Osteoporosis International

, Volume 15, Issue 4, pp 263–273

Attainment of peak bone mass at the lumbar spine, femoral neck and radius in men and women: relative contributions of bone size and volumetric bone mineral density

Authors

  • Yvette M. Henry
    • Bone Metabolism Group, Division of Clinical Science (North)Northern General Hospital
  • Diana Fatayerji
    • Bone Metabolism Group, Division of Clinical Science (North)Northern General Hospital
    • Bone Metabolism Group, Division of Clinical Science (North)Northern General Hospital
Original Article

DOI: 10.1007/s00198-003-1542-9

Cite this article as:
Henry, Y.M., Fatayerji, D. & Eastell, R. Osteoporos Int (2004) 15: 263. doi:10.1007/s00198-003-1542-9

Abstract

The age at which peak bone mineral content (peak BMC) is reached remains controversial and the mechanism underlying bone mass “consolidation” is still undefined. The aims of this study were to investigate; (1) the timing of peak BMC by studying bone size and volumetric BMD (vBMD) as separate entities and (2) to determine the relative contributions of bone size and vBMD to bone mass “consolidation”. A total of 132 healthy Caucasian children (63 boys and 69 girls, ages 11–19 years) and 134 healthy Caucasian adults (66 men and 68 women, ages 20–50 years) were studied. BMC was measured by DXA at the AP and lateral lumbar spine (LS) femoral neck (FN) and ultradistal radius (UDR). vBMD and bone volume (size) were estimated. Bone mass “consolidation” was examined between age 16 years to the age peak bone values were attained. During growth, BMC and bone size increased steeply with age and approximately 80–90% of peak values were achieved by late adolescence. vBMD at the spine and UDR (in women) increased gradually, but vBMD at the FN and UDR in men remained almost constant. During “consolidation”, bone size continued to increase with little change in vBMD. Peak vBMD at the lumbar spine was reached at 22 and 29 years in men and women, respectively, but earlier at the FN at 12 years. At the UDR peak vBMD was achieved at age 19 years in women, with little change in men. In conclusion, peak vBMD and bone size are almost fully attained during late adolescence. Although speculative, the lack of change in vBMD during consolidation implies that the continued increase in bone mass may primarily be due to increases in bone size rather than increases in either trabecular volume, cortical thickness or the degree of mineralisation of existing bone matrix (vBMD). Skeletal growth and maturation is heterogeneous, but crucial in understanding how the origins of osteoporosis may begin during childhood and young adulthood.

Keywords

Bone sizeConsolidationGenderGrowthVolumetric bone density

Introduction

Peak bone mass can be defined as the amount of bony tissue present at the end of skeletal growth. Peak bone mineral content (peak BMC) or peak areal bone mineral density (peak aBMD) and subsequent bone loss are important determinants for the risk of osteoporotic fracture in later life. The importance of peak aBMD in fracture risk is evident from the familial resemblance in BMD, whereby bone density in daughters of women with osteoporotic fractures has been reported to be lower compared to normal premenopausal women [1, 2, 3].

Despite the known importance of peak bone mineral density, the age at which peak bone values are reached remains controversial. It is important to understand the time course for attaining peak bone density if preventative lifestyle changes for osteoporosis are to be adequately implemented, and to understand how the origins of osteoporosis may begin during childhood and young adulthood. The timing of peak bone density has received considerable attention, but with varying results. Earlier studies measuring BMC of the forearm by single-photon absorptiometry [4] and more recent studies measuring aBMD at the spine and hip report peak values to be achieved during the 3rd and 4th decades [5]. Some have suggested that bone mass increases slowly into young adulthood and peaks during the 4th decade of life [6], while others have reported no changes in bone mass during the 3rd and 4th decades [7]. In more recent years, it has been more generally accepted that the majority of bone mass accumulation is achieved by late adolescence [8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19] followed by a period of “consolidation” [10, 20]. These discrepancies in the timing of peak aBMD warrant further investigation. Those studies that have examined aBMD over a wide age range have studied women only, and bone development is gender-specific.

