Analysis of the Effect of Osteon Diameter on the Potential Relationship of Osteocyte Lacuna Density and Osteon Wall Thickness

An important hypothesis is that the degree of infilling of secondary osteons (Haversian systems) is controlled by the inhibitory effect of osteocytes on osteoblasts, which might be mediated by sclerostin (a glycoprotein produced by osteocytes). Consequently, this inhibition could be proportional to cell number: relatively greater repression is exerted by progressively greater osteocyte density (increased osteocytes correlate with thinner osteon walls). This hypothesis has been examined, but only weakly supported, in sheep ulnae. We looked for this inverse relationship between osteon wall thickness (On.W.Th) and osteocyte lacuna density (Ot.Lc.N/B.Ar) in small and large osteons in human ribs, calcanei of sheep, deer, elk, and horses, and radii and third metacarpals of horses. Analyses involved: (1) all osteons, (2) smaller osteons, either ≤150 μm diameter or less than or equal to the mean diameter, and (3) larger osteons (>mean diameter). Significant, but weak, correlations between Ot.Lc.N/B.Ar and On.W.Th/On.Dm (On.Dm = osteon diameter) were found when considering all osteons in limb bones (r values ?0.16 to ?0.40, P < 0.01; resembling previous results in sheep ulnae: r = ?0.39, P < 0.0001). In larger osteons, these relationships were either not significant (five/seven bone types) or very weak (two/seven bone types). In ribs, a negative relationship was only found in smaller osteons (r = ?0.228, P < 0.01); this inverse relationship in smaller osteons did not occur in elk calcanei. These results do not provide clear or consistent support for the hypothesized inverse relationship. However, correlation analyses may fail to detect osteocyte‐based repression of infilling if the signal is spatially nonuniform (e.g., increased near the central canal). Anat Rec,, 2011. © 2011 Wiley‐Liss, Inc.     

Secondary osteon variants and remodeling in human bone

Histomorphometric analysis of human cortical bone has documented the occurrence of secondary osteon variants. These include drifting osteons which form tails as they move erratically through the cortex and Type II osteons which show partial resorption and redeposition within the cement line of the osteon. Little is known about the biological significance of these variants. Prior studies suggested correlations with age, biomechanics, diet, and mineral homeostasis. No study has yet tested for osteon variant associations with static measures of bone remodeling. In this study, thin sections (n = 112) of the posterior femur representing a late English Medieval adult human osteological collection, subdivided by age, sex, and socio-economic status, were examined to determine whether remodeling indicators reconstructed from osteon parameters (area, diameter, area ratios) and densities differed between categories of presence or absence of Type II and drifting osteon variants. Of the 112 sections, 33 presented with Type II osteons, and 38 had drifting osteons. Sporadic statistically significant results were identified. Haversian canal:osteon area ratio differed (p = 0.017) with Type II osteon presence, Type II osteons were more prevalent in males than females (p = 0.048), and drifting osteons were associated with smaller osteon (p = 0.049) and Haversian canal area (p = 0.05). These results may be explained through some biological (sex) and social (status) processes such as a period of physiological recovery (e.g., following lactation, malnutrition). However, the general lack of consistent relationships between osteon variants and remodeling indicators suggests they occur as a result of natural variation.     

Histomorphometric assessment of Haversian canal and osteocyte lacunae in different-sized osteons in human rib

There is no detailed information available concerning the variations in bone, the Haversian canal, and osteocyte populations in different-sized osteons. In this study a total of 398 secondary osteons were measured in archived rib sections from nine white men (20-25 years old). The sections were stained with basic fuchsin. The parameters included the osteon area (On.Ar), Haversian canal area (HC.Ar) and perimeter (HC.Pm), bone area (B.Ar), and osteocyte lacunar number (Lc.N). From these primary measurements the following indices were deduced: 1) lacunar number per bone area (Lc.N/B.Ar) and per osteon (Lc.N/On); 2) the ratio between Haversian canal perimeter and bone area (HC.Pm/B.Ar); and 3) the fraction of Haversian canal area (HC.Ar/On.Ar) and its complement, the fraction of bone area (B.Ar/On.Ar). The results showed that the osteons varied greatly in size, but very little in the fraction of bone area. Regression analyses showed that HC.Ar, HC.Pm, and Lc.N/On were positively associated with On.Ar (P < 0.001 for all). A significant negative correlation was found between On.Ar and Lc.N/B.Ar (P < 0.05) and HC.Pm/B.Ar (P < 0.0001). HC.Ar and HC.Pm increased significantly with increasing Lc.N/On (both P < 0.0001) rather than Lc.N/B.Ar. Lc.N/B.Ar had a significant positive correlation with HC.Ar/On.Ar (P < 0.05) and HC.Pm/B.Ar (P < 0.01). We conclude that: 1) the size of the osteon is determined by the quantum of bone removed by osteoclasts, 2) the osteon is well designed for molecular exchange, and 3) a well designed osteon may be produced via the regulation of bone apposition by osteocytes during the process of osteon refilling.     

