Measurements Of Bone Geometry Research Articles

Familial resemblance in trabecular and cortical volumetric bone mineral density and bone microarchitecture as measured by HRpQCT.

To estimate the heritability of bone geometry, volumetric bone mineral density (vBMD) and microarchitecture of trabecular (Tb) and cortical (Ct) bone measured by high resolution peripheral quantitative computerised tomography (HRpQCT) at the distal radius and tibia and to investigate the genetic correlations of these measures. Participants were 177 mother-offspring pairs from 162 families (mothers, mean age (SD) = 52.1 (4.7) years; offspring, 25.6 (0.73) years). Trabecular and cortical bone measures were obtained by HRpQCT. Multivariable linear regression was used to analyse the association of bone measures between mother and offspring. Sequential Oligogenic Linkage Analysis Routines (SOLAR) software was utilised to conduct quantitative genetic analyses. All maternal bone measures were independently associated with the corresponding bone measures in the offspring before and after adjustment for age, sex, weight and height. Heritability estimates ranged from 24% to 67% at the radius and from 42% to 74% at the tibia. The relationship for most bone geometry measures was significantly stronger in mother-son pairs (n = 107) compared with mother-daughter pairs (n = 70) (p < 0.05). In contrast, the heritability for most vBMD and microarchitecture measures were higher in mother-daughter pairs. Bivariate analyses found moderate to strong genetic correlations across all measures between radius and tibia (Rg = 0.49 to 0.93). Genetic factors have an important role in the development of bone geometry, vBMD and microarchitecture. These factors are strongly shared for the radius and tibia but vary by sex implying a role for imprinting.

Rural vs. non-rural differences and longitudinal bone changes by DXA and pQCT in men aged 20-66 years: A population-based study

The purpose of this research was to determine whether there were differences in estimated means and rates of change in BMC, bone area, BMD and measures of bone geometry among men (n=544) from three distinct populations (Hutterite [rural], rural non-Hutterite, non-rural), and whether activity levels or calcium intake explain these population differences. Men were enrolled in the South Dakota Rural Bone Health Study and followed for 7.5years to estimate means and rates of change in bone mass, density, size and geometry. Femoral neck (FN) and spine measurements were obtained every 18months by DXA and distal radius (4% and 20%) measurements by pQCT. Activity measurements and calcium intake were obtained quarterly for the first 3years and at 54, 72, and 90months. Rural men had greater percent time in moderate plus vigorous activity (mean±SD: 22±10 vs. 15±8%, p<0.001) and greater lean mass (69±9 vs. 66±10kg, p=0.05) than non-rural men. Both rural populations (Hutterite and rural men) had larger femoral neck (FN) bone area and greater 20% radius cross-sectional area than non-rural men ([least square means±SE] FN area: 5.90±0.02 and 5.86±0.02 vs. 5.76±0.03cm2, p<0.001 and p=0.03 respectively and cross-sectional area: 171.0±1.3 and 165.5±1.5 vs. 150.3±1.6mm2, both p<0.001). Despite lower cortical vBMD in Hutterite and rural men compared to non-rural men (1182±2 and 1187±2 vs. 1192±2mm2, p<0.001 and p=0.06 respectively), bone strength (pSSI) was greater (429±5 and 422±5 vs. 376±6mm3, both p<0.001). The rates of change in femoral neck BMC and aBMD and trabecular vBMD also differed by rural lifestyle, with greater losses among non-rural men in their 20s and 60s compared to both Hutterite and rural populations (time-by-age-by-group interactions, both p<0.01). Physical activity was not found to be a potential mediator of population differences. Baseline calcium intake was associated with FN aBMD (p=0.04), and increases in calcium intake were associated with spine BMC (p=0.04) and inversely associated with cortical area (p=0.02). There was some evidence for mediation by either baseline calcium intake or changes in calcium intake over the study period, but the influence on population differences were negligible. We speculate that rural–non-rural differences in bone occur earlier in life or are a result of factors that have not yet been identified.

Bone geometry, bone mineral density, and micro-architecture in patients with myelofibrosis: a cross-sectional study using DXA, HR-pQCT, and bone turnover markers.