Measurement of aBMD by DXA is a planar measurement dependent on bone size [21, 22]. aBMD measurements incorporate information about bone width and height but not depth. Therefore, a bigger bone will be reported as having a higher aBMD compared to a smaller bone when both bones could have the same density of bone within the periosteal envelope (volumetric BMD, vBMD). vBMD is a better measure of mineral status since bone size is taken into account. In terms of the attainment of peak aBMD, during young adulthood bone volume continues to increase, but if the amount of bone tissue in the periosteal envelope remains constant (due to concurrent endosteal resorption), aBMD would continue to increase due to the effect of bone size but vBMD would remain constant. Consequently, it may be more informative to examine the timing of peak vBMD, which has not been previously investigated. Although in late puberty there is rapid accrual of bone mineral within the periosteal envelope, puberty affects bone size more than vBMD so that when vBMD is measured by QCT or estimated mathematically it increases only slightly (approximately 10–30%) during adolescence, which is much smaller than the corresponding increases in bone size and mineral mass [11]. Therefore, the inaccuracy of aBMD measurements on the interpretation of BMD results during growth and young adulthood should be considered. More studies investigating peak vBMD and changes with age in vBMD and bone size separately are needed so that changes in BMC can be apportioned to either changes in bone size, vBMD or both.

“Consolidation” is the term referring to the process of increase in bone mass after the cessation of linear growth, at the end of pubertal development. Bone mass “consolidation” has rarely been studied successfully due to the lack of studies covering a wide enough age range to fully investigate this process [9, 10]. Therefore, the mechanism by which bone mass continues to increase after linear growth has stopped remains unclear. However, to gain further understanding of the process of “consolidation”, the following questions need to be addressed. Does bone mass continue to increase during this period due to a continued increase in bone volume (size) implicating an increase in periosteal apposition? Or does bone mass continue to increase due to an increase in vBMD, which would implicate an increase in cortical width, a reduction in cortical porosity, an increase in trabecular volume, or an increase in the degree of mineralisation of bone matrix? Also, are there gender differences in these possible mechanisms?

Therefore, a cohort of adolescent children and young adults spanning a wide age range (11–50 years) were studied to examine the following aims; (1) to determine whether the majority of peak BMC and peak vBMD at the lumbar spine, femoral neck (FN) and ultradistal radius (UDR) is attained by late adolescence, (2) to determine whether the timing of peak bone mass is affected by examining bone size and vBMD separately, (3) to determine the relative contributions of bone size and vBMD to bone mass “consolidation” by separating bone mass into bone volume and vBMD and (4) to determine whether the mechanism of consolidation differs between skeletal sites and the genders.

Materials and methods

Subjects

One hundred and thirty-two healthy Caucasian children (63 boys and 69 girls) aged 11–19 years were recruited randomly from local schools in the Sheffield area. Written permission was gained from the head teacher in all the schools approached. One hundred and thirty-four healthy Caucasian adults (66 men and 68 premenopausal women) aged 20–50 years were also recruited randomly from general practitioner (GP) registers by letter of invitation. All subjects gave written informed consent and parental consent was obtained additionally for those subjects under 18 years. All subjects were measured once. A questionnaire on health status and medication was completed. No subjects had any history of bone disease or were taking any drugs known to affect bone metabolism or calcium homeostasis. Volunteers were excluded if they had any past use of steroids, diuretics, heparin, chemotherapy or anticonvulsants. Height was measured in metres using a wall-mounted stadiometer (Holtain, Crymych, Dyfed, Wales) and weight was measured in kg with a set of upright balance scales (Seca, Hallamshire Scales, Sheffield, UK). Body mass index (BMI) was calculated as weight/height squared. The study was approved by the North Sheffield Local Research Ethics Committee.

