Elsevier

Bone

Volume 46, Issue 2, February 2010, Pages 294-305
Bone

Review
Maximizing bone mineral mass gain during growth for the prevention of fractures in the adolescents and the elderly

https://doi.org/10.1016/j.bone.2009.10.005Get rights and content

Abstract

Bone mass is a key determinant of fracture risk. Maximizing bone mineral mass during childhood and adolescence may contribute to fracture risk reduction during adolescence and possibly in the elderly. Although more than 60% of the variance of peak bone mass (PBM), the amount of bone present in the skeleton at the end of its maturation process, is genetically determined, the remainder is likely influenced by factors amenable to positive intervention, such as adequate dietary intake of dairy products as a natural source of calcium and proteins, vitamin D, and regular weight-bearing physical activity. Low calcium and vitamin D intakes are associated with negative effects on bone, including suboptimal PBM acquisition. As suggested by intervention studies, regular intake of dairy products may have positive and possibly sustained effects on bone mineral mass gain, contributing thereby to fracture risk reduction. Further evidence from intervention studies suggests that weight-bearing physical activities, such as jumping, may contribute to bone mineral mass gain in children. Optimizing PBM acquisition through dietary and physical exercise measures may represent a valuable primary method for the prevention of fractures.

Introduction

Osteoporosis and its consequential fractures are among the leading causes of morbidity in industrialized countries, and are associated with considerable and growing individual, societal, and economical burden [1], [2], [3]. At the age of 50 years, the remaining lifetime probability of suffering any major osteoporotic (hip, distal forearm, proximal humerus, and spine) fracture is 20% for men and 50% for women [4], [5]. The key determinants of bone strength and, conversely, of bone fragility are areal bone mineral density (aBMD) and bone structure [6], [7]. This is reflected in the World Health Organization (WHO) definition of osteoporosis as “a systemic skeletal disease characterized by low bone mass and microarchitectural deterioration of bone tissue, with a consequent increase in bone fragility and susceptibility to fracture” [6].

At any given age, the key determinants of fracture risk, bone mineral mass and bone structure, result from the difference between the amounts of bone gained and lost [1], [8]. Following menopause and in the elderly, the amount of bone resorbed usually exceeds the amount of bone formed, leading to a net loss of bone mineral mass. Areal BMD measured by dual energy X-ray absorptiometry (DXA) is an important predictor of fracture risk in women and men after the age of 50 years [9]. Fracture risk approximately doubles with each standard deviation of bone lost from mean PBM [9], [10]. According to a computer simulation of the bone remodeling process, the onset of osteoporosis is predicted to be delayed by 13 years if young adult aBMD is 10% higher than the mean [11] (Fig. 1).

Childhood is a period characterized by growth, development and maturation of the various body systems, including the skeletal tissue. Bone modeling begins with the development of the skeleton during fetal life and continues until the end of the second decade, when the epiphyseal growth plates are closed and longitudinal growth of the skeleton is completed. During this phase bones are modeled by bone formation and resorption occurring in distinct locations, leading to the various bone shapes in adults [12]. While bone remodeling also starts during fetal life, the highest level of remodeling is achieved during adolescence. Remodeling replaces old bone with new without changing the shape of the bone. This process allows for the preservation of skeletal mechanical integrity (e.g. through (micro-)fracture repair) and the control of calcium homeostasis by releasing calcium into the circulation when necessary [12]. PBM, which is defined as the amount of bone present in the skeleton at the end of its maturation process, is considered to be achieved by the end of the second decade of life [13]. Indeed, prospective observational studies suggest that more than 95% of the adult skeleton is formed by the end of adolescence [14], [15]. However, some consolidation could take place during the 3rd decade, particularly in peripheral skeleton in males.

Up to half of all children experience a fracture between the age of 5 and 18 years, i.e. throughout growth during which PBM is acquired [16]. The risk of sustaining a fracture is higher in boys than in girls. The most common site affected in both sexes is the distal end of the radius/ulna [17], [18]. Children and adolescents with fractures have been shown to have lower BMC, bone size, and bone accrual than nonfractured controls, with low aBMD being a predictor of new fracture(s) [19], [20]. Furthermore, the association between bone mineral mass and fracture risk in childhood was shown in a prospective study of a cohort of 6213 children, with an average age of 9.9 years, followed for 24 months [21], and by the findings of a recent meta-analysis [22]. Interestingly, reduced bone size relative to body size and low humeral vBMD in children with fracture compared to nonfractured matched controls were shown to contribute to fracture risk, following either slight, moderate or severe trauma [23], suggesting that fractures in childhood are related not only to the common falls and injuries of that age group, but also to underlying skeletal fragility [21].

