AP-1) component though its function in skeletal system is still not fully understood. To elucidate the role of JunD in the regulation of bone metabolism, we analyzed JunD-deficient mice. JunD deficiency significantly increased bone mass and trabecular number. This bone mass enhancement was due to JunD deficiency-induced increase in bone formation activities in vivo. Such augmentation of bone formation was associated with simultaneous increase in bone resorption while the former was dominant over the latter as accumulation of bone mass occurred in JunD-deficient mice. In a pathological condition relevant to postmenopausal osteoporosis, ovariectomy reduced bone mass in wild type (WT) mice as known before. Interestingly, JunD deficiency suppressed ovariectomy-induced increase in bone resorption and kept high bone mass. In addition, JunD deficiency also enhanced new bone formation after bone marrow ablation. Examination of molecular bases for these observations revealed that JunD deficiency enhanced expression levels of c-jun, fra-1, and fra-2 in bone in conjunction with elevated expression levels of runx2, type I collagen, and osteocalcin. Thus, JunD is involved in estrogen depletion-induced osteopenia via its action to suppress bone formation and to enhance bone resorption.     

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 diseases associated with human immunodeficiency virus infection: pathogenesis, risk factors and clinical management

Bone disorders such as osteopenia and osteoporosis have been recently reported in patients infected with the human immunodeficiency virus (HIV), but their etiology remains still unknown. The prevalence estimates vary widely among the different studies and can be affected by concomitant factors such as the overlapping of other possible conditions inducing bone loss as lypodystrophy, advanced HIV-disease, advanced age, low body weight or concomitant use of other drugs. All the reports at the moment available in the literature showed a higher than expected prevalence of reduced bone mineral density (BMD) in HIV-infected subjects both na?ve and receiving potent antiretroviral therapy compared to healthy controls. This controversial can suggest a double role played by both antiretroviral drugs and HIV itself due to immune activation and/or cytokines disregulation. An improved understanding of the pathogenesis of bone disorders can result in better preventative and therapeutic measures. However, the clinical relevance and the risk of fractures remains undefined in HIV-population. The clinical management of osteopenia and osteoporosis in HIV-infected subjects is still being evaluated. Addressing potential underlying bone disease risk factors (e.g., smoking and alcohol intake, use of corticosteroids, advanced age, low body weight), evaluating calcium and vitamin D intake, and performing dual x-ray absorptiometry in HIV-infected individuals who have risk factors for bone disease can be important strategies to prevent osteopenia and osteoporosis in this population. The administration of bisphosphonates (e.g., alendronate), with calcium and vitamin D supplementation, may be a reasonable and effective option to treat osteoporosis in these subjects.     

Major stages in the evolution of primate neurocrania

An important constraint on the evolution of primate skeletons is the isometric relationship which exists between skeletal weight and body weight. The evolution of primate skulls during the Tertiary and Quaternary periods indicates that redeployment of bone mass took place largely within the skull (i.e. between proximate ossifying centres) and that the major vector was from the splanchnocranium towards the neurocranium. This vector of bone mass redeployment accords well with the general treand within primates of increased encephalisation over time. There are however, several interesting examples of vectors which were oriented in the opposite sense, in particular in the robust australopithecine lineage, in which the emphasis on bone mass deployment was towards the splanchnocranium and away from the neurocranium. A fuller understanding of skeletal isometry, and a wider application in comparative anatomy may throw much light on the evolution of skeletal systems, and it may resolve somelong-standing debates. Among these may be identification of the selection pressures which have led to dental and alveolar reduction inHomo sapiens sapiens (bone mass redeployment into the neurocranium) and perhaps an explanatation for some types of osteoporosis in old people whose body weight decreases may result in isometric skeletal mass decreases (for every 100 gms muscle tissue loss, there will be about 7 gms of bone tissue loss).     

Calcium Nutrition and the Aging Process: A Review

Adequate supply of calcium is essential for proper maintenance of the skeletal system. Recent studies suggest that, in the United States, dietary calcium in most women is inadequate to maintain skeletal integrity. Additionally, postmenopausal women will lose bone mass more rapidly because of estrogen deficiency and possibly tack of exercise. Severe loss of bone mass can result in several serious skeletal diseases, the most frequent of which is osteoporosis. This disease is a major contributor (25–30%) to hip fractures and spinal compression fractures in elderly people. Indirect sequelae of these fractures are responsible for 12% to 15% mortality in these patients within three months. Recent research indicates that osteoporitic bone loss may directly affect alveolar bone and may, in fact, exacerbate existing periodontally-induced bone loss. This article will review the literature concerning physiological and biochemical parameters related to the absorption and metabolism of calcium with special emphasis on calcium alterations in the aging process. The following areas will be discussed: Ingestion, Absorption, Factors Effecting Absorption and Bone Maintenance, Calcium/Protein Interactions Affecting the Aging Process, Altered Bone States Associated with the Aging Person, Osteoporosis, Osteomalacia, Paget's Disease, Calcium Affecting Drug Action, and Calcium Affecting Alveolar Bone.     

