Most often, when a man first has problems with lowered potency or with sexual dysfunction buy viagra australia shipping to pharmacies, paying purveyors, training personnel, or having a huge advertising budget.

Volume 16, Number 6, 2001
2001 American Society for Bone and Mineral Research

Structural Adaptation to Changing Skeletal Load in the Progression Toward Hip Fragility: The Study of Osteoporotic Fractures* THOMAS J. BECK,1 TAMMY L. ORESKOVIC,1 KATIE L. STONE,2 CHRISTOPHER B. RUFF,3 KRISTINE ENSRUD,4 MICHAEL C. NEVITT,2 HARRY K. GENANT,5 and STEVEN R. CUMMINGS2 Longitudinal, dual-energy X-ray absorptiometry (DXA) hip data from 4187 mostly white, elderly women from the Study
of Osteoporotic Fractures were studied with a structural analysis program. Cross-sectional geometry and bone mineral
density (BMD) were measured in narrow regions across the femoral neck and proximal shaft. We hypothesized that
altered skeletal load should stimulate adaptive increases or decreases in the section modulus (bending strength index) and
that dimensional details would provide insight into hip fragility. Weight change in the
3.5 years between scan time
points was used as the primary indicator of altered skeletal load. "Static" weight was defined as within 5% of baseline
weight, whereas "gain" and "loss" were those who gained or lost >5%, respectively. In addition, we used a frailty index
to better identify those subjects undergoing changing in skeletal loading. Subjects were classified as frail if unable to rise
from a chair five times without using arm support. Subjects who were both frail and lost weight (reduced loading) were
compared with those who were not frail and either maintained weight (unchanged loading) or gained weight (increased
loading). Sixty percent of subjects (n
2559) with unchanged loads lost BMD at the neck but not at the shaft, while
section moduli increased slightly at both regions. Subjects with increasing load (n
580) lost neck BMD but gained shaft
BMD; section moduli increased markedly at both locations. Those with declining skeletal loads (n
105) showed the
greatest loss of BMD at both neck and shaft; loss at the neck was caused by both increased loss of bone mass and greater
subperiosteal expansion; loss in shaft BMD decline was only caused by greater loss of bone mass. This group also showed
significant declines in section modulus at both sites. These results support the contention that mechanical homeostasis in
the hip is evident in section moduli but not in bone mass or density. The adaptive response to declining skeletal loads, with
greater rates of subperiosteal expansion and cortical thinning, may increase fragility beyond that expected from the
reduction in section modulus or bone mass alone. (J Bone Miner Res 2001;16:1108–1119)

Key words:
section modulus, dual-energy X-ray absorptiometry, adaptation to skeletal loading, subperios-
teal expansion, skeletal homeostasis, Wolff's law, Frost's mechanostat, structural geometry

These observations suggest that physical decline andmuscular weakness have a role in the etiology of bone COMMON OBSERVATIONS about persons with hip fracture fragility. Indeed, Wolff in 1869 postulated that bone are that they are physically inactive,(1,2) have low dynamically adapts throughout life to the mechanical body mass indices,(3) and often have lost weight.(2,4) demands placed on it by life's activities,(5) a concept nowcommonly known as Wolff's law. Because skeletal loads *Presented in part at the 21st annual meeting of the American Society for Bone and Mineral Research, St. Louis, MO, USA, 1999.
are dominated by muscle mechanical forces,(6) it is likely 1Department of Radiology, The Johns Hopkins University School of Medicine, Baltimore, Maryland, USA.
2Osteoporosis Research Group, Department of Medicine, University of California San Francisco, San Francisco, California, USA.
3Department of Cell Biology and Anatomy, The Johns Hopkins University School of Medicine, Baltimore, Maryland, USA.
4Center for Chronic Disease Outcomes Research, Minneapolis Veterans Administration Medical Center and Division of Epidemiology, University of Minneapolis, Minneapolis, Minnesota, USA.
5Department of Radiology, University of California San Francisco, San Francisco, California, USA.
that those forces in the elderly are diminished from levels MATERIALS AND METHODS
earlier in life, particularly in those who have become Study population physically frail.
Bone strength is influenced by the properties of the ma- The SOF is a large multicenter prospective study of terial (difficult to measure in vivo) as well as its structural nonblack postmenopausal women(9) coordinated by the distribution. For long bones, the structural distribution is University of California at San Francisco with participants described mathematically by the cross-sectional moment of recruited from four areas in the United States: Baltimore, inertia (CSMI). The CSMI quantifies the fact that the further MD; Minneapolis MN; Portland OR, and the Monongahela away mass is distributed from its central bending axis, the Valley of Pennsylvania. Subjects were enrolled at the age of greater its contribution to bending and torsional strength.
65 years or older with the baseline exam between Septem- Because the maximum stress in bending or torsion is on the ber 1986 and October 1988. At the second clinic visit to the outer (subperiosteal) surface, the structural component of centers, between January 1989 and December 1990, each strength is determined by the section modulus. The section subject received a scan of the left hip using a Hologic QDR1000 (Hologic, Inc. Waltham, MA, USA) DXA scanner.
modulus is CSMI/y, where y is the distance from the center Scans were repeated at the fourth clinic visit (August 1992– of mass to the subperiosteal surface. In a recent study, we July 1994), an average of 3.5 years later (range, 1.8 –5.2 measured bone mineral density (BMD), section modulus, and other geometric properties at the femoral neck and The osteogenic effect of skeletal loads is believed to be a proximal shaft of a large cross-sectional sample of the adult function of frequencies and magnitudes of applied U.S. population (Third National Health and Nutrition Ex- loads,(10,11) that is, a function of muscle strength and activ- amination Survey [NHANES III]).(7) In both genders, we ity level. Muscle strength was measured on SOF partici- saw a much smaller age-related decline in section modulus pants at both study time points but results were not useful than in BMD; moreover, the age-related decline in section for categorization (see Results and Discussion sections).
modulus diminished further when adjusted for body weight.