Dual-energy X-ray absorptiometry (DXA)

BMC at the lateral lumbar spine (LS, L2–L3) was measured by DXA using a Hologic Acclaim 4500A densitometer (Hologic Inc., Waltham, Mass., USA) and obtained from the lateral lumbar spine DXA scan. vBMD and bone volume were estimated by combining data from anterior-posterior (AP) and lateral bone scans based on assuming the vertebrae to be cylindrical [21]. Therefore, lumbar spine bone volume was estimated as area×π×width/4 whereby the area is the total area of L2–L3 and the width was the average width of L2–L3 as determined for each subject by combining AP and lateral bone scans. Lateral vBMD was calculated as BMC/volume of a cylinder. This method of estimating vBMD is not a true measure of bone density (mineral mass per unit volume of mineralised bone matrix) because we are examining bone as an organ. Treating bone as an organ incorporates the whole bone including bone marrow and intracortical canals. Therefore, the estimated vBMD is an “apparent” bone density measurement referred to as vBMD in this paper. The coefficient of variation for AP and lateral lumbar spine aBMD was 1.3% and 2.8%, respectively, which was calculated from the differences between duplicate measurements in 22 female volunteers recruited from local general practitioner registers (ages 52–71 years).

BMC at the femoral neck (FN) and ultradistal radius (UDR) were measured using a Lunar DPX densitometer (Lunar Corp., Madison, Wisc., USA). vBMD and bone volume at the FN and UDR were estimated using DXA-derived measurements. At the FN and UDR, vBMD was estimated as BMC/bone volume, where volume=area×π×width/4, by assuming these skeletal sites were cylindrical.

Pubertal staging

Pubertal staging was determined according to the grading system of Tanner [23], by self-assessment using line drawings and written descriptions of the five stages of puberty. This method has been validated in adolescents [24]. This approach was chosen for reasons of compliance and to minimise the invasion of privacy. In the ascertainment of pubertal staging, only the pattern of breast development was used in girls and both penile and testicular development was used in boys.

Statistical analysis

Data sets from both groups (adults and children) were combined to examine the timing of peak values and changes in BMC, bone volume and vBMD with age (11–50 years). This age range was selected to demonstrate changes during adolescence (growth) through to young adulthood (“consolidation”). To evaluate the appropriate timing of peak bone mass and trends with age two approaches were undertaken. In the first analysis, the Lowess procedure for scatterplot smoothing was used to produce smooth curves, allowing estimates of the age when peak values may be attained. No prior assumptions were made about the type of model that would best fit the data. In the second analysis, based on the number of inflections generated in the Lowess curves, the variables of interest were best fit by either first, second, third or fourth order polynomial regression equations. Thus the models were expressed as:
$$ \begin{array}{*{20}l} {{{\text{First}}\;{\text{order}}} \hfill} & {{y = \beta _{0} + \beta _{1} {\text{age}}} \hfill} \\ {{{\text{Second}}\;{\text{order}}} \hfill} & {{y = \beta _{0} + \beta _{1} {\text{age}} + \beta _{2} {\text{age}}^{2} } \hfill} \\ {{{\text{Third}}\;{\text{order}}} \hfill} & {{y = \beta _{0} + \beta _{1} {\text{age}} + \beta _{2} {\text{age}}^{2} + \beta _{3} {\text{age}}^{3} } \hfill} \\ {{{\text{Fourth}}\;{\text{Order}}} \hfill} & {{y = \beta _{0} + \beta _{1} {\text{age}} + \beta _{2} {\text{age}}^{2} + \beta _{3} {\text{age}}^{3} {\text{ }}\beta _{4} {\text{age}}^{4} } \hfill} \\ \end{array} $$

The 95% confidence intervals for each term in the model were calculated. Peak bone size below age 40 years and peak bone values for all other parameters were calculated using the coefficients. Age 16 years was used as an indication of the cessation of linear growth because the increase in vertebral height appeared to plateau around age 15 years in girls and 17 years in boys, which is supported by other work examining sitting height in children [25]. To estimate the extent of growth in bone size and mass at age 16 years, each variable was expressed as a percentage of the predicted adult peak derived from the polynomial regression equation.

