Julie M. Hughes

Bone mass and strength in older men with type 2 diabetes: The Osteoporotic Fractures in Men Study

The effects of type 2 diabetes mellitus (T2DM) on bone volumetric density, bone geometry, and estimates of bone strength are not well established. We used peripheral quantitative computed tomography (pQCT) to compare tibial and radial bone volumetric density (vBMD, mg/cm3), total (ToA, mm2) and cortical (CoA, mm2) bone area and estimates of bone compressive and bending strength in a subset (n = 1171) of men (≥65 years of age) who participated in the multisite Osteoporotic Fractures in Men (MrOS) study. Analysis of covariance–adjusted bone data for clinic site, age, and limb length (model 1) and further adjusted for body weight (model 2) were used to compare data between participants with (n = 190) and without (n = 981) T2DM. At both the distal tibia and radius, patients with T2DM had greater bone vBMD (+2% to +4%, model 1, p < .05) and a smaller bone area (ToA −1% to −4%, model 2, p < .05). The higher vBMD compensated for lower bone area, resulting in no differences in estimated compressive bone strength at the distal trabecular bone regions. At the mostly cortical bone midshaft sites of the radius and tibia, men with T2DM had lower ToA (−1% to −3%, p < .05), resulting in lower bone bending strength at both sites after adjusting for body weight (−2% to −5%, p < .05) despite the lack of difference in cortical vBMD at these sites. These data demonstrate that older men with T2DM have bone strength that is low relative to body weight at the cortical‐rich midshaft of the radius despite no difference in cortical vBMD.

Bone Structure and Volumetric BMD in Overweight Children: A Longitudinal Study†

The effect of excess body fat on bone strength accrual is not well understood. Therefore, we assessed bone measures in healthy weight (HW) and overweight (OW) children. Children (9–11 yr) were classified as HW (n = 302) or OW (n = 143) based on body mass index. We assessed total (ToD) and cortical (CoD) volumetric BMD and bone area, estimates of bone strength (bone strength index [BSI]; stress‐strain index [SSIp]), and muscle cross‐sectional area (CSA) at the distal (8%), midshaft (50%), and proximal (66%) tibia by pQCT. We used analysis of covariance to compare bone outcomes at baseline and change over 16 mo. At baseline, all bone measures were significantly greater in OW compared with HW children (+4–15%; p ≤ 0.001), with the exception of CoD at the 50% and 66% sites. Over 16 mo, ToA increased more in the OW children, whereas there was no difference for change in BSI or ToD between groups at the distal tibia. At the tibial midshaft, SSIp was similar between groups at baseline when adjusted for muscle CSA, but low when adjusted for body fat in the OW group. At both sites, bone strength increased more in OW because of a greater increase in bone area. Changes in SSIp were associated with changes in lean mass (r = 0.70, p < 0.001) but not fat mass. In conclusion, although OW children seem to be at an advantage in terms of absolute bone strength, bone strength did not adapt to excess body fat. Rather, bone strength was adapted to the greater muscle area in OW children.

Muscle power and physical activity are associated with bone strength in older men: The osteoporotic fractures in men study

The purpose of these analyses was to explore whether physical activity score, leg power or grip strength were associated with tibia and radius estimates of bone strength, cortical density, or total bone area. Peripheral quantitative computed tomography (pQCT) was used to compare tibial and radial bone volumetric density (vBMD, mg/cm(3)), total (ToA, mm(2)) and cortical (CoA, mm(2)) bone area, and estimates of bone compressive strength (bone strength index, BSI) and bending strength (polar strength strain index, SSIp) in a subset (n=1171) of men (> or = 65 years) who participated in the multi-site Osteoporotic Fractures in Men (MrOS) study. Physical activity was assessed by questionnaire (PASE), leg power by Nottingham Power Rig, and grip strength by a hand-held Dynamometer. Participants were categorized into quartiles of PASE, grip strength or leg power. The model was adjusted for age, race, clinic, weight, and limb length. In the tibia, BSI (+7%) and SSIp (+4%) were highest in the most active physically quartile compared to the least active (p<0.05). At the 4% site of the tibia, men with the greatest leg power had both greater ToA (+5%, p<0.001) and BSI (+5.3%, p=0.086) compared to men with the least leg power. At the 66% site of the tibia, the men with the highest leg power, compared to the men with the lowest leg power, had greater ToA (+3%, p=0.045) SSIp (+5%, p=0.008). Similar results were found at both the distal and midshaft of the radius. The findings of this study suggest the importance of maintaining levels of physical activity and muscle strength in older men to prevent bone fragility.