Primary myelofibrosis (MF) is a severe chronic myeloproliferative neoplasm, progressing towards a terminal stage with insufficient haematopoiesis and osteosclerotic manifestations. Whilst densitometry studies have showed MF patients to have elevated bone mineral density, data on bone geometry and micro-structure assessed with non-invasive methods are lacking. We measured areal bone mineral density (aBMD) using dual-energy X-ray absorptiometry (DXA). Bone geometry, volumetric BMD, and micro-architecture were measured using high-resolution peripheral quantitative computed tomography (HR-pQCT). We compared the structural parameters of bones by comparing 18 patients with MF and healthy controls matched for age, sex, and height. Blood was analysed for biochemical markers of bone turnover in patients with MF. There were no significant differences in measurements of bone geometry, volumetric bone mineral density, and micro-structure between MF patients and matched controls. Estimated bone stiffness and bone strength were similar between MF patients and controls. The level of pro-collagen type 1 N-terminal pro-peptide (P1NP) was significantly increased in MF, which may indicate extensive collagen synthesis, one of the major diagnostic criteria in MF. We conclude that bone mineral density, geometry, and micro-architecture in this cohort of MF patients are comparable with those in healthy individuals.

Insights Into Relationships Between Body Mass, Composition and Bone: Findings in Elite Rugby Players

Recent reports indicate that bone strength is not proportional to body weight in obese populations. Elite rugby players have a similar body mass index (BMI) to obese individuals but differ markedly with low body fat, high lean mass, and frequent skeletal exposure to loading through weight-bearing exercise. The purpose of this study was to determine relationships between body weight, composition, and bone strength in male rugby players characterized by high BMI and high lean mass. Fifty-two elite male rugby players and 32 nonathletic, age-matched controls differing in BMI (30.2 ± 3.2 vs 24.1 ± 2.1 kg/m2; p = 0.02) received 1 total body and one total hip dual-energy X-ray absorptiometry scan. Hip structural analysis of the proximal femur was used to determine bone mineral density (BMD) and cross-sectional bone geometry. Multiple linear regression was computed to identify independent variables associated with total hip and femoral neck BMD and hip structural analysis–derived bone geometry parameters. Analysis of covariance was used to explore differences between groups. Further comparisons between groups were performed after normalizing parameters to body weight and to lean mass. There was a trend for a positive fat-bone relationship in rugby players, and a negative relationship in controls, although neither reached statistical significance. Correlations with lean mass were stronger for bone geometry (r2: 0.408–0.520) than for BMD (r2: 0.267–0.293). Relative to body weight, BMD was 6.7% lower in rugby players than controls (p < 0.05). Rugby players were heavier than controls, with greater lean mass and BMD (p < 0.01). Relative to lean mass, BMD was 10%–14.3% lower in rugby players (p < 0.001). All bone geometry measures except cross-sectional area were proportional to body weight and lean mass. To conclude, BMD in elite rugby players was reduced in proportion to body weight and lean mass. However, their superior bone geometry suggests that overall bone strength may be adequate for loading demands. Fat-bone interactions in athletes engaged in high-impact sports require further exploration.

Pregnant growth restricted female rats have bone gains during late gestation which contributes to second generation adolescent and adult offspring having normal bone health

Low birth weight, due to uteroplacental insufficiency, results in programmed bone deficits in the first generation (F1). These deficits may be passed onto subsequent generations. We characterized the effects of being born small on maternal bone health during pregnancy; and aimed to characterize the contribution of the maternal environment and germ line effects to bone health in F2 offspring from mothers born small.Bilateral uterine vessel ligation (or sham) surgery was performed on female F0 WKY rats on gestational day 18 (term 22days) to induce uteroplacental insufficiency and fetal growth restriction. Control and Restricted F1 female offspring were allocated to a non-pregnant or pregnant group. To generate F2 offspring, F1 females were allocated to either non-embryo or embryo transfer groups. Embryo transfer was performed on gestational day 1, where second generation (F2) embryos were gestated (donor-in-recipient) in either a Control (Control-in-Control, Restricted-in-Control) or Restricted (Control-in-Restricted, Restricted-in-Restricted) mother.Restricted F1 females were born 10–15% lighter than Controls. Restricted non-pregnant females had shorter femurs, reduced trabecular and cortical bone mineral contents, trabecular density and bone geometry measures determined by peripheral quantitative computed tomography (pQCT) compared to non-pregnant Controls. Pregnancy restored the bone deficits that were present in F1 Restricted females.F2 non-embryo transfer male and female offspring were born of normal weight, while F2 embryo transfer males and females gestated in a Control mother (Control-in-Control, Restricted-in-Control) were heavier at birth compared to offspring gestated in a Restricted mother (Restricted-in-Restricted, Control-in-Restricted). Male F2 Restricted embryo groups (Restricted-in-Control and Restricted-in-Restricted) had accelerated postnatal growth. There was no transmission of bone deficits present at 35days or 6months in F2 offspring. Embryo transfer procedure had confounding effects preventing the separation of maternal environment and germ line contribution to outcomes.Deficits present in F1 non-pregnant Restricted females were absent during late gestation, indicating that pregnant F1 Restricted females experienced gains in bone. These beneficial maternal pregnancy adaptations may have prevented transmission of bone deficits to F2 offspring.

