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Keywords:

  • ADOLESCENT GROWTH;
  • BONE MICROSTRUCTURE;
  • BONE STRENGTH;
  • HR-pQCT;
  • FINITE ELEMENT ANALYSIS

Abstract

  1. Top of page
  2. Abstract
  3. Introduction
  4. Materials and Methods
  5. Results
  6. Discussion
  7. Disclosures
  8. Acknowledgements
  9. References

The aim of this study was to determine the sex- and maturity-related differences in bone microstructure and estimated bone strength at the distal radius and distal tibia in children and adolescents. We used high-resolution pQCT to measure standard morphological parameters in addition to cortical porosity (Ct.Po) and estimated bone strength by finite element analysis. Participants ranged in age from 9 to 22 years (n = 212 girls and n = 186 boys) who were scanned annually for either one (11%) or two (89%) years at the radius and for one (15%), two (39%), or three (46%) years at the tibia. Participants were grouped by the method of Tanner into prepubertal, early pubertal, peripubertal, and postpubertal groups. At the radius, peri- and postpubertal girls had higher cortical density (Ct.BMD; 9.4% and 7.4%, respectively) and lower Ct.Po (–118% and–56%, respectively) compared with peri- and postpubertal boys (all p < 0.001). Peri- and postpubertal boys had higher trabecular bone volume ratios (p < 0.001) and larger cortical cross-sectional areas (p < 0.05, p < 0.001) when compared with girls. Based upon the load-to-strength ratio (failure load/estimated fall force), boys had lower risk of fracture than girls at every stage except during early puberty. Trends at the tibia were similar to the radius with differences between boys and girls in Ct.Po (p < 0.01) and failure load (p < 0.01) at early puberty. Across pubertal groups, within sex, the most mature girls and boys had higher Ct.BMD and lower Ct.Po than their less mature peers (prepuberty) at both the radius and tibia. Girls in early, peri-, and postpubertal groups and boys in peri- and postpubertal groups had higher estimates of bone strength compared with their same-sex prepubertal peers (p < 0.001). These results provide insight into the sex- and maturity-related differences in bone microstructure and estimated bone strength. © 2012 American Society for Bone and Mineral Research


Introduction

  1. Top of page
  2. Abstract
  3. Introduction
  4. Materials and Methods
  5. Results
  6. Discussion
  7. Disclosures
  8. Acknowledgements
  9. References

Fragility fractures of the distal radius are common injuries sustained during adolescence1, 2 and are more prevalent in boys than in girls.3 The incidence of distal radius fractures peaks during the pubertal growth spurt,4–6 and epidemiological evidence suggests that the incidence of these fractures has increased by more than 30% over the past 30 years.3 The majority of these fractures occur during play and sport; however, changes in physical activity levels and sports participation fail to explain the increasing fracture rate.3 Alternatively, impaired bone quality during adolescence such as a deficiency in cortical bone may contribute to forearm fracture risk. Because 26% of adult bone mass is accrued during the pubertal growth spurt, impaired bone quality during growth may not only increase fracture risk during adolescence but also later in life.7

Early dual-energy X-ray absorptiometry (DXA) studies suggest that a transient deficit in bone mass may underpin the peak incidence of forearm fractures during puberty.7–9 In boys and girls, rapid accrual of bone mass lags behind linear growth by approximately one year.7 However, DXA is not capable of measuring volumetric bone mineral density (BMD) or bone microstructure elements that contribute to whole bone strength, nor can it distinguish between trabecular and cortical bone.10 Peripheral quantitative computed tomography (pQCT) measures trabecular and cortical volumetric BMD and bone geometry, and it provides estimates of bone strength in the growing skeleton.11–17 Previous pQCT studies found that total volumetric BMD at the distal radius did not differ between girls and boys across pubertal groups.11, 17 However, there was a sex difference in cortical BMD at the distal tibia.15 In addition, estimated bone strength assessed by pQCT lags behind linear growth, suggesting a possible transient deficit in bone strength.17 Although pQCT provides valuable information on bone structure and BMD, this technology is limited by the resolution (∼400 µm in-plane) and is therefore limited in its ability to accurately measure aspects of bone microstructure such as cortical porosity.11