Results

The characteristics of the study population are shown in Table 1 and Table 2. Height, weight and BMI were compared to reference curves estimated for children in 1990 by Freeman et al. 1995 [26]. Standard deviation scores (SDS) were calculated using Cole’s LMS method [26] (data not shown). For height SDS, weight SDS and BMI SDS only 9%, 3% and 1% of children, respectively, had SDS >4, indicating that the study population were within normal standards. The R2 values for the relationship between all bone measurements and age and values at peak and 16 years are given in Table 3 for women and Table 4 for men. Differences in bone mass and size in relation to age and sex were observed.
Table 1

Characteristics of the study population. Results are expressed as mean (SD)

Characteristic

Children (11–19 years)

Adults (20–50 years)

Boys (n=63)

Girls (n=69)

Men (n=66)

Women (n=68)

Age (years)

15.3 (2.2)

15.1 (2.1)

36.9 (8.7)

34.5 (8.1)

Height (m)

1.69 (0.1)

1.62 (0.1)

1.77 (0.1)

1.65 (0.1)

Weight (kg)

62.8 (18.6)

56.6 (12.4)

80.0 (12.1)

66.6 (11.3)

BMI (kg/m2)

21.5 (4.5)

21.6 (5.2)

25.7 (3.6)

24.5 (3.8)

AP BMD (g/cm2)

0.880 (0.2)

0.904 (0.2)

1.07 (0.1)

1.09 (0.1)

Lateral BMD (g/cm2)

0.742 (0.1)

0.725 (0.1)

0.759 (0.1)

0.806 (0.1)

FN BMD (g/cm2)

1.05 (0.2)

0.970 (0.1)

1.07 (0.1)

1.01 (0.1)

UDR BMD (g/cm2)

0.501 (0.1)

0.451 (0.1)

0.519 (0.1)

0.441 (0.1)

Table 2

Number of children in each pubertal stage

Tanner stage

Boys

Girls

I

0

1

II

7

5

III

14

29

IV

12

22

V

29

12

Table 3

The age at which peak values occur, values at peak and 16 years, percentage peak at 16 years with R2 values for all bone measurements in women. ns not significant

Measurement

Age at peak (years)

Values at peak

Values at 16 years

% Peak at 16 years

Sy.x

R2 (%)

Lateral spine

BMC, g

28

17.71

14.06

79

2.92

35*

Bone volume, cm3

39

58.66

50.75

87

7.89

39*

vBMD, g/cm3

29

0.300

0.282

94

0.03

11*

Femoral neck

BMC, g

23

5.197

4.686

90

0.65

31*

Bone volume, cm3

37

19.47

16.49

85

3.13

19*

vBMD, g/cm3

12

0.277

0.275

99

0.04

3*

UDR

BMC, g

23

1.635

1.545

94

0.26

6*

Bone volume, cm3

ns

ns

ns

ns

ns

ns

vBMD, g/cm3

19

0.276

0.271

98

0.05

6*

*P<0.05

Table 4

The age at which peak values occur, values at peak and 16 years, percentage peak at 16 years with R2 values for all bone measurements in men. ns not significant

Measurement

Age at peak (years)

Values at peak

Values at 16 years

% Peak at 16 years

Sy.x

R2 (%)

Lateral spine

BMC, g

22

19.92

16.28

82

3.35

48*

Bone volume, cm3

23

72.21

59.87

83

11.0

52*

vBMD, g/cm3

22

0.279

0.270

97

0.03

8*

Femoral neck

BMC, g

21

6.663

5.873

88

0.81

46*

Bone volume, cm3

23

25.16

21.93

87

3.30

43*

vBMD, g/cm3

12

0.266

0.263

99

0.04

6*

UDR

BMC, g

21

2.362

2.093

89

0.34

43*

Bone volume, cm3

21

9.192

8.234

90

1.21

52*

vBMD, g/cm3

ns

ns

ns

ns

ns

ns

*P<0.05

Lumbar spine BMC, bone volume and vBMD

Lateral spine BMC increased steeply with age in men and women to peak at age 22 years in men but later in women at 28 years (Fig. 1a). By age 16 years, the percentage of peak BMC attained was 82% in boys but slightly lower in girls at 79%. Vertebral bone volume also increased with age, more steeply in boys than girls. During the period of observation (11–50 years), the age at which the rapid increase in bone size begins to slow down occurred at approximately age 23 years in men but somewhat later in women at 43 years (Fig. 1b). By age 16 years, the percentage of bone volume achieved was comparable in both sexes; 83% for boys and 85% for girls. vBMD increased gradually with age in men and women, with peak values reached at around age 22 years in men but later in women at age 29 years (Fig. 1c). The percentage of peak vBMD achieved was comparable in both sexes; 97% for boys and 94% for girls.
Fig. 1