Past sporting activity during growth induces greater bone mineral content and enhances bone geometry in young men and women

We aimed to determine the effect of past sporting activity on bone mineral content (BMC), areal bone mineral density (aBMD) in the lumbar spine and proximal femur, and bone geometry of the mid femur in young men and women. We assessed 142 subjects, comprising 79 young men (21.2±0.8years) and 63 premenopausal young women (21.4±0.6years). The subjects were classified into three groups, two on the basis of the age of starting to participate in sport [elementary school starters (6-12years), junior high school to university starters (13-22years)], and the third group had no participation in sport. We measured BMC and aBMD by dual-energy X-ray absorptiometry (DXA) in the lumbar spine and proximal femur, and bone geometric characteristics of the mid femur by magnetic resonance imaging (MRI), and calculated the osteogenic index (OI) of previous sporting activity. The OI correlated significantly with many MRI-determined measures of bone geometry; DXA-measured BMC and aBMD were effective indicators of previous sporting activity in both sexes. The female elementary school starters had significantly greater femoral mid-diaphyseal perimeters (vs the no-sport group), bone cross-sectional area (vs the 13-22-year-old starters and the no-sport group), and maximum and minimum second moment of area at the mid-diaphysis point of the femur (vs the no-sport group). The OI is a proven practicable and useful index. DXA- and MRI-determined geometric characteristics showed that high-impact, weight-bearing exercise before and in early puberty induces greater total proximal femur BMC and enhances femoral mid-diaphyseal size and shape, and that these benefits persisted in young adult women.

AB0441 Bone geometry, density and microarchitecture: Relationship between peripheral and periarticular skeletal site assessed by high resolution peripheral quantitative computed tomography in patients with rheumatoid arthritis

BackgroundPatients with rheumatoid arthritis (RA) are associated with an increased risk of periarticular and generalized bone loss. A 3D high resolution peripheral quantitative computed tomography (HR-pQCT) system has been developed...

Vitamin C and Zinc Intakes are Related to Bone Macroarchitectural Structure and Strength in Prepubescent Girls

The extent to which nutrient intake may influence bone structure and strength during maximal rates of skeletal growth remains uncertain. We examined the relationship of dietary intake of micronutrients and bone macroarchitectural structure in young girls. This cross-sectional analysis included baseline data from 363 fourth- and sixth-grade girls enrolled in the Jump-In study. Nutrient intake was assessed using the Harvard Youth/Adolescent Food Frequency Questionnaire. Volumetric BMD (vBMD), bone geometry, and strength were measured by peripheral quantitative computed tomography. Correlations and regression modeling assessed relations between usual nutrient intake and bone parameters. In fourth-grade girls, metaphyseal and diaphyseal area and circumferences as well as diaphyseal strength were associated with vitamin C intake (r = 0.15-0.19, p < 0.05). Zinc intake was correlated with diaphyseal vBMD (r = 0.15-0.16, p < 0.05). Using multiple linear regression to adjust for important covariates, we observed significant independent associations for vitamin C and zinc with bone parameters. For every milligram per day of vitamin C intake trabecular area increased by 11 %, cortical strength improved by 14 %, and periosteal and endosteal circumferences increased by 5 and 8.6 %, respectively. For every milligram per day of zinc intake, cortical vBMD increased by <1 %. No significant associations were observed in sixth-grade girls. Results of this study suggests that vitamin C and zinc intake are positively associated with objective measures of bone geometry, size, and strength in fourth-grade girls. This indicates that potential differences in micronutrient and bone associations at various age-associated stages of bone maturation may be indicative of competing hormonal influences.

