BONE MINERAL DENSITY OF LUMBAR SPINE IN BRAZILIAN
CHILDREN AND ADOLESCENTS AGED FROM 6 TO 14 YEARS
Antonio
Sergio Macedo Fonseca 1
Vera
Lucia Szejnfeld2
Maria
Teresa Terreri3
José
Goldenberg2
Marcos
Bosi Ferraz2
Maria
Odete Esteves Hilário 4
1. Assistant
Professor, Department of Pediatrics Universidade Federal do Rio Grande do Norte
2. Associate
Professor, Division of Rheumatology, Department of Medicine - UNIFESP/EPM
3. Pediatric
Rheumatologist, Division of Allergy, Immunology and Rheumatology, Department of Pediatrics
- UNIFESP/EPM
4. Associate
Professor, Division of Allergy, Immunology and Rheumatology, Department of Pediatrics -
UNIFESP/EPM
Division of
Allergy, Immunology and Rheumatology, Department of Pediatrics and Division of Rheumatology, Department of Medicine -
UNIFESP/EPM
Address for
correspondence:
Maria
Teresa Terreri
Rua
Loefgreen 2381- ap.141
CEP:04040-004
São
Paulo SP - Brasil
Telephone
number: (011) 576-4426
Fax number:
(011) 5579-1590
E-mail address:
terreri@uninet.com.br
Main subject of
the paper: bone mineral density in normal Brazilian children and adolescents
The paper is
intended to be a full original paper in the Clinical Investigation Section
The authors
wish that their names act as referees.
Running title:
bone mineral density in normal Brazilian children and adolescents
BONE MINERAL
DENSITY OF LUMBAR SPINE IN BRAZILIAN CHILDREN AND ADOLESCENTS AGED FROM 6 TO 14 YEARS
ABSTRACT;
INTRODUCTION
The authors
performed a study of bone mass in eutrophic Brazilian children and adolescents using DXA,
in order to obtain curves of bone mineral
content (BMC) and bone mineral density (BMD) by chronological age and correlate these
values with weight and height. Health Caucasian children and adolescents, 120 boys and 135
girls, aged from 6 to 14, residents in São
Paulo, Brazil, were selected from the Pediatric Department, outpatient clinic of Hospital
São Paulo (Universidade Federal de São Paulo). The measurement of bone mineral content
(BMC), bone mineral density (BMD) and the area of the vertebral body of the L2-L4 segment
were obtained through a unit of DXA. BMC and BMD values for the lumbar spine (L2-L4)
showed a progressive increase between 6 and 14 years of age, in both sexes, presenting a
distribution that fitted an exponential curve. We identified an increase of mineral gain
in female patients older than 11 years which was
maintained until 13 years of age, when there was a new decrease in the velocity of bone
mineralization. Male patients presented a period of accelerated gain of bone mass after 11
years of age that was maintained until 14 years of age. At 14 years of age the BMD mean
values for boys and girls were 0.984 g/cm2
and 1.017 g/cm2, respectively. In a
stepwise multiple regression analysis, the results of pairs of variables showed that the
pair vertebral area-age was the most significant in the determination of the
BMD values and the introduction of a third variable (weight or height), did not
significantly raise the coefficient of determination.
Key-Words:
Bone mineral density - Lumbar spine densitometry - Children Adolescents
The increase of
the life-span in developing countries has turned osteoporosis into a major health issue,
as it had already been observed in developed countries1.
The problems
concerning the control of loss of bone mass after adulthood, which is a characteristic of
this disease, has motived an increased interest regarding prophylactic procedures, such as
the accomplishment of an adequate peak of bone mass2,3, since the bone mass
that is present at any time during adulthood is the ratio between the amount obtained
during adulthood and the loss caused by the aging process4.
Despite the
different opinions about the period when this peak of bone is reached5,6,7,8
the authors agree that the peak of the mineral bone mass is acquired up to the end of
puberty9,10,11, which has caused the rise of interest in the study of bone
mineral content during childhood and adolescence.