Muscle mass generally is correlated with physical perfor- These findings suggest that (1) the age-related decline in mance(12) and should be useful in assessing skeletal loading BMD may be mechanically compensated to minimize loss effects. Unfortunately, body composition was measured of bending strength and (2) this adaptation is modulated by only at the first time point. We therefore decided to use body weight. The apparent mechanism for the discrepancy weight change as the primary descriptor of altered skeletal between trends in BMD and section modulus is a small but loading, based on knowledge that muscle mass generally mechanically significant subperiosteal expansion of bone at scales with body mass. This decision is supported by earlier both femoral neck and shaft. This expansion helps to main- work showing that (1) the section modulus is related most tain the section modulus at a level appropriate for current strongly to body weight,(13,14) (2) weight loss is a risk factor skeletal loads. These observations suggest that in long for osteoporotic fracture,(2,15–20) and (3) weight gain might bones at least, this structural adaptation adjusts the bending confer a protective effect.(2,17) Therefore, we restricted anal- strength to the loading conditions. Perhaps bone fragility in yses to participants with BMD and measured weight at both the frail elderly results at least in part from relative disuse as time points and measured height for at least one time point.
the skeleton adapts to diminished mechanical loads.(8) A total of 4532 scan pairs met these criteria although a total The NHANES III data are from a cross-sectional sample of 345 pairs were excluded for technical reasons leaving and thus are not suitable for examination of the role of 4187 data pairs for analysis.
changing skeletal load on bone geometry. To explore thisissue, we applied the same structural analysis to hip dual- Exclusion criteria for data pairs energy X-ray absorptiometry (DXA) data from a large lon- In a longitudinal study, the DXA-based structural analy- gitudinal sample of predominantly white, elderly women sis is sensitive to inconsistent patient position (mainly be- from the Study of Osteoporotic Fractures (SOF).(9) In this cause of hip rotation) and to inconsistent region location on study we used hip DXA data acquired at two time points, the hip image. To minimize these effects, the analysis averaging 3.5 years apart. We expected that changes in program was modified so that a template of the proximal skeletal loading would result in adaptation in proximal femur from the baseline scan was saved with positions of all bending strength. To estimate changes in skeletal load we analysis regions. On subsequent scans the template was used weight change and a measure of frailty. Our specific retrieved and superimposed on the current hip image by the hypotheses were the following: user. If inconsistent hip positioning prevented templatealignment, data for that scan pair was rejected; a total of 186 Those with unchanged skeletal loads would maintain scan pairs were rejected in this manner. Further, we ex- bending strength, as estimated by static section moduli.
cluded data with unlikely extremes in differences in bone Those with reduced skeletal loads would experience a width between pairs because inconsistent region location or reduced bending strength, as estimated by a decline in patient position between scans tends to have the greatest section moduli.
effect on width dimensions. Extreme differences were de- Those with increased skeletal loads would require an fined as ⬎3 SD above and below the mean difference in increase in bending strength as estimated by an in- bone width at either the femoral neck or the shaft, corre- crease in section moduli.
sponding to ⫾5 mm and ⫾3 mm at the neck and shaft, BECK ET AL.
Location of narrow "cross-sectional" analysis regions across narrowest point on fem-oral neck and across the femoral shaft 2 cmdistal to the lesser trochanter. Typical mass pro-files, shown on left, are used to derive subperi-osteal widths, BMD, CSA, and section modulus.
Estimates of cortical thickness employ assump-tions of cross-sectional shape (see text).
respectively. These differences were considered biologi- as the profile integral divided by the effective density of cally unlikely over a 4-year span based on results of a bone mineral (␳ ⫽ 1.05).(23) After deriving the center of cross-sectional study of the U.S. population where mean mass of the profile, the CSMI was derived from the integral difference in femoral neck width between the third and of mass times the square of the distance from the center of eighth decade (over a 50-year span) in white women was 3 mass, divided by (␳ ). Conventional BMD was measured in mm.(7) A total of 159 data pairs were excluded for this the standard manner. Note that CSA represents the total area reason. The remaining data set included 4187 hip scan data of bone in the cross-section with soft tissue voids removed and is linearly related to the bone mineral content (BMC;total mineral mass) in the cross-section. Section modulus Analysis of structural parameters was computed as the ratio of CSMI to half the subperiostealwidth. Estimates of mean cortical thickness were derived The hip structure analysis (HSA) program has been de- using simple models of neck and shaft cross-sections as scribed previously.(7,21) In brief, the program measures hollow annuli. The neck region model further assumed that BMD and geometry within narrow regions corresponding to a fixed 60% of the neck mass was in the cortex, with the thin cross-sectional slabs of bone viewed on edge. Regions space within filled with the mass remainder as trabecular were located across the femoral neck at its narrowest point bone.(7) We include an estimate of the relative thickness of and across the shaft, 2 cm distal to the midpoint of the lesser the femoral neck cortex, expressed here as the buckling trochanter (Fig. 1). As in the previous study,(7) we concen- ratio,(24) and defined as the ratio of the subperiosteal radius trated on these mixed cortical/trabecular and purely cortical (width/2) to the mean cortical thickness.(24) The femoral sites, respectively. Since the NHANES analysis was con- neck region (Fig. 1) across its narrowest point is narrower (5 ducted in 1995, the program was altered to lengthen the mm vs. 15 mm) and located more proximally than the analysis regions from 3 to 5 mm along the bone axis to standard Hologic neck region; while BMD trends are com- improve precision (signal-to-noise ratio). Between-scan parable,(7) absolute values differ somewhat because of dif- measurement precision using the template methodology was ferences in region position and algorithmic details.
assessed with five repeated hip scans on 3 adult individualsas part of a separate project.(22) Subjects were repositioned Categorization of change in skeletal loading between scans taken with a Hologic QDR1000 DXA scan-ner. Averaged coefficients of variation for each measured Weight change was calculated as the difference in weight parameter are listed in Table 1. Measured precision ranged between exams 2 and 4 and expressed as percent change from 1% to 2.4% and was somewhat better in the femoral relative to weight at exam 2. Subjects were grouped into shaft than in the neck region, probably because the shaft's three categories by percent change in body weight. "Static" nearly circular cross-section is less influenced by variation weight was defined as within 5% of visit 2 weight; "gain" in femoral rotation.
and "loss" categories were those with weight changes For the two analysis regions, profiles of bone mass (Fig.
