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Effects of calcium supplementation on bone density in healthy children: meta-analysis of randomised controlled trials

BMJ 2006; 333 doi: (Published 12 October 2006) Cite this as: BMJ 2006;333:775

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We welcome the chance to respond to the letter from Drs Heaney and
Weaver. We disagree with their viewpoint in several areas.

1. The key question with calcium supplementation in children is
whether this prevents fractures. There are no trials that have been large
enough to answer this question in either younger or later life. The
relationship between peak bone mass and fracture risk in later life
appears substantial (1) but estimating an effect of calcium
supplementation in children on fracture in later life would be at best a
guess. The next question is which bone variable is the best surrogate
marker of fracture in children. While the response from Drs Heaney and
Weaver has some theoretical merit, this is not actually supported by hard
data in children. In direct contrast to their assertion, we have recently
reported that volumetric density (an estimate of true bone density) is the
best correlate of fracture risk in children and is closely followed by
areal BMD (2). The small change in bone size is of uncertain significance
as there is little data relating it to fracture in children and BMC and
bone area (which are the DXA variables that correlate most closely with
bone size) were unable to discriminate children with fracture from
controls (2). Furthermore, increasing bone size may actually be harmful as
increased tibial cross-sectional area increases the risk of subsequent
cartilage damage (3) which leads to cartilage loss (4) based on recent
prospective MRI based studies from our institution. In the meta-analysis,
we wanted to use volumetric density as the primary outcome but this was
not reported in any studies. Areal BMD was, therefore, the next most valid
measure. We also had data relating BMD to fracture as well as fracture
incidence in children in our location (5) which allowed us to estimate the
effect of calcium supplementation on fracture which was small. Other bone
measures which are associated with fractures in children such as
metacarpal index (6), skeletal age deviation (7) and heel ultrasound (G
Jones, unpublished) may also be suitable for use as surrogate markers but
again there is little data relating them to calcium intake.

2. The criticism about a lack of an appropriate control group is
untenable. From a meta-analysis of calcium balance studies, Dr Heaney
suggests around 1400 mg/day is needed (8), much more than the average 700
mg/day in the control groups, thus, according to this standard, all the
studies in our review could be regarded as low intake. However, even
restricting the analysis to the lowest quartile of supplementation
(<_582 mg="mg" day="day" showed="showed" no="no" beneficial="beneficial" effect="effect" even="even" though="though" three="three" out="out" of="of" four="four" studies="studies" in="in" this="this" subgroup="subgroup" had="had" mean="mean" baseline="baseline" intakes="intakes" _400="_400" day.="day." our="our" analysis="analysis" that="that" increasing="increasing" to="to" levels="levels" suggested="suggested" as="as" necessary="necessary" maintain="maintain" increase="increase" calcium="calcium" balance="balance" did="did" very="very" little="little" casting="casting" doubt="doubt" on="on" the="the" validity="validity" and="and" perhaps="perhaps" indicating="indicating" bodys="bodys" ability="ability" adjust="adjust" much="much" lower="lower" intakes.="intakes." p="p"/> 3. We were disappointed and a little surprised that such well
respected bone investigators seemed unaware of our group’s longstanding
bone research program with its emphasis on children. The assumption that
we lack content expertise is erroneous. Our review protocol was designed
with content and methodological input. We would suggest that Dr’s Heaney
and Weaver reassess their own viewpoints in the light of our results,
rather than shooting the messenger when the data don’t support their


1. Jones G. Relevance of peak bone mass to osteoporosis and fracture risk
in later life. In Lane N, Sambrook P (eds). Osteoporosis and the
osteoporosis of rheumatic diseases. Mosby, New York, 2006, p22-26.

2. Jones G, Ma D, Cameron F. Bone density interpretation and relevance in
Caucasian children aged 9-17 years of age: insights from a population
based fracture study. Journal of Clinical Densitometry 2006 9:202-9

3. Ding C, Cicuttini F, Scott F, Cooley H, Boon C, Jones G. Natural
history of knee cartilage defects and factors influencing change. Archives
of Internal Medicine 2006 166:651-8.

4. Ding C, Cicuttini F, Scott F, Boon C, Jones G. Prevalent and incident
knee cartilage defects are associated with knee cartilage loss: a
longitudinal study. Arthritis and Rheumatism 2005 12:3918-27.

5. Jones G, Cooley H. Symptomatic fracture incidence in those under 50
years of age in Southern Tasmania. Journal of Paediatrics and Child Health
2002 33:278-83.

6. Ma D, Jones G. The association between bone mineral density, metacarpal
morphometry and upper limb fractures in children: a population based case-
control study. Journal of Clinical Endocrinology and Metabolism 2003

7. Jones G, Ma D. Skeletal age deviation assessed by the Tanner Whitehouse
2 method is associated with bone mass and fracture risk in children. Bone
2005 36:352-7.

8. Heaney RP, Abrams S, Dawson-Hughes B, et al. Peak bone mass. Osteoporos
Int 2000;11:985-1009.

Competing interests:
None declared

Competing interests: No competing interests

03 October 2006
Graeme Jones
Professor and Head, Musculoskeletal Unit, Menzies Research Institute
Tania Winzenberg
Menzies Research Institute, Level2, 199 Macquarie St Hobart, Tasmania, Australia 7000