The dual-energy
X-ray absorptiometry (DXA), with its low radiation dose and high level of accuracy and
precision, has been extensively employed to measure bone mass in children and adolescents.
The authors
performed a study of bone mass in eutrophic children and adolescents using DXA, in order
to obtain curves of bone mineral content
(BMC) and bone mineral density (BMD) by chronological age which can allow later
comparisons with groups of children and adolescents with diseases or other osteopenizing
conditions and correlate these values with anthropometric data.
Health
Caucasian eutrophic children and adolescents, 120 boys and 135 girls, aged from 6 to 14,
residents in São Paulo, Brazil, were selected from the Pediatric Department of Hospital
São Paulo (Universidade Federal de São Paulo), from May 1995 to January 1998, and
invited to take part in this study. The exclusion criteria were: history of
endocrinopathy, nephropathy, gastroenteropathy, or rheumatic diseases, bronquial asthma,
malnutrition, short stature (below 10 percentile), obesity (over 120% of weight for
height), premature birth, prolonged immobility period (more than two weeks), history of
two or more accidental fractures or one pathological bone fracture, treatment with
corticosteroids or other drugs that affect bone metabolism.
All children
were clinically assessed by a pediatrician (ASMF). Weight and height were measured by
using electronic scale and wall anthropometer.
The measurement
of bone mineral content (BMC), expressed as g; bone mineral density (BMD), expressed as
g/cm2; and the area of the vertebral
body of the L2-L4 segment, expressed as cm2;
were obtained through a unit of DXA available commercially (DPX, Lunar Radiation Corp.,
Madison, WI, USA) using medium mode scan. The BMD was only studied at lumbar spine, since
the evaluation of the femoral neck may be biased due to the presence of growth cartilage
as well as to the technical difficulties related to the posicioning in this age group.
Statistical
analysis: The Kruskal-Wallis test was employed to compare the values of BMD, BMC,
vertebral area, weight and height between genders. The analyses of multiple linear
regression, which tested BMD, BMC, vertebral area (L2-L4), weight, height and age with BMC
and BMD as dependent variables were performed through the stepwise, forward and backward
methods. The statistical package SPSS/PC was used for processing the data. The significant
level was set as 0.05.
The mean values
of BMC, BMD, vertebral area (L2-L4), weight
and height for age and gender with their standard deviations are shown on tables 1 and 2.
The BMC and BMD
results for the lumbar spine (L2-L4) showed a progressive increase between 6 and 14 years
of age, in both sexes, presenting a distribution that fitted an exponential curve (figure 1 and 2). This distribution showed that the
increase of bone mass was not steady, being observed periods with distinct velocities of bone mineralization.
Female children
between 6 and 10 years of age presented a period of slight increase of bone mass. We
identified an increase of mineral gain in female patients older than 10 years which was maintained until 13 years of age, when there
was a new decrease in the velocity of bone mineralization.
Male children
also presented a primary period of less intense mineralization that continued until 11
years of age, followed by a period of accelerated gain of bone mass that was maintained
until 14 years of age.
It was
observed, in both sexes, a statistically significant difference between the BMD at 6 years
and BMD in children 11 years old and older (H observed=98.1 and 62.7 for girls and boys,
respectively; H critical=15.5; p<0.05).
The values of
BMD during the interval between 6 and 14 years of age increased 54% and 59% in boys and
girls, respectively. At 14 years of age the BMD mean values were 0.984 g/cm2 and 1.017 g/cm2, which corresponds to 81% and 85% of the
expected bone density for Brazilian Caucasian men and women between 35 and 40 years of
age, respectively12.
The analysis of
the relationship between the weight and height and bone mass showed a striking correlation
between BMC and the following variables: vertebral area (r2= 0.91 and 0.87 for females and males,
respectively), weight (r2 = 0.73 and
0.69, respectively) and height (r2
= 0.70 and 0.76, respectively). However, after vertebral area and age adjusts, weight and
height did not present additional influence
in the determination of the BMC measurements, as demonstrated by the analysis of multiple
regression and for this reason the regression equation, that considers the vertebral area
and children age was chosen (BMC = -17.468 +
1.246 VA + 0.618 Ag, r2= 0.92 for girls and BMC = -12.102 + 1.059 VA + 0.423
Ag, r2= 0.87 for boys).