greater or less than 5%, respectively. Even in an elderly 1) were derived from one bone margin to the other and then population, weight change may not necessarily represent averaged along the 5-mm length of the region. Subperiosteal change in musculoskeletal load; hence, we used an available width was computed as the blur-corrected distance between measure of functional ability for further discrimination. The profile margins. Cross-sectional area (CSA) was computed ability of the subject to rise from a chair five times in STRUCTURAL ADAPTATION TO CHANGING SKELETAL LOAD
TABLE 1. SHORT-TERM PRECISION IN BMD AND SECTION PROPERTIES FROM FIVE SCAN REPETITIONS Relationships between bone properties and strength ON 3 ADULT SUBJECTS measurements, fat-free mass, and body weight The choice of body weight as the primary descriptor of Narrow neck skeletal loading effects was made after examination of univariate regressions of BMD and structural properties on body weight, fat-free mass (FFM), and the measurements of Subperiosteal width muscle strength recorded at visit 2. FFM was measured using bioelectric impedence at visit 2.(2) Coefficients of Estimated mean cortical thickness determination (R2) from these regressions are listed in Table2 for bone measurements at the neck and shaft regions. The Values are percent CVs averaged over the 3 subjects for analyses strongest relationships were between FFM and section mod- employing the image template.
ulus, explaining 30% and 46% of variability in the neck andshaft, respectively. Relationships between FFM and CSAwere nearly as strong at both sites whereas those with BMD succession without using arm support has been shown pre- and estimated cortical thickness were weaker. Correlations viously to be an independent predictor of osteoporotic frac- between FFM and subperiosteal width were significant (p ⬍ ture.(2) This functional parameter was used here to separate 0.0001) but relatively poor. The strong relationship between those with declining physical abilities from those with static FFM and bone geometry suggests its use in the investigation or increasing weight, that is, to reduce ambiguity in classi- of skeletal loading effects, but FFM was not measured at fications of unchanged and increased skeletal loading. By visit 4. Although relationships between bone measurements including only frail individuals in the weight losers group, and muscle strength measurements were significant (Table we sought to identify a test group of those with clearly 2), they were much weaker than with FFM or body weight.
diminished musculoskeletal loading. For the indicator of Because correlations between bone geometry and weight frailty we used whether or not the subject was able or were nearly as strong as with FFM, weight was chosen as willing to rise from a chair five times in succession without the primary skeletal loading descriptor.
supporting themselves with their arms.(2) This variable wasmeasured at visit 4 and was used here to exclude those withreductions in neuromuscular function from the static and Physical condition and general characteristics increasing weight groups to ensure that these groups repre-sented individuals with unchanged and increasing musculo- Table 3 lists means and SDs for general characteristics of skeletal loading, respectively. The frailty indicator was then the study sample as well as characteristics of the different used to isolate those individuals with reduced weight who skeletal loading comparison groups at visits 2 and 4. All had become frail and thus could be reasonably characterized strength measurements and walk speeds in the subgroups as having undergone reduced musculoskeletal loading. To were adjusted for knee height, weight, and age.
further characterize the physical condition of these loading On average, these elderly women lost 0.3 kg of weight categories, we also used other measures of physical strength and 1 cm of height between the two examinations. At visit and performance recorded at visits 2 and 4. Details of these 4 about 50% of subjects overall walked for exercise and 9% measurements have been described previously(2) and in- were classified as frail (i.e., unable to rise from a chair five clude abductor, quadriceps and grip strengths, normal and times without using their arms). Two-thirds of these women fast walking speeds, and whether or not subjects walked for maintained their body weight within 5% of the visit 2 exercise. Because strength measures and walking speeds are baseline, while weight declined in 18% and increased in body size and age dependent, subgroup means were ad- 15%. The proportion of women in the frail category was justed for age and body size (knee height and weight).
largest among weight losers (13.7%), intermediate amonggainers (9.8%), and least among those with static weight (7.9%). Those in the frail category were 2.7 years older andbased on knee and standing heights, were slightly taller on Results were imported into Statview version 5.0 (SAS average. The frail subgroup overall had weaker abductor Institute, Inc., Carey, NC, USA) for statistical analysis. The strength at visit 2 and weaker grip and quadriceps strengths significance of differences in BMD and structural variables at both visits; both normal and fast walking speeds were between visits 2 and 4 was assessed with a paired t-test.
significantly slower than in the nonfrail subjects at visit 4 Changes in these variables were then expressed as percent (p ⬍ 0.0001). Less than one-half as many frail subjects change per year relative to the baseline (visit 2) value and indicated that they walked for exercise (23%) compared adjusted for age. Differences in BMD, geometry, and other with nonfrail subjects (53%).
variables between weight change and frailty categories were With regard to physical performance differences among analyzed by two-way analysis of variance (ANOVA) to test weight change categories, independent of frailty category, the independent effects of frailty and weight change. Un- weight losers had lower grip and quadriceps strengths at paired t-tests were used to delineate differences between both time points and slower walk speeds than other weight change groups (p ⬍ 0.0001). At visit 4 but not visit 2, BECK ET AL.
TABLE 2. R2 VALUES FROM UNIVARIATE REGRESSIONS OF BMD AND GEOMETRIC PARAMETERS AT THE NECK AND SHAFT REGION ON FFM, BODY WEIGHT, AND MEASURED STRENGTHS FROM THE SOF Mean cortical Narrow neck region Abductor strength Abductor strength All measurements were acquired at visit 2. Except as noted, all regressions were significant at the p ⬍ 0.0001 level.
*p ⬍ 0.05.
weight gainers had lower grip strengths (p ⫽ 0.05) than reach significance in the femoral neck (p ⫽ 0.09). Among those with static weight but their lower quadriceps strength frail weight losers, the section modulus declined more rap- did not reach statistical significance (p ⫽ 0.06). Neither idly in the purely cortical shaft than in the neck. Underlying walk speeds were significantly slower in weight gainers these adaptive changes in section modulus are mass and compared with those with static weight.
dimensional changes that differ in pattern between themixed cortical/trabecular neck and the purely cortical shaft.