Most recently, high-resolution pQCT (HR-pQCT) can accurately measure cortical and trabecular microstructure at the distal radius18 and the distal tibia.19 For example, at 82 µm, the resolution is sufficient to quantify cortical porosity using customized analysis tools.20–22 Cortical porosity may increase during puberty because of increased demands for calcium.23 However, because of the resolution required to quantify cortical pores, cortical porosity has yet to be directly measured in vivo in children and adolescents. Porosity is negatively associated with bone strength.24, 25 Importantly, bone strength can now be estimated using finite element (FE) models generated from HR-pQCT images.26

Most HR-pQCT studies to date have focused on adult populations and provided insight into the differences in bone quality between sexes and across age groups.27–29 There are few HR-pQCT studies of adolescents, and all published data are cross-sectional30–32 and do not provide insight into the changes across puberty. These studies described microstructural differences during adolescence and suggested that deficiencies in cortical bone may account for the high incidence of fractures.30, 31 HR-pQCT analyses that include standard morphological and density measurements enhanced by novel measures of cortical porosity and FE-estimated bone strength are needed to advance our understanding of bone growth and development. Because the radius and the tibia serve different weight-bearing and non-weight-bearing roles, it is important to evaluate both to establish site specificity. These advancements may provide insight into the high incidence of distal radius fractures during the pubertal growth spurt.

Therefore, the objective of this study was to use HR-pQCT to investigate differences in bone microstructure and estimated bone strength across puberty and between sexes. We also aimed to explore site-specific differences in microarchitecture and strength by evaluating both the distal radius and distal tibia.

Materials and Methods

  1. Top of page
  2. Abstract
  3. Introduction
  4. Materials and Methods
  5. Results
  6. Discussion
  7. Disclosures
  8. Acknowledgements
  9. References

Participants

Participants were healthy girls (n = 212) and boys (n = 186) aged 9 to 22 years. The older participants (14 to 22 years, n = 278) were part of the Healthy Bones (HBS) III follow-up study at the University of British Columbia.33–35 The younger participants (9 to 12 years, n = 120) were recruited from five elementary schools in Vancouver and Richmond, British Columbia, in 2009. The older participants were first scanned with HR-pQCT in 2008 at the distal tibia. In 2009 the distal radius was added to the scanning protocol for both the younger and older cohorts. Across both age cohorts at the distal tibia, there were 34 girls and 26 boys with one scan, 93 girls and 61 boys with two scans, and 85 girls and 99 boys with three scans. At the distal radius, there were 22 girls and 12 boys with one scan, and 152 girls and 131 boys with two scans (Fig. 1).

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Figure 1. Number of participants at baseline recruited from each cohort and number of follow-up scans analyzed for boys and girls at the distal radius and distal tibia.

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Our methods are described in detail elsewhere.32–35 Briefly, we measured height and weight to the nearest 0.1 cm and 0.1 kg, respectively, using standard protocols. Radius length was measured as the distance from the distal medial edge of the ulna to the proximal olecranon process. Tibia length was measured as the distance from the distal edge of the medial malleolus to the tibial joint line. We assessed maturity using standard definitions based on the method of Tanner by self-reported breast stage for girls and pubic hair stage for boys.36 We categorized Tanner stage 1 participants as prepubertal (PRE), Tanner stage 2 and 3 as early pubertal (EARLY), Tanner stage 4 as peripubertal (PERI), and Tanner stage 5 as postpubertal (POST).12, 30

We determined ethnicity from health history questionnaires that were previously completed by each participant's parents or guardians. As in previous studies,32, 33 participants were considered white (47%) if both parents (or all four grandparents) were born in North America or Europe. They were considered Asian (46%) if both parents (or all four grandparents) were born in China, India, Philippines, Vietnam, Korea, Taiwan, or other Asian countries. The remaining 7% of the participants were of mixed or other ethnicities. All participants were healthy, and none reported use of medications known to influence bone metabolism, mineralization, or calcium balance. All participants and parents provided informed written consent, and the University of British Columbia Clinical Research Ethics Board approved this study.

HR-pQCT scan acquisition

As in previous studies,32 all participants were scanned using HR-pQCT (XtremeCT; Scanco Medical, Brüttisellen, Switzerland) at the nondominant radius and tibia unless there was a previous fracture at the desired site, in which case the opposite limb was scanned. A single highly trained technician positioned each participant according to the standard manufacturer protocol.