Regarding BMD,
we observed a less intense correlation when compared to BMC, although it was equally
important: vertebral area (r2 = 0.68
and 0.52 for females and males respectively), weight (r2 = 0.62 and 0.45, respectively) and height (r2 = 0.59 and 0.49, respectively). During the
stepwise multiple regression analysis, the results of pairs of variables showed again that
the pair vertebral area-age was the most significant. The introduction of a
third variable (weight or height), as previously observed with BMC, did not raise the
coefficient of determination (r2)
significantly and for this reason the regression equation, that considers the vertebral
area and children age was chosen (BMD = 0.225 + 0.012 VA + 0.025 Ag, r2= 0.72
for girls and BMD = 0.336 + 0.099 VA + 0.017 Ag, r2= 0.55 for boys).
The mean values of BMD in the lumbar spine per age
obtained in our study were quite equivalent to those obtained in studies performed with a
smaller group of Finnish children13, using a similar equipment (Lunar DPX,
Medium mode).
The values of
BMC and BMD in the lumbar spine showed a progressive increase with age, a kind of
distribution that approached an exponential function, as observed by other authors14.
This arching relationship was determined by the variation in the velocity of mineral gain
that happened at different ages. After an initial period with slight increases of the
values of BMC and BMD, we observed a period of rapid
growth and accumulation of bone mass in the lumbar spine, especially striking after 10 and
11 years of age in the female and male sex, respectively. This acceleration of bone mass
gain between 10 and 14 years of age, later in the male sex, has been extensively
documented in the literature2,7,10,11,15,16,17,18 and it seems to be associated
with pubertal growth. Unfortunately, evaluation of Tanner puberal state could not been
done which could have partially explained the increase in bone mass.
The striking
increase of BMC and BMD, reaching values that are similar to those expected for a young
Brazilian adult12 demonstrates the importance of this period to attainment an
adequate peak of bone mass. However, this
increase of bone mass variables does not only reflect the real increase of bone mineral
density, but also the increase of bone volume that happens with the growth process.
In DXA, such as
in other projection methods, BMD is calculated from the BMC, expressed as g and the
projected area of the region of interest (in this case, vertebral body) without taking the
bone thickness into account. Thus the increase of bone size causes an unreal increase of
BMD obtained by this method. Since the vertebras are complex structures that grow in all
dimensions during childhood and adolescence, it is justifiable to suppose that this method
underestimates the BMD value of smaller children and overestimates that of bigger ones. In
diseases states where disturbs of growth occur, this systematic error can produce
distortions in the results, making the mineral bone mass evaluation by DXA cumbersome19.
In order to
minimize this error, Katzman et al8 and Kröger et al10 introduced
some equations which objective was to obtain corrected or
volumetric BMD (vBMD), expressed as g/cm3. Although these corrected values
still present distortions, the vBMD curves obtained by these authors showed an increase
with age that was less intense than those obtained from BMD without correction or
areal BMD. Those results confirm the limited data of vBMD in lumbar spine
utilizing quantitative computed tomography (QCT), that did not show a significant increase
with age20 or showed a little expansion of bone mass only in puberal period 21.
In our series, we observed a strong correlation
between the values of BMC and BMD and the variables weight and height, in both sexes. This
close relationship between the bone mass and anthropometric variables, had already been
identified in the early studies of Mazess and Cameron22 and later confirmed in
studies performed in bone from the appendicular bone structure19,23,24,25,26,27,28
and from the lumbar spine10,11,15,16,29,30.
For the
analysis of stepwise multiple regression we decided to use additionally the variable
vertebral area (L2-L4), in a like manner as used
by De Priester et al.26, who considered the values of bone width, obtained by
screening, in the regression analysis, when elaborating a predictive equation for BMC
values of the forearm obtained by single photon absorptiometry (SPA).