Lateral lumbar spine BMC (a), bone volume (b) and vBMD (c) versus age in children and adults in both sexes. In men, BMC and bone volume were best fit by 4th order polynomial equations and vBMD was best fit by a 3rd order polynomial equation. In women, BMC, bone volume and vBMD were best fit by 3rd, 4th and 2nd order polynomial equations, respectively. The numbers given refer to the percentage of values attained by 16 years and the age peak values were achieved

Femoral neck BMC, bone volume and vBMD

As shown in Fig. 2a, FN BMC increased with age in both sexes to peak at age 21 years in men but slightly later in women at 23 years. By age 16 years, the percentage of peak BMC attained was comparable in both sexes; 88% for boys and 90% for girls. FN bone volume increased with age, more steeply in boys than girls (Fig. 2b). The age at which the rapid increase in bone size begins to slow down occurred at approximately age 23 years in men but somewhat later in women at 37 years. The percentage bone volume attained was 87% in boys but slightly lower in girls at 85%. For the estimate of vBMD, there was little change with age in adolescent children but a slight linear decline with age was observed in adult men and women (Fig. 2c). The highest values occurred at 12 years or earlier; therefore due to the linear decline in vBMD the percentage achieved at age 16 was 99% in both boys and girls (Fig. 2c).
Fig. 2

Femoral neck BMC (a), bone volume (b) and vBMD (c) in children and adults in both sexes. In both sexes, BMC and FN BMAD were best fit by 4th and 1st (straight line) order polynomial equations, respectively. Bone volume in men and women was best fit by 4th and 2nd order polynomial equations, respectively. The numbers given refer to the percentage of peak values attained by 16 years and the age peak values were achieved

Ultradistal radius BMC, bone volume and vBMD

Similar to the FN, BMC at the UDR increased with age in men and women to peak at age 21 years in men but later in women at age 23 years. The increase was steeper in boys than girls. The percentage of peak BMC accrued in boys was 89% but higher in girls at 94% (Fig. 3a). In contrast to the FN where bone volume increased in both sexes, radial bone volume increased with age in men only, with no change in women (Fig. 3b). In men, the age at which the rapid increase in bone volume begins to slow down occurred at approximately age 21 years with 90% of peak values attained in boys. vBMD changed little with age in men, but in contrast to the FN where there was little change in vBMD with age in women, at the radius vBMD increased in women to peak at around age 19 years. 98% of peak vBMD was attained in girls by 16 years (Fig. 3c).
Fig. 3

Ultradistal radius BMC (a), bone volume (b) and vBMD (c) in children and adults in both sexes. In men and women, BMC was best fit by 4th and 3rd order polynomial equations, respectively. Bone volume in men and vBMD in women were best fit by 4th order polynomial equations. There was no significant effect of age on bone volume in women and vBMD in men The numbers given refer to the percentage of peak values attained by 16 years and the age peak values were achieved

Discussion

BMC, vBMD and bone volume during growth

Lumbar spine

BMC at the lumbar spine increased steeply with age in children and into young adulthood in both sexes. The majority (approximately 80%) of peak BMC was achieved by late adolescence, which is supported by several other studies [8, 9, 10, 11, 12, 13, 14, 17, 18, 19]. Thus, the findings in the present study and in others emphasise that puberty is a critical time for rapid accrual of bone mass.

In contrast to the steep increase in BMC, vBMD increased gradually during growth in children and into young adulthood in both sexes. By late adolescence peak vBMD had almost (94%) been achieved. The steeper increase in BMC compared to vBMD is explained by the effect of the increase in vertebral bone volume that was observed at this site. Up to the age at which the rapid increase in bone volume begins to slow down, 85% of bone volume was attained by age 16 years. A similar gradual increase in vBMD at the spine during growth has been reported by others, despite different measurement techniques of vBMD by QCT [27, 28, 29] or estimated from mathematical formulae [17, 18, 30]. vBMD increases during growth because the increase in bone mass must be greater than the increase in external bone size.

