Sensitivity of proximal femoral stiffness and areal bone mineral density to changes in bone geometry and density

Areal bone mineral density (aBMD) is the most common surrogate measurement for assessing the bone strength of the proximal femur associated with osteoporosis. Additional factors, however, contribute to the overall strength of the proximal femur, primarily the anatomical geometry. Finite element analysis (FEA) is an effective and widely used computerbased simulation technique for modeling mechanical loading of various engineering structures, providing predictions of displacement and induced stress distribution due to the applied load. FEA is therefore inherently dependent upon both density and anatomical geometry. FEA may be performed on both three-dimensional and two-dimensional models of the proximal femur derived from radiographic images, from which the mechanical stiffness may be redicted. It is examined whether the outcome measures of two-dimensional FEA, two-dimensional, finite element analysis of X-ray images (FEXI), and three-dimensional FEA computed stiffness of the proximal femur were more sensitive than aBMD to changes in trabecular bone density and femur geometry. It is assumed that if an outcome measure follows known trends with changes in density and geometric parameters, then an increased sensitivity will be indicative of an improved prediction of bone strength. All three outcome measures increased non-linearly with trabecular bone density, increased linearly with cortical shell thickness and neck width, decreased linearly with neck length, and were relatively insensitive to neck-shaft angle. For femoral head radius, aBMD was relatively insensitive, with two-dimensional FEXI and threedimensional FEA demonstrating a non-linear increase and decrease in sensitivity, respectively. For neck anteversion, aBMD decreased non-linearly, whereas both two-dimensional FEXI and three dimensional FEA demonstrated a parabolic-type relationship, with maximum stiffness achieved at an angle of approximately 15o. Multi-parameter analysis showed that all three outcome measures demonstrated their highest sensitivity to a change in cortical thickness. When changes in all input parameters were considered simultaneously, three and twodimensional FEA had statistically equal sensitivities (0.41±0.20 and 0.42±0.16 respectively, p = ns) that were significantly higher than the sensitivity of aBMD (0.24±0.07; p = 0.014 and 0.002 for three-dimensional and two-dimensional FEA respectively). This simulation study suggests that since mechanical integrity and FEA are inherently dependent upon anatomical geometry, FEXI stiffness, being derived from conventional two-dimensional radiographic images, may provide an improvement in the prediction of bone strength of the proximal femur than currently provided by aBMD.

The relationship between muscle size and bone geometry during growth and in response to exercise

As muscles become larger and stronger during growth and in response to increased loading, bones should adapt by adding mass, size, and strength. In this unilateral model, we tested the hypothesis that (1) the relationship between muscle size and bone mass and geometry (nonplaying arm) would not change during different stages of puberty and (2) exercise would not alter the relationship between muscle and bone, that is, additional loading would result in a similar unit increment in both muscle and bone mass, bone size, and bending strength during growth. We studied 47 competitive female tennis players aged 8–17 years. Total, cortical, and medullary cross-sectional areas, muscle area, and the polar second moment of area (Ip) were calculated in the playing and nonplaying arms using magnetic resonance imaging (MRI); BMC was assessed by DXA. Growth effects: In the nonplaying arm in pre-, peri- and post-pubertal players, muscle area was linearly associated BMC, total and cortical area, and Ip (r = 0.56–0.81, P < 0.09 to < 0.001), independent of age. No detectable differences were found between pubertal groups for the slope of the relationship between muscle and bone traits. Post-pubertal players, however, had a higher BMC and cortical area relative to muscle area (i.e., higher intercept) than pre- and peri-pubertal players (P < 0.05 to < 0.01), independent of age; pre- and peri-pubertal players had a greater medullary area relative to muscle area than post-pubertal players (P < 0.05 to < 0.01). Exercise effects: Comparison of the side-to-side differences revealed that muscle and bone traits were 6–13% greater in the playing arm in pre-pubertal players, and did not increase with advancing maturation. In all players, the percent (and absolute) side-to-side differences in muscle area were positively correlated with the percent (and absolute) differences in BMC, total and cortical area, and Ip (r = 0.36–0.40, P < 0.05 to < 0.001). However, the side-to-side differences in muscle area only accounted for 11.8–15.9% of the variance of the differences in bone mass, bone size, and bending strength. This suggests that other factors associated with loading distinct from muscle size itself contributed to the bones adaptive response during growth. Therefore, the unifying hypothesis that larger muscles induced by exercise led to a proportional increase in bone mass, bone size, and bending strength appears to be simplistic and denies the influence of other factors in the development of bone mass and bone shape.