Ontogenetic changes to bone microstructure in an archaeologically derived sample of human ribs

There is considerable variation in the gross morphology and tissue properties among the bones of human infants, children, adolescents, and adults. Using 18 known-age individuals (n_female = 8, n_male = 9, n_unknown = 1; birth to 21 years old), from a well-documented cemetery collection, Spitalfields Christ Church, London, UK, this study explores growth-related changes in cortical and trabecular bone microstructure. Micro-CT scans of mid-shaft middle thoracic ribs are used for quantitative analysis. Results are then compared to previously quantified conventional histomorphometry of the same sample. Total area (Tt.Ar), cortical area (Ct.Ar), cortical thickness (Ct.Th), and the major (Maj.Dm) and minor (Min.Dm) diameters of the rib demonstrate positive correlations with age. Pore density (Po.Dn) increases, but age-related changes to cortical porosity (Ct.Po) appear to be non-linear. Trabecular thickness (Tb.th) and trabecular separation (Tb.Sp) increase with age, whereas trabecular bone pattern factor (Tb.Pf), structural model index (SMI), and connectivity density (Conn.D) decrease with age. Sex-based differences were not identified for any of the variables included in this study. Some samples display clear evidence of diagenetic alteration without corresponding changes in radiopacity, which compromises the reliability of bone mineral density (BMD) data in the study of past populations. Cortical porosity data are not correlated with two-dimensional measures of osteon population density (OPD). This suggests that unfilled resorption spaces contribute more significantly to cortical porosity than do the Haversian canals of secondary osteons. Continued research using complementary imaging techniques and a wide array of histological variables will increase our understanding of age- and sex-specific ontogenetic patterns within and among human populations.     

Does 3D orientation account for variation in osteon morphology assessed by 2D histology?

The primary microstructural unit of cortical bone, the secondary osteon or Haversian system, is widely assumed to have a cylindrical shape. It is generally accepted that osteons are roughly circular in cross-section and deviations from circularity have been attributed to deviations from longitudinal orientation. To our knowledge this idealized geometric relationship, which assumes osteons are perfect cylinders, has not been rigorously explored. As such, we sought to explore two research questions: (i) Does the orientation of osteons in 3D explain variation in shapes visualized in 2D? (ii) Can differences in osteon 3D orientation explain previously reported age-related differences observed in their 2D cross-sectional shape (e.g. more circular shape and decreased area with age)? To address these questions we utilized a combination of 2D histology to identify osteon shape and superimposed micro-computed tomography data to assess osteon orientation in 3D based upon the osteonal canal. Shape was assessed by the inverse of Aspect Ratio (On.AspR⁻¹, based on a fitted ellipse) – which ranged from 0 (infinitely elongated shape) to 1 (perfectly circular). A sample (n = 27) of human female anterior femoral cortical bone samples from across the human lifespan (20–87 years) were included in the analysis, which involved 1418 osteons. The overall mean measure of On.AspR⁻¹ was 0.703 (1.42 Aspect Ratio). Mean osteon orientation was 79.1° (90° being longitudinal). While we anticipated a positive relation between orientation and On.AspR⁻¹, we found the opposite – a weak negative correlation (with more oblique 3D osteon alignment, the 2D shape became more circular as reflected by increased On.AspR⁻¹). When analysis of covariance was performed with age and orientation as covariates, the negative relation with orientation was replaced by a significant relation with age alone. This relation with age accounted for 41% of the variation of On.AspR⁻¹. The results revealed that osteons, on average, are not circular in cross-section and that 3D orientation cannot account for deviation from circular shape. Osteons thus are strictly speaking not cylinders, as they tend to have elliptical cross-sections. We observed that osteons did become less elliptical in cross-section with age independent of orientation – suggesting this is a real change in morphology.     

