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Age-related changes in cortical porosity of the midshaft of the human femur were investigated using automatic video image analysis. Males had consistently larger bones with a greater height normalised TSPA in the 70s as compared with the 20s. Females had significantly greater TSPP by the time they reached the 50s, while in males this did not occur till the 80s.
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Age Related Changes in the Cortical Porosity of the Midshaft of the Human Femur
Age-related changes in cortical porosity of the midshaft of the human femur were investigated using automatic video image analysis. Males had consistently larger bones with a greater height normalised TSPA in the 70s as compared with the 20s. Females had significantly greater TSPP by the time they reached the 50s, while in males this did not occur till the 80s.
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Age-related changes in cortical porosity of the midshaft of the human femur were investigated using automatic video image analysis. Males had consistently larger bones with a greater height normalised TSPA in the 70s as compared with the 20s. Females had significantly greater TSPP by the time they reached the 50s, while in males this did not occur till the 80s.
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Attribution Non-Commercial (BY-NC)
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Age-related changes in cortical porosity of the midshaft of the human femur S. A. FEIK, C. D. L. THOMAS AND J. G. CLEMENT School of Dental Science, University of Melbourne, Victoria, Australia (Accepted 8 July 1997) :ns1r:c1 Complete cross-sections from the femoral midshaft of 180 individuals of known height and weight, aged 2197 y, from a modern Australian population were examined using automatic video image analysis to quantify total subperiosteal porosity (TSPP). More specically, the aim was to investigate whether age changes were similar in both sexes in (1) total subperiosteal area (TSPA), cortical area (CA) and medullary area (MA), (2) intracortical porosity (ICP), and (3) the respective contributions to TSPP made by MA and intracortical void area (ICVA). Our ndings indicated that both sexes showed a signicantly greater height normalised TSPA in the 70s as compared with the 20s. Males had consistently larger bones with a greater height normalised CA. In both sexes CA showed a tendency to increase till the 7th decade and then to decline, more so in females. MA approximately trebled in females and doubled in males over the age range studied. Although ICP also increased, from 46% in young adults to over 9% in the elderly, it showed a signicant dierence between the sexes only in the 3rd decade, being greater in males at this stage. By contrast, TSPP became signicantly greater in females (from that recorded in the 3rd decade) by the time they reached the 50s, while in males this did not occur till the 80s. It increased from "25% in young adults of both sexes to "50% in females and "37% in males in their 80s. However, in the elderly there was great variability in both sexes in the appearance of bones from individuals of similar chronological age. Some bones diered little from those in younger subjects, others showed greatly increased ICP, still others displayed reduced cortical widths with low ICP. The femoral midshaft resembles other skeletal sites in that age changes in TSPP are more marked in females than males. Key words: Femur; age changes; porosity; medullary area; remodelling. i N1robic1i oN Age and sex dierences in the development of porosity in bone are currently of great interest worldwide because of the high prevalence of osteoporosis with its associated risk of fracture (Melton, 1993). Australian epidemiological data on osteoporosis resemble those derived fromother urbanised populations in USAand Europe (Seeman et al. 1993). Bone mineral density (BMD) values are widely used to diagnose osteo- porosis and to predict future fracture risk (Melton et al. 1993; Kanis et al. 1994). These areal BMD values are presented in g\cm# and take no account of bone architecture. Since bone density is determined more accurately by the relationship between bone organ size and the amount of bone tissue contained within Correspondence to Dr Sophie A. Feik, School of Dental Science, 711 Elizabeth St, Melbourne, Victoria 3000 Australia. Tel. : j61 3 9341 0445; fax:j61 3 9341 0339; e-mail : s.feik!dent.unimelb.edu.au its periosteal surface (Seeman, 1995) quantitation of these parameters becomes important when interpret- ing observed bone mineral density changes with age. With the advent of automated image analysis techniques it has become possible to examine entire cross-sections of bone to determine concurrently the percentage area occupied by bone tissue and voids within the bone perimeter. The authors have used this method to examine the femoral midshaft and, al- though this region is not usually implicated in osteoporotic fractures, it has long been the subject of numerous studies on bone ageing because of its relative availability. It has also been shown recently that