For the distal radius, a two-dimensional scout view image was first acquired, and the technician placed the reference line at the medial edge of the distal radius. The region of interest scanned was at a distance of 7% of the total ulnar length from the reference line32 (Fig. 2). This site ensured that we did not scan the growth plate and that we could scan the same relative region in follow-up scans. The distal tibia was scanned at the 8% site from a reference line placed at the tibial plafond32 (Fig. 2). We scanned all participants using 60 kVp effective energy, 900 µA current, and 100 ms integration time to acquire 110 slices (approximately 9.02 mm) of the tibia and radius at an 82 µm nominal isotropic resolution.

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Figure 2. Scout view images of the distal radius (A) and distal tibia (B) illustrating the 7% and 8% measurement sites, respectively.

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Image processing and measurements

We used the standard manufacturer's method to filter and binarize the HR-pQCT images.37 To segment the cortical and trabecular regions, we used an automatic segmentation algorithm implemented in Image Processing Language (IPL V5.07, Scanco Medical).20 Standard morphological microstructure outcomes included total bone mineral density (Tt.BMD, mg HA/cm3), trabecular bone volume ratio (BV/TV), trabecular thickness (Tb.Th, mm), trabecular separation (Tb.Sp, mm), and trabecular number (Tb.N, 1/mm).37, 38 These measurements were validated against micro-computed tomography18, 39 and in adult populations have in vivo short-term reproducibility of <4.5%.26 Reproducibility in our lab is <3.8% for all parameters at the radius and tibia.

In addition to standard morphological outcomes, we assessed cortical bone microstructure with our customized segmentation algorithm. Outcomes included cortical porosity (Ct.Po, %) calculated as the number of void voxels within the cortex,20–22 cortical thickness (Ct.Th, mm) using a distance transform,40 and cortical bone mineral density (Ct.BMD, mg HA/cm3). We also calculated macrostructural parameters: cortical (Ct.Ar, mm2), trabecular (Tb.Ar, mm2), and total (Tt.Ar, mm2) cross-sectional areas based on our customized segmentation.

Finite element analysis

Using the three-dimensional HR-pQCT images, we generated FE meshes using the voxel conversion approach.41, 42 We simulated uniaxial compression on each radius and tibia section up to 1% strain using a Young's modulus of 6829 MPa and Poisson's ratio of 0.3.26

As previously reported, we used a custom FE solver (FAIM, Version 4.0, Numerics88 Solutions, Calgary, Canada) on a desktop workstation (Mac Pro, OSX, Version 10.5.6, Apple Inc., Cupertino, CA, USA; 2 × 2.8 GHz Quad-Core Intel Xenon) to solve the models.27 We estimated bone strength (ultimate stress, MPa) and failure load (N). 26 To estimate the risk of forearm fracture, we calculated the load-to-strength ratio (Φ)43, 44 based on a subject-specific fall force that incorporates subject height.45

Statistical analysis

We used a generalized estimating equation (GEE) model that incorporates follow-up scans as repeated measures to investigate the differences between sexes and across maturity groups. This model allows for the analysis of correlated, longitudinal data and was calculated using the following equation:46

  • equation image

The regression parameters, β, can be obtained where Yi is the vector of measurements for the ith subject, µi is the vector of means, and V is the covariance matrix. The dependent variables were bone microstructure measurements and FE estimates of bone strength, whereas the fixed factors were maturity and sex. We used limb length and height as covariates in the model. If there was a significant interaction effect detected between maturity × sex, we also evaluated the simple effects of maturity and sex. We performed pairwise comparisons between girls and boys within each maturity group. To determine changes across puberty, we performed comparisons within each sex between the least mature group (PRE) and the other maturity groups. We used SPSS Statistics (IBM, Version 19.0; Somers, NY, USA) for all analyses and a Bonferroni correction to account for multiple comparisons.

Results

  1. Top of page
  2. Abstract
  3. Introduction
  4. Materials and Methods
  5. Results
  6. Discussion
  7. Disclosures
  8. Acknowledgements
  9. References

Participant descriptives

Descriptive characteristics of the participants by maturity groups are provided in Table 1. Within each sex, as expected, more mature boys and girls were significantly taller, heavier, and had longer radii and tibias compared with their less mature peers. Between sexes, there were significant differences in height, weight, and limb length in the PERI and POST groups.