Several epidemiological studies have suggested a site- and sex-specific distribution of lifetime fracture incidence with peaks at both puberty and old age [24], [25], [26], [27]. A population-based British cohort study showed that the peak incidence of fractures during childhood (boys, 3%; girls, 1.5%) was only surpassed at 85 years of age among women but never among men [17]. As the relationship between bone mineral mass and bone strength remains valid throughout life [28], [29], maximizing PBM may be an important contributor to fracture risk reduction in children as well as in the elderly. There is growing evidence that the consequences of age-related or postmenopausal bone loss on fracture risk will depend on the level of PBM achieved during childhood and adolescence, as well as on the rate of bone loss [11], [13], [28], [29], [30]. Some experimental studies, however, indicate that gains in bone mineral accretion during childhood may only be transient and have triggered the argument that surmises bone mass is ultimately governed by a homeostatic system which tends to return towards a yet-to-be defined set point [31], [32]. As acknowledged by the authors themselves, the sustainability of the effects on PBM may depend on the type of intervention as well as its magnitude, timing, and duration. In any case, and although most of today's efforts in fracture prevention have been directed at slowing the rate or postponing the time of onset of bone loss among elderly people, maximizing PBM is a potential primary strategy to prevent osteoporotic fractures later in life [33], [34]. In addition, maximizing bone mass during growth may have immediate beneficial consequences by reducing fracture incidence during puberty.

The aim of this review is to discuss those determinants of bone health that are amenable to intervention during childhood, and that may contribute to the primary prevention of osteoporosis and thus to the reduction of fracture risk.

Section snippets

Quantitative assessment of bone mineral mass

Bone mineral mass is the only surrogate of bone strength accessible to measurement [35]. Bone mineral content (BMC) and bone mineral density (BMD) are measured by DXA, the method of choice due to the low radiation exposure and its high precision and accuracy [36]. BMC measures the amount of bone mineral in grams. Areal BMD (aBMD) expresses bone mineral content as a function of the projected bone scanned area in grams per square centimeter, while volumetric BMD (vBMD) measures bone mineral

Evidence from clinical studies

Numerous associations studies between bone mineral mass (or density) and calcium intakes have been performed in children and adolescents. Most, if not all, suggest a positive association across different populations such as Scandinavians [52], [53], Chinese [54], [55], [56], [57], UK and US [58], [59], [60]. The effect of calcium supplementation on height, BMC and aBMD gain at various skeletal sites (radius, lumbar spine and femoral neck) has also been studied in several prospective randomized

The role of vitamin D in bone mineralization

Vitamin D plays a key role in calcium-phosphate homeostasis. Dietary sources of vitamin D (vitamin D2 or ergocalciferol and vitamin D3 or cholecalciferol) are scarce and mainly limited to oily fish species; however, vitamin D also has an endogenous origin, as the ultraviolet B radiation from the sun catalyses the conversion of 7-dehydrocholesterol to cholecalciferol in the skin. Vitamin D2 and D3 are converted into 25-hydroxy-vitamin D (25-(OH)D) in the liver and subsequently to

The role of physical activity

One of the main functions of the skeleton is to ensure mechanical integrity for locomotion. Throughout life, bone mass and architecture are adapted to the strains produced by mechanical load and muscular activity. Muscle mass and strength have been identified as important predictors of bone strength [126]. Conversely, skeletal unloading due to prolonged bed rest or cast immobilization leads to bone loss [127]. Therefore, weight-bearing physical activity may play an important role in the accrual

Conclusion

Peak bone mass acquired through bone mineral accrual during childhood and adolescence may be a key determinant of bone health and future fracture risk during adulthood (Fig. 1). While the larger part of the variance of PBM is attributable to genetic factors, some determinants of PBM are amenable to intervention during childhood and adolescence. Increasing daily calcium and protein intake with dairy products, preventing or correcting highly prevalent vitamin D insufficiency, and increasing

Acknowledgments

We are grateful to Dr. Philippe Kress and Dr. Tara C. Brennan for their contribution to the medical writing and copy editing of the manuscript, and to M. Perez for secretarial assistance.

Statement of financial support

This review was supported by an unrestricted research grant from Danone Research, Paris, France.

References (178)

  • M. Huncharek et al.

    Impact of dairy products and dietary calcium on bone-mineral content in children: results of a meta-analysis

    Bone

    (2008)
  • A. Goulding et al.

    Children who avoid drinking cow's milk are at increased risk for prepubertal bone fractures

    J. Am. Diet. Assoc.

    (2004)
  • J.P. Bonjour et al.

    Gain in bone mineral mass in prepubertal girls 3.5 years after discontinuation of calcium supplementation: a follow-up study

    Lancet

    (2001)
  • K. Zhu et al.

    Growth, bone mass, and vitamin D status of Chinese adolescent girls 3 y after withdrawal of milk supplementation

    Am. J. Clin. Nutr.

    (2006)
  • V. Matkovic et al.

    Calcium supplementation and bone mineral density in females from childhood to young adulthood: a randomized controlled trial

    Am. J. Clin. Nutr.

    (2005)
  • U. Alexy et al.

    Long-term protein intake and dietary potential renal acid load are associated with bone modeling and remodeling at the proximal radius in healthy children

    Am. J. Clin. Nutr.

    (2005)
  • R.E. Black et al.

    Children who avoid drinking cow milk have low dietary calcium intakes and poor bone health

    Am. J. Clin. Nutr.

    (2002)
  • W. Bounds et al.