ClC-3基因过表达对小鼠骨量和骨结构的影响

 目的: 研究过表达电压门控氯通道家族蛋白成员3(voltage-gated chloride channel family protein 3,ClC-3)基因对小鼠骨骼的影响。方法: 3月龄雄性FVB小鼠用鼠尾基因检测法确定基因型后分为2组:野生型(WT)组和ClC-3过表达(ClC-3 transgene)组,每组各8只。分别测量2组小鼠体重,右侧胫骨长度和重量。取胫骨上段和中段进行脱钙,石蜡包埋,切片,HE染色后,采用骨形态计量学分析胫骨上段松质骨的骨小梁面积百分数(percent trabecular area,%Tb.Ar)、骨小梁数量(trabecular number,Tb.N)、骨小梁宽度(trabecular width,Tb.Wi)、骨小梁分离度(trabecular separation,Tb.Sp)和胫骨中段皮质骨的骨组织总面积(total tissue area,T.Ar)、皮质骨面积(cortical area,Ct.Ar)、皮质骨面积百分数(percent cortical area,%Ct.Ar)、骨髓腔面积(marrow area,Ma.Ar)、骨髓腔面积百分数(percent marrow area,%Ma.Ar)。结果: 小鼠经鼠尾基因检测后确认为野生型或ClC-3过表达型。与WT组相比,ClC-3 transgene组小鼠体重及胫骨长度重量均减小(P<0.05);松质骨的%Tb.Ar和Tb.Wi均减小(P<0.05),Tb.Sp增大(P<0.05),Tb.N的变化无统计学意义;皮质骨的T.Ar、Ct.Ar和%Ct.Ar均减小(P<0.05),%Ma.Ar增大(P<0.05),Ma.Ar的变化无统计学意义。结论: ClC-3过表达导致小鼠的皮质骨和松质骨骨量减少,骨结构变差,提示ClC-3可能参与了骨形成和/或骨吸收。     

Cortical indices of the shaft of weight bearing and non-weight bearing long bones in the adult human

This study was conducted on X-ray films of the shaft of normal femur and second metacarpal bones of adult male and female Nigerians to compare the percentage cortical thickness relative to the subperiosteal diameter (cortical index) of these bones. Age was correlated with cortical index (CI) using Pearson's product of moment correlation coefficient. Confidence limits of CI were calculated for clinical use. Results obtained were analysed for each sex and compared at P<0.05 level of significane. CI of the second metacarpal is significantly greater than of the femur in both the male and female. Age maintained significant inverse correlation with CI of the femur and nonsignificant correlation with the second metacarpal in the female. In the male, age had nonsignificant correlation with the femur or with the second metacarpal bone. It is concluded that (i) the amount of percentage relative cortical bone to subperiosteal diameter of the second metacarpal, a nonweight-bearing bone, is greater than that of the femur, a weight-bearing bone, (ii) age of the adult has significant effect on the amount of cortical bone of the femur in the female but not in the male, and (iii) age of the adult does not have significant effect on the amount of cortical bone of the second metacarpal in both sexes.     