Table 1. Participant Descriptives by Puberty Group for Girls and Boys (Mean [SD])
Puberty groupGirlsBoys
PREEARLYPERIPOSTPREEARLYPERIPOST
  • Note: All p values after Bonferroni correction.

  • a,d

    p < 0.001,

  • b,d

    p < 0.01: significant difference between girls and boys within the same puberty group.

  • d

    p < 0.001,

  • e

    p < 0.01,

  • f

    p < 0.05: significant difference between puberty group and the PRE group within sex.

No.3169625019256775
Age (years)10.6 (0.7)12.9 (3.0)b,d16.7 (1.8)d18.8 (1.4)b,d10.8 (0.5)11.5 (1.1)e16.1 (1.5)d17.9 (1.5)d
Height (cm)140.7 (6.1)151.9 (7.3)d162.8 (6.0)a,d163.9 (6.7)a,d141.6 (6.3)150.0 (7.6)d171.5 (7.7)d176.6 (6.5)d
Weight (kg)33.2 (6.3)44.7 (9.1)d58.4 (10.7)d61.2 (8.8)a,d37.4 (6.2)44.9 (10.1)e61.8 (11.3)d72.1 (12.3)d
Radius length (cm)222 (14)240 (13)d260 (16)a,d259 (13)a,d228 (10)237 (15)f279 (21)d290 (14)d
Tibia length (cm)338 (19)366 (22)d386 (23)a,d386 (26)a,d346 (23)369 (25)e411 (27)d426 (23)d

Comparison between sexes within maturity categories

For all parameters with the exception of Tb.Sp and Tb.N at both sites and Tb.Th at the distal tibia, there was a statistically significant sex × maturity interaction (Tables 2 and 3).

Table 2. Bone Microstructure at the Distal Radius and Distal Tibia Across Puberty Groups for Girls and Boys (Mean [SD])
Puberty groupGirlsBoys
PREEARLYPERIPOSTPREEARLYPERIPOST
No.3169625019256775
  • Note: All p values after Bonferroni correction.

  • a

    p < 0.001,

  • b

    p < 0.01,

  • c

    p < 0.05: significant difference between girls and boys within the same puberty group.

  • d

    p < 0.001,

  • e

    p < 0.01,

  • f

    p < 0.05: significant difference between puberty group and the PRE group within sex.

