The Open Nutrition Journal




ISSN: 1874-2882 ― Volume 13, 2019

Micronutrients and Bone Growth in Preadolescent Children from Developing Countries



Marlena Kruger1, 2, 3, *, Gerda Gericke2, 3, Zelda White2, 3
1 School of Food and Nutrition, Massey Institute for Food Science and Technology, Massey University, Palmerston North, New Zealand
2 Department of Human Nutrition, School of Health Care Sciences, Faculty of Health Sciences, University of Pretoria, Pretoria, South Africa
3 Associate of the Institute for Food, Nutrition and Well-being, University of Pretoria, Pretoria, South Africa

Abstract

Objective:

Childhood undernutrition may result in poor physical development, and negatively impact on the workforce and society. We examined from the literature how micronutrient deficiencies may affect bone growth in preadolescent children in developing countries.

Results:

Overall data from many studies carried out during the past 30 years show that dietary supplementation of children in developing countries may improve growth and development. Although the first few months and years of life have been considered key to these improvements, supplementation at any age may be able to influence bone health and physical development. There is considerable data in support of calcium supplementation, either in tablet form or from increased intake of dairy products, but it now seems likely that calcium alone may not be sufficient to enhance growth, unless other vital micronutrients are also provided. The recent societal changes in South Africa have resulted in an influx of cheap, nutrient-poor foods, leading to widespread childhood undernourishment in mainly black children in resource-constrained communities. Data on dietary supplementation and long-term outcomes in these children are still lacking.

Conclusion:

An understanding of the complex interactions between macro- and micronutrients in enhancing physical growth and development, and a consensus on the optimal timing and delivery system of supplementation is required to improve child health in developing countries, including Africa. The efficacy and efficiency of food based programmes versus supplementation should be critically assessed.

Keywords: Bone health, Children, Growth, Preadolescent, Physical development, Undernutrition.


Article Information


Identifiers and Pagination:

Year: 2016
Volume: 10
First Page: 13
Last Page: 22
Publisher Id: TONUTRJ-10-13
DOI: 10.2174/1874288201610010013

Article History:

Received Date: 05/07/2016
Revision Received Date: 13/10/2016
Acceptance Date: 17/10/2016
Electronic publication date: 28/12/2016
Collection year: 2016

Article Metrics:

CrossRef Citations:
0

Total Statistics:

Full-Text HTML Views: 1134
Abstract HTML Views: 687
PDF Downloads: 182
ePub Downloads: 148
Total Views/Downloads: 2151

Unique Statistics:

Full-Text HTML Views: 603
Abstract HTML Views: 476
PDF Downloads: 148
ePub Downloads: 119
Total Views/Downloads: 1346
Geographical View

© Kruger et al.; Licensee Bentham Open

open-access license: This is an open access article licensed under the terms of the Creative Commons Attribution-Non-Commercial 4.0 International Public License (CC BY-NC 4.0) (https://creativecommons.org/licenses/by-nc/4.0/legalcode), which permits unrestricted, non-commercial use, distribution and reproduction in any medium, provided the work is properly cited.


* Address correspondence to this author at the School of Food and Nutrition, Massey Institute for Food Science and Technology, Massey University, Private Bag 11222, Palmerston North, New Zealand; Tel: +646 350 5905; Fax: +646 350 5446; E-mail: m.c.kruger@massey.ac.nz




INTRODUCTION

Investment in children’s health that enhances their ability to grow and develop cognitively and optimises healthy status is essential to their future development, the workforce and the nation. Childhood undernutrition occurs when children do not eat or absorb sufficient nutrients to cover their energy needs, and allow for growth and the maintenance of a healthy immune system. Undernutrition, which encompasses stunting, wasting, and deficiencies of essential vitamins and minerals (micronutrients) remains a major public health concern in developing countries [1Ramakrishnan U, Aburto N, McCabe G, Martorell R. Multimicronutrient interventions but not vitamin a or iron interventions alone improve child growth: results of 3 meta-analyses. J Nutr 2004; 134(10): 2592-602.
[PMID: 15465753]
]. Annually, more than one-third of all child deaths worldwide can be attributed to undernutrition [2UNICEF. Facts for life. 2010. Available at: http://www.factsforlifeglobal.org]. Undernutrition often starts in utero, resulting in slower physical and mental development, and the ensuing growth retardation usually extends into the second or third year of life [3Muthayya S, Rah JH, Sugimoto JD, Roos FF, Kraemer K, Black RE. The global hidden hunger indices and maps: an advocacy tool for action. PLoS One 2013; 8(6): e67860.
[http://dx.doi.org/10.1371/journal.pone.0067860] [PMID: 23776712]
].