BMD and cross-sectional geometry CSA declined at the neck and shaft in those who lost weightwhereas women with static weight had decreased CSA only The average percent changes per year in BMD and cross- at the neck. Those who gained weight maintained CSA at sectional geometry are displayed in Table 4 for the total the neck and increased CSA at the shaft. Some subperiosteal population and the weight change subgroups. The differ- expansion appears to be nearly universal in this elderly ences between time points in the total population were cohort, but the degree of expansion is both greater in mag- significant by paired t-test and on average, changes were nitude and more variable between groups in the femoral relatively greater at the femoral neck than at the shaft. BMD neck than in the shaft. Shaft subperiosteal width increased declined in both regions but more rapidly at the neck. In overall in the population, but rates of change were not addition, CSA declined and subperiosteal width increased.
detectably influenced by weight change or frailty category.
Despite the decline in CSA at both sites, section modulus In contrast, femoral neck subperiosteal expansion was in- increased by approximately 0.2%/year at both neck and fluenced by both weight change and frailty. Both weight shaft. The estimated mean cortical thicknesses declined at losers and gainers showed increased rates of femoral neck both sites and buckling ratio of the femoral neck increased expansion compared with the static weight group, and this by 1.2%/year.
effect was enhanced considerably by the presence of frailty.
After changes in BMD and geometry were age-adjusted Among weight losers, the decline in femoral neck BMD was and divided into weight change and frailty subgroups, dif- associated with decreased CSA and subperiosteal expansion ferences between groups are evident. Significance levels for whereas the decline in shaft BMD was associated with the independent effects of weight change and frailty cate- decreased CSA only. When subperiosteal expansion is ac- gories from the two-way ANOVA are listed in the last two companied by increased CSA, as in the shafts of weight columns of Table 4. Weight change has a highly significant gainers, the change in CSA exceeds that of BMD, indicating effect on all parameters except shaft subperiosteal width.
that BMD underestimated the gain in bone. The changes The independent effects of the frailty category are signifi- among frail weight losers, who show increased rates of both cant in the femoral neck for all parameters except CSA and femoral neck bone loss and subperiosteal expansion, lead to section modulus and in the shaft for all parameters except a wider, thinner-walled neck. These combined effects pro- duce a 3%/year change in the neck cortical buckling ratio At both neck and shaft regions, section moduli show significant declines among weight losers, improvementsamong weight gainers, and small positive changes amongthose with static weight. Overall, frailty had a negative influence on weight change effects on section moduli, re-ducing or eliminating positive changes and exacerbating The methods used in this longitudinal study permit us to negative changes, although the influence of frailty did not investigate simultaneously conventional BMD as well as STRUCTURAL ADAPTATION TO CHANGING SKELETAL LOAD
⫾ ⫾ ⫾ ⫾ ⫾ ⫾ ⫾ ⫾ ⫾ ⫾ ⫾ ⫾ ⫾ ⫾ ⫾ ⫾ ⴞ ⴞ ⴞ ⴞ ⴞ ⴞ ⴞ ⴞ ⴞ ⴞ ⴞ ⴞ ⴞ ⴞ ⴞ ⴞ ⫾ ⫾ ⫾ ⫾ ⫾ ⫾ ⫾ ⫾ ⫾ ⫾ ⫾ ⫾ ⫾ ⫾ ⫾ ⫾ ⴞ ⴞ ⴞ ⴞ ⴞ ⴞ ⴞ ⴞ ⴞ ⴞ ⴞ ⴞ ⴞ ⴞ ⴞ ⴞ ⴞ ⴞ ⴞ ⴞ ⴞ ⴞ ⴞ ⴞ ⴞ ⴞ ⴞ ⴞ ⴞ ⴞ ⴞ ⴞ ⫾ ⫾ ⫾ ⫾ ⫾ ⫾ ⫾ ⫾ ⫾ ⫾ ⫾ ⫾ ⫾ ⫾ ⫾ ⫾ ⫾ ⫾ ⫾ ⫾ ⫾ ⫾ ⫾ ⫾ ⫾ ⫾ ⫾ ⫾ ⫾ ⫾ ⫾ ⫾ BECK ET AL.
Pictorial representation (not to scale) of geometric and mass changes observed in the main skeletal loading comparison groups at the neck and shaft regions. Unchanged and increased loading groups are those with unchanged or increasing weight between study visits, afterexcluding those categorized as frail. The loading decrease group includes only frail weight losers (see text). Corresponding rates of change peryear in these parameters are summarized below the representation.
engineering properties dependent on the shape and size of subperiosteal surface. At any given bending or torsional the bone cross-section. In this article we are concerned load, peak stress magnitudes are related inversely to the primarily with how hip bone mass and structural geometry section modulus. To maintain long bone strength over time, adapt to changes in skeletal loading over time and whether adaptation should ensure that maximum stresses do not that adaptation provides insight into the onset of hip fragil- exceed certain levels, thus should be evident in the section ity. Although weight change effects alone were highly sig- modulus. Indeed, despite declines in BMD, those with con- nificant, the clearest picture is seen by looking at the three stant skeletal loads (Fig. 2) not only maintained section subgroups in which loading changes are least ambiguous, moduli at the neck and shaft but also showed slight in- that is, those with static or increasing weight who did not creases. Among those with increasing skeletal loads, we become frail, and those who lost weight and were classified observed greater increases in section moduli, consistent as frail. These groups best represented subjects with un- with their increased skeletal loads. Most importantly, for changed, increasing, and decreasing skeletal loads, respec- implications in hip fragility, those with decreasing skeletal tively. The observed changes for these subgroups are shown load showed significant reductions in section moduli. A pictorially in Fig. 2, for the neck and shaft regions, with the generalized implication of these results is that section mod- corresponding annual changes in BMD and geometry listed uli represent an endpoint in mechanical homeostasis in long below the representation. The results are consistent with our bones. That is, as aging progresses, bone modeling and hypotheses; changes in hip loading are associated with remodeling processes adjust the geometry to increase or mechanically appropriate alteration in the section modulus, decrease the section modulus as demands of skeletal loading an index of bending and torsional strength. However, the change. However, because in aging long bones the bending details of how that adaptation is achieved differ in important strength represented by a given amount of mass or density ways between the purely cortical shaft and the mixed changes as the bone expands, one should not expect ho- cortical/trabecular neck. These differences help to explain meostasis in BMD or BMC. That mass or density should not why BMD changes as it does with age and why reduced necessarily be conserved differs from the concept of me- loading might be more likely to cause fragility in the fem- chanical homeostasis described by Kimmel,(26) but the end oral neck than in the shaft.