Indeed, during
multiple regression by the stepwise method, vertebral
area (cm2), chronological age
(years), weight (kg), and height (cm) were used as independent variable, with BMC (g) and
BMD (g/cm2) as dependent variables. Borderline p values were reached while only
the vertebral area and age were considered. The use of other variables (weight and
height), after the vertebral area and age adjustments did not prove to be significant to
predict BMC or BMD.
These results
support the idea that correlations between the BMD and the anthropometric variables weight
and height are in great part due the increase of bone dimension during childhood and
adolescence, and confirm that BMD depends on age and growth in this period.
Although the
present study has obtained equations for the predictive values of BMC and BMD for children
and adolescents between 6 and 14 years of age with statistical significance and high
coefficients of correlation, which permit comparisons with groups of sick children31,
the distinctive characteristics of our series call for additional studies in order to
establish the validation of its application from other parts of the country.
1.
Avioli,
LV; & Heaney, RP (1991). Calcium intake and bone health. Calcif. Tissue Int,
48:221-223.
2.
Anderson,
JJB & Henderson, RC. Dietary factors in the development of peak bone mass. In:
Burckhardt, P & Heaney, RP. Nutritional aspects of osteoporosis, Raven Press, 1991,
p3-19.
3.
Bonjour
JP, Theintz G, Law F, Slosman D, Rizzoli P (1994). Peak bone mass. Osteoporosis
Int, 4 (suppl 1):7-13.
4.
Johnston,
CC & Slemenda CW. The relative importance of nutrition compared to the genetic factors
in the development of bone mass. In: Burckhardt, P & Heaney, RP (eds): Nutritional
aspects of osteoporosis, Press, 1991,
p21-25.
5.
Rodin
A, Murby B, Smith MA, Caleffi M, Feutiman I, Chapman MG, Fogelman I (1990). Premenopausal
bone loss in the lumbar spine and neck of femur: a study of 225 Caucasian women. Bone, 11: 1-5.
6.
Gilsanz
V, Gibbens DT, Carlson M, Boechat MI, Cann CE, Schulz EE (1988a). Peak trabecular
vertebral density: a comparison of adolescent and adult females. Calcif Tissue Int, 43:
260-262.
7.
Bonjour
JP, Theintz G, Buchs B, Slosman D, Rizzoli P (1991). Critical years and stages of puberty
for spinal and femoral bone mass
accumulation during adolescence. J Clin Endocrinol Metab, 73: 555-563.
8.
Katzman
DK, Bachrach LK, Carter DR, Marcus R (1991). Clinical and anthropometric correlates of
bone mineral acquisition in health adolescent girls.
J Clin Endocrinol Metab, 73: 1332-1339.
9.
Chesnut
III CH (1989). Is osteoporosis a pediatric disease ? Peak
bone mass attainment in the adolescent female. Public Health
Rep, 104 (suppl): 50-54.
10. Kröger H,
Kotaniemi A, Kröger L, Alhava E (1993). Development
of bone mass and bone density of spine and femoral neck. A prospective study of 65
children. Bone Miner, 23: 171-82.
11. Lu
PW, Briody JN, Ogle GD, Morley K, Humphries IR, Allen J, Howman-Giles R, Sillence D,
Cowell CT (1994). Bone mineral density of total body, spine and femoral neck in children
and young adult. A cross-sectional and longitudinal study. J Bone Miner
Res, 9: 1451-8.
12. Szejnfeld VL,
Atra E, Baracat EC, Aldrighi J, Civitelli R (1995). Bone
density in white Brazilian women: rapid loss at time around the menopause. Calcif. Tissue
Int 56:186-191.
13. Kröger H,
Kotaniemi A, Vainio P, Alhava E (1992). Bone
densitometry of the spine and femur in children by dual- energy X-ray absorptiometry. Bone
Miner, 17: 75-85.