Regional maps of rib cortical bone thickness and cross‐sectional geometry

Here we present detailed regional bone thickness and cross‐sectional measurements from full adult ribs using high resolution CT scans processed with a cortical bone mapping technique. Sixth ribs from 33 subjects ranging from 24 to 99 years of age were used to produce average cortical bone thickness maps and to provide average ± 1SD corridors for expected cross‐section properties (cross‐sectional areas and inertial moments) as a function of rib length. Results obtained from CT data were validated at specific rib locations using direct measurements from cut sections. Individual thickness measurements from CT had an accuracy (mean error) and precision (SD error) of ?0.013 ± 0.167 mm (R² coefficient of determination of 0.84). CT‐based measurement errors for rib cross‐sectional geometry were ?0.1 ± 13.1% (cortical bone cross‐sectional area) and 4.7 ± 1.8% (total cross‐sectional area). Rib cortical bone thickness maps show the expected regional variation across a typical rib's surface. The local mid‐rib maxima in cortical thickness along the pleural rib aspect ranged from range 0.9 to 2.6 mm across the study population with an average map maximum of 1.4 mm. Along the cutaneous aspect, rib cortical bone thickness ranged from 0.7 to 1.9 mm with an average map thickness of 0.9 mm. Average cross‐sectional properties show a steady reduction in total cortical bone area from 10% along the rib's length through to the sternal end, whereas overall cross‐sectional area remains relatively constant along the majority of the rib's length before rising steeply towards the sternal end. On average, male ribs contained more cortical bone within a given cross‐section than was seen for female ribs. Importantly, however, this difference was driven by male ribs having larger overall cross‐sectional areas, rather than by sex differences in the bone thickness observed at specific local cortex sites. The cortical bone thickness results here can be used directly to improve the accuracy of current human body and rib models. Furthermore, the measurement corridors obtained from adult subjects across a wide age range can be used to validate future measurements from more widely available image sources such as clinical CT where gold standard reference measures (e.g. such as direct measurements obtained from cut sections) are otherwise unobtainable.     

Respective roles of organic and mineral components of human cortical bone matrix in micromechanical behavior: an instrumented indentation study

Bone is a multiscale composite material made of both a type I collagen matrix and a poorly crystalline apatite mineral phase. Due to remodeling activity, cortical bone is made of Bone Structural Units (BSUs) called osteons. Since osteon represents a fundamental level of structural hierarchy, it is important to investigate the relationship between mechanical behavior and tissue composition at this scale for a better understanding of the mechanisms of bone fragility. The aim of this study is to analyze the links between ultrastructural properties and the mechanical behavior of bone tissue at the scale of osteon.Iliac bone biopsies were taken from untreated postmenopausal osteoporotic women, embedded, sectioned and microradiographed to assess the degree of mineralization of bone (DMB). On each section, BSUs of known DMB were indented with relatively high load (∼500 mN) to determine local elastic modulus (E), contact hardness (H_c) and true hardness (H) of several bone lamellae. Crystallinity and collagen maturity were measured by Fourier Transform InfraRed Microspectroscopy (FTIRM) on the same BSUs. Inter-relationships between mechanical properties and ultrastructural components were analyzed using multiple regression analysis.This study showed that elastic deformation was only explained by DMB whereas plastic deformation was more correlated with collagen maturity. Contact hardness, reflecting both elastic and plastic behaviors, was correlated with both DMB and collagen maturity. No relationship was found between crystallinity and mechanical properties at the osteon level.     

Morphometric analysis of osteonal architecture in bones from healthy young human male subjects using scanning electron microscopy

The shape and structure of bones is a topic that has been studied for a long time by morphologists and biologists with the goal of explaining the laws governing their development, aging and pathology. The osteonal architecture of tibial and femoral mid‐diaphyses was examined morphometrically with scanning electron microscopy in four healthy young male subjects. In transverse sections of the mid‐diaphysis, the total area of the anterior, posterior, lateral and medial cortex sectors was measured and analysed for osteonal parameters including osteon number and density, osteon total and bone area and vascular space area. Osteons were grouped into four classes including cutting heads (A), transversely cut osteons (B), longitudinally cut osteons (C) and sealed osteons (D). The morphometric parameters were compared between the inner (endosteal) and outer (periosteal) half of the cortex. Of 5927 examined osteons, 24.4% cutting heads, 71.1% transversely cut osteons, 2.3% longitudinally cut osteons and 2.2% sealed osteons were found. The interosteonic bone (measured as the area in a lamellar system that has lost contact with its own central canal) corresponded to 51.2% of the endosteal and 52.4% of the periosteal half‐cortex. The mean number of class A cutting heads and class B osteons was significantly higher in the periosteal than in the endosteal half‐cortex (P < 0.001 and P < 0.05, respectively), whereas there was no significant difference in density. The mean osteon total area, osteon bone area and vascular space area of both classes A and B were significantly higher (P < 0.001 for all three parameters) in the endosteal than in the periosteal half‐cortex. The significant differences between the two layers of the cortex suggest that the osteoclast activity is distributed throughout the whole cortical thickness, with more numerous excavations in the external layer, but larger resorption lacunae closer to the marrow canal. A randomly selected population of 109 intact class B osteons was examined at higher magnification (350×) to count osteocyte lacuna and to analyse their relationship with osteon size parameters. The distribution frequency of the mean number of osteocyte lacunae increased with the increment in the sub‐classes of osteon bone area, whereas the density did not show significant differences. The number of osteocyte lacunae had a direct correlation with the osteon bone area and the mean osteon wall thickness, as well as the mean number of lamellae. The osteocyte lacunae density showed an inverse relationship. These data suggest a biological regulation of osteoblast activity with a limit to the volume of matrix produced by each cell and proportionality with the number of available cells in the space of the cutting cone (total osteon area). The collected data can be useful as a set of control parameters in healthy human bone for studies on bone aging and metabolic bone diseases.     