result is theoretically consistent.(26) Why section modulus and not BMD? It is not surprising that adaptation to changing load should be evident in the section modulus. Normal physical activi- The underlying mechanism for skeletal adaptation was ties load long bones mainly in bending and torsion,(6,25) articulated in Frost's mechanostat theory.(8) Although the modes that produce mechanical stresses that peak on the precise details of the process are incompletely understood, BECK ET AL.
bone tissue is believed to respond to daily variations in the panied by net bone loss and cortical thinning. Reduction in microscopic distortions (strains) caused by loading forces.
femoral neck BMD in this case was caused by both bone The mechanostat operates to maintain skeletal strains be- loss and subperiosteal expansion.
tween certain optimal limits. When average skeletal strains When skeletal loads were altered, differences in adapta- fall consistently below the lower limit, bone remodeling tion response between the neck and shaft were even more rates increase so that net loss continues until average strains remarkable. With increased loads, the amount of bone re- increase back into the optimal range. Strains exceeding the mained the same at the femoral neck and increased at the upper limit cause bone formation (modeling); bone is added shaft. However, because of subperiosteal expansion, BMD until strains are reduced to the optimal range. In a long bone changed at both sites, decreasing at the neck and increasing under bending and torsional load, strains are lowest on in the shaft. The effects of decreasing loads may be partic- internal surfaces near the center of mass and increase radi- ularly important in helping to explain the relatively greater ally outward through the cross-section peaking on the sub- femoral neck fragility in the frail elderly. In the shaft, periosteal surface. Remodeling occurs mainly on the en- reduced loading mainly increased endosteal bone loss with dosteal and trabecular surfaces(27) where bending and no accompanying subperiosteal expansion. This contrasts torsional strains are smallest; modeling occurs mainly on with the femoral neck, where declining skeletal loads ap- the subperiosteal surface where those strains are highest.
parently accelerate both endosteal bone loss and subperios- Increased loading should therefore stimulate modeling in teal bone formation. This latter observation implies that in the form of subperiosteal expansion and/or down-regulate the elderly femoral neck, stimulatory subperiosteal strains turnover on endocortical and trabecular surfaces. Dimin- are actually increased under reduced skeletal loads. This ished loading should reduce strains on internal endosteal apparent paradox may be ultimately consistent with the and trabecular surfaces, up-regulating remodeling rates. Su- mechanostat and is important in explaining why bone loss is perimposed on this adaptation to changing loading condi- more likely to cause fragility at the neck than at the shaft. In tions are the effects of normal remodeling on endocortical the femoral neck, reduced loading should stimulate accel- and trabecular surfaces.
erated resorption on both endocortical and trabecular sur- Van der Meulen and colleagues(28,29) provided a theoret- faces. An important function of femoral neck trabeculae is ical model of a long bone that illustrates response to remod- to brace the thin cortical shell from within, but as trabeculae eling turnover during normal aging as well as to altered thin and lose connectivity, it is likely that this internal skeletal loading. Predictions of this theoretical model gen- cortical support is compromised. Loss of trabecular support erally are consistent with the overall patterns of geometric may in turn cause increased subperiosteal strains and sub- change we observed in this study. The loss phase of normal periosteal bone apposition, even under diminished loads.
bone turnover causes a temporary reduction of (endocorti- There are alternative explanations to these observed cal) bone mass; continued mechanical loading causes skel- changes in the femoral neck; much work remains to be done etal strains to increase, not at the site of loss, but on the to model these processes to determine if they are theoreti- subperiosteal surface. With constant loading levels through cally viable.
adulthood, the model predicted gradual increases in en-docortical diameter as bone is lost and a competing increase Toward femoral neck fragility in subperiosteal diameter as bone is added.(30) This patterncaused a slight upward trend in the section modulus with As skeletal loading demands diminish in the elderly, the age consistent with our observations in those with un- mechanostat calls for a reduction in the section modulus.
changed skeletal loading (Fig. 2). Although not discussed Theoretically, this adaptation in a tubular bone could occur by these authors,(28–30) the aforementioned changes produce by either contraction of the outer diameter or expansion of a downward trend in BMD that we observed in this study.
the inner diameter. However, as far as we know, the former Because the bending strength contribution of bone mass process requiring subperiosteal resorption does not accom- varies as the square of its distance from the center of mass pany normal aging.(31) The unidirectional expansion of long of the cross-section, less subperiosteal gain is needed to bones through adult life leaves the elderly with larger di- compensate for a given endosteal loss. Strength is main- ameter, but thinner-walled bones. A small loss of bone mass tained or increased in the presence of net loss of bone mass may lead to a greater increment in bone fragility than in a (and density) because the bone gets bigger in diameter.
younger, narrower, and thicker-walled bone. We furthersuspect that the way that the femoral neck adapts to reduced Differences in adaptation between neck and shaft loading, for example, by causing a wider, thinner-walledbone, may generate a dimensionally unstable condition and There were differences in the details of section modulus may be responsible for its relatively greater fragility in the adaptation between the neck and shaft (Fig. 2). Unchanged elderly. When thick-walled tubes are bent to failure, they loading produced comparable increases in neck and shaft crack from the outer curvature of bending (e.g., break a section moduli. But in the purely cortical shaft, this was pencil in your hands). However, when tubes with thin walls accomplished by a slight increase in subperiosteal width; relative to their diameters are subjected to bending, they changes in the amount of bone (CSA), cortical thickness, or tend to fail by local buckling (crumpling inward on the inner in BMD were nonsignificant. In the femoral neck, the sec- curvature like a bent soda straw). The importance of this tion modulus was adjusted by expanding subperiosteal distinction is that failure of the thick-walled tube is pre- width at twice the rate of that in the shaft. This was accom- dicted by the section modulus. However, in the thin-walled STRUCTURAL ADAPTATION TO CHANGING SKELETAL LOAD
tube, the section modulus would overestimate the load re- Limitations of this work quired to cause failure by local buckling. Whether local There are reports that show that change in body compo- buckling is at all likely in a femoral neck internally sup- sition may cause systematic error in DXA-measured param- ported by trabecular bone is the subject of a separate theo- eters with Hologic scanners.(46–48) Our algorithms differ retical investigation. However, it is worth noting that the somewhat from those of Hologic, particularly in bone mar- buckling ratio changed at a greater rate than any other gin definition. We have yet to analyze systematically these parameter in the SOF population overall and increased error sources with our methods, but the error observed by fastest among those with decreased loads.