Until recently, the most common cause of growth retardation was considered to be protein and energy malnutrition, but in the last few years, micronutrient intake has gained considerable attention. Micronutrient deficiencies, also known as “hidden hunger”, are found in a number of countries in sub-Saharan Africa at alarmingly high levels [3Muthayya S, Rah JH, Sugimoto JD, Roos FF, Kraemer K, Black RE. The global hidden hunger indices and maps: an advocacy tool for action. PLoS One 2013; 8(6): e67860.
[http://dx.doi.org/10.1371/journal.pone.0067860] [PMID: 23776712]
]. These multiple micronutrient deficiencies are associated with several adverse outcomes throughout life, such as loss of muscle mass, and obstetric risk in females [4Shenkin A. Micronutrients in health and disease. Postgrad Med J 2006; 82(971): 559-67.
[http://dx.doi.org/10.1136/pgmj.2006.047670] [PMID: 16954450]
, 5Christian P. Micronutrients and reproductive health issues: an international perspective. J Nutr 2003; 133(6): 1969S-73S.
[PMID: 12771347]
]. Deficiencies develop due to inadequate food intake, poor dietary quality, and poor bioavailability due to the presence of inhibitors of absorption in the food [6Ramakrishnan U. Prevalence of micronutrient malnutrition worldwide. Nutr Rev 2002; 60(5 Pt 2): S46-52.
[PMID: 12035858]
]. People in developing countries often consume a plant-based diet which is high in phytate (a potent inhibitor of zinc absorption) and fibre, and low in other nutrients, resulting in decreased bioavailability of iron, zinc and calcium.

This article aims to examine how micronutrient poor diets impact on bone growth in children, the optimal timing of intervention, and how differences in the type of intervention (supplementation vs. food based approaches) might affect overall growth and long-term outcomes for children in developing countries. The measurement of bone growth and density is also briefly discussed. Although reports from many countries were examined, this article was designed to focus particularly on available data from Africa, with the emphasis on preadolescent children, aged >2 to 12 years.