Radius
 Tt.BMD (mg HA/cm3)255.8 (34.8)262.4 (52.7)328.4 (69.9)d361.1 (58.6)d260.4 (39.1)250.7 (40.9)313.0 (71.8)e369.4 (61.6)d
 Ct.BMD (mg HA/cm3)669.2 (51.6)677.2 (87.0)813.3 (100.8)a,d874.8 (53.4)a,d661.6 (44.5)654.3 (52.0)743.8 (85.5)d815.5 (68.6)d
 BV/TV0.136 (0.018)0.142 (0.018)0.140 (0.020)a0.141 (0.019)a0.148 (0.017)0.148 (0.015)0.157 (0.023)0.162 (0.023)
 Tb.Th (mm)0.068 (0.007)0.071 (0.010)0.073 (0.011)c0.074 (0.009)a,e0.067 (0.008)0.071 (0.009)0.081 (0.015)d0.085 (0.013)d
 Tb.Sp (mm)0.431 (0.047)0.436 (0.055)0.465 (0.081)f0.468 (0.072)f0.397 (0.045)0.418 (0.044)0.440 (0.072)0.444 (0.061)e
 Tb.N (1/mm)2.04 (0.19)2.00 (0.21)1.88 (0.28)e1.88 (0.23)e2.19 (0.18)2.09 (0.18)1.94 (0.26)d1.92 (0.22)d
 Ct.Th (mm)0.69 (0.11)0.72 (0.19)1.02 (0.23)d1.10 (0.14)c,d0.72 (0.14)0.71 (0.18)1.03 (0.29)d1.23 (0.22)d
 Ct.Po (%)4.3 (1.5)4.1 (1.8)b1.9 (1.7)a,d1.1 (0.5)a,d5.0 (1.5)5.1 (1.3)4.2 (1.9)2.8 (1.8)d
 Tt.Ar (mm2)174.3 (23.2)199.0 (26.9)d211.3 (26.8)a,d216.4 (26.5)a,d191.1 (28.7)216.5 (30.5)d274.6 (43.4)d272.9 (39.8)d
 Tb.Ar (mm2)138.2 (23.2)158.9 (25.6)d156.9 (28.4)a,e157.0 (26.1)a,e151.6 (29.5)175.2 (32.8)e209.5 (43.5)d196.6 (38.1)d
 Ct.Ar (mm2)31.3 (5.5)34.9 (11.1)e52.1 (14.0)c,d57.4 (9.6)a,d33.9 (6.0)35.1 (8.0)61.1 (18.8)d74.1 (13.4)d
Tibia
 Tt.BMD (mg HA/cm3)256.7 (24.7)262.1 (34.9)295.5 (32.4)d308.0 (32.3)d271.9 (27.8)275.1 (29.8)293.5 (34.3)e321.1 (36.1)d
 Ct.BMD (mg HA/cm3)717.7 (43.2)743.8 (72.4)d835.3 (52.1)a,d866.0 (43.1)a,d714.5 (31.9)723.2 (41.1)768.5 (50.9)d821.7 (42.7)d
 BV/TV0.155 (0.013)0.153 (0.015)b0.153 (0.014)a0.154 (0.013)a0.163 (0.011)0.164 (0.011)0.165 (0.015)0.169 (0.016)
 Tb.Th (mm)0.080 (0.008)0.082 (0.011)0.089 (0.009)d0.089 (0.009)d0.081 (0.008)0.081 (0.008)0.090 (0.008)d0.090 (0.009)d
 Tb.Sp (mm)0.459 (0.047)0.473 (0.061)b0.488 (0.050)c0.475 (0.044)b0.440 (0.030)0.438 (0.033)0.458 (0.053)0.443 (0.053)
 Tb.N (1/mm)1.89 (0.17)1.84 (0.21)c1.76 (0.17)c,e1.80 (0.16)b1.95 (0.13)1.96 (0.14)1.87 (0.18)1.91 (0.19)
 Ct.Th (mm)0.83 (0.11)c0.90 (0.19)d1.17 (0.19)d1.25 (0.19)a,d0.89 (0.19)0.93 (0.26)1.27 (0.31)d1.45 (0.24)d
 Ct.Po (%)5.1 (1.7)4.9 (2.0)b3.6 (1.4)a,e3.3 (1.0)a,d6.1 (1.3)6.3 (1.4)6.3 (1.8)5.2 (1.6)
 Tt.Ar (mm2)591.5 (49.7)635.5 (59.4)a,d636.1 (60.2)a,d636.6 (52.7)a,d650.4 (65.1)721.7 (82.3)d776.7 (81.5)d761.5 (87.1)d
 Tb.Ar (mm2)505.8 (50.0)541.6 (57.8)b,d531.4 (60.0)a529.2 (52.3)a542.2 (63.4)603.9 (81.5)d650.0 (80.7)d624.6 (85.4)d
 Ct.Ar (mm2)72.0 (8.8)a82.5 (16.4)b,d102.9 (14.2)a,d109.3 (14.2)a,d85.7 (14.9)96.4 (20.6)d120.5 (20.5)d137.1 (21.5)d
Table 3. Finite Element Estimated Bone Strength Parameters at the Distal Radius and Distal Tibia Across Puberty Groups for Girls and Boys (Mean [SD])
Puberty groupGirlsBoys
PREEARLYPERIPOSTPREEARLYPERIPOST
No.3169625019256775
  • Note: All p values after Bonferroni correction.

  • a

    p < 0.001,

  • b

    p < 0.01,

  • c

    p < 0.05: significant difference between girls and boys within the same puberty group.

  • d

    p < 0.001,

  • e

    p < 0.01,

  • f

    p < 0.05: significant difference between puberty group and the PRE group within sex.