reduced thickness of the femoral shaft cortex is an independent predictor of hip fracture (Gluer et al. 1994). Hence a study of porosity changes at this site might reasonably be expected to enhance under- standing of femoral neck fractures. In studies of porosity undertaken to date either intracortical porosity (ICP) or, alternatively, changes in medullary area (MA) and cortical width have been determined in selected areas of bone cross-sections. To our knowledge no studies of entire cross-sections relating both ICP and MA to bone size have been conducted, yet all 3 variables contribute to bone density as dened above and thereby inuence bone strength. The early studies of Jowsey (1960) and Atkinson (1965) showed that ICP increased with age but made no mention of sex dierences. An investi- gation by Martin et al. (1980), albeit on men only, similarly showed an increase with age, fromabout 9 to 18% between ages 40 and 90 y. Martin & Burr (1984), on a small sample of 19 subjects, demonstrated no signicant ICP dierences between males and females. Cortical width loss in conjunction with ICP has been considered in a few studies (Atkinson, 1965; Thomp- son, 1980). Thompson concluded that males and females had similar patterns of intracortical bone loss but the patterns of cortical width loss were dissimilar between the sexes, with only the females demon- strating a signicant decline in cortical width values with age. He attributed gender anomalies in some of his results to inadequate numbers of subjects in the younger cohorts. The problems of sampling small cohorts and limited areas of femoral cross-sections, which apply to all the studies cited above, are compounded by Arnolds (1970) observation that porosity distribution is not uniform around the shaft. It is much greater endosteally and in the anterior and posterior regions (Martin & Burr, 1984). Diculties such as these have prompted a number of investigators to state that the results of their studies need verication. The aim of this study was to compare ageing trends in total subperiosteal porosity (TSPP) in men and women from a large sample of cadavers in a contemporary Australian population. Complete fem- oral cross-sections were examined to determine whether age changes were similar in both sexes in (1) total subperiosteal area (TSPA), cortical area (CA) and medullary area (MA), (2) intracortical porosity (ICP), and (3) the respective contributions to total subperiosteal porosity (TSPP) made by MA and intracortical void area (ICVA). x:1rri :is :Nb xr1nobs Bone specimens (nl180) were collected at the Victorian Institute of Forensic Medicine, Melbourne, Australia, from people who had died suddenly with no known diseases directly aecting their bones. The sample was almost exclusively Anglo-Celtic, as judged by the names. Information on the age, sex, supine length, weight and, in almost every case, the cause of death was available. Collection of specimens from both sexes representing each year from21 to 100 y was attempted. Details of the sample are included as part of Figure 2. Specimens 24 cm in length were sawn by mortuary sta from the midshaft of either femur and xed in 70% ethanol. No attempt was made to record the orientation of the specimens. The specimens were cleaned manually and transverse sections, 110200 m thick, were obtained using a Leitz 1600 sawing microtome. Macroscopic measurements Images of the bone sections were acquired using a monochrome, 700 line resolution video camera (Dage- MTI Model 65, Michigan City, Indiana, USA) tted with a 50 mm focal length macro lens and a video digitiser (PIP-512, Matrox Ltd, Dorval, Quebec, Canada). The programs used were Bioscan Optimas V4.02 image processing software (Bioscan, Edmonds, Washington, USA) and Microsoft Excel V5.0. The system was calibrated by acquiring and measuring an image of a scale with divisions of 0.1 mm (stage micrometer no. 310345. Wild, Heerbrugg, Switzer- land). TSPA and CA (as total foreground) were automatically acquired and MA calculated from these measurements. Microradiography and microscopic measurements For radiomicrography, planoparallel sections (100p5 m) were obtained by lapping the sawed sections on 1200 grade wet and dry carborundum paper using a custom built hand-lapping tool. The sections were radiomicrographed using a Matchlett Laboratories OEG x-ray tube with a copper target operated at 25 kV and 10 mA. The lm used was Kodak SO-343 at a distance of 195 mmfromthe target. An aluminium step wedge was radiomicrographed with each section. The radiomicrographs were mounted on glass slides and masked with black tape to dene the borders and exclude extraneous light. An array of contiguous monochrome images from entire cross-sections was recorded by tiling on a computer-controlled X-Y stage (Lang Electronics MCC 11\12\13-JS-RS 232) tted to a Leitz Dialux 20 microscope. The camera used was a 3-chip colour video camera with a resolution of 768 by 486 pixels (Sony DXC-930P). The 408 S. A. Feik, C. D. L. Thomas and J. G. Clement video digitiser and computer were the same as described above. The eld of viewof the camera, using a i1 microscope objective (Leitz PL 1\0.04), was "3 mmi2 mm