Tothill(47) of an increase in bone area with increasing BMCshould cause an equivalent increase in subperiosteal widthwith CSA in our methods. A univariate regression of sub- periosteal width on CSA yielded a positive correlation witha slope of 0.11 although the regression explained only 2.4% For many years it has been believed that because the (R2) of the variability in bone width. After correcting these femoral neck lacks a true periosteum, it should not be parameters for age and body size the slope was reduced to subject to expansion in adulthood.(32) There has been ample 0.048 and R2 was reduced to 0.3%, suggesting little effect evidence, mostly cross-sectional, that femoral shaft diame- other than that caused by body (bone) size. The multiple ters increase with age.(7,33–39) Some evidence shows expan- linear regression of femoral neck section modulus on FFM sion of the femoral neck,(7,36,40,41) though this is mostly and fat mass was significant (p ⬍ 0.0001) for both param- based on low-resolution imaging methods. A noteworthy eters with positive ␤-coefficients of 0.025 for FFM and exception is the article by Heaney and colleagues who used 0.002 for fat mass. The addition of fat mass to the model serial radiographs on 170 middle-aged white women to only improved the R2 from 0.297 to 0.300, suggesting that show average subperiosteal expansions of 0.14%/year and the additive influence of body composition on femoral neck 0.23%/year at the femoral neck and shaft, respectively.(42) section modulus is small.
In this article subperiosteal expansion averaged 0.28%/year There also are methodological limitations to use of two- at the neck and 0.09%/year in the shaft in a much larger but dimensional DXA data to measure bone geometry; no com- considerably older postmenopausal cohort. This is double mercial DXA scanner was designed with this purpose in the rate of expansion observed by Heaney in the neck and mind. Clearly, there are problems in the measurement of one-half the rate he observed in the shaft. Perhaps rates of subtle dimensional changes on three-dimensional bones femoral neck subperiosteal expansion increase in the el- from relatively poor quality DXA images. The assumption derly. Our data do show a weak but significant increase in used to estimate cortical thickness in the femoral neck, that the rates of subperiosteal expansion at the neck with age 60% of the mass is in the cortex, is obviously an approxi- (R ⫽ 0.05; p ⫽ 0.002), not apparent in the shaft. Results mation. There is evidence of disproportionate loss of neck from the cross-sectional NHANES study(7) suggest that this cortical bone in hip fracture cases; hence, our neck cortical might be true in women but this should be verified in dimensions may be overestimated.(49,50) It is critical that longitudinal data including younger individuals.
these dimensional observations be corroborated by othersusing higher-resolution imaging methods in longitudinalstudy.
Body weight and skeletal load In this longitudinal study on the effects of changing skeletal load on hip BMD and geometry in elderly women, Although it is believed that muscle force dominates skel- the hip appears to adapt by adjusting the section modulus, etal adaptation,(6,43) the observable changes in skeletal dy- an engineering index of bending strength, to the new load- namics occur over long timescales presumably from the ing conditions. This suggests that mechanical homeostasis cumulative influence of daily strains generated from normal is achieved with respect to bending strength. A feature of activities. In this article we have looked at weight change as the adaptation is subperiosteal expansion at both the neck the primary index of changing skeletal load but weight per and the shaft. One consequence of subperiosteal expansion se cannot represent a mechanical stimulus because bone is is that it will reduce BMD; any observed change in BMD in not known to respond to static loads.(44,45) Certainly the a long bone may or may not reflect bone loss. The adapta- effect of weight change is in the magnitudes of the dynamic tion to reduced loading conditions results in reduction in the muscle loads on the skeleton required to move the body in section modulus. But in the femoral neck, adaptation accel- normal activities. The stimulatory influence of the resulting erated both rates of cortical thinning and subperiosteal ex- dynamic strains is also a function of strain frequency, for pansion, resulting in a broader but thinner-walled (low- example, the activity level of the individual—not captured density) femoral neck. This condition may be dimensionally by weight change. Because changes in activity level appear unstable, causing a greater increase in fragility than appar- more quickly in muscle, an examination of the effects of ent in the reduced section modulus.
changes in muscle mass by DXA or bioelectric impedencemay provide a more accurate assessment of the effects of changing skeletal load on bone. The relatively strong cor-relation between FFM and section modulus (Table 2) sug- The authors are grateful to Mr. Maurice Dockrell for the gests that this might be the case.
tedious work of extracting thousands of DXA scans from BECK ET AL.
the data archive; Ms. Gabrielle Milani for assistance in 18. Huang Z, Himes JH, McGovern PG 1996 Nutrition and sub- statistical analysis and data management; and Ms. Renee sequent hip fracture risk among a national cohort of white Arcement, Mr. Santosh Chelliah, Ms. Maria Brennan, and women. Am J Epidemiol 144:124 –134.
Mr. Marius Pruessner for their many hours of DXA scan 19. Meyer HE, Tverdal A, Falch JA 1993 Risk factors for hip fracture in middle-aged Norwegian women and men. Am J analysis. This work was supported by a research grant (R01 AR44655) from the National Institute of Musculoskeletal 20. Meyer HE, Henriksen C, Falch JA, Pedersen JI, Tverdal A and Skin Diseases, National Institutes of Health (NIH).
1995 Risk factors for hip fracture in a high incidence area: A
case-control study from Oslo, Norway. Osteoporos Int 5:239 –
21. Beck TJ, Ruff CB, Warden KE, Scott WW, Rao GU 1990 Predicting femoral neck strength from bone mineral data: A
structural approach. Invest Radiol 25:6 –18.