    The relationship of dietary and lifestyle factors to bone mineral indexes in children

    J. Am. Diet. Assoc.

    (2005)
  • G.M. Chan et al.

    Effects of dairy products on bone and body composition in pubertal girls

    J. Pediatr.

    (1995)
  • R.C. Henderson et al.

    Bone mineralization in children and adolescents with a milk allergy

    Bone Miner.

    (1994)
  • D. Teegarden et al.

    Previous milk consumption is associated with greater bone density in young women

    Am. J. Clin. Nutr.

    (1999)
  • V. Matkovic et al.

    Nutrition influences skeletal development from childhood to adulthood: a study of hip, spine, and forearm in adolescent females

    J. Nutr.

    (2004)
  • H.J. Kalkwarf et al.

    Milk intake during childhood and adolescence, adult bone density, and osteoporotic fractures in US women

    Am. J. Clin. Nutr.

    (2003)
  • S. Cheng et al.

    Effects of calcium, dairy product, and vitamin D supplementation on bone mass accrual and body composition in 10–12-y-old girls: a 2-y randomized trial

    Am. J. Clin. Nutr.

    (2005)
  • K. Zhu et al.

    Effects of school milk intervention on cortical bone accretion and indicators relevant to bone metabolism in Chinese girls aged 10–12 y in Beijing

    Am. J. Clin. Nutr.

    (2005)
  • K.L. Tucker et al.

    Colas, but not other carbonated beverages, are associated with low bone mineral density in older women: the Framingham Osteoporosis Study

    Am. J. Clin. Nutr.

    (2006)
  • Prevention and management of osteoporosis. World Health Organ Tech Rep Ser 2003;921: 1–164, back...
  • O. Johnell et al.

    An estimate of the worldwide prevalence, mortality and disability associated with hip fracture

    Osteoporos. Int.

    (2004)
  • L.J. Melton

    Hip fractures: a worldwide problem today and tomorrow

    Bone

    (1993)
  • O. Johnell et al.

    Epidemiology of osteoporotic fractures

    Osteoporos. Int.

    (2005)
  • K. Lippuner et al.

    Remaining lifetime and absolute 10-year probabilities of osteoporotic fracture in Swiss men and women

    Osteoporos. Int.

    (2008)
  • Consensus development conference: diagnosis, prophylaxis, and treatment of osteoporosis. Am J Med 1993;94:...
  • D.A. Nelson et al.

    Cross-sectional geometry, bone strength, and bone mass in the proximal femur in black and white postmenopausal women

    J. Bone Miner. Res.

    (2000)
  • J.A. Kanis et al.

    European guidance for the diagnosis and management of osteoporosis in postmenopausal women

    Osteoporos. Int.

    (2008)
  • O. Johnell et al.

    Predictive value of BMD for hip and other fractures

    J. Bone Miner. Res.

    (2005)
  • D. Marshall et al.

    Meta-analysis of how well measures of bone mineral density predict occurrence of osteoporotic fractures

    BMJ

    (1996)
  • C.J. Hernandez et al.

    A theoretical analysis of the relative influences of peak BMD, age-related bone loss and menopause on the development of osteoporosis

    Osteoporos. Int.

    (2003)
  • T.A. Einhorn

    The bone organ system: form and function

    (1996)
  • J.P. Bonjour et al.

    Peak bone mass

    Osteoporos. Int.

    (1994)
  • D.A. Bailey et al.

    A six-year longitudinal study of the relationship of physical activity to bone mineral accrual in growing children: the university of Saskatchewan bone mineral accrual study

    J. Bone Miner. Res.

    (1999)
  • I.E. Jones et al.

    How many children remain fracture-free during growth? A longitudinal study of children and adolescents participating in the Dunedin Multidisciplinary Health and Development Study

    Osteoporos. Int.

    (2002)
  • C. Cooper et al.

    Epidemiology of childhood fractures in Britain: a study using the general practice research database

    J. Bone Miner. Res.

    (2004)
  • L.A. Landin

    Epidemiology of children's fractures

    J. Pediatr. Orthop. B

    (1997)
  • S.L. Ferrari et al.

    Childhood fractures are associated with decreased bone mass gain during puberty: an early marker of persistent bone fragility?

    J. Bone Miner. Res.

    (2006)
  • A. Goulding

    Risk factors for fractures in normally active children and adolescents

    Med. Sport Sci.

    (2007)
  • E.M. Clark et al.

    Association between bone mass and fractures in children: a prospective cohort study

    J. Bone Miner. Res.

    (2006)
  • E.M. Clark et al.

    Association between bone density and fractures in children: a systematic review and meta-analysis

    Pediatrics

    (2006)
  • E.M. Clark et al.

    Bone fragility contributes to the risk of fracture in children, even after moderate and severe trauma

    J. Bone Miner. Res.

    (2008)
  • P.A. Alffram et al.

    Epidemiology of fractures of the forearm. A biomechanical investigation of bone strength

    J. Bone Joint Surg. Am.

    (1962)
  • W.M. Garraway et al.

    Limb fractures in a defined population: I. Frequency and distribution

    Mayo Clin. Proc.

    (1979)
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