Long-term effects of calcium-vitamin-D3-fortified milk on bone geometry and strength in older men

The long-term effects of calcium and vitamin D supplementation on bone material and structural properties in older men are not known. The aim of this study was to examine the effects of high calcium (1000 mg/day)- and vitamin-D3 (800 IU/day)-fortified milk on cortical and trabecular volumetric BMD (vBMD) and bone geometry at the axial and appendicular skeleton in men aged over 50 years. One hundred and eleven men who were part of a larger 2-year randomized controlled trial had QCT scans of the mid-femur and lumbar spine (L1–L3) to assess vBMD, bone geometry and indices of bone strength [polar moment of inertia (Ipolar)]. After 2 years, there were no significant differences between the milk supplementation and control group for the change in any mid-femur or L1–L3 bone parameters for all men aged over 50 years. However, the mid-femur skeletal responses to the fortified milk varied according to age, with a split of ≤62 versus >62 years being the most significant for discriminating the changes between the two groups. Subsequent analysis revealed that, in the older men (>62 years), the expansion in mid-femur medullary area was 2.8% (P < 0.01) less in the milk supplementation compared to control group, which helped to preserve cortical area in the milk supplementation group (between group difference 1.1%, P < 0.01). Similarly, for mid-femur cortical vBMD and Ipolar, the net loss was 2.3 and 2.8% less in the milk supplementation compared to control group (P < 0.01 and <0.001, respectively). In conclusion, calcium–vitamin-D3-fortified milk may represent an effective strategy to maintain bone strength by preventing endocortical bone loss and slowing the loss in cortical vBMD in elderly men.

Bone geometry in response to long-term tennis playing and its relationship with muscle volume : a quantitative magnetic resonance imaging study in tennis players

The benefit of impact-loading activity for bone strength depends on whether the additional bone mineral content (BMC) accrued at loaded sites is due to an increased bone size, volumetric bone mineral density (vBMD) or both. Using magnetic resonance imaging (MRI) and dual energy X-ray absorptiometry (DXA), the aim of this study was to characterize the geometric changes of the dominant radius in response to long-term tennis playing and to assess the influence of muscle forces on bone tissue by investigating the muscle–bone relationship. Twenty tennis players (10 men and 10 women, mean age: 23.1 ± 4.7 years, with 14.3 ± 3.4 years of playing) were recruited. The total bone volume, cortical volume, sub-cortical volume and muscle volume were measured at both distal radii by MRI. BMC was assessed by DXA and was divided by the total bone volume to derive vBMD. Grip strength was evaluated with a dynamometer. Significant side-to-side differences (P < 0.0001) were found in muscle volume (+9.7%), grip strength (+13.3%), BMC (+13.5%), total bone volume (+10.3%) and sub-cortical volume (+20.6%), but not in cortical volume (+2.6%, ns). The asymmetry in total bone volume explained 75% of the variance in BMC asymmetry (P < 0.0001). vBMD was slightly higher on the dominant side (+3.3%, P < 0.05). Grip strength and muscle volume correlated with all bone variables (except vBMD) on both sides (r = 0.48–0.86, P < 0.05–0.0001) but the asymmetries in muscle parameters did not correlate with those in bone parameters. After adjustment for muscle volume or grip strength, BMC was still greater on the dominant side. This study showed that the greater BMC induced by long-term tennis playing at the dominant radius was associated to a marked increase in bone size and a slight improvement in volumetric BMD, thereby improving bone strength. In addition to the muscle contractions, other mechanical stimuli seemed to exert a direct effect on bone tissue, contributing to the specific bone response to tennis playing.

Greater association of peak neuromuscular performance with cortical bone geometry, bone mass and bone strength than bone density : a study in 417 older women

BACKGROUND: We evaluated which aspects of neuromuscular performance are associated with bone mass, density, strength and geometry. METHODS: 417 women aged 60-94years were examined. Countermovement jump, sit-to-stand test, grip strength, forearm and calf muscle cross-sectional area, areal bone mineral content and density (aBMC and aBMD) at the hip and lumbar spine via dual X-ray absorptiometry, and measures of volumetric vBMC and vBMD, bone geometry and section modulus at 4% and 66% of radius length and 4%, 38% and 66% of tibia length via peripheral quantitative computed tomography were performed. The first principal component of the neuromuscular variables was calculated to generate a summary neuromuscular variable. Percentage of total variance in bone parameters explained by the neuromuscular parameters was calculated. Step-wise regression was also performed. RESULTS: At all pQCT bone sites (radius, ulna, tibia, fibula), a greater percentage of total variance in measures of bone mass, cortical geometry and/or bone strength was explained by peak neuromuscular performance than for vBMD. Sit-to-stand performance did not relate strongly to bone parameters. No obvious differential in the explanatory power of neuromuscular performance was seen for DXA aBMC versus aBMD. In step-wise regression, bone mass, cortical morphology, and/or strength remained significant in relation to the first principal component of the neuromuscular variables. In no case was vBMD positively related to neuromuscular performance in the final step-wise regression models. CONCLUSION: Peak neuromuscular performance has a stronger relationship with leg and forearm bone mass and cortical geometry as well as proximal forearm section modulus than with vBMD.