and most sections were contained within a rectangle 30 mmi35 mm, thus approxi- mately 180 frames (tiles) were needed per specimen. Frame boundaries matched to a precision of 0.1 m. Within each tile, bone tissue and voids were isolated by thresholding (conversion to a 2-level image with grey levels above a xed reference value becoming white and those below being set to black) and their areas measured. For each tiled specimen, the microscopically mea- sured cortical bone area (summed bone area j summed void area) was compared with the macro- scopically measured bone area; the average dierence between these measurements was 2.8%. The former measurement was used for all subsequent calculations. Tiling of a number of sections was repeated both by the same and a dierent operator. The intra- and interoperator coecients of variation (c.v.) for repeat measurements of the microscopically determined bone and void areas ranged from 1% to 7%, averaging 5%. To determine the eect of a frame shift on the measurements one section was tiled ve times keeping all conditions constant but moving the section to a new starting position each time. This resulted in a c.v. for the bone area of 1.4% and for the void area of 4.5%. The dierence between the 2 c.v.s could be explained as follows. The measurement of total bone area was simply a count of the pixels in the tile image that were above the threshold (i.e. nonblack) and thus fairly consistent, while the measured void area varied slightly with the location of tile boundaries. Voids that intersected tile boundaries were not counted (it was not possible to ascertain for certain that they were not part of the MA) and thus a shift in tile position changed the population of voids that was measured. Data analysis and size normalisation Ru (1984) and his coworkers (Ru et al. 1993) have demonstrated that femoral cross-sectional size varies with bone length. The dierences in height between individuals may thus have an eect, unconnected with ageing, on the measured parameters. For this reason the results for TSPA and CA but not MA, which is discussed below, are presented as height normalised. A simple allometric model (Albrecht et al. 1993) was used for the size adjustment. A power law equation was tted to the measurements for all variables as a function of height, data from both sexes being combined for this purpose. The variables TSPA and CA were found to be correlated with height and were proportional to height to the power of 1.72 (r# l0.41) and 2.36 (r# l0.43) respectively. However, MA showed a much poorer correlation (r# l0.16) and so height normalisation was not carried out for this parameter. Using SPSS software (SPSS Inc., Chicago, Illinois) LOWESS regression lines were used to show age trends in MA, ICP and TSPP. The denition of Laval- Jeantet et al. (1983) was adopted for ICP, i.e. the percentage of cortical bone occupied by vascular and resorption cavities. TSPP was dened as MA plus intracortical void area (ICVA) as a proportion of total subperiosteal area (TSPA), i.e. (MAjICVA)\TSPA. Age trends were explored further by grouping the subjects into decades and plotting mean values. The TukeyHSD test with a signicance level of 0.05 was used to determine dierences between decade means and t tests used for the determination of sex dierences. To highlight sex dierences in age-related changes in TSPP, the MA and ICVA were expressed as fractions of TSPA. This approach removed the eects on these parameters of bone size dierences between the sexes. LOWESS curve tting was again used for a qualitative assessment of age trends in the variables. Linear least squares regression was then applied to grouped values (55 and l55 y) of MA and ICVA (taken as a percentage of TSPA) in order to study dierences between young and old. The age of 55 y was chosen as the majority of women beyond this age could be considered to have passed menopause; the grouping is also consistent with a previous study using the same specimen collection (Feik et al. 1996). rrsii1s Total subperiosteal area and cortical area (Table 1) Height normalised TSPA was consistently greater in males than females over the age range studied and showed a tendency to increase from the 20s on, being signicantly greater in the 7th decade than in the 3rd. Dierences between the nal 4 decades were not signicant, suggesting that no real change occurred beyond the 70s. In females, TSPA remained relatively constant till around the age of menopause when it tended to decrease. It then increased to around the 7th decade and, as in males, showed no signicant increase beyond this time (the nal decade was excluded because the number of specimens was small). The pattern of change with age in height normalised CA was very similar to that of TSPA up to the 70s, then Age changes in femoral cortical porosity 409 Table 1. Measured values of parameters (meansp1 S.D.) Height normalised Total subperiosteal Cortical area Medullary area Total subperiosteal Intracortical Age (y) Number area (mm#) (mm#) (mm#) porosity porosity Females 2130 14 142.6 p17.7 220.9p19.3 101.3 p48.2 0.2371 p0.06 0.0456 p0.01 3140 8 143.9 p17.3 223.2p26.1 103.5 p29.7 0.2532 p0.04 0.0591 