Bone Geometry, Strength, and Muscle Size in Runners with a History of Stress Fracture

PURPOSE Our primary aim was to explore differences in estimates of tibial bone strength, in female runners with and without a history of stress fractures. Our secondary aim was to explore differences in bone geometry, volumetric density, and muscle size that may explain bone strength outcomes. METHODS A total of 39 competitive distance runners aged 18-35 yr, with (SFX, n = 19) or without (NSFX, n = 20) a history of stress fracture were recruited for this cross-sectional study. Peripheral quantitative computed tomography (XCT 3000; Orthometrix, White Plains, NY) was used to assess volumetric bone mineral density (vBMD, mg x mm(-3)), bone area (ToA, mm(2)), and estimated compressive bone strength (bone strength index (BSI) = ToA x total volumetric density (ToD(2))) at the distal tibia (4%). Total (ToA, mm(2)) and cortical (CoA, mm(2)) bone area, cortical vBMD, and estimated bending strength (strength-strain index (SSIp), mm(3)) were measured at the 15%, 25%, 33%, 45%, 50%, and 66% sites. Muscle cross-sectional area (MCSA) was measured at the 50% and 66% sites. RESULTS Participants in the SFX group had significantly smaller (7%-8%) CoA at the 45%, 50%, and 66% sites (P <or= 0.05 for all), significantly lower SSIp (9%-10%) at the 50% and 66% sites, and smaller MCSA (7%-8%) at the 66% site. The remaining bone parameters including vBMD were not significantly different between groups. After adjusting for MCSA, there were no differences between groups for any measured bone outcomes. CONCLUSIONS These findings suggest that cortical bone strength, cortical area, and MCSA are all lower in runners with a history of stress fracture. However, the lower strength was appropriate for the smaller muscle size, suggesting that interventions to reduce stress fracture risk might be aimed at improving muscle size and strength.

Proximal Femur Mechanical Adaptation to Weight Gain in Late Adolescence: A Six‐Year Longitudinal Study

The effect of weight gain in late adolescence on bone is not clear. Young women who consistently gained weight (n = 23) from 17 to 22 yr of age had increased BMD but a lack of subperiosteal expansion compared with stable weight peers (n = 48). Bone strength increased appropriately for lean mass in both groups but decreased relative to body weight in weight gainers, suggesting increased bone fragility in weight gainers.

The Biomechanical Basis of Bone Strength Development during Growth

Understanding the development of the material composition and structure of bone during growth, both key determinants of bone strength, and identifying factors that regulate the development of these properties are important for developing effective lifestyle interventions to optimize peak bone strength. New imaging technologies provide the ability to measure estimates of both the material composition and structure of bone, and thus, estimates of whole bone strength. During childhood and adolescence, bone structure is altered by growth in length and width, which is associated with increases in mass, and alterations in tissue density. These processes lead to a bone with an optimal size, shape, and architecture to withstand the normal physiological loads imposed on it. Longitudinal bone growth is the result of endochondral ossification, a process that continues throughout childhood and rapidly increases during the adolescent growth spurt. Along the shaft, long bones continually grow in width, thus improving the resistance to bending forces by depositing new bone on the periosteal surface with simultaneous resorption on the endocortical surface. Sexual dimorphism in periosteal bone formation and endosteal bone resorption result in sex-specific differences in adult bone conformation. Changes in linear and periosteal growth are closely tied to changes in bone mass, with approximately one quarter of adult total body bone mineral accrued during the 2 years around the adolescent growth spurt. These structural and material changes are under mechanical regulation and influenced by the hormonal environment. Overall, bones must continually adapt their geometry and mass to withstand loads from increases in bone length, muscle mass and external forces during growth. However, the tempo, timing, and extent of such adaptations are also closely regulated by several systemic hormones.

Bone volumetric density, geometry, and strength in female and male collegiate runners

PURPOSE To explore differences in tibial bone geometry, volumetric density, and estimates of bone strength in runners and healthy controls. METHODS Male (n = 21) and female (n = 38) runners (49.1 +/- 13.2 miles x wk(-1)) and inactive healthy controls (17 males and 32 females; mean age = 22 +/- 3.3 yr) were recruited to participate. Peripheral quantitative computed tomography was used to assess total volumetric bone mineral density (vBMD, mg x mm(-3)), total bone area (ToA, mm2), and an estimate of compressive bone strength (bone strength index (BSI) = ToA x total bone volumetric density (ToD2)) at the distal (4%) site of the tibia. ToA (mm2) and cortical bone area (CoA, mm2), cortical vBMD (CoD, mg x mm(-3)), cortical thickness (CoTh, mm), and an estimate of bone bending strength (polar strength strain index (SSIp), mm3) were measured at 50% and 66% sites. RESULTS ToA and BSI were significantly greater (+11%-19%, P < 0.05) in female runners than controls at the 4% site. At the proximal sites, female runners had significantly greater ToA, CoA, CoTh, and SSIp (+9%-19%, all P < 0.001) compared with female controls. vBMD was similar at all tibia sites. Compared with controls, male runners had significantly greater CoTh at the 50% and 66% sites (+8% and 14%, respectively, P < 0.05) as well as greater CoA (+11%, P < 0.009) at the 66% site. There were no differences in bone strength or density at any site in the male runners. CONCLUSIONS Greater bone strength in female runners was attributable to greater bone area rather than density. Although male runners did not show greater bone strength, they did exhibit favorable bone geometric properties. These data further document that running has osteogenic potential.