14. De
Schepper J, Derde MP, Van den Broeck M, Piepsz A, Jonckheer MH (1991). Normative data for
lumbar spine bone mineral content in children: influence of age, height, weight and
puberal stage. J Nucl Med, 32: 216-220.
15. Glaster
C, Braillon P, David L, Cochat P, Meunier PJ, Dalmas PD (1990). Measurement of bone
mineral content of the lumbar spine by dual energy x-ray absorptiometry in normal
children: correlations with growth parameters. J
Clin Endocrinol Metab, 70: 1330-1333.
16. Southard
RN, Morris JD, Mahan JD, Hayes JR, Torch MA, Sommer A, Zipf WB (1991). Bone mass in
healthy children: measurement with quantitative DXA. Radiology, 179(3):735-738.
17. Boot
AM, de Ridder MAJ, Pols AP, Krenning EP, de Munick Keizer-Schrama SMPF (1997). Bone
mineral density in children and adolescents: relation to puberty, calcium intake, and
physical activity. J Clin Endocrinol Metab 82:57-62.
18. Warner
JT, Cowan FJ, Dunstan FDJ, Evans WD, Webb DKH, Gregory JW (1998). Measured and predicted
bone mineral content in healthy boys and girls aged 8-16 years. Acta Paediatr 87:244-249.
19. Molgaard
C, Lykke Thomsen B, Michaelsen KF (1998). Influence of weight, age and puberty on bone
size and bone mineral content in healthy children and adolescents. Acta Paediatr
87:494-499.
20. Mora S,
Goodman WG, Loro ML, Roe TF, Gilsanz V (1994). Age-related
changes in cortical and cancellous vertebral bone density in girls: assessment with
quantitative CT. Am J Roentgenol, 162: 405-9.
21. Gilsanz
V, Gibbens DT, Roe TF, Carlson M, Senge HO, Boechat MI, Huang HK, Schulz EE, Libanati CR,
Cann CC (1988b). Vertebral bone density in children: effect of puberty. Radiology, 166:
847-850.
22. Mazess
RB & Cameron JR. Skeletal growth in school children: maturation and bone mass (1971).
Am J Phys Anthrop, 35:399-408.
23. Specker
B, Brazerol W, Tsang R, Levin R, Searcy J, Steichen J (1987). Bone mineral content in
children 1 to 6 years of age. Am J Dis Child, 141:343-344.
24. Landin
L, Nilssen BE (1981). Forearm bone mineral content in children: normative data. Acta
Paeditr Scand, 70:919-923.
25. Li
JY, Specker BL, Ho ML, Tsang RC (1989). Bone content in black and white children into 6
years of age. Am J Dis Child, 143:1346-1349.
26. De Priester
JA, Cole TJ, Bishop NJ (1991). Bone
growth and mineralization in children aged 4 to 10 years. Bone Miner, 12: 57-65.
27. Bell
NH, Shary J, Stevens J, Garza M, Gordon L, Edwards J (1991). Demonstration that bone mass
is greater in black than in white children. J Bone Miner Res, 6:719-723.
28. Troverbach
WT, Man SA, Gommers D, Zwamborn AW, Grobbee DE (1991). Determinants of bone mineral
content in childhood. Bone Miner, 13:55-67.
29. Dhuper
S, Warren MP, Brooks-Gunn J, Fox R (1990). Effects
of hormonal status on bone density in adolescent girls. J Clin Endocrinol Metab, 71:
1083-1088.
30. Ponder
SW, Mc Cormick DP, Fawcett D, Palmer JL, Mc Kernan MG, Brouhard BH (1990). Spinal bone mineral density in children aged 5.00
through 11.99 years. AJDC, 144:
1346-1348.
31. Goldenberg J,
Fonseca AS, Len C, Hilário MO, Szejnfeld V, Atra E (1992). Bone
density in juvenile systemic lupus erythematosus. American College of Rheumatology, 56th
annual scientific meeting, Atlanta, Abstract C135.