Radius
 Failure load (N)1050 (178)1346 (359)d1815 (418)a,d1983 (344)a,d1162 (216)1402 (269)d2347 (623)d2749 (538)d
 Ultimate stress (MPa)21.5 (5.6)25.2 (8.2)f35.2 (8.6)d38.4 (8.2)d22.3 (7.6)24.1 (7.4)35.5 (11.6)d42.4 (9.4)d
 Load-to-strength ratio1.76 (0.29)c1.45 (0.40)d1.03 (0.23)b,d0.94 (0.14)a,d1.58 (0.32)1.32 (0.28)d0.86 (0.27)d0.73 (0.14)d
Tibia
 Failure load (N)4058 (503)b4591 (780)b,d5269 (703)a,d5498 (684)a,d4697 (656)5354 (848)d6361 (864)d6895 (947)d
 Ultimate stress (MPa)26.1 (4.2)28.3 (6.2)e34.2 (5.3)d36.2 (5.2)d28.2 (5.2)29.3 (5.8)34.2 (5.4)d38.5 (5.5)d

At the distal radius, the sex difference in bone density and microstructure was most evident in children in the PERI and POST groups (Table 2). In these groups, girls had higher Ct.BMD (p < 0.001) and lower Ct.Po (p < 0.001; Fig. 3) than boys. In contrast, boys in the PERI and POST groups had higher BV/TV (both p < 0.001) and Tb.Th (PERI p < 0.05, POST p < 0.001) compared with girls. Boys in the PERI and POST groups had a larger Ct.Ar compared with girls in the same groups (p < 0.05 and p < 0.001, respectively). Estimated distal radius bone strength (ultimate stress), which accounts for cross-sectional area, was not significantly different between girls and boys at any stage. In contrast, estimated failure load was higher in boys than girls in the PERI and POST groups (both p < 0.001). Based on the calculated load-to-strength ratio, boys had a significantly lower risk of radial fracture at every stage, with the exception of the EARLY group (Table 3).

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Figure 3. Plots of cortical density (Ct.BMD; A), cortical porosity (Ct.Po; B), cortical area (Ct.Ar; C), and failure load (D) at the distal radius for girls and boys by puberty group. Error bars represent SE. a, p < 0.001; b, p < 0.01; c, p < 0.05: significant difference between girls and boys within the same puberty group. d, p < 0.001; e, p < 0.01; significant difference between puberty group and the PRE group within sex. All p values are after Bonferroni correction.

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We observed similar sex differences in bone outcomes at the distal tibia in children in the PERI and POST groups; however, sex differences in some variables were also present in the EARLY group (Table 2). With the exception of the PRE group, girls had lower Ct.Po compared with boys (p < 0.01, p < 0.001, p < 0.001, EARLY to POST, respectively; Fig. 4). Boys had a larger Tt.Ar in the EARLY, PERI, and POST groups and Ct.Ar in all groups compared with girls. Although ultimate stress at the distal tibia was not significantly different between boys and girls, failure load estimates at the distal tibia were higher in boys compared with girls in each pubertal group (p < 0.01, p < 0.01, p < 0.001, p < 0.001, PRE to POST, respectively).

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Figure 4. Plots of cortical density (Ct.BMD; A) and cortical porosity (Ct.Po; B) at the distal tibia for girls and boys by puberty group. Error bars represent SE. a, p < 0.001; b, p < 0.01; significant difference between girls and boys within the same puberty group. d, p < 0.001; e, p < 0.01; significant difference between the puberty group and the PRE group within sex. All p values are after Bonferroni correction.

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Comparison across maturity categories within sex

At the distal radius, both girls and boys in all groups had higher Tb.Ar, Tt.Ar, failure load, and load-to-strength ratios than their same-sex peers in the PRE group (Tables 2 and 3). For both sexes, BV/TV was not different in any of the groups compared with the PRE group. For boys and girls, Ct.BMD and Tt.BMD were higher in the PERI and POST groups compared with the same-sex PRE group (all p < 0.001). Girls had lower Ct.Po in the PERI and POST groups compared with the PRE girls, and POST boys had lower Ct.Po compared with PRE boys (all p < 0.001). Ultimate stress estimates from FE analysis were higher in girls in all groups and in boys in the PERI and POST groups compared with the same-sex PRE group (EARLY girls p < 0.05; remainder p < 0.001).

For both girls and boys at the distal tibia, Tt.Ar, Ct.Ar, and failure load were higher in all groups compared with the PRE group (Tables 2 and 3). Similar to the distal radius, BV/TV was not significantly different across pubertal groups in boys or girls. For girls, Ct.Th was higher in all groups compared with the PRE group (all p < 0.001), whereas boys had higher Ct.Th only in the PERI and POST groups compared with boys in the PRE group (both p < 0.001). In boys, Ct.Po was not significantly different across pubertal groups. In girls, Ct.Po was lower in PERI (p < 0.01) and POST (p < 0.001) girls compared with PRE girls. Finite element estimates of ultimate stress were higher in girls in all groups compared with PRE girls (all p < 0.001), and higher in PERI and POST boys compared with PRE boys (both p < 0.001).