Female biological resiliency: Differential stress response by sex in human remains from ancient Nubia

This research presents male-female differences in stress response evidenced in human remains from the Medieval site of Kulubnarti in Sudanese Nubia. This analysis is unique in that a direct comparison of subadult males and females is rarely possible using archaeological remains. Rather, such analyses invariably rely on evidence of subadult differences retained in adult (sexable) skeletons. In the case of Kulubnarti, natural mummification has made it possible to measure sex-specific differences among subadults as well as adults following five avenues of investigation: 1) mortality, 2) growth and development, 3) enamel hypoplasia, 4) cribra orbitalia, and 5) cortical bone maintenance. A comparison of mean life expectancy (eox) values for males and females aged 10–55+ years revealed a consistent pattern of greater female survivorship, particularly in childhood (age 10 category) where female life expectancy exceeds that of males by 19%. Measures of growth and development, enamel hypoplasia, cribra orbitalia, and cortical bone loss were subsequently used to test a hypothesis of greater female resiliency based on the mortality data. Male-female differences in skeletal maturation are pronounced with male skeletal ages averaging a significant 2.9 years below their dental age. Females show no significant differences with an average skeletal age 0.75 years ahead of dental age. Males begin hypoplasia formation one year earlier than females and, prior to age four, average 18% more hypoplasias (p<0.05). Also, by age 8, males have on average more than twice the frequency of cribra orbitalia (p<0.05). In contrast to their consistent pattern of reduced childhood stress, adult females lose significantly more cortical bone than their male counterparts and have less cortical bone across the adult age range. Nevertheless, females outnumber males of all ages with a sex-ratio below but parallel to that observed in modern populations. The rapid age-related reduction in males relative to females, even in old age, suggests a continuing female resiliency in spite of their greater rate of osteopenia and may reflect a reproductive advantage to the population through heightened female survival and adaptability.     

Relationships between bone mass and micro-architecture at the mandible and iliac bone in edentulous subjects: a dual X-ray absorptiometry, computerised tomography and microcomputed tomography study

doi: 10.1111/j.1741‐2358.2011.00527.x Relationships between bone mass and micro‐architecture at the mandible and iliac bone in edentulous subjects: a dual X‐ray absorptiometry, computerised tomography and microcomputed tomography study Objectives: To compare bone volume, bone mineral density, cortical thickness and bone micro‐architecture in a series of paired mandibular and iliac bone samples analysed by various imagery techniques to see whether relationships exist between the various techniques and between mandibular and iliac bone. Materials and methods: Bone samples from the mandible and ilium were harvested in 20 cadavers and analysed by dual energy X‐ray absorptiometry (DXA), computerised tomography (CT) on a conventional hospital machine and microCT. Results: Significant correlations were found between Hounsfield density obtained by CT, and bone mass determined by microCT but not with DXA values. Cortical thickness measurements were well correlated between CT and microCT. No relationships were found between mandibular and iliac bone, when considering mineral density, cortical thickness, bone volume or micro‐architecture. Conclusion: In clinical practice, CT remains the most appropriate routine means for bone qualitative and quantitative evaluation at the mandible. In this ex vivo study, these results confirm that mandibular bone status does not reflect the axial skeletal one and assist in the placement of implants with dental prostheses in old or osteoporotic patients.     

同型半胱氨酸水平与女性绝经期骨质疏松相关性研究

目的:通过分析女性绝经期不同骨密度人群的血浆同型半胱氨酸(HCY)指标,探讨同型半胱氨酸在女性绝经期骨质疏松发生过程中的作用及其潜在的临床价值。方法:收集2014年3月至2016年3月我院体检中心进行体检的女性绝经期妇女(60岁)血样标本共计625例,根据体检的骨密度报告对其进行分组,骨质疏松组215例,骨量减少组309例,骨量正常组101例,测量每组的同型半胱氨酸水平。结果:骨密度程度与同型半胱氨酸水平存在负相关关系(rs=-0.763,P=0.046),三组之间的同型半胱氨酸水平也存在显著差异(F=4.807,P0.016),其中骨质疏松组指标最高,骨量正常组指标最低。结论:同型半胱氨酸是重要的骨代谢指标,在衡量绝经期妇女骨质疏松进展中具有重要的意义。