Ankle joint mechanics and foot proportions differ between human sprinters and non-sprinters

Recent studies of sprinters and distance runners have suggested that variations in human foot proportions and plantarflexor muscle moment arm correspond to the level of sprint performance or running economy. Less clear, however, is whether differences in muscle moment arm are mediated by altered tendon paths or by variation in the centre of ankle joint rotation. Previous measurements of these differences have relied upon assumed joint centres and measurements of bone geometry made externally, such that they would be affected by the thickness of the overlying soft tissue. Using magnetic resonance imaging, we found that trained sprinters have shorter plantarflexor moment arms (p = 0.011) and longer forefoot bones (p = 0.019) than non-sprinters. The shorter moment arms of sprinters are attributable to differences in the location of the centre of rotation (p < 0.001) rather than to differences in the path of the Achilles tendon. A simple computer model suggests that increasing the ratio of forefoot to rearfoot length permits more plantarflexor muscle work during plantarflexion that occurs at rates expected during the acceleration phase following the sprint start.

Calcium supplementation does not rescue the programmed adult bone deficits associated with perinatal growth restriction

Low birth weight and poor childhood growth program a variety of adult diseases including bone disorders such as osteoporosis. We have previously reported that offspring born small, as a result of uteroplacental insufficiency, have shorter femurs, lower bone mineral content and a bone strength deficit as adults. The aim of this study was to determine the effects of calcium supplementation from adolescence on growth restricted male and female offspring which have a programmed bone deficit. Bilateral uterine vessel ligation (Restricted) or sham surgery (Control) was performed on gestational day 18 in WKY rats to induce uteroplacental insufficiency and growth restriction. At 2 months pups were allocated to one of four diet groups: diet 1—constant normal calcium diet, diet 2—variable normal calcium diet, diet 3—constant high calcium diet, diet 4—variable high calcium diet. Diet groups 1 and 3 were fed their respective diets constantly for the duration of the study. In groups 2 and 4, rats were fed one diet for 5 days, followed by a switch to a low calcium diet for the next 5 days. At 6 months Dual Energy Xray Absorptiometry (DXA) and Peripheral Quantitative Computed Tomography (pQCT) were performed on the right femur. Bone turnover markers were measured at 4 months. Male and female Restricted offspring were born 14% lighter compared to Controls ( p < 0.05). At 6 months both male and female Restricted offspring remained smaller and had shorter femurs compared to Controls ( p < 0.05). Restricted males and females had reduced trabecular and cortical content compared to Controls, regardless of diet ( p < 0.05). Trabecular bone density was lower in Restricted females only ( p < 0.05). A constant high calcium diet increased cortical BMD in Restricted male and both female groups ( p < 0.05). Measures of bone geometry indicated that Restricted offspring have narrower bones with preservation of absolute cortical thickness ( p < 0.05). Importantly, the stress strain index of bone bending strength was lower in male and female Restricted offspring, regardless of diet by up to 9.0% and 7.8%, respectively. DXA results were similar to pQCT results. Being born small, due to uteroplacental insufficiency, programs reduced adult femur length, dimensions and stress strain index. Supplementation with a high calcium diet from adolescence can increase adult cortical bone density in low birth weight males and females, and normal weight females. This increase in bone density was not sufficient to rescue the bone dimension and strength deficits which were programmed in utero, suggesting that the early life environment is critical for bone programming.

Adolescent exercise associated with long-term superior measures of bone geometry: a cross-sectional DXA and MRI study

Objective:To investigate whether childhood sports participation, particularly weight-bearing sports, has any effect on bone mineral content (BMC), areal bone mineral density (aBMD) and bone geometric characteristics in middle-aged postmenopausal women.Design/setting:In...

