Age-related cortical bone loss in women from a 3rd-4th century AD population from England

Age-dependent cortical bone loss in adult females from a skeletal assemblage from 3rd-4th century AD England was studied using metacarpal radiogrammetry. Results showed reduced peak cortical bone thickness compared with modern subjects, and the magnitude of cortical bone loss in older females compared with their younger counterparts was greater than that documented for a modern reference population. An elevated prevalence of fractures classically associated with osteoporosis was also observed in the over-50-year cohort. The severity of osteoporosis in this group is difficult to explain in terms of extraneous factors relating to 3rd-4th century lifestyles. Given the important genetic component in osteoporosis, the results may indicate some inherent susceptibility in this particular population to the disease, and ways in which this possibility might be further explored are suggested.     

Intraskeletal variability in bone mass

For methodological or other reasons, a variety of skeletal elements are analyzed and subsequently used as a basis for describing general bone loss and mass. However, bone loss and mass may not be uniform within and among skeletal elements of the same individual because of biomechanical factors. We test the hypothesis that a homogeneity in bone mass exists among skeletal elements of the same individual. Measures indicative of bone mass were calculated from the midshafts of six skeletal elements from the same individuals (N = 41). The extent of intraskeletal variability in bone mass (relative cortical area) was then examined for the entire sample, according to age, sex, and pathological status. The results of the analysis showed that all measures reflect a heterogeneity in bone mass (P 相似文献   

Effects of age and occupation on cortical bone in a group of 18th-19th century British men

The effects of age and occupation on cortical bone in a group of adult males from the 18th-19th century AD skeletal collection from Christ Church Spitalfields, London, were investigated. Cortical bone was monitored using metacarpal radiogrammetry. Individual age at death was known exactly from coffin plates. Occupation for individuals was known from historical sources. Results showed that continued periosteal apposition was evident throughout adult life, but from middle age onwards this was outstripped by about 2:1 by endosteal resorption, so that there was net thinning of cortical bone. The rate of cortical thinning resembled that seen in modern European males. Cross-sectional properties, as measured by second moments of area, bore no relationship to occupation. The results may suggest that, firstly, patterns of loss of cortical bone have remained unchanged in males for at least two centuries in Britain, and secondly, that biomechanical analyses of metacarpal cortical bone may be rather insensitive indicators of intensity of manual activity.     

Diversity of cortical bone morphology in anuran amphibians

The cortical bones of mammals, birds, and reptiles are composed of a complex of woven bone and lamellar bone (fibrolamellar bone) organized into a variety of different patterns; however, it remains unclear whether amphibians possess similar structures. Importantly, to understand the evolutionary process of limb bones in tetrapods, it is necessary to compare the bone structure of amphibians (aquatic to terrestrial) with that of amniotes (mostly terrestrial). Therefore, this study compared the cortical bones in the long bones of several frog species before and after metamorphosis. Using micro-computed tomography (CT), we found that the cortical bones in the fibrolamellar bone of Xenopus tropicalis (Pipoidea superfamily) and Lithobates catesbeianus (Ranoidea superfamily) froglets are dense, whereas those of Ceratophrys cranwelli (Hyloidea superfamily) are porous. To clarify whether these features are common to their superfamily or sister group, four other frog species were examined. Histochemical analyses revealed porous cortical bones in C. ornata and Lepidobatrachus laevis (belonging to the same family, Ceratophryidae, as C. cranwelli). However, the cortical bones of Dryophytes japonicus (Hylidae, a sister group of Ceratophryidae in the Hyloidea superfamily), Microhyla okinavensis (Microhylidae, independent of the Hyloidea superfamily), and Pleurodeles waltl, a newt as an outgroup of anurans, are dense with no observed cavities. Our findings demonstrate that at least three members of the Ceratophryidae family have porous cortical bones similar to those of reptiles, birds, and mammals, suggesting that the process of fibrolamellar bone formation arose evolutionarily in amphibians and is conserved in the common ancestor of amniotes.     

Effects of age,sex, and heredity on measures of bone mass in baboons (Papio hamadryas)

Abstract: Bone mass and bone density were estimated in 219 pedigreed baboons (Papio hamadryas) by radiographic morphometry of the left second metacarpal. Compact bone width (total bone width – medullary canal diameter) and bone ratio (compact bone width/total bone width) decreased with increasing age squared in both sexes. The heritability of medullary canal diameter was 0.64±0.11, of compact bone width was 0.40±0.15 and of bone ratio was 0.67±0.13. The results indicate baboons are a useful model for studies of age, sex and genetic effects on bone mass.     