1. Johnell O, Gullberg B, Kanis JA, Allander E, Elffors L, 22. Nelson D, Barondess D, Hendrix S, Beck T 2000 Cross- Dequeker J, Dilsen G, Gennari C, Lopes Vaz A, Lyritis G 1995 sectional geometry, bone strength and bone mass in the prox- Risk factors for hip fracture in European women: The MEDOS imal femur in African-American and white postmenopausal Study. Mediterranean Osteoporosis Study. J Bone Miner Res women. J Bone Miner Res 15:1992–1997.
23. Martin R, Burr D 1984 Non-invasive measurement of long 2. Cummings SR, Nevitt MC, Browner WS, Stone K, Fox KM, bone cross-sectional moment of inertia by photon absorptiom- Ensrud KE, Cauley J, Black D, Vogt TM 1995 Risk factors for etry. J Biomech 17:195–201.
hip fracture in white women. Study of Osteoporotic Fractures 24. Roark R, Young W 1989 Formulas For Stress and Strain, 6th Research Group. N Engl J Med 332:767–773.
ed. McGraw-Hill, New York, NY, USA, p. 688.
3. Joakimsen RM, Fonnebo V, Magnus JH, Tollan A, Sogaard AJ 25. Duda GN, Heller M, Albinger J, Schulz O, Schneider E, Claes 1998 The Tromso Study: Body height, body mass index and L 1998 Influence of muscle forces on femoral strain distribu- fractures. Osteoporos Int 8:436 – 442.
tion. J Biomech 31:841– 846.
4. Meyer HE, Tverdal A, Selmer R 1998 Weight variability, 26. Kimmel DB 1993 A paradigm for skeletal strength homeosta- weight change and the incidence of hip fracture: A prospective sis. J Bone Miner Res 8(Suppl 2):S515–S522.
study of 39,000 middle-aged Norwegians. Osteoporos Int 27. Frost HM 1992 The role of changes in mechanical usage set points in the pathogenesis of osteoporosis. J Bone Miner Res 5. Wolff J 1869 The Law of Bone Remodeling. Springer Verlag, 28. van der Meulen MC, Beaupre GS, Carter DR 1993 Mechano- 6. Burr DR 1997 Muscle strength, bone mass, and age-related biologic influences in long bone cross-sectional growth. Bone bone loss. J Bone Miner Res 12:1547–1551.
7. Beck T, Looker A, Ruff C, Sievanen H, Wahner H 2000 29. Beaupre G 1990 An approach for time-dependent modeling Structural trends in the aging femoral neck and proximal shaft: and remodeling—theoretical development. J Orthop Res Analysis of NHANES III DXA data. J Bone Miner Res 15:
30. Carter DR, Van Der Meulen MC, Beaupre GS 1996 Mechan- 8. Frost H 1987 The mechanostat: A proposed pathogenic mech- ical factors in bone growth and development. Bone 18(Suppl
anism of osteoporoses and the bone mass effects of mechanical and nonmechanical agents. Bone Miner 2:73– 85.
31. Dequeker J 1976 Quantitative radiology: Radiogrammetry of 9. Cummings SR, Black DM, Nevitt MC, Browner WS, Cauley cortical bone. Br J Radiol 49:912–920.
JA, Genant HK, Mascioli SR, Scott JC, Seeley DG, Steiger P 32. Einhorn T 1996 The bone organ system: form and function. In: 1990 Appendicular bone density and age predict hip fracture in Marcus R, Feldman D, Kelsey J (eds.) Osteoporosis. Aca- women. The Study of Osteoporotic Fractures Research Group.
demic Press, pp. 3–22.
JAMA 263:665– 668.
10. Rubin CT, Lanyon LE 1984 Regulation of bone formation by 33. Martin R, Atkinson P 1977 Age and sex related changes in the applied dynamic loads. J Bone Joint Surg Am 66:397– 402.
structure and strength of the human femoral shaft. J Biomech 11. Lanyon LE 1984 Functional strain as a determinant for bone remodeling. Calcif Tissue Int 36(Suppl 1):S56 –S61.
34. Ruff C, Hayes W 1982 Subperiosteal expansion and cortical 12. Zamboni M, Turcato E, Santana H, Maggi S, Harris TB, remodeling of the human femur and tibia with aging. Science Pietrobelli A, Heymsfield SB, Micciolo R, Bosello O 1999 The relationship between body composition and physical perfor- 35. Smith R, Walker R 1964 Femoral expansion in aging women: mance in older women. J Am Geriatr Soc 47:1403–1408.
Implications for osteoporosis and fractures. Science 145:156 –
13. van der Meulen MC, Carter DR 1995 Developmental mechan- ics determine long bone allometry. J Theor Biol 172:323–327.
36. Sievanen H, Uusi-Rasi K, Heinonen A, Oja P, Vuori I 1999 14. Selker F, Carter DR 1989 Scaling of long bone fracture Disproportionate, age-related bone loss in long bone ends: A strength with animal mass. J Biomech 22:1175–1183.
structural analysis based on dual energy x-ray absorptiometry.
15. Ensrud KE, Palermo L, Black DM, Cauley J, Jergas M, Orwoll Osteoporos Int 10:295–302.
ES, Nevitt MC, Fox KM, Cummings SR 1995 Hip and calca- 37. Ruff CB, Hayes WC 1988 Sex differences in age related neal bone loss increase with advancing age: Longitudinal remodeling of the femur and tibia. J Orthop Res 6:886 – 896.
results from the study of osteoporotic fractures. J Bone Miner 38. Stein M, Thomas C, Feik S, Wark J, Clement J 1998 Bone size Res 10:1778 –1787.
and mechanics at the femoral diaphysis across age and sex.
16. Farmer ME, Harris T, Madans JH, Wallace RB, Cornoni- J Biomech 31:1101–1110.
Huntley J, White LR 1989 Anthropometric indicators and hip 39. Feik SA, Thomas CD, Bruns R, Clement JG 2000 Regional fracture. The NHANES I epidemiologic follow-up study. J Am variations in cortical modeling in the femoral mid-shaft: Sex Geriatr Soc 37:9 –16.
and age differences. Am J Phys Anthropol 112:191–205.