The morphological basis for the increase in vBMD is most likely to be an increase in trabecular thickness rather than number, since studies have shown increases in trabecular thickness [31] with either no change [32] or a decrease in trabecular number [33]. Also, the number of trabeculae is determined early in development, since it depends on the number of capillaries that invade the zone of provisional calcification [33]. The increase in vertebral bone size is likely to be due to an increase in all dimensions by endochondral ossification and periosteal apposition.

In the present study, the increase in vertebral bone size was steeper with age in boys than girls, which is in agreement with the greater vertebral size reported in boys [28, 29, 34, 35]. Greater vertebral size in boys appears to result from their wider vertebrae, since vertebral width has been found to be greater in boys with no gender differences in vertebral height [28, 35, 36]. Failure to achieve maximum vertebral bone size at any given age during growth has important implications in the risk of osteoporotic fracture in later life. Vertebral width and volume may be reduced in men and women with spine fractures compared to controls, suggesting that reduced bone size may be a risk factor for osteoporotic fracture [37, 38, 39, 40]. If bone size is reduced in patients with fractures, this could result from either reduced periosteal apposition during growth, ageing or both [3]. However, it is not clear whether the magnitude of these possible geometric differences is great enough to affect fracture prevalence.

Femoral neck

At the femoral neck, peak vBMD had already been achieved by 12 years (or earlier) in both sexes. Therefore, by late adolescence peak vBMD had already begun to decline marginally, with 99% of peak values present at this time. Similar to the lumbar spine, this lack of change in vBMD with age during growth clearly contrasts with the steeper size dependent increases in BMC with age that were observed at this site in the present study and in others [8, 9, 10, 13, 14, 17, 18]. vBMD at the femoral neck is almost constant during growth because the increase in bone mass and in bone volume are almost proportional. The femoral neck consists predominantly (75%) of cortical bone, and this lack of change in cortical volumetric bone density with age during growth has been consistently reported by others [17, 18, 21, 27, 29, 41, 42]. The consistency of vBMD during growth is not widely recognised because most studies of skeletal growth express their results as BMC or aBMD as a function of age [6, 8, 15, 43, 44, 45].

In the present study, the increase in bone size at the femoral neck was steeper with age in boys than girls. This could be explained by greater bone width in the appendicular skeleton observed in boys, at the femoral neck [46, 47] and metacarpals [48, 49], due to greater periosteal apposition at puberty [49]. Greater periosteal apposition in boys could be androgen-mediated, since testosterone deficiency has been reported to decrease periosteal bone formation and reduce bone size in male rats [50, 51], while oestrogen deficiency increases periosteal apposition in female rats [50, 52]. This would imply that in girls periosteal expansion is less compared to boys due to the inhibitory effect of oestrogen. However, studies using animal models need interpreting with caution before any strong inferences in humans can be made.

Ultradistal radius (UDR)

The changes in bone size and vBMD at the UDR were different in boys and girls. In boys, there was no significant effect of age on vBMD during growth. However, bone size increased steeply, with 90% of peak values achieved by age 16 years. Thus, the increase in BMC was due to the increase in size since there was very little change in vBMD, as observed in other work [48]. Similar to the femoral neck, the increase in bone mass and size is proportional, resulting in the lack of change in vBMD. However in contrast, Rauch and colleagues [53] measured vBMD at the distal radius by peripheral QCT (pQCT) and observed an increase in vBMD after age 14–15 years in boys. The reasons for these differences are unclear.