Lessons learned from school-based skeletal loading intervention trials: putting research into practice.

In recent years, there have been a number of school-based physical activity intervention trials aimed at optimizing bone development. Various approaches have been taken including interventions ranging from 3 to 50 min in length performed 2-5 times per week incorporated within the school day (typically in physical education) or as an after-school program. Overall, these studies showed that school-based skeletal loading interventions are efficacious, safe, and feasible. Furthermore, studies to date have shown that interventions are most effective when initiated during prepuberty and early puberty, and consist of dynamic activities that are high in magnitude (i.e. jumping, skipping, hopping) and include multidirectional movements. Recent work also suggests that adding rest intervals and performing short bouts of activity a few times per day may enhance the effectiveness of loading on bone health. In this chapter, we discuss important training principles and lessons learned from these intervention trials and provide practical guidelines, tips and sample programs that can be used by health care professionals interested in optimizing bone health of children and adolescents.

Bone mass, microarchitecture and strength are influenced by race/ethnicity in young adult men and women

Lower rates of fracture in both Blacks compared to Whites, and men compared to women are not completely explained by differences in bone mineral density (BMD). Prior evidence suggests that more favorable cortical bone microarchitecture may contribute to reduced fracture rates in older Black compared to White women, however it is not known whether these differences are established in young adulthood or develop during aging. Moreover, prior studies using high-resolution pQCT (HR-pQCT) have reported outcomes from a fixed-scan location, which may confound sex- and race/ethnicity-related differences in bone structure. PURPOSE We determined differences in bone mass, microarchitecture and strength between young adult Black and White men and women. METHODS We enrolled 185 young adult (24.2±3.4yrs) women (n=51 Black, n=50 White) and men (n=34 Black, n=50 White) in this cross-sectional study. We used dual-energy X-ray absorptiometry (DXA) to determine areal BMD (aBMD) at the femoral neck (FN), total hip (TH) and lumbar spine (LS), as well as HR-pQCT to assess bone microarchitecture and failure load by micro-finite element analysis (μFEA) at the distal tibia (4% of tibial length). We used two-way ANOVA to compare bone outcomes, adjusted for age, height, weight and physical activity. RESULTS The effect of race/ethnicity on bone outcomes did not differ by sex, and the effect of sex on bone outcomes did not differ by race/ethnicty. After adjusting for covariates, Blacks had significantly greater FN, TH and LS aBMD compared to Whites (p<0.05 for all). Blacks also had greater cortical area, vBMD, and thickness, and lower cortical porosity, with greater trabecular thickness and total vBMD compared to Whites. μFEA-estimated FL was significantly higher among Blacks compared to Whites. Men had significantly greater total vBMD, trabecular thickness and cortical area and thickness, but greater cortical porosity than women, the net effects being a higher failure load in men than women. CONCLUSION These findings demonstrate that more favorable bone microarchitecture in Blacks compared to Whites and in men compared to women is established by young adulthood. Advantageous bone strength among Blacks and men likely contributes to their lower risk of fractures throughout life compared to their White and women counterparts.

An Integrated Musculoskeletal-Finite-Element Model to Evaluate Effects of Load Carriage on the Tibia During Walking

Prior studies have assessed the effects of load carriage on the tibia. Here, we expand on these studies and investigate the effects of load carriage on joint reaction forces (JRFs) and the resulting spatiotemporal stress/strain distributions in the tibia. Using full-body motion and ground reaction forces from a female subject, we computed joint and muscle forces during walking for four load carriage conditions. We applied these forces as physiological loading conditions in a finite-element (FE) analysis to compute strain and stress. We derived material properties from computed tomography (CT) images of a sex-, age-, and body mass index-matched subject using a mesh morphing and mapping algorithm, and used them within the FE model. Compared to walking with no load, the knee JRFs were the most sensitive to load carriage, increasing by as much as 26.2% when carrying a 30% of body weight (BW) load (ankle: 16.4% and hip: 19.0%). Moreover, our model revealed disproportionate increases in internal JRFs with increases in load carriage, suggesting a coordinated adjustment in the musculature functions in the lower extremity. FE results reflected the complex effects of spatially varying material properties distribution and muscular engagement on tibial biomechanics during walking. We observed high stresses on the anterior crest and the medial surface of the tibia at pushoff, whereas high cumulative stress during one walking cycle was more prominent in the medioposterior aspect of the tibia. Our findings reinforce the need to include: (1) physiologically accurate loading conditions when modeling healthy subjects undergoing short-term exercise training and (2) the duration of stress exposure when evaluating stress-fracture injury risk. As a fundamental step toward understanding the instantaneous effect of external loading, our study presents a means to assess the relationship between load carriage and bone biomechanics.