Discussion

  1. Top of page
  2. Abstract
  3. Introduction
  4. Materials and Methods
  5. Results
  6. Discussion
  7. Disclosures
  8. Acknowledgements
  9. References

Our findings characterize the many sex- and maturity-related differences in growing bone microstructure and strength at the weight-bearing tibia and the non-weight-bearing radius. We extend the existing pediatric bone quality literature by supplementing standard HR-pQCT morphological analysis of the growing radius and tibia with novel measures of cortical porosity, estimated bone strength, and failure load. At both skeletal sites, we report significant differences in cortical and trabecular bone macro- and microstructure between girls and boys across pubertal stages (Fig. 5).

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Figure 5. A schematic representation of differences in total bone size and cortical bone density for girls (G) and boys (B) across puberty (assessed using the method of Tanner [T]). For our purposes, we defined Tanner stage 1 as prepuberty (PRE), Tanner stages 2 and 3 as early puberty (EARLY), Tanner stage 4 as peripuberty (PERI), and Tanner stage 5 as postpuberty (POST). Significant differences between girls and boys are shown for finite element estimated failure load, where boys' values exceed girls' after early puberty, and cortical porosity (Ct.Po), where boys' values exceed girls' after prepuberty. (Diagram not exact scale.)

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In particular, as others30 and we47 previously reported, bone size was consistently larger in boys compared with girls, and girls' cortices were denser compared with boys. However, we also report girls' less porous cortices compared with boys in the more mature groups (EARLY, PERI, POST). Thicker trabeculae underpin the significant differences in trabecular outcomes in PERI and POST boys compared with PERI and POST girls. The relevance of our findings relates to the transient deficit in cortical bone that may explain the high incidence of distal radius fractures in boys and girls during the pubertal growth spurt.1, 6

To date, one HR-pQCT study examined the distal radius and distal tibia during growth,30 whereas another only examined the distal radius.31 Although the small sample size in the study by Wang and colleagues30 limited their ability to detect significant maturity- and sex-related differences, the trends in radius trabecular microstructure, Ct.BMD, and Tt.Ar and all tibia measurements were similar to our findings. However, unlike Wang and colleagues, we did not observe lower Ct.Th in EARLY boys compared with PRE boys. This discrepancy may be because of differences in the methods used to segment the cortical and trabecular regions. In the current study, we used a validated automatic segmentation method,20, 21 whereas Wang and colleagues defined cortical bone as five consecutive bone voxels. However, this approach may be undermined by high Ct.Po along the endocortical surface in boys during early puberty. This would result in lower values for Ct.Th and Ct.Ar. Our findings align with the only other study to use HR-pQCT to assess the distal radius of adolescents.31 Kirmani and colleagues found that Ct.Th did not differ between Tanner stage 1 and Tanner stage 3 boys.31 As reported in a previous pQCT study,17 we found that Ct.Th was significantly higher at the distal radius in boys than in girls in the POST group only.

Across maturity groups, we found a difference in cortical bone structure and strength between girls and boys. Although Ct.BMD was similar between PRE and EARLY girls and boys, PERI and POST girls had less porous and denser cortices compared with boys at both the radius and tibia. Parfitt thought this sex difference in Ct.BMD may be because of increased demand for calcium during the pubertal growth spurt, a demand met by increased intracortical bone turnover.23 During this transient process, increased bone turnover would, in turn, lead to increased cortical porosity. Boys experience a greater height velocity (4.9 versus 2.9 cm/year) on average, as well as at peak5 and a longer growth spurt,48 compared with girls. Thus, the higher values for Ct.Po and lower Ct.BMD we observed in boys may well be explained by boys' greater height velocity.