Setup of a bone aging experimental model in the rabbit comparing changes in cortical and trabecular bone: Morphological and morphometric study in the femur

Bone aging was studied in an experimental model (rabbit femur) in three populations aged 0.5, 1.5, and 7.5 years. Cortical bone histology was compared with a data set from a 1.5‐month‐old population of an earlier published paper. From 0.5‐year‐old onward, the mean femur length did not increase further. Thereafter, the mean marrow area increased and the cortical area decreased significantly with aging. This was associated with a structural pattern transformation from plexiform to laminar and then Haversian‐like type. The distal meta‐epiphysis bone trabecular density of the oldest populations also was significantly lower in specific regions of interest (ROI). Percentage sealed primary vascular canals in laminar bone significantly increased with aging without variation of percentage sealed secondary osteons. Remodeling rate reflected by the density of cutting cones did not significantly change among the age populations. These data suggest that laminar bone vascular pattern is more functional in the fast diaphyseal expansion but not much streamlined with the renewal of blood flow during secondary remodeling. Bone aging was characterized by: 1) secondary remodeling subendosteally; 2) increment of sealed primary vascular canals number; 3) increased calcium content of the cortex; 4) cortical and trabecular bone mass loss in specific ROIs. Taken together, the present data may give a morphological and morphometric basis to perform comparative studies on experimental models of osteoporosis in the rabbit. J. Morphol. 276:733–747, 2015. © 2015 Wiley Periodicals, Inc.     

Simulation of creep in non-homogenous samples of human cortical bone

Characterising the mechanisms causing viscoelastic mechanical properties of human cortical bone, as well as understanding sources of variation, is important in predicting response of the bone to creep and fatigue loads. Any better understanding, when incorporated into simulations including finite element analysis, would assist bioengineers, clinicians and biomedical scientists. In this study, we used an empirically verified model of creep strain accumulation, in a simulation of 10 non-homogeneous samples, which were created from micro-CT scans of human cortical bone of the femur midshaft obtained from a 74-year-old female cadaver. These non-homogeneous samples incorporate the presence of Haversian canals and resorption cavities. The influence of inhomogeneity on the response and variation in the samples in both creep and stress relaxation tests are examined. The relationship between steady-state creep rate, applied loads (stress relaxation and creep tests) and microstructure, that is bone apparent porosity, is obtained. These relations may provide insight into damage accumulation of whole human bones and be relevant to studies on osteoporosis.     

The effect of restriction of dietary calcium on trabecular and cortical bone mineral density in the rats

This study aimed to investigate effects of restricted calcium intake on cortical and trabecular bone density in white rats. Low Ca diet was fed for six weeks, and bone density and bone metabolism parameters were assessed in blood. This study was carried out on 12 male white rats aged 12 weeks (Sprague-Dawley; SD). These rats were bred for 1 week and randomly assigned to the standard calcium diet group (SCa group, n = 6) and the low calcium diet group (LCa group; n = 6). The SCa group was given a modified AIN-93M mineral mix (with 0.5% Ca), which was made by adding calcium to a standard AIN93 diet, and the LCa Group was fed a modified AIN-93 Mineral mix (with 0.1% Ca). Femoral BMD and BMC were measured by DEXA in each rat. After trabecular bone was separated from cortical bone, volumetric bone mineral density (vBMD) was measured using pQCT. Serum Ca and P levels were measured as parameters of bone metabolism, and S-ALP, S-TrACP and-Dpd levels were also measured. The results revealed no significant differences in weight, growth rate, feed consumption and feed efficiency between the two groups before and after calcium-restricted diet (p > .05). No significant differences were also observed in bone length and bone mass between the two groups (p > .05). Although bilateral femoral BMDs were not significantly different between the two groups, bilateral femoral BMCs significantly decreased in the LCa group, compared with the SCa group (p = .023, p = .047). Bilateral cortical MDs were not significantly different between the two groups, either. However, trabecular BMD significantly decreased in the LCa group, compared with the SCa group (p = .041). U-Dpd and S-TrACP levels significantly declined in the LCa group, compared to the SCa group (p = .039, p = .010). There were no significant differences in serum Ca and P levels between the two groups (p > .05). However, a significant decrease in urinary Ca level (p = .001) and a significant increase in urinary P (p = .001) were observed in the LCa group, compared to the Sca group. These findings described that six-week low calcium diet led to decreased trabecular bone density, reduced urinary excretion of Ca and increased urinary excretion of P. As a result, Ca hemeostasis can be maintained.     