Abnormal bone geometry at the metacarpal bone shaft of rheumatoid arthritis patients with maintained muscle-bone relationship

OBJECTIVES:: Metacarpal juxta-articular bone is altered in Rheumatoid Arthritis (RA). However, a detailed analysis of disease related geometrical adaptations of the metacarpal shaft is missing. The aim of the present study was to assess the role of RA disease, forearm muscle cross-sectional area (CSA), age and sex on bone geometry at the metacarpal shaft. METHODS:: In 64 RA patients and 128 control subjects geometric properties of the third metacarpal bone mid-shaft and forearm muscle CSA were measured by peripheral quantitative computed tomography (pQCT). Linear models were performed for cortical CSA, total bone CSA, polar stress-strain Index (polar SSI, a surrogate for bone's resistance to bending and torsion), cortical thickness and Metacarpal Index (MI=cortical CSA/total CSA) with explanatory variables muscle CSA, age, RA status and sex. RESULTS:: Forearm muscle CSA was associated with cortical and total metacarpal CSA, and polar SSI. RA group status was associated with all bone parameters except cortical CSA. There was a significant interaction between RA status and age, indicating that the RA group had a greater age-related decrease in cortical CSA, cortical thickness and MI. CONCLUSIONS:: Bone geometry of the metacarpal shaft is altered in RA patients compared to healthy controls. While bone mass of the metacarpal shaft is adapted to forearm muscle mass, cortical thickness and MI are reduced but outer bone shaft circumference and polar SSI increased in RA patients. These adaptations correspond to an enhanced aging pattern in RA patients.

Muscle determinants of bone mass, geometry and strength in prepubertal girls

Purpose: The aim of this study was to compare the relative contribution of peak muscle force (isokinetic peak torque) with surrogate estimates of muscle force, including leg lean tissue mass (LTM) and vertical jump height (VJH), on bone mass, geometry and strength in healthy prepubertal girls (n = 103).

Methods: Total leg and FN BMC and leg LTM were measured by DXA; the hip strength analysis program was used to assess FN diameter, cross-sectional area (CSA) and section modulus (Z). Isokinetic peak torque of the knee extensors and flexors (60°·s-1) were used as direct measures of peak muscle force. VJH was measured as an estimate of neuromuscular function. Total leg length or femoral length was used as a surrogate measure of moment arm length.

Results: All estimates of muscle function, except VJH, were positively associated with leg BMC (r = 0.72 - 0.90) and FN BMC, geometry and strength (r = 0.35-0.65) (all, P < 0.001). Multiple linear regression analyses revealed that leg LTM and isokinetic peak torque were independently and equally predictive of leg BMC and FN BMC, bone geometry and strength, explaining 8 to 28% of the variance in each of the bone traits after accounting for moment arm length. When isokinetic peak torque was corrected for both leg LTM and moment arm length, it remained an independent predictor of BMC, CSA and Z, but only accounted for an additional 2 to 5% of the variance.

Conclusion: These data suggest that DXA-derived leg LTM can be used as a reasonable surrogate for isokinetic peak muscle forces when assessing bone strength in relation to muscular function in healthy pre-pubertal girls.

Patients with diffuse idiopathic skeletal hyperostosis do not have increased peripheral bone mineral density and geometry

Recent studies have suggested that areal BMD (aBMD) measured by DXA is elevated in patients with DISH. We used peripheral QCT (pQCT) to assess volumetric BMD (vBMD) and bone geometry of the radius, tibia and the third metacarpal bone.

Lifetime sport and leisure activity participation is associated with greater bone size, quality and strength in older men

Introduction: It remains uncertain whether long-term participation in regular weight-bearing exercise confers an advantage to bone structure and strength in old age. The aim of this study was to investigate the relationship between lifetime sport and leisure activity participation on bone material and structural properties at the axial and appendicular skeleton in older men (>50 years).