Bone remodeling and cyclical loading in maxillae of New Zealand white rabbits (Oryctolagus cuniculus)

Mammalian feeding behaviors are altered when mechanically challenging (e.g., tough, stiff) foods require large bite forces or prolonged mastication. Bony responses to high bite forces are well-documented for the mammalian skull, but osteogenesis due to cyclical loading, caused by repetitive chewing, is more poorly understood. Previous studies demonstrate that cyclical loading results in greater bone formation in the rabbit masticatory apparatus and in substantial Haversian remodeling in primate postcrania. Here we assess the relationship between cyclical loading and remodeling in the rabbit maxilla. Twenty male New Zealand white rabbits (Oryctolagus cuniculus) were raised on either an overuse or control diet (10 per group) for 48 weeks, beginning at weaning onset. The control group was raised on a diet of rabbit pellets (E = 29 MPa, R = 1031 J/m²), whereas the overuse group ate rabbit pellets and hay, which has high stiffness (E = 3336 MPa) and toughness (R = 2760 J/m²) properties. Hay requires greater chewing investment (475 chews/g) and longer chewing durations (568 s/g) than pellets (161 chews/g and 173 s/g), therefore causing cyclical loading of the jaws. Remodeling was measured as osteon population density (OPD), percent Haversian bone (%HAV), and osteon cross-sectional area (On.Ar). The only significant difference found was greater On.Ar in the alveolar region of the maxilla (p < 0.001) in the overuse group. The hypothesis that cyclical loading engenders Haversian remodeling in the developing maxilla is not supported. The continuation of modeling throughout the experimental duration may negate the need for remodeling as newly laid bone tends to be more compliant and resistant to crack propagation.     

Differences in osteonal micromorphology between tensile and compressive cortices of a bending skeletal system: Indications of potential strain-specific differences in bone microstructure

Background: It has been hypothesized that bone has the capacity to accommodate regional differences in tension and compression strain mode and/or magnitude by altering its osteonal microstructure. We examined a simple cantilevered bone to determine whether regional differences in particular strain-related features are reflected in the microstructural organization of compact bone. Methods & Results: The artiodactyl (e.g., sheep and deer) calcaneus has a predominant loading condition which is typified by prevailing compressive and tensile strains on opposite cortices, and variations in strain magnitudes across each of these cortices. Microscopic examination showed osteon density and cortical porosity differences between tension (caudal) and compression (cranial) cortices, averaging 11.4% more osteons in the compression cortex (P < 0.01) and 80.2% greater porosity in the tension cortex (P < 0.01). There is 43.5% more interstitial bone in the compression cortex (P < 0.01). Osteons in the compression cortex also have smaller areas in contrast to the larger area per osteon in the tension cortex. Although no definite transcortical gradient in osteonal density or cortical porosity is found, fractional area of interstitial bone is largest and osteon population density is lowest in the endocortical regions of both tension and compression cortices. The endocortical regions also have greater porosity than their corresponding middle and pericortical regions (P < 0.01). Conclusions: These osteonal microstructure and cortical porosity differences may be adaptations related to regional differences in strain mode and/or strain magnitude. This may be related to the disparity in mechanical properties of compact bone in tension vs. compression. These differences may reflect a capacity of bone to process local and regional strain-related information. © 1994 Wiley-Liss, Inc.