Sex Differences in Parameters of Bone Strength in New Recruits

Stress fracture (SF) injuries in new recruits have long been attributed to low bone mineral density (BMD). Low areal BMD assessed using two-dimensional dual-energy x-ray absorptiometry imaging, however, reflects structural density and is affected by smaller measures of bone geometry. Recent studies support a relationship between bone size and SF and indicate that slender bones are more susceptible to damage under identical loading conditions. Peripheral quantitative computed tomography (pQCT) is a three-dimensional imaging tool that provides measures of tissue density and geometry parameters of the tibia, a common site of SF. To evaluate sex differences in parameters of volumetric BMD (vBMD), geometry, and strength of the tibia in new recruits using a novel pQCT image analysis procedure. pQCT images were obtained from 128 healthy men and women (20 male, 108 female, aged 18-21 yr) entering a 4-month gender-integrated combat training program in the Israeli Defense Forces. Tibial scans taken at sites 4% (trabecular bone), 38%, and 66% (cortical bone) from the distal end plate were analyzed using MATLAB to assess whole-bone and regional parameters. Measures included vBMD, geometry (diameter, area, cortical thickness, and canal radius), and strength (moments of inertia and bone strength and slenderness indices). With the exception of normalized canal radius, which did not differ between sexes, all measures of bone geometry (P < 0.0001) and strength (P < 0.0001 to P = 0.07) were greater in men. Women exhibited 2.7% to 3.0% greater cortical vBMD than men, whereas trabecular vBMD was 8.4% lower in women (P < 0.001). These differences remained significant after adjusting for body size. Sex differences in bone geometry and mineralization of the tibia may contribute to a decreased ability to withstand the demands imposed by novel, repetitive exercise in untrained individuals entering recruit training.

Analyzing Cortical Bone Cross-Sectional Geometry by Peripheral QCT: Comparison With Bone Histomorphometry

A distinct advantage of peripheral quantitative computed tomography (pQCT) is its ability to assess bone strength by measuring cross-sectional geometry and density of cortical bone. For accurate determination of cortical bone cross-sectional area (CoA), it is important to select the appropriate analysis mode and thresholds. No study has assessed which analysis protocol best represents tibial bone geometry—as determined by histomorphometry. We measured bone geometry from 16 human cadaver tibiae (mean age 74 [SD 6] yr) with pQCT (XCT 2000) at the 25% site, measured proximally from the distal tibia plafond. We conducted histomorphometry at the same site as the criterion standard. Scans were analyzed using modes and thresholds recommended by the manufacturer (Norland Stratec Medizintechnic GmbH, Pforzheim, Germany). We also investigated agreement of two additional thresholds (calculated by half-maximum height and inflection point methods) to define the endosteal border of cortical bone. Compared to the criterion, the smallest error (−1.0%, p = 0.002) in total cross-sectional area (ToA) was obtained using Contour mode 3 with an outer threshold of 169 mg/cm 3. The smallest error (0.1%, NS) in CoA was obtained with Separation mode 4 (outer threshold 200 mg/cm 3, inner threshold 670 mg/cm 3). CoA was overestimated by 5–7% ( p < 0.001) from the criterion when an inner threshold of 480 mg/cm 3 was used in combination with any of the recommended outer thresholds. pQCT measurements of bone geometry in vitro vary to some extent between modes and thresholds selected. The effect of variation in bone geometry measurements on the predictive ability of bone strength indices derived from CoA needs to be assessed.

Bone geometry and skeletal fragility

Although low bone mineral density is among the strongest risk factors for fracture, a number of clinical studies have demonstrated the limitations of bone mineral density measurements in assessing fracture risk and monitoring the response to therapy. These observations have brought renewed attention to the broader array of factors that influence skeletal fragility, including bone size, shape, and microarchitecture. This article reviews the relationship between bone geometry and skeletal fragility, focusing on the impact of bone geometry on bone strength and fracture risk. It also reviews recent data on the effect of osteoporosis therapies on femoral geometry. It is clear that characteristics of a bone's size and shape strongly influence its biomechanical strength, but there is no consensus as to the geometric parameters that improve prediction of fracture risk. Recent data from hip structure analysis indicate that antiresorptive and anticatabolic treatments alter femoral geometry, but this observation depends on several assumptions that have not been tested in subjects treated with osteoporosis therapies. Current knowledge is limited, in part, by the predominant use of two-dimensional techniques to assess bone geometry. Additional studies that incorporate three-dimensional imaging are needed to better define the relationship between bone geometry and skeletal fragility, and to establish the clinical utility of bone geometry measurements.