p0.02 4150 11 141.2 p21.9 224.4p31.6 93.3 p35.1 0.2348 p0.04 0.0520 p0.02 5160 11 149.4 p15.2 200.6p38.2 158.8 p63.2 0.3668 a p0.11 0.0707 p0.02 6170 11 165.3 a p12.9 235.3p34.0 148.4 p38.9 0.3398 p0.08 0.0794 a p0.03 7180 14 159.5 p13.7 201.9p33.3 190.5 a p63.6 0.4085 a p0.10 0.0757 a p0.03 8190 15 171.0 a p15.2 193.5p41.4 232.5 a p73.0 0.4887 a p0.10 0.0948 a p0.03 91100 3 188.7 a p33.9 179.1p23.9 308.4 a p122.8 0.5596 a p0.09 0.0960 a p0.02 Males 2130 12 154.7 p21.3 222.2p43.3 141.2 p60.5 0.2708 p0.09 0.0577 p0.02 3140 12 158.1 p14.3 231.8p27.9 132.9 p32.3 0.2572 p0.04 0.0521 p0.02 4150 15 169.5 p15.3 241.1p27.7 159.7 p63.2 0.2881 p0.08 0.0612 p0.02 5160 13 175.4 p17.4 242.4p33.0 171.8 p69.4 0.3066 p0.08 0.0665 p0.02 6170 13 181.0 a p26.4 254.3p45.7 175.2 p38.1 0.3083 p0.06 0.0688 p0.03 7180 12 177.2 p15.3 240.8p38.9 190.7 p78.0 0.3428 p0.10 0.0824 p0.03 8190 12 179.4 a p16.9 236.7p45.0 204.4 p83.2 0.3743 p0.11 0.0924 a p0.04 91100 4 188.5 a p18.8 212.1p40.4 290.2 a p142.8 0.4398 a p0.12 0.0754 p0.02 a , Dierences between the marked values and that for the 2130 decade are signicant at the 0.05 level. Fig. 1. Change with age of medullary area. The means for subjects were classied by decades. Statistically signicant dierences (P 0.05) between the mean results for the 3rd decade (*) and all other decades are indicated by the letter a. CA showed a tendency to decline in both sexes, but more so in females. Medullary area From early adulthood to middle age there was a tendency towards a decrease in MA, particularly in females, although this trend was not statistically signicant (Fig. 1, Table 1). From the 3rd to the 7th decades MA increased on average at 6% per decade in males and 11% per decade in females. However, between the 5th and 7th decades, MA in males increased by about 10% whereas in females the increase was close to 60%. Females had signicantly Fig. 2. Change with age of intracortical porosity. The means for subjects were classied by decade; n denotes the number of subjects in each decade. Statistically signicant dierences (P0.05) between the mean results for the 3rd decade (*) and all other decades are indicated by the letter a. smaller medullary cavities than males in the 5th decade (P0.05) but, because of the marked changes in the immediate postmenopausal decades, females beyond 70 y tended to have larger mean marrow cavities than males, despite their smaller bone size. Intracortical porosity In both sexes ICP increased from 46% in the 3rd decade to over 9% in the 9th decade (Fig. 2, Table 1). However, gender patterns diered in that ICP in- creased rapidly in postmenopausal females, becoming signicantly dierent from the young adult in the 60s 410 S. A. Feik, C. D. L. Thomas and J. G. Clement Table 2. Values from regression analyses with age as the independent variable 95% condence interval 95% condence interval Measured parameter Slope P value Lower Upper Intercept P value Lower Upper R# MA as % of TSPA Females 2055 y 0.077 0.50 k0.150 0.304 19.76 0.00 11.20 28.31 k0.02 Females 55 y and older 0.697 0.00 0.379 1.015 k9.58 0.43 k33.81 14.64 0.28 Males 2055 y k0.056 0.65 k0.302 0.189 26.41 0.00 16.93 35.88 0.01 Males 55 y and older 0.423 0.00 0.157 0.689 1.59 0.87 k18.08 21.26 0.16 Intracortical voids as 0.014 0.02 0.003 0.025 3.77 0.00 3.07 4.46 0.35 % of TSPA while in males the increase was more gradual and signicance was not attained till the 80s. LOWESS regression lines showed a trend towards the main- tenance of slightly higher ICP levels in females after the rise in the postmenopausal period. However, the only signicant dierence between the sexes was in the 3rd decade when males showed greater ICP. Total subperiosteal porosity Changes in whole bone porosity were determined by examining the fraction of TSPA occupied by MA and ICVAconsidered individually and together. Total bone loss was therefore taken to be the sum of the increase in MAplus the increase in ICVA. When these areas were summed and expressed as a fraction of TSPA the result was equivalent to TSPP. The fractional changes in MA and ICVA were considered indicators of the extent of endosteal and intracortical bone loss respectively, although it is acknowledged that this is an oversimplication of the situation as it exists in life. LOWESS curve tting to a scatter diagram of MA as a fraction of TSPA indicated that rates of change diered between the sexes and varied over age for females. In males there was little evidence for a change in the rate of endosteal bone loss with age. Further analysis, where both sexes were divided into two age groups ( 55 and 55 y), yielded the following results. Details are presented in Table 2. There was a highly signicant dierence ( P0.001) in the rate of change of MA as a fraction of TSPA between the younger and older groups of females but this dierence was not signicant for males ( Pl0.08) (Fig. 3). In the younger group there was no signicant dierence between the sexes. Between the sexes in the older group the dierence was greater but still not signicant (Pl0.11). The same analysis was done for ICVA as a fraction of TSPA but in this case no signicant dierences Fig. 3. Change with age in medullary area as