17. Gunnes M, Lehmann EH, Mellstrom D, Johnell O 1996 The 40. Beck TJ, Ruff CB, Bissessur K 1993 Age-related changes in relationship between anthropometric measurements and frac- female femoral neck geometry: Implications for bone strength.
tures in women. Bone 19:407– 413.
Calcif Tissue Int 53(Suppl 1):S41–S46.
41. Beck TJ, Ruff CB, Scott WW, Plato CC, Tobin JD, Quan CA of total-body bone mineral during weight change using Lunar, 1992 Sex differences in geometry of the femoral neck with Hologic and Norland instruments. Br J Radiol 72:661– 669.
aging: A structural analysis of bone mineral data. Calcif Tissue 49. Crabtree N, Loveridge N, Parker M, Rushton N, Power J, Beck Int 50:24 –29.
T, Reeve J 2001 Intracapsular hip fracture and the region 42. Heaney RP, Barger-Lux MJ, Davies KM, Ryan RA, Johnson specific loss of cortical bone: Analysis by peripheral quanti- ML, Gong G 1997 Bone dimensional change with age: Inter- tative computed tomography (pQCT) J Bone Miner Res (in actions of genetic, hormonal, and body size variables. Osteo- poros Int 7:426 – 431.
50. Bell KL, Loveridge N, Power J, Garrahan N, Stanton M, Lunt 43. Frost HM 1997 On our age-related bone loss: Insights from a M, Meggitt BF, Reeve J 1999 Structure of the femoral neck in new paradigm. J Bone Miner Res 12:1539 –1546.
hip fracture: Cortical bone loss in the inferoanterior to supero- 44. Lanyon LE, Rubin CT 1984 Static vs dynamic loads as an posterior axis. J Bone Miner Res 14:111–119.
influence on bone remodelling. J Biomech 17:897–905.
45. Forwood MR, Turner CH 1995 Skeletal adaptations to me- chanical usage: Results from tibial loading studies in rats.
Address reprint requests to: Bone 17(Suppl 4):197S–205S.
46. Patel R, Blake GM, Herd RJ, Fogelman I 1997 The effect of Thomas J. Beck, Sc.D. weight change on DXA scans in a 2-year trial of etidronate The Johns Hopkins Outpatient Center therapy. Calcif Tissue Int 61:393–399.
601 North Caroline Street 47. Tothill P, Hannan WJ, Cowen S, Freeman CP 1997 Anomalies Baltimore, MD 21287-0849, USA in the measurement of changes in total-body bone mineral by
dual-energy X-ray absorptiometry during weight change.
J Bone Miner Res 12:1908 –1921.
48. Tothill P, Laskey MA, Orphanidou CI, van Wijk M 1999 Received in original form September 21, 2000; in revised form Anomalies in dual energy X-ray absorptiometry measurements December 22, 2000; accepted January 11, 2001.


Evaluación intraoperatoria de la distensibilidad de la unión gastroesofágica en fundoplicatura Raul Aponte,1 Alberto Cardozo,2 Leonardo Rejon,2 Marjori Echenique,3 María Gabriela Cardozo,3 Johanan Davila,3 Maiveline Guardia4 1Neuro gastroenterólogo Director Médico Clínica Gastro Bariátrica, Maracay, Venezuela. 2Cirujano Bariátrico, Lap-

Microsoft word - dsd352.docx

Dear CM/PLM Professional, Please find enclosed DSD's newsletter, addressing news in CM, PLM, ERP and Process Improvements that we thought might interest you. We would appreciate receiving comments and suggestions to make this newsletter more helpful and interesting. We encourage you to send us news you hear that might be of interest to others of the CM community. Subscription to this newsletter is free-of-charge. To subscribe to our mailing list please send us an e-mail with SUBSCRIBE in the subject. If you do not want to receive further issues please send us an e-mail with REMOVE in the subject. CAD AND DESIGN TOOLS 1. ANSYS Reports First Quarter 2016 Financial Results ANSYS, Inc. today announced its financial results for the first quarter of 2016. The Company reported GAAP and non-GAAP revenue growth in constant currency of 6% and 5%, respectively, and GAAP and non-GAAP diluted earnings per share of $0.63 and $0.77, respectively, for the quarter. Recurring revenue, which is comprised of lease license and maintenance revenue, totaled 78% of revenue for the first quarter . 2. Gerber Technology's Digital Solution Links Data, Smart Machines to Drive Mass Production and Mass Customization Gerber Technology is showcasing its Digital Solution at the Texprocess Americas show in Atlanta. Apparel and industrial companies are under significant competitive pressures to design, develop and produce their products faster and more efficiently while ensuring they get the right products to market at the right time and at the right price. Whether producing volume for the masses or customizing small lots, companies are struggling because of an inability to move data from process to process and machine to machine. At Texprocess, Gerber will demonstrate each step of its Digital Solution to illustrate how companies can network their software and smart machines to form an end-to-end solution to help meet the workflow challenges of mass production and mass customization. 3. FARO Reports First Quarter 2016 Financial Results FARO Technologies, Inc. (FARO) today announced its financial results for the first quarter ended March 31, 2016. Sales for the quarter ended March 31, 2016 were $75.7 million, up 8.3% compared with $69.9 million in the first quarter last year. Excluding approximately $0.9 million of unfavorable foreign exchange impacts, first quarter sales would have increased approximately 10% as compared with the first quarter of 2015. The Company's sales growth was driven primarily by higher metrology sales within the Americas and Asia-Pacific regions. Gross margin for the quarter was 56.3% compared with 56.6% in the prior year period with product and service margins remaining relatively consistent with the prior year period. Operating income for the quarter was $4.3 million compared with $1.9 million in the prior year period, reflecting increased sales volume partially offset by a modest increase in operating expenses. 4. Cadence Expands OrCAD Solution to Address Flex and Rigid-Flex Design Challenges for IoT, Wearables and Mobile Devices Today at CDNLive EMEA, Cadence Design Systems, Inc. announced the OrCAD 17.2-2016 release with new capabilities for OrCAD® Capture, PSpice® Designer and PCB Designer that address challenges with flex and rigid-flex design as well as mixed-signal simulation complexities