Determining the degree of cortical bone asymmetry in bilateral, nonpathological, human femur pairs

When testing the effects of a femoral component on cortical bone following total hip arthroplasty, the patient's implanted femur is often compared with his/her contralateral nonimplanted femur, with differences attributed to the femoral component. However, if normal anatomical differences exist between bilateral femurs, they need to be quantified in order to validate whether the differences between implanted and nonimplanted bilateral femurs are due to the implant or possibility due to intrinsic differences before implantation. This study quantified the geometric properties of cortical bone shape between seven pairs of bilateral, cadaveric, human femurs. The null hypothesis tested stated that the bilateral femurs would not be significantly different in cortical bone geometry. Digitized images of cortical bone cross-sections taken at percent biomechanical lengths (levels 1-8) were used to calculate bone geometry measurements. The paired t-test showed that the only significant difference was in the location of principal axes at the most proximal location, level 1 (p = 0.015). All other measurements and levels were not significant with percent differences less than 6.6%. In conclusion, the data supports attributing cortical bone shape differences between implanted and contralateral nonimplanted femurs in levels 2-8 to the presence of the implant when the significant differences are greater than 6.6%.

Quantitative trait loci that modulate femoral mechanical properties in a genetically heterogeneous mouse population.

The goal of this study was to investigate genetic effects on mechanical properties of the mouse femur. We found evidence for QTL on eight chromosomes that affect mechanical traits. Some of these QTL may have primary effects on body weight or femoral geometry, and others seem to affect bone quality directly. Previous studies have shown a dependence of fragility-related fracture risk on genetic background. Although many of these studies investigated the effect of genetics on BMD, basic measures of bone geometry and mechanical integrity may provide a more comprehensive characterization of the genetic effects on bone fragility. The purpose of this study was to identify quantitative trait loci (QTL) that affect mechanical and material properties of cortical bone in a genetically heterogeneous mouse population. A total of 486 female UM-HET3 mice was used for this study. UM-HET3 mice are produced as the offspring of (BALB/cJ x C57BL/6J) F(1) females and (C3H/HeJ x DBA/2J) F(1) males. Femurs from 18-month-old mice were tested to failure in four-point bending to assess mechanical properties of cortical bone; these properties were compared with genotype data from 185 biallelic loci. A permutation-based test was used to detect significant associations between genetic markers and mechanical traits. This test generates p values that account for the effect of testing multiple hypotheses. Throughout the experiment, p < or = 0.05 was considered statistically significant. Analysis of covariance was used to examine possible effects of body weight and femoral geometry. We found evidence for genes on maternal chromosomes 11 and 13 and paternal chromosomes 2, 4, 7, 10, 11, and 17 that affect mechanical and material properties of femoral bone. The total variance explained by genetic effects on each mechanical trait ranges from 2.9% to 15.4%. Most of the identified polymorphisms influence mechanical traits even after adjustment for body weight. Adjustment for femoral geometry reduces the effects of some of the QTL, but those on chromosomes 2 and 10 do not seem to be influenced by femoral geometry. Many genes and chromosomes are involved in the genetic control over mechanical integrity of cortical bone. QTL on paternal chromosomes 4 and 11 may mediate mechanical properties, at least in part, by modulation of femoral geometry. Other QTL identified here may directly affect bone tissue quality.

Effects of age, density, and geometry on the bending strength of human metatarsals.

In this basic study, we investigated the relative roles of donor age, bone density, and bone geometry in determining structural strength of human metatarsals tested in a four-point bending configuration. Density measurements were made noninvasively using dual energy X-ray absorptiometry, and geometric measurements were made by digitally imaging cross-sections of specimens. Correlations between area bone mineral density and metatarsal strength were strong (r2 = 0.83, 0.81 for second and third metatarsals, respectively) and were not improved by including cross-sectional area or minimum moment of inertia in multiple regression analyses. Increased donor age was associated with decreased bending strength (r2 = 0.51 and 0.45, respectively), which was expected because increased age correlated significantly with decreased bone density (r2 = 0.69 and 0.80, respectively). These results indicate that the strength of human metatarsals generally decreases with age and that this decrease is likely attributable to decreased bone density. Moreover, the results indicate that noninvasive dual energy x-ray absorptiometry measurements of metatarsal density are useful for assessing metatarsal strength and that additional measurements of bone geometry are not required.