a fraction of total subperiosteal area. Fig. 4. Change with age in intracortical void area as a fraction of total subperiosteal area. were found between younger and older groups or between the sexes. In light of this uniformity the sexes and age groups were combined and a regression line tted over the age range studied. For the combined sample, the regression results were highly signicant Age changes in femoral cortical porosity 411 Fig. 5. Change with age in the area occupied by intracortical voids, cortical bone and medullary cavity within the total subperiosteal area. (Pl0.01) and indicated that the increase from"4% to "5% with age, although small, was real (Fig. 4; Table 2). TSPP was similar in both sexes in early adulthood showing values of 2426% i.e. approximately three- quarters of the total area beneath the perimeter consisted of bone, the remainder voids (Table 1). Females in their 50s showed a signicant rise in TSPP which continued to increase so that in the 80s it was approximately 50%; only half TSPA was then occupied by bone. This was signicantly dierent from males ("37% TSPP in the 80s) in whom the increase was more gradual and of lesser magnitude; the change in bone area was "11% (vs "25% in females) between the 3rd and 9th decades (Fig. 5). In summary, by far the largest contribution to the change in the amount of bone present was from the increase in MA, i.e. from endosteal resorption. The change in the intracortical component, although statistically signicant, was very small and appeared to play little part in the increasing TSPP of the femur that occurred with age. However, great variability in the development of TSPP in elderly individuals of similar chronological age was seen (Fig. 6). Some had bones that diered little from those in younger subjects having small medullary cavities and little ICP, others displayed greatly increased ICP and little change in cortical width, while others still showed reduced cortical widths with low ICP. bi scissi oN In this study we compared ageing trends between the sexes in the development of porosity within the total subperiosteal area of femoral midshaft cross-sections. Both sexes showed a signicantly greater height normalised TSPA in the 70s as compared with the 20s, with males having consistently larger bones and a greater cortical area. The latter parameter showed a tendency to decline beyond the 7th decade particularly in females. Endosteal resorption (as reected in changes in MA) showed diering patterns in the 2 sexes, being relatively stable in females till the menopausal decade, then rising steeply, so that MA trebled over the age range studied and the marrow cavities of females were, on average, larger than males in the nal decades despite their smaller bone size. In males the increase in endosteal resorption commenced a decade earlier than in females and was more uniform and not as great, MA doubling over the age range studied. ICP showed less change with age and sex, increasing less than 5% over 6 decades in both sexes. As in the case of endosteal resorption, females displayed a greater change in ICP in the postmeno- pausal decades. Therefore, ICP diered signicantly from that in the young adult approximately 2 decades earlier in females than in males. Whole bone porosity reects bone lost both intracortically and through an increase in MA. Females showed a much greater decrease between the 3rd and 9th decades in the fraction of TSPA occupied by bone, a change from 76 to 50% in females contrasting with 74 to 63% in males, i.e. "25% loss in females as against "11% in males. In both sexes the intracortical loss was only "1% over this time period. We believe this study to be unique in that entire cross-sections of the femoral midshaft were measured directly to ascertain concurrently both the intracor- tical and medullary components of bone loss within the total perimeter taking bone size into account. In no previous study, as far as we know, has such a task been undertaken using a relatively precise and objective method with good reproducibility on such a large number of well-documented specimens. The 412 S. A. Feik, C. D. L. Thomas and J. G. Clement Female Male Fig. 6. Microradiographs of transverse sections of the femoral midshaft from(left) females and (right) males in their 80s showing the variation found in intracortical porosity and medullary area in individuals of similar chronological age.i1.8 sample represented a modern urban population and covered the age range from 21 y onwards. Details such as the age, height, weight, and in most cases the cause of death of each subject were known. The ndings should be widely applicable to other urban- ised Western countries, as the prevalence of osteo- porosis in Melbourne, Australia resembles that in similar communities in USA and Europe (Seeman et Age changes in femoral cortical porosity 413 al. 1993). The study, however, was of necessity cross- sectional and, therefore, the age changes reported may be subject to cohort bias. In Australia the secular increase in height of young adults early this century and approximately 70 y later was on average 3.3 cmin females and 4.6 cm in males (Meredith, 