Calcium-Enriched Foods and Bone Mass Growth in Prepubertal Girls
J. Clin. Invest.
© The American Society for Clinical Investigation, Inc.
Volume 99, Number 6, March 1997, 1287–1294
Calcium-enriched Foods and Bone Mass Growth in Prepubertal Girls:
A Randomized, Double-blind, Placebo-controlled Trial
Jean-Philippe Bonjour,* Anne-Lise Carrie,
and Rene Rizzoli*
Division of Bone Diseases, formerly Division of Clinical Pathophysiology, WHO Collaborating Center for Osteoporosis and Bone
Disease, Department of Internal Medicine,
Division of Nuclear Medicine, Department of Radiology,
and Reproduction, Department of Pediatrics, University Hospital, Geneva; and
Serge Ferrari,* Helene Clavien,* Daniel Slosman,
Division of Biology of Growth
Nestle Research Center, Vaud, Switzerland
High calcium intake during childhood has been suggested
to increase bone mass accrual, potentially resulting in a
greater peak bone mass. Whether the effects of calcium sup-
plementation on bone mass accrual vary from one skeletal
region to another, and to what extent the level of spontaneous
calcium intake may affect the magnitude of the response
has, however, not yet been clearly established. In a double-
blind, placebo-controlled study, 149 healthy prepubertal
girls aged 7.9
0.1 yr (mean
two food products containing 850 mg of calcium (Ca-suppl.)
or not (placebo) on a daily basis for 1 yr. Areal bone mineral
density (BMD), bone mineral content (BMC), and bone size
were determined at six sites by dual-energy x-ray absorpti-
ometry. The difference in BMD gain between calcium-sup-
plemented (Ca-suppl.) and placebo was greater at radial
(metaphysis and diaphysis) and femoral (neck, trochanter,
and diaphyses) sites (7–12 mg/cm
bar spine (2 mg/cm
per yr). The difference in BMD gains
between Ca-suppl. and placebo was greatest in girls with a
spontaneous calcium intake below the median of 880 mg/d.
The increase in mean BMD of the 6 sites in the low-calcium
consumers was accompanied by increased gains in mean
BMC, bone size, and statural height. These results suggest a
possible positive effect of calcium supplementation on skel-
etal growth at that age. In conclusion, calcium-enriched
foods significantly increased bone mass accrual in prepu-
bertal girls, with a preferential effect in the appendicular
skeleton, and greater benefit at lower spontaneous calcium
J. Clin. Invest.
1997. 99:1287–1294.) Key words:
bone mineral density
SEM) were either allocated
per yr) than in the lum-
The bone mass accrual occurring during childhood and adoles-
cence is a major determinant of peak bone mass, and thereby
of the risk of osteoporotic fractures occurring in advanced age
(1–3). At the end of the growth period, a large variance in
bone mineral density (BMD)
and content (BMC), in either
the axial or the appendicular skeleton, is observed both in
healthy females and males (4–8). Many genetic and environ-
mental factors have been suggested to influence bone mass ac-
cumulation during this period (9–15).
It is usually accepted that increasing calcium intake during
childhood and adolescence can promote a greater increase in
bone mass, and thereby a higher peak bone mass (16–21). An-
alyzing the relationship between bone mass and spontaneous
calcium intake, however, indicates that not all studies (22–27)
have found a positive correlation between these two variables.
Only a few prospective randomized double-blind interven-
tion trials have examined the effects of calcium supplements in
children and adolescents (12, 28–30). Although the results of
these studies suggest that calcium supplementation can posi-
tively influence bone mass gain in this population, the magni-
tude of the effects appears to be different in the axial and ap-
pendicular skeleton as well as at the metaphyseal or diaphyseal
levels (12, 28–30). Significantly, the mean bone mass gain in re-
sponse to calcium supplements has been found to be only
modest at the lumbar spine and proximal femur, two major
sites of subsequent osteoporotic fracture (12, 28, 30). The diffi-
culty of consistently demonstrating a significant effect of cal-
cium in the various parts of the skeleton may be related to dif-
ferences in the osteodensitometric method used (for example,
dual photon absorptiometry [DPA] [12, 28] versus the more
precise dual-energy x-ray absorptiometry [DXA] ), to dif-
ferences in the stage of pubertal maturation at the time of cal-
cium supplementation (28, 29), or to differences in the level of
spontaneous calcium intake, as observed in adult subjects (31).
We conducted a randomized, double-blind, placebo-con-
trolled study in a homogenous cohort of prepubertal girls to
assess the effects of calcium supplementation on bone mass
gain at various sites of the skeleton. In the context of a large-
scale program for nutritional prevention during childhood of
osteoporosis, as well as to anticipate the risk of low long-term
compliance to pharmaceutical calcium supplements at a popu-
lation level, we administered palatable calcium-enriched foods
commonly taken at breakfast or as snacks to children living in
an affluent western society.
Subjects and study design.
Committee of the Department of Pediatrics of the University Hospi-
The protocol was approved by the Ethical
Address correspondence to Prof. Jean-Philippe Bonjour, M.D., Divi-
sion of Bone Diseases, formerly Division of Clinical Pathophysiology,
Department of Internal Medicine, University Hospital, CH-1211
Geneva 14, Switzerland. Phone: 41-22-3729950; FAX: 41-22-3829973.
Received for publication 23 July 1996 and accepted in revised form
7 January 1997.
density; BMC, bone mineral content; BMD, bone mineral density;
Ca-suppl., calcium-supplemented; DXA, dual energy x-ray absorpti-
ometry; ROI, region of interest.
Abbreviations used in this paper:
BMAD, bone mineral apparent
Bonjour et al.
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