In contrast to the boys, vBMD increased during growth in girls, with 98% of peak values attained by late adolescence, but with little change in bone size. The observed increase in vBMD in girls contrasts with the study by Zamberlan et al. 1996 [48] (in which vBMD remained constant), but suggests that with the observed lack of change in bone size, the increase in BMC in girls in the current study may primarily be due to a greater accrual of bone mass within the periosteal envelope (vBMD). The contrasting findings in the study by Zamberlan et al. 1996 [48] may arise from their use of radiographs to estimate bone density, whereas DXA was used in the current study. Radiographs are not accurate for measuring aBMD because they are more subject to change in soft tissue. The increase in vBMD observed in girls in the present study may arise due to an increase in trabecular volume, cortical width by endosteal apposition, the degree of mineralisation of bone matrix or a decrease in cortical porosity, since the growth in bone size appears to be complete. Work based on measurements at the distal radius by pQCT has shown little change in cortical thickness up to age 13 years but a rapid increase thereafter, with little change in trabecular vBMD [53]. Therefore, the increase in vBMD may be mainly due to an increase in cortical thickness by endosteal apposition.

The increase in vBMD at the UDR in girls contrasts the lack of change in vBMD at the femoral neck. The differing results between these skeletal sites are not fully understood, but if the increase in vBMD at the UDR occurs due to an increase in cortical thickness as mentioned previously [53], it may be possible that endocortical apposition differs between these two sites. At the UDR, endocortical apposition may be greater as the increase in bone size ceases, whereas at the femoral neck minimal endocortical apposition may be matched by increasing bone size and so vBMD remains constant.

The increase in bone size observed at the radius in boys will occur by an increase in bone width by periosteal apposition and an increase in bone length by endochondral ossification. As mentioned previously, periosteal apposition is greater in boys than girls. This greater periosteal apposition in bones translates into greater bone strength, since some indices of bone strength (section modulus and strength strain index) have been reported to be greater in boys compared to girls [54]. This may occur because boys add bone to the periosteum where the effect on bone strength is highest, whereas girls add bone to the endosteum, which has less effect on bone strength [54]. Hence, at the radius the gender differences in bone size and vBMD during growth illustrates the sexual dimorphism of the growing skeleton.

Bone mass “consolidation”

In the present study, bone mass consolidation was investigated as the period between ages 16 years to the age peak bone values were achieved. This incorporates the time from the end of skeletal maturation into young adulthood. It is generally thought that after skeletal maturation when the epiphyses have fused, any further increase in aBMD is due to “consolidation” of the skeleton with no further increase in bone size, thereby implicating an increase in trabecular volume, cortical width, the degree of mineralisation of bone matrix or a decrease in cortical porosity. There is little data to support these concepts, since few studies have examined bone density over a wide enough age range to consider growth and the events taking place after skeletal maturity [9, 10].

In the present study, by examining bone size and bone mass separately, it would appear that the continued increase in BMC after skeletal maturity may be primarily due to an increase in bone size. The continued increase in bone volume into young adulthood with little increase in vBMD at the spine, femoral neck and UDR (in men) supports this concept.

The continued increase in bone size during young adulthood (except the radius in women), although not widely recognised, has been reported by others [38, 46, 55, 56, 57, 58]. If bone mass “consolidation” was primarily due to an increase in vBMD, then vBMD would continue to increase to a greater degree compared to bone volume, but this was not case in the current study. Therefore, with the findings in the present study of an increase in bone volume with very little increase in vBMD, we can speculate that the increase in BMC following the cessation of longitudinal growth may primarily be due to a continued increase in bone size implicating an increase in periosteal apposition. To further support the concept of continuing increase in bone size, Libanati et al. 1999 [59] studied metacarpal bone indexes in pubertal girls and found that increases in metacarpal length ceased at Tanner stage III but increases in metacarpal width and cortical thickness continued beyond this Tanner stage.

Timing of peak vBMD

The timing of peak BMC in the present study is in accordance with several studies reporting the majority of peak bone mass to be achieved during adolescence followed by small increases thereafter [8, 9, 10, 11, 12, 13, 14, 17, 18, 19]. It would be more accurate to examine the timing of peak vBMD because aBMD being dependent on size will be influenced by the continued increase in bone size during this time as previously described. During young adulthood bone volume increases, but if the amount of bone tissue in the enlarging vertebrae remains constant, aBMD would continue to increase due to the effect of bone size but vBMD would remain constant. Hence, it may be more informative to look at peak vBMD, although this would prevent direct comparisons with many other studies.