The anabolic action of intermittent parathyroid hormone on cortical bone depends partly on its ability to induce nitric oxide‐mediated vasorelaxation in BALB/c mice

There is strong evidence that vasodilatory nitric oxide (NO) donors have anabolic effects on bone in humans. Parathyroid hormone (PTH), the only osteoanabolic drug currently approved, is also a vasodilator. We investigated whether the NO synthase inhibitor L‐NAME might alter the effect of PTH on bone by blocking its vasodilatory effect. BALB/c mice received 28 daily injections of PTH[1–34] (80 µg/kg/day) or L‐NAME (30 mg/kg/day), alone or in combination. Hindlimb blood perfusion was measured by laser Doppler imaging. Bone architecture, turnover and mechanical properties in the femur were analysed respectively by micro‐CT, histomorphometry and three‐point bending. PTH increased hindlimb blood flow by >30% within 10 min of injection (P < 0.001). Co‐treatment with L‐NAME blocked the action of PTH on blood flow, whereas L‐NAME alone had no effect. PTH treatment increased femoral cortical bone volume and formation rate by 20% and 110%, respectively (P < 0.001). PTH had no effect on trabecular bone volume in the femoral metaphysis although trabecular thickness and number were increased and decreased by 25%, respectively. Co‐treatment with L‐NAME restricted the PTH‐stimulated increase in cortical bone formation but had no clear‐cut effects in trabecular bone. Co‐treatment with L‐NAME did not affect the mechanical strength in femurs induced by iPTH. These results suggest that NO‐mediated vasorelaxation plays partly a role in the anabolic action of PTH on cortical bone. © 2016 The Authors. Cell Biochemistry and Function published by John Wiley & Sons, Ltd.     

Nupr1 deficiency downregulates HtrA1, enhances SMAD1 signaling,and suppresses age-related bone loss in male mice

Nuclear protein 1 (NUPR1) is a stress-induced protein activated by various stresses, such as inflammation and oxidative stress. We previously reported that Nupr1 deficiency increased bone volume by enhancing bone formation in 11-week-old mice. Analysis of differentially expressed genes between wild-type (WT) and Nupr1-knockout (Nupr1-KO) osteocytes revealed that high temperature requirement A 1 (HTRA1), a serine protease implicated in osteogenesis and transforming growth factor-β signaling was markedly downregulated in Nupr1-KO osteocytes. Nupr1 deficiency also markedly reduced HtrA1 expression, but enhanced SMAD1 signaling in in vitro-cultured primary osteoblasts. In contrast, Nupr1 overexpression enhanced HtrA1 expression in osteoblasts, suggesting that Nupr1 regulates HtrA1 expression, thereby suppressing osteoblastogenesis. Since HtrA1 is also involved in cellular senescence and age-related diseases, we analyzed aging-related bone loss in Nupr1-KO mice. Significant spine trabecular bone loss was noted in WT male and female mice during 6−19 months of age, whereas aging-related trabecular bone loss was attenuated, especially in Nupr1-KO male mice. Moreover, cellular senescence-related markers were upregulated in the osteocytes of 6−19-month-old WT male mice but markedly downregulated in the osteocytes of 19-month-old Nupr1-KO male mice. Oxidative stress-induced cellular senescence stimulated Nupr1 and HtrA1 expression in in vitro-cultured primary osteoblasts, and Nupr1 overexpression enhanced p16^ink4a expression in osteoblasts. Finally, NUPR1 expression in osteocytes isolated from the bones of patients with osteoarthritis was correlated with age. Collectively, these results indicate that Nupr1 regulates HtrA1-mediated osteoblast differentiation and senescence. Our findings unveil a novel Nupr1/HtrA1 axis, which may play pivotal roles in bone formation and age-related bone loss.     

Hibernation does not reduce cortical bone density,area or second moments of inertia in woodchucks (Marmota monax)

Long periods of inactivity in most mammals result in bone loss that may not be completely recoverable during an individual's lifetime regardless of future activity. Prolonged inactivity is normal during hibernation, but it remains uncertain whether hibernating mammals suffer decreased bone properties after hibernation that affects survival. We test the hypothesis that relative cortical area (C_A), apparent density, bone area fraction (B.Ar/T.Ar), and moments of inertia do not differ between museum samples of woodchucks (Marmota monax) collected before and after hibernation. We used peripheral quantitative computed tomography to examine bone geometry in the femur, tibia, humerus and mandible. We see little evidence for changes in bone measures with hibernation supporting our hypothesis. In fact, when including subadults to increase sample sizes and controlling age statistically, we observed a trend toward increased bone properties following hibernation. Diaphyses were significantly denser in the humerus, femur, and tibia after hibernation, and relative mandibular cortical area was significantly larger. Similarly, relative mechanical indices were significantly larger in the mandible after hibernation. Although tests of individual measures in many cases were not significantly different prehibernation versus posthibernation, the overall pattern of average increase posthibernation was significant for relative C_A and densities as well as relative diaphyseal mechanical indices when examining outcomes collectively. The exception to this pattern was a reduction in metaphyseal trabecular bone following hibernation. Individually, only humeral B.Ar/T.Ar was significantly reduced, but the average reduction in trabecular measures post‐hibernation was significant when examined collectively. Because the sample included subadults, we suggest that much of the increased bone relates to their continued growth during hibernation. Our results indicate that woodchucks are more similar to large hibernators that maintain skeletal integrity compared to smaller‐bodied hibernators that may lose bone. This result suggests a potential size‐related trend in bone response to hibernation across mammals. J. Morphol., 2012. © 2012Wiley Periodicals, Inc.