1976). Height normalisation compensated to some extent for this secular increase but not all the measured parameters could be height normalised and, inevitably, other unknown secular changes may have aected the dierent-aged cohorts. The method lends itself to a detailed study of the regional distribution of porosity and how this alters with age. Unfortunately further studies, which are dependent on a precise knowledge of specimen orientation, are limited with this sample as, at removal from the body, the specimens were not oriented with respect to the rest of the femur. Similarly, because only midshaft specimens were available, studies of the development of porosity in regions more prone to fracture and hence of greater interest, are precluded. The large spread of values around the decade means may reect the heterogeneity of the population of Melbourne. The variability was greater in males in our sample as Garn (1970) also found and more pronounced in the older age groups, akin to the ndings of Mazess et al. (1990) on bone density. Radiomicrographs of the specimens clearly illustrated this, for specimens of similar chronological age varied widely in appearance and it was impossible to estimate an individuals age on the basis of the degree of TSPP present. Some individuals in their 80s showed very little ICP or cortical thinning, in others ICP was very marked and the cortex honeycombed by large re- sorption cavities with little reduction in cortical width. Still others displayed cortices a few millimetres wide with very little ICP. The method of measurement consistently, but arbitrarily, classies any void as either intracortical or as part of the medullary cavity. The situation in life is much more complex and constantly changing. As cortical bone becomes increasingly porous and trabe- culised discontinuities appear in the endosteal surface and precise delineation into 2 separate and distinct compartments is not possible. The study was cross- sectional and it was not possible to determine the sequence and timing of events in this resorptive process. Did all the femoral midshafts go through a stage of high ICP preceding the reduction in cortical width and was this stage largely undetected because such porous structures are transient and of short duration? Partt (1996) has pointed out that, although structures intermediate between cortical bone with its low porosity and surface-to-volume ratio, and cancel- lous bone, where these values are high, do occur they are infrequent and tend to be temporary (Fyhrie et al. 1994). Our study supports this for ICP increased minimally with age, "1% as a fraction of TSPA, whereas total bone loss was substantial, implying that shafts with reduced cortical widths were the norm in old age. Atkinson (1965) and others (Martin et al. 1980) have reported that ICP is greater near the medullary cavity than near the periosteal surface. Our observations concur with this. As these resorption cavities enlarge, not only is the surface-to-volume ratio of cortical bone raised but bone surface contact with the marrow cavity is also increased as the intervening bone is resorbed. Since fractional bone loss is proportional to surface- to-volume ratio (Partt, 1995), and absolute rates of loss are much greater from the endosteal surface (Partt, 1989), the turnover rate in appendicular cortical bone (Partt, 1983) can be greatly enhanced. Similar mechanisms can be invoked to explain the rise in ICP and MA seen in this study in females in the postmenopausal period. With oestrogen deciency bone loss increases (Riggs & Melton, 1986) with increasing turnover rate: the greater resorption depth (Partt, 1989) and consequent negative balance in remodelling produce irreversible bone loss (Eriksen, 1986). This loss is exacerbated by the concurrent rise in activation frequency (Eriksen & Mosekilde, 1990) thus increasing the remodelling space. Our results showed that beyond the immediate postmenopausal decades the rate of increase in % ICP and MA slowed somewhat, presumably as the oestrogen eect waned and the rise in activation frequency declined (Stepan et al. 1987). However, since residual surface-to- volume ratios would be greater because of the previous irreversible loss, bone removal continued into old age at a faster rate than premenopausally. In males the rates were more uniform (Stepan et al. 1985), consistent with the well-documented age-related de- cline in their bone mass (Garn, 1970). Age changes in MA from a comparable sample representing the whole lifespan were discussed in an earlier publication (Feik et al. 1996) and will be discussed only briey here. The greater endosteal resorption seen in females in this study concurs with that in an archaeological population (Ru & Hayes, 1982) where sex dierences were marked. In a modern US population sex dierences in MA were not statistically signicant and the percentage increase in MA ranged from 8 to 11% per decade in both sexes (Ru & Hayes, 1988). Comparable gures from our study were 6 to 11% per decade, not greatly dierent. 