In their recent cross-sectional study, Kirmani and colleagues calculated a cortical porosity index using the volume of cortical pores divided by the total cortical volume31 using the Gaussian filter-threshold method to segment the cortical and trabecular regions, which was different from our approach. They observed significantly greater values for this index in boys at bone-age group 4 and girls at bone-age group 3 (which approximates our PERI and EARLY groups, respectively). Despite girls' advantage at the cortex, boys are conferred a substantial structural advantage by their having larger bones (represented by total cross-sectional area). Specifically, small additions of bone to the periosteal surface confer increased resistance to compressive forces and exponentially increased resistance to bending forces.49

To provide better insight into the peak incidence of forearm fractures during puberty, we used finite element analysis to estimate bone strength. Because ultimate stress is adjusted by bone cross-sectional area, it was not significantly different between boys and girls at any maturity time point. However, when we predicted failure load and the load-to-strength ratio44 (which incorporates estimated fall force), boys were significantly higher than girls in their same maturity category except for the EARLY group. Despite adjusting for limb length and height, the apparent paradox of no difference in estimated failure load between early pubertal girls and boys, rather than higher failure loads in girls, may speak to the inability of FE analysis to adequately capture the high porosity that leads to a transient weakness in growing bone. One solution in the future may be to impose other loading conditions in addition to compressive loading to assess bone strength.

The apparent site-specificity for sex differences in bone microstructure and FE estimates of bone strength50, 51 at this site is indicated by higher failure loads compared with girls. The tibia had higher failure loads than the radius as well as higher estimates of size-adjusted ultimate stress likely the result of the weight-bearing nature of the site.

We note that our study has limitations. Because of the northern location of the participants (latitude 49 degrees), it is possible that some participants may suffer from a degree of hypovitaminosis D. Because of similar exposure across participants, we do not expect this to influence our results. However, the absolute values may differ from a population in a more southern geographical location. Also, we did not account for the ethnic diversity of our cohort in our analysis. There are documented differences in bone mass52 between Asians and Caucasians however, as our cohort also included children of mixed ethnicity, we chose to include participants of all ethnicities in our analysis. In addition, we accept that based on the maturational indices used, we were unable to align boys and girls at exactly the same maturational time point. Longer-term prospective studies that span the pubertal growth spurt and that allow more direct and comparable measures of maturity (ie, age at peak height velocity) are needed to more specifically ascertain the differences in bone quality between boys and girls. It is also important to note that our customized method used to quantify cortical porosity21 cannot detect pores smaller than 82 µm. These smaller pores may be more prevalent in children and adolescents. In addition, our estimates of bone strength and failure load were based on uniaxial compression, which may not be an accurate representation of the forces applied in an actual fall on an outstretched hand. Thus, future research should incorporate a greater variety of loading conditions. Finally, load-to-strength ratios based on fall force calculations have not been validated in adolescent populations; however, this estimate of fracture risk was used in recent studies of young adults27, 28 and adolescents.31

Despite these limitations, our findings provide a comprehensive description of maturity-related differences in bone quality and strength in girls and boys. It also encourages research to delve further into the high incidence of distal radius fractures during the pubertal growth spurt. Prospective studies of bone microstructure comparing children who have sustained a fracture with their nonfractured age- or maturity-matched counterparts would serve to further elucidate the concept of transient bone fragility.

Disclosures

  1. Top of page
  2. Abstract
  3. Introduction
  4. Materials and Methods
  5. Results
  6. Discussion
  7. Disclosures
  8. Acknowledgements
  9. References

All the authors state that they have no conflicts of interest.

Acknowledgements

  1. Top of page
  2. Abstract
  3. Introduction
  4. Materials and Methods
  5. Results
  6. Discussion
  7. Disclosures
  8. Acknowledgements
  9. References

We thank the students, staff, and parents in the Vancouver and Richmond School Districts for their continued support and participation in the Healthy Bones III Study. We also thank the staff at the Centre for Hip Health and Mobility, in particular Danmei Liu, for their assistance with data collection and ongoing support of this research.

This study was funded by Canadian Institutes of Health Research (MOP-84575 and MOP-106611). HAM is a Michael Smith Foundation for Health Research Senior Scholar; SKB is an Alberta Innovates-Health Solutions Senior Scholar.

Authors' roles: KKN contributed to the design, data analysis, and interpretation. SAM contributed to data acquisition and analysis. TF contributed to the statistical design and data analysis. HMM, SKB, and HAM contributed to the conception, design, and interpretation. All authors contributed to drafting or critically revising the manuscript.

References

  1. Top of page
  2. Abstract
  3. Introduction
  4. Materials and Methods
  5. Results
  6. Discussion
  7. Disclosures
  8. Acknowledgements
  9. References