Methods: We used dual-energy X-ray absorptiometry (DXA) to assess hip, spine and ultradistal (UD) radius areal bone mineral density (aBMD) (n=161), quantitative ultrasound (QUS) to measure heel bone quality (n=161), and quantitative computed tomography (QCT) to assess volumetric BMD, bone geometry and strength at the spine (L₁–L₃) and mid-femur (n=111). Current (>50+ years) and past hours of sport and leisure activity participation during adolescence (13–18 years) and adulthood (19–50 years) were assessed by questionnaire. This information was used to calculate the total time (min) spent participating in sport and leisure activities and an osteogenic index (OI) score for each participant, which provides a measure of participation in weight-bearing activities.

Results: Regression analysis revealed that a greater lifetime (13–50+ years) and mid-adulthood (19–50 years) OI, but not total time (min), was associated with a greater mid-femur total and cortical area, cortical bone mineral content (BMC), and the polar moment of inertia (I _p) and heel VOS (p ranging from <0.05 to <0.01). These results were independent of age, height (or femoral length) and weight (or muscle cross-sectional area). Adolescent OI scores were not found to be significant predictors of bone structure or strength. Furthermore, no significant relationships were detected with areal or volumetric BMD at any site. Subjects were then categorized into either a high (H) or low/non-impact (L) group during adolescence (13–18 years) and adulthood (19–50+ years) according to their OI scores during each of these periods. Three groups were subsequently formed to reflect weight-bearing impact categories during adolescence and then adulthood: LL, HL and HH. Compared to the LL group, mid-femur total and cortical area, cortical BMC and I _p were 6.5–14.2% higher in the HH group. No differences were detected between the LL and HL groups.

Conclusions: In conclusion, these findings indicate that long-term regular participation in sport and leisure activities categorized according to an osteogenic index [but not the total time (min) spent participating in all sport and leisure activities] was an important determinant of bone size, quality and strength, but not BMD, at loaded sites in older men. Furthermore, continued participation in weight-bearing exercise in early to mid-adulthood appears to be important for reducing the risk of low bone strength in old age.

History of amenorrhoea compromises some of the exercise-induced benefits in cortical and trabecular bone in the peripheral and axial skeleton : a study in retired elite gymnasts

Background : Female gymnasts frequently present with overt signs of hypoestrogenism, such as late menarche or menstrual dysfunction. The objective was to investigate the impact of history of amenorrhoea on the exercise-induced skeletal benefits in bone geometry and volumetric density in retired elite gymnasts.
Subjects and methods

24 retired artistic gymnasts, aged 17–36 years, who had been training for at least 15 h/week at the peak of their career and had been retired for 3–18 years were recruited. They had not been engaged in more than 2 h/week of regular physical activity since retirement. Former gymnasts who reported history of amenorrhoea (‘AME’, n = 12: either primary or secondary amenorrhoea) were compared with former gymnasts (‘NO-AME’, n = 12) and controls (‘C’, n = 26) who did not report history of amenorrhoea. Bone mineral content (BMC), total bone area (ToA) and total volumetric density (ToD) were measured by pQCT at the radius and tibia (4% and 66%). Trabecular volumetric density (TrD) and bone strength index (BSI) were measured at the 4% sites. Cortical area (CoA), cortical thickness (CoTh), medullary area (MedA), cortical volumetric density (CoD), stress–strain index (SSI) and muscle and fat area were measured at the 66% sites. Spinal BMC, areal BMD and bone mineral apparent density (BMAD) were measured by DXA.
Results

Menarcheal age was delayed in AME when compared to NO-AME (16.4 ± 0.5 years vs. 13.3 ± 0.4 years, p < 0.001). No differences were detected between AME and C for height-adjusted spinal BMC, aBMD and BMAD, TrD and BSI at the distal radius and tibia, CoA at the proximal radius, whereas these parameters were greater in NO-AME than C (p < 0.05–0.005). AME had lower TrD and BSI at the distal radius, and lower spinal BMAD than NO-AME (p < 0.05) but they had greater ToA at the distal radius (p < 0.05).
Conclusion

Greater spinal BMC, aBMD and BMAD as well as trabecular volumetric density and bone strength in the peripheral skeleton were found in former gymnasts without a history of menstrual dysfunction but not in those who reported either primary or secondary amenorrhoea. History of amenorrhoea may have compromised some of the skeletal benefits associated with high-impact gymnastics training.