At the lumbar spine, peak vBMD was achieved at ages 22 and 29 years in men and women, respectively. The age of peak vBMD in women is comparable to work by Matkovic et al. 1994 [10] who estimated vBMD of the third lumbar vertebra using the same method as in the present study but in women only. It is not fully understood why peak vBMD occurred earlier in men than women, especially since pubertal development is later in boys. However, the early work by Garn et al. 1964 [60] at the second metacarpal has shown that with age cortical thickness increases in both sexes but increases more rapidly in men to peak earlier at approximately 25 years. The increase in women is more gradual and peaks later at 45 years. Thus, peak bone mass would occur earlier in men than in women. In terms of skeletal sites, the metacarpals being part of the appendicular skeleton and the vertebrae part of the axial skeleton, would make it inappropriate to make assumptions about the vertebrae based on the metacarpals. However, the findings in Garn’s work add another dimension to the events involved in the attainment of peak bone mass.

At the femoral neck, peak vBMD had already been achieved by 12 years of age in both sexes, which is much earlier compared to the radius, although also part of the appendicular skeleton. This difference in the timing of peak vBMD suggests that the pattern of bone development is region-specific, which has also been reported by others [9, 13, 18, 43, 44]. Also, the differences between skeletal sites may be related to whether the site is predominantly trabecular (UDR) or cortical (femoral neck) in nature. It has been suggested that trabecular and cortical bone may respond differently to metabolic and mechanical stimuli during growth [9], due to the relatively larger surface area involved in remodelling activity in trabecular compared to cortical bone[61]. Studies have also shown longitudinally that before puberty, growth of the legs was more rapid than growth in the spine while the converse was true at puberty [11, 19].

At the radius, the timing of peak vBMD differed greatly between men and women. In women, peak vBMD was achieved as early as 19 years, but in men there was little change in vBMD with age. As mentioned previously, it appears that in men, the timing of peak BMC we are accustomed to observing is driven by the increase in bone size. The rapid increase in bone size began to slow down at 21 years. For that reason, the majority of bone size in men needs to be attained before 21 years to minimise risk of fracture.

Limitations

There are some limitations of the study. The cross-sectional study design will be affected by secular changes and we recognise that the best approach is a prospective study. However, cross-sectional studies like this one can provide the basis for prospective studies. Regarding the increase in bone size observed in the present study, reports have shown a significant correlation between longitudinal changes in BMC and bone area [62, 63]. Therefore, an increase in BMC causes an increase in area, which is an artefact of DXA. This may result from the edge-detection algorithms used in DXA machines. As a result, some of the increase in bone size observed in the current study may be due to this artefact. This limitation may be overcome by using QCT. Additionally, the method used in the present study to estimate vBMD does not take subsiding cortical porosity into account, which is thought to contribute to bone mass “consolidation” [64].

During growth, there will be associated increases in lean and fat mass. Work has reported the increase in fat mass to be greater than the increase in lean mass [65]. This inhomogeneous distribution of soft tissue will affect DXA measurements, since the technique corrects for soft tissue based on a homogeneous distribution [48]. Hangartner and Johnston 1990 [66] have shown that this inhomogeneous distribution of soft tissue altered (increase or decrease) DXA measurements by 10%. However, this will be a greater problem in longitudinal studies, where the same region of interest is studied more than once and so body composition will differ between measurements and hence influence aBMD results.

Conclusion

Based on our results, we conclude that; (1) the majority of peak bone mass and size are acquired by late adolescence followed by small increases thereafter at some skeletal sites (period of “consolidation”); (2) the pattern of bone growth during adolescence, and the timing of peak bone values are sex- and region-specific; (3) during growth, the skeleton becomes much larger but only slightly denser and (4) the mechanism of bone mass “consolidation” may be due to continued increases in bone size at some skeletal sites but due to increases in volumetric bone density at other sites. Skeletal growth and maturation is heterogeneous but crucial in understanding how the origins of osteoporosis may begin during childhood and young adulthood.

Acknowledgements

We would like to thank all the staff at the Osteoporosis Centre, Sheffield and the volunteers who took part in the study.

Copyright information

© International Osteoporosis Foundation and National Osteoporosis Foundation 2004