1 This article is a US Government work and, as such, is in the public dotmain in the United states of America

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Intracortical Remodeling Parameters Are Associated With Measures of Bone Robustness

Prior work identified a novel association between bone robustness and porosity, which may be part of a broader interaction whereby the skeletal system compensates for the natural variation in robustness (bone width relative to length) by modulating tissue‐level mechanical properties to increase stiffness of slender bones and to reduce mass of robust bones. To further understand this association, we tested the hypothesis that the relationship between robustness and porosity is mediated through intracortical, BMU‐based (basic multicellular unit) remodeling. We quantified cortical porosity, mineralization, and histomorphometry at two sites (38% and 66% of the length) in human cadaveric tibiae. We found significant correlations between robustness and several histomorphometric variables (e.g., % secondary tissue [R² = 0.68, P < 0.004], total osteon area [R² = 0.42, P < 0.04]) at the 66% site. Although these associations were weaker at the 38% site, significant correlations between histological variables were identified between the two sites indicating that both respond to the same global effects and demonstrate a similar character at the whole bone level. Thus, robust bones tended to have larger and more numerous osteons with less infilling, resulting in bigger pores and more secondary bone area. These results suggest that local regulation of BMU‐based remodeling may be further modulated by a global signal associated with robustness, such that remodeling is suppressed in slender bones but not in robust bones. Elucidating this mechanism further is crucial for better understanding the complex adaptive nature of the skeleton, and how interindividual variation in remodeling differentially impacts skeletal aging and an individuals' potential response to prophylactic treatments. Anat Rec, 297:1817–1828, 2014. © 2014 Wiley Periodicals, Inc.     

Morphometric analysis of variation in the ribs with age and sex

Rib cage morphology changes with age and sex are expected to affect thoracic injury mechanisms and tolerance, particularly for vulnerable populations such as pediatrics and the elderly. The size and shape variation of the external geometry of the ribs was characterized for males and females aged 0–100 years. Computed tomography (CT) scans from 339 subjects were analyzed to collect between 2700 and 10 400 homologous landmarks from each rib. Rib landmarks were analyzed using the geometric morphometric technique known as Procrustes superimposition. Age‐ and sex‐specific functions of 3D rib morphology were produced representing the combined size and shape variation and the isolated shape variation. Statistically significant changes in the size and shape variation (P < 0.0001) and shape variation (P < 0.0053) of all 24 ribs were found to occur with age in males and females. Rib geometry, location, and orientation varied according to the rib level. From birth through adolescence, the rib cage experienced an increase in size, a decrease in thoracic kyphosis, and inferior rotation of the ribs relative to the spine within the sagittal plane. From young adulthood into elderly age, the rib cage experienced increased thoracic kyphosis and superior rotation of the ribs relative to the spine within the sagittal plane. The increased roundedness of the rib cage and horizontal angling of the ribs relative to the spine with age influences the biomechanical response of the thorax. With the plane of the rib oriented more horizontally, loading applied in the anterior‐posterior direction will result in increased deformation within the plane of the rib and an increased risk for rib fractures. Thus, morphological changes may be a contributing factor to the increased incidence of rib fractures in the elderly. The morphological functions derived in this study capture substantially more information on thoracic skeleton morphology variation with age and sex than is currently available in the literature. The developed models of rib cage anatomy can be used to study age and sex variations in thoracic injury patterns due to motor vehicle crashes or falls, and clinically relevant changes due to chronic obstructive pulmonary disease or other diseases evidenced by structural and anatomic changes to the chest.     