414 S. A. Feik, C. D. L. Thomas and J. G. Clement Even though in the elderly the absolute magnitude of MA in males and females was not signicantly dierent, the proportional medullary cavity expansion was much greater in females. They had signicantly smaller marrow cavities than males in the 5th decade yet ended up with the same or larger ones despite their smaller bone size. The greater endosteal resorption in females was particularly striking in the immediate postmenopausal decades (5th to 7th) where the average increase per decade was "5% in males and "30% in females. Such variations with time are not usually reported (Ru & Hayes, 1988) for they are obscured if simple age regressions are used. The sex dierence during this period can be explained in terms of hormonal changes aecting bone turnover, as discussed above. It is dicult to compare our ndings on ICP directly with other studies for none has examined entire cross-sections. Yet it is known that regional variations in ICP in the femoral midshaft do occur (Arnold, 1970) and, with age, porosity is much greater endosteally and in the anterior and posterior regions (Martin & Burr, 1984). However most studies, like ours, have either shown that there is little dierence in ICP in elderly males and females (Thompson, 1980; Martin &Burr, 1984) or the authors make no mention of sex dierences (Atkinson, 1965; Jowsey, 1960). Again there seems to be general agreement that ICP increases with age (Jowsey, 1960; Atkinson, 1965), although the reported levels may vary somewhat. Partt (1994) stated that ICP averages 25% in dierent bones in adults. Laval-Jeantet et al. (1983) in their study of the humerus gave gures of "4% at age 40 increasing to 10% or more at age 80. These values accord closely with ours at 46% in adults 50 y, rising to over 9%in the elderly. Slightly higher ICP values at 918% from 40 to 90 y were presented by Martin et al. (1980) in their study of men only. However, they stated that because of sample variation, conrmation of their results was needed. The signi- cantly greater ICP shown in our study in males in the 3rd decade may be a consequence of their later maturation relative to females. Statural growth in males may not cease till 21 y or beyond, depending on the generation and the population studied, although the average for modern Western man is approximately 18 y. During rapid growth bone turnover increases, accompanied by a proportional increase in ICP (Partt, 1981). This porosity declines as growth ceases and bone density is increased during the subsequent process of consolidation (Partt, 1994). Peak bone mineral content (BMC) was shown to be achieved by "26 y in females (Teegarden et al. 1995) and presumably occurs somewhat later in males. The mechanism proposed above could explain the greater ICP seen in males in their 20s in this study. Alterations in the fraction of TSPA occupied by MA, CA and ICVA provide a measure of the amount and location of bone loss with age. In young adults of both sexes MA as a fraction of TSPA was 2224%, the corresponding values for CA were 7074% and ICVA "4%. By the 80s the fraction occupied by CA had declined by "29% in females and "12% in males, whereas ICVA had only increased 12% in both sexes. Thus bone loss was largely due to marrow cavity expansion leading to cortical thinning, rather than to an increase in ICP. These results are remarkably similar to those of Laval-Jeantet et al. (1983) on the humerus, the only study that is comparable to ours. They found a 28% decrease in CA due to thinning and 2% by an increase of ICP in females between 40 and 80 y. In men an almost identical increase of porosity without provable loss of CA was observed. However, other studies on the femur have shown declines in CA in males (Ru & Hayes, 1988), particularly beyond age 80 (Martin et al. 1980). This study, examining entire cross-sections, clearly shows age-related sex dierences in the pattern of bone loss in appendicular cortical bone. The loss from changes in MA, which is much greater in females, far outweighs the small amount lost from increasing ICP which, by contrast, shows little sex dierence with age. Such changes may explain why exponential increases in fracture rates are not seen in diaphyseal bone in either sex, for as shown here and previously (Feik et al. 1996), continued periosteal apposition, at least into the 70s, largely compensates for this medullary loss. :ciNovirbcrxrN1s The authors wish to thank the sta at the Victorian Institute of Forensic Medicine for collection of the specimens, Dr P. Bertelsen for advice and considerable specimen preparation, Dr M. Stein for critical analysis and Sherie Blackwell for technical assistance. They are also grateful to the National Institute of Forensic Science for providing much of the computer equip- ment and software used for this study. rrrrrrNcrs Ainrrcn1 GH, GriviN BR, H:r1x:N SE (1993) Ratios as a size adjustment in morphometrics. Americal Journal of Physical Anthropology 91, 441468. ArNoib JS (1970) Focal excessive endosteal resorption in aging and senile osteoporosis. In Osteoporosis (ed. Barzel US), pp. 80100. New York: Grune and Stratton. Age changes in femoral cortical porosity 415 A1iiNsoN PJ (1965) Changes in resorption spaces in femoral cortical bone with age. Journal of Pathology and