Histomorphometric and osteocytic characteristics of cortical bone in male subtrochanteric femoral shaft

The histomorphometric properties of the subtrochanteric femoral region have rarely been investigated. The aim of this study was to investigate the age‐associated variations and regional differences of histomorphometric and osteocytic properties in the cortical bone of the subtrochanteric femoral shaft, and the association between osteocytic and histological cortical bone parameters. Undecalcified histological sections of the subtrochanteric femoral shaft were obtained from cadavers (n = 20, aged 18–82 years, males). They were cut and stained using modified Masson‐Goldner stain. Histomorphometric parameters of cortical bone were analysed with ×50 and ×100 magnification after identifying cortical bone boundaries using our previously validated method. Within cortical bone areas, only complete osteons with typical concentric lamellae and cement line were selected and measured. Osteocytic parameters of cortical bone were analyzed under phase contrast microscopy and epifluorescence within microscopic fields (0.55 mm² for each). The cortical widths of the medial and lateral quadrants were significantly higher than other quadrants (P < 0.01). Osteonal area per cortical bone area was lower and cortical porosities were higher in the posterior quadrant than in the other quadrants (P < 0.05). Osteocyte lacunar number per cortical bone area was found higher in the young subjects (≤ 50 years) than in the older ones (> 50 years) both before and after adjustments for body height and weight (P < 0.05). Moreover, significant but low correlations were found between the cortical bone and osteocytic parameters (0.20 ≤ R² ≤ 0.35, P < 0.05). It can be concluded that in healthy males, the cortical histomorphometric parameters differ between the anatomical regions of the subtrochanteric femoral shaft, and are correlated with the osteocytic parameters from the same site. These findings may be of use when discussing mechanisms that predispose patients to decreasing bone strength.     

Age reduces cortical reciprocal inhibition in humans

Age alters the control of voluntary movement. A widely observed age-related adaptation is the heightened activation of the antagonist muscles during voluntary movements. We examined the possibility that age also modifies cortical reciprocal inhibition. In young (age 27, n=6) and old (age 73, n=6) adults a mild conditioning electrical stimulus was delivered to the median nerve at the elbow. The test stimulus, delivered by transcranial magnetic stimulation (TMS) at 1-ms increments between 11 and 24 ms after the electrical conditioning stimulus, evoked motor potentials (MEP) in the extensor carpi radialis (ECR) and flexor carpi radialis (FCR). The absolute TMS intensity, expressed as the percent of stimulator output, used to produce 1-mV control MEPs in the ECR was similar in young (mean 58.5, standard deviation ±12.8%) and old adults (60.3±20.3%, P=0.855). The size of the control MEP in the ECR was also similar in young (0.98±0.10 mV) and old subjects (0.90±0.14 mV, P=0.686). The age by conditioning interval interaction (P=0.001) showed that the MEPs in the ECR were significantly depressed at 14, 15, 16, 17, 18, and 19 ms (range 55.5--65.9% of control, all P<0.05) compared with control value of 100% and with old adults who showed no depression. The MEPs remained at control level in the FCR and were also unaffected in the first dorsal interosseus. These data confirm the existence of cortical reciprocal inhibition reported previously in young humans and show that age reduces this inhibition similarly to the previously reported reduction of spinal reciprocal inhibition reported in old adults. Activation of agonist and antagonist muscle pairs are most likely organized around a dual system of cortically and spinally mediated reciprocal inhibition that is altered by age. The data also indicate the need to use age-matched control subjects when comparing individuals with abnormalities resulting from disorders that occur at an old age.     

Direct measurement of tibial cortical bone surface area

Cortical bone surface area estimation is generally performed by analysis of medical images but its accuracy has not yet been verified by direct bone measurements. This study was performed to evaluate the reproducibility of direct ex vivo estimations of cross sectional tibial cortical bone surface area. Ten tibiae were evaluated by two observers using direct 3D‐digitization at 38 and 66% of total tibial length using a ‘critical’ and a ‘general’ criterion for differentiation between cortical and cancellous bone. The results of the analysis using the more severe ‘critical’ differentiation criterion yielded high intra and interobserver agreement. Mean intraobserver reliability was demonstrated by R = 0.98 (Spearman rank correlation between 0.98 and 0.97; P < 0.01) and inter observer reliability by R = 0.91 (Spearman rank correlation between 0.95 and 0.88; P < 0.01). When using strict criteria to differentiate between cortical and cancellous bone, intra and interobserver reliability of the presented method of direct cortical bone surface area estimation is very high. The results indicate that cross‐sectional cortical bone surface estimation by direct 3D‐digitization can serve as a gold standard for validation of other estimations methods. Clin. Anat. 23:720–725, 2010. © 2010 Wiley‐Liss, Inc.     

Age‐related hypermineralization in the female proximal human femur

Hip fracture incidence increases exponentially with age in virtually every human population that has been studied. In spite of this, relatively few studies have examined age‐related changes in the metaphyseal cortex of the proximal femur. The present study investigates cortical aging changes in the female proximal femur, with particular reference to regions of hypermineralization. Thirty‐three femora from Caucasian females were obtained at autopsy and analyzed using backscattered electron imaging. Variations in hypermineralized tissue area, cortical bone area, and porosity were quantified with standard stereological methods. Cortical width was quantified with digital calipers. Gender differences were examined by statistical comparison with previously published results. Hypermineralized tissue volume was significantly (P < 0.001) greater in elderly individuals. Hypermineralized tissue preferentially appeared near ligamentous or tendinous insertion sites, suggesting the hypermineralized tissue may be a calcified fibrocartilage. Cortical width significantly (P < 0.001) decreased with age and porosity significantly (P < 0.001) increased with age, however the changes were site‐specific. The femoral neck and intertrochanteric cortices had a smaller change in cortical width and porosity with age than the diaphysis, but the femoral neck and intertrochanteric cortices had a larger increase in hypermineralized tissue. Comparison with previous data suggests that cortical aging in the proximal femur is similar between males and females and is unlikely to explain the higher incidence of fracture in females. However, the data strongly indicates that age‐related changes in the femoral diaphysis cannot be directly extrapolated to either the femoral neck or intertrochanteric cortices. Anat Rec 255:202–211, 1999. © 1999 Wiley‐Liss, Inc.     

Histomorphological and geometric properties of human femoral cortex in individuals over 50: Implications for histomorphological determination of age-at-death

Cortical area, area moment of inertia, and polar moment of inertia were determined from the midshafts of a series of 62 femurs (34 female and 28 male) from a U. S. white population, ages 51–95. The density of osteons and osteon fragments (per mm²) was also determined. Neither osteon nor osteon fragment density was significantly correlated with age. These variables were correlated, however, with normalized cortical and endosteal areas, normalized area moment of inertia, and polar moment of inertia. Osteon fragment numbers alone are not highly correlated with cross-sectional properties. This research suggests that osteon density and osteon fragment density are significantly related to cortical mass and distribution in older people, but are not a direct function of age in persons over 50 years of age. Histological age estimates in older individuals must, therefore, be used with extreme caution. © 1994 Wiley-Liss, Inc.     

Super‐osteons (remodeling clusters) in the cortex of the femoral shaft: Influence of age and gender

Previous studies of cortical remodeling in the fractured femoral neck indicated that the merging of spatially clustered remodeling osteons could result in the formation of deleteriously large cavities associated with femoral neck fracture. This study aimed to identify whether remodeling osteons in the femoral shaft were also clustered and to assess the influence of age and gender. Microradiographic images of femoral mid‐shaft cross‐sections from 66 subjects over 21 years of age were analyzed to determine the number, size and location of all Haversian canals. Those most recently remodeled were identified using an edge‐detection algorithm highlighting the most marked differential gradients in grey levels. Cluster analysis (JMP software) of these osteons identified the proportion of recently remodeled osteons that were within 0.75mm clusters. As in the femoral neck, remodeling osteons were significantly more clustered than could occur by chance (real, 59.4%; random, 39.4%; P < 0.0001). The density of these clusters (number/mm²) was not significantly associated with subject age or gender but was greatest near the periosteum and decreased toward the marrow cavity (periosteal 0.043 ± 0.004; mid‐cortex 0.028 ± 0.003; endosteal 0.017 ± 0.002). Cortical porosity increased with age. The presence of giant canals (diameter >385μm) was inversely related to the presence of clusters (R² = 0.237, P < 0.0001). This data suggest that remodeling osteons tend to be spatially colocalized in the shaft as they are in the neck of the femur and their presence is independent of age or gender. We propose that these remodeling clusters be termed super‐osteons. The negative relationship between super‐osteons and giant canals raises the intriguing possibility that loss of the control of remodeling depth results in the merging of osteonal systems to form deleteriously large cortical cavities with a marked reduction in bone strength. Anat Rec 264:378–386, 2001. © 2001 Wiley‐Liss, Inc.