Bacteriology 89, 173178. EriisrN EF (1986) Normal and pathological remodeling of human trabecular bone: three-dimensional reconstruction of the re- modeling sequence in normals and in metabolic bone disease. Endocrine Reviews 7, 379408. EriisrN EF, Mosriiibr L (1990) Estrogens and bone. In Bone and Mineral Research. vol. 7 (ed. Heersche JNM, Kanis JA), pp. 273312. New York: Elsevier Science. Frii SA, Tnox:s CDL, CirxrN1 JG (1996) Age trends in remodeling of the femoral midshaft dier between the sexes. Journal of Orthopaedic Research 14, 590597. F.nrir DP, L:Nc SM, P:rri11 AM (1994) Cortical and cancellous bone structure in the ilia of normals and osteoporotics. Orthopaedic Research Society, 40th Annual Meeting, p.443 (Abstract). G:rN SM (1970) The Earlier Gain and the Later Loss of Cortical Bone. Springeld, Illinois: Charles C. Thomas. Giirr C-G, CixxiNcs SR, Prrssx:N A, Li J, Giirr K, F:iiiNrr KG et al. (1994) Prediction of hip fractures from pelvic radiographs: the study of osteoporotic fractures. Journal of Bone and Mineral Research 9, 671677. Jovsr. J (1960) Age changes in human bone. Clinical Orthopaedics and Related Research 17, 210217. K:Nis JA, Mri1oN LJ, Cnris1i:NsrN C, JonNs1oN CC, Kn:i1:rv N (1994) The diagnosis of osteoporosis. Journal of Bone and Mineral Research 9, 11371141. L:v:i-Jr:N1r1 AM, Brrco1 C, C:rroii R, G:rci:-Scn:rrrr F (1983) Cortical bone senescence and mineral bone density of the humerus. Calcied Tissue International 35, 268272. M:r1iN RB, Birr DB (1984) Mechanical implications of porosity distribution in bone of the appendicular skeleton. Orthopaedic Transactions 8, 342343. M:r1iN RB, Picir11 JC, ZiN:icn S (1980) Studies of skeletal remodeling in aging men. Clinical Orthopaedics and Related Research 149, 268282. M:zrss RB, B:rbrN HS, DriNi: PJ, B:ivrNs SF, Orvoii ES, Brii NH (1990) Inuence of age and body weight on spine and femur bone mineral density in US white men. Journal of Bone and Mineral Research 5, 645652. Mri1oN LJ (1993) Hip fractures; a worldwide problem today and tomorrow. Bone 14, S1-S8. Mri1oN LJ, A1iiNsoN EJ, OF:iioN WM, W:nNrr HW, Riccs BL (1993) Long term fracture prediction by bone mineral assessed at dierent sites. Journal of Bone and Mineral Research 8, 12271233. Mrrrbi1n HV (1976) Findings from Asia, Australia, Europe, and North America on secular change in mean height of children, youths, and young adults. Americal Journal of Physical Anthro- pology 44, 315326. P:rri11 AM(1981) Integration of skeletal and mineral homeostasis. In Osteoporosis: Recent Advances in Pathogenesis and Treatment (ed. DeLuca HF, Frost H, Jee W, Johnson C, Partt AM), pp. 115126. Baltimore: University Park Press. P:rri11 AM (1983) The physiologic and clinical signicance of bone histomorphometric data. In Bone Histomorphometry: Techniques and Interpretations (ed. Recker RR), pp. 142223. Boca Raton: CRC Press. P:rri11 AM (1989) Surface specic bone remodeling in health and disease. In Clinical Disorders of Bone and Mineral Metabolism (ed. Kleerekoper M, Krane S), pp. 714. New York: Mary Ann Liebert. P:rri11 AM (1994) The two faces of growth: benets and risks to bone integrity. Osteoporosis International 4, 382398. P:rri11 AM (1995) Is the rate of bone loss inuenced by the initial value? Biological and statistical issues. Osteoporosis International 5, 309310 (Abstract). P:rri11 AM(1996) Skeletal heterogeneity and the purposes of bone remodeling. In Osteoporosis (ed. Marcus R, Feldman D, Kelsey J), pp. 315329. San Diego: Academic Press. Riccs BL, Mri1oN LJ (1986) Involutional osteoporosis. New England Journal of Medicine 314, 16761686. Rirr CB (1984) Allometry between length and cross-sectional dimensions of the femur and tibia in Homo sapiens sapiens. Americal Journal of Physical Anthropology 65, 347358. Rirr CB, H:.rs WC (1982) Subperiosteal expansion and cortical remodeling of the human femur and tibia with aging. Science 217, 945948. Rirr CB, H:.rs WC (1988) Sex dierences in age-related remodeling of the femur and tibia. Journal of Orthopaedic Research 6, 886896. Rirr RB, TriNi:is E, W:iirr A, L:rsrN CS (1993) Postcranial robusticity in Homo. I: Temporal trends and mechanical interpretation. American Journal of Physical Anthropology 91, 2153. Srrx:N E (1995) Overview. Advances in Osteoporosis 2, 189195. Srrx:N E, EbxoNbs J, Ko1ovicz M, NicnoisoN G, CixxiNc RG, M:r1iN TJ (1993) The incidence of hip fractures in women and men in Australia. Queenstown, New Zealand: Australian and New Zealand Bone and Mineral Society. S1ri:N JJ, Trs:rov: A, H:vr:Nri T, Jobi J, Forx:Niov: J, P:covsi. V (1985) Age and sex dependency of the biochemical indices of bone remodelling. Clinica Chimica Acta 151, 273283. S1ri:N JJ, Posiicn:i J, Prrsi J, P:covsi. V (1987) Bone loss and biochemical indices of bone remodeling in surgically induced postmenopausal women. Bone 8, 279284. Trrc:rbrN D, Proiix WR, M:r1iN BR, Zn:o J, McC:nr GP, L.ir RM et al. (1995) Peak bone mass in young women. Journal of Bone and Mineral Research 10, 711715. TnoxisoN DD (1980) Age changes in bone mineralisation, cortical thickness, and Haversian canal area. Calcied Tissue Inter- national 31, 511. 416 S. A. Feik, C. D. L. Thomas and J. G. Clement