BONE GROWTH DURING CHILDHOOD

Attaining height is the result of the interaction between genetic background and macro-/ micronutrient availability during the growth period [7Weaver CM. The role of nutrition on optimizing peak bone mass. Asia Pac J Clin Nutr 2008; 17(Suppl. 1): 135-7.
[PMID: 18296321]
]. The process of longitudinal growth involves increases in the number of the cells on the growth plate of bone, as well as increases in cell size, leading to expansion of the growth plate. The key hormones involved are growth hormone and insulin-like growth factor 1 (IGF-1) [8Giustina A, Mazziotti G, Canalis E. Growth hormone, insulin-like growth factors, and the skeleton. Endocr Rev 2008; 29(5): 535-59.
[http://dx.doi.org/10.1210/er.2007-0036] [PMID: 18436706]
]. IGF-1 receptors are found in proliferating bone chondrocytes, and a rise in IGF-1 stimulates chondrogenesis. Growth hormones can stimulate growth independent of IGF-1, but can also raise levels of IGF-1, stimulating linear growth [9Loveridge N, Noble BS. Control of longitudinal growth: the role of nutrition. Eur J Clin Nutr 1994; 48(2): 75-84.
[PMID: 8194496]
]. Plasma IGF-1 levels are affected by nutrition, specifically by protein and energy restriction, with lack of protein having the largest impact [10Estívariz CF, Ziegler TR. Nutrition and the insulin-like growth factor system. Endocrine 1997; 7(1): 65-71.
[http://dx.doi.org/10.1007/BF02778066] [PMID: 9449035]
]. Some micronutrients also affect IGF-1 levels, including zinc, potassium, magnesium, copper and manganese. It is also well known that deficiencies in vitamin D and calcium can affect bone development and growth [11Rivera JA, Hotz C, González-Cossío T, Neufeld L, García-Guerra A. The effect of micronutrient deficiencies on child growth: a review of results from community-based supplementation trials. J Nutr 2003; 133(11)(Suppl. 2): 4010S-20S.
[PMID: 14672304]
]. Peak bone mass is the highest bone mass achievable within a person’s genetic potential, and is usually accrued during adolescence [7Weaver CM. The role of nutrition on optimizing peak bone mass. Asia Pac J Clin Nutr 2008; 17(Suppl. 1): 135-7.
[PMID: 18296321]
]. Up to 90% of peak bone mass is accrued by the age of 18 years, although bone mass can still increase up to the third decade of life. In white children, research has shown that the average skeletal calcium retention at the peak rate of accretion is 325 mg/day for girls and 409 mg/day for boys [12Bailey DA, McKay HA, Mirwald RL, Crocker PR, Faulkner RA. 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; 14(10): 1672-9.
[http://dx.doi.org/10.1359/jbmr.1999.14.10.1672] [PMID: 10491214]
]. Due to the significant growth at this time, any modulation of accretion could affect lifelong bone health.

MEASURING BONE GROWTH AND DENSITY IN CHILDREN

Measurement of growth hormone and IGF-1 in children is challenging [13Hawkes CP, Grimberg A. Measuring growth hormone and insulin-like growth factor-I in infants: what is normal? Pediatr Endocrinol Rev 2013; 11(2): 126-46.
[PMID: 24575549]
], and likely to be impractical in developing countries. Therefore, to assess growth, measurements of length (for children less than two years of age) or height (for children aged 2 years or older), and weight are generally used [14World Health Organization. Training course on child growth assessment. 2010. Available at: http://www.who.int/ childgrowth/training/ module_b_measuring_growth.pdf, 15Darteh EK, Acquah E, Kumi-Kyereme A. Correlates of stunting among children in Ghana. BMC Public Health 2014; 14: 504.
[http://dx.doi.org/10.1186/1471-2458-14-504] [PMID: 24884653]
], and compared with World Health Organization (WHO) child growth standards [16World Health Organization. WHO child growth standards. 2006. Available at: http://www.who.int/childgrowth/standards/en/, 17WHO Multicentre Growth Reference Study Group. WHO Child Growth Standards based on length/height, weight and age. Acta Paediatr Suppl 2006; 450: 76-85.
[PMID: 16817681]
]. Equipment needed to measure length or height requires only a piece of smooth, moisture-resistant wood, and a measuring tape, forming an infantometer (length) or stadiometer (height) [14World Health Organization. Training course on child growth assessment. 2010. Available at: http://www.who.int/ childgrowth/training/ module_b_measuring_growth.pdf]. In general, standing height is about 0.7 cm less than recumbent length [14World Health Organization. Training course on child growth assessment. 2010. Available at: http://www.who.int/ childgrowth/training/ module_b_measuring_growth.pdf]. This difference was taken into account in developing the WHO growth standards, and it is important to adjust the measurements if length is taken instead of height, and vice versa [16World Health Organization. WHO child growth standards. 2006. Available at: http://www.who.int/childgrowth/standards/en/, 17WHO Multicentre Growth Reference Study Group. WHO Child Growth Standards based on length/height, weight and age. Acta Paediatr Suppl 2006; 450: 76-85.
[PMID: 16817681]
]. For measuring weight, electronic scales measuring to a precision of 0.1 kg are recommended [14World Health Organization. Training course on child growth assessment. 2010. Available at: http://www.who.int/ childgrowth/training/ module_b_measuring_growth.pdf]. Height and weight measurements can then be compared with the WHO standards, and children assigned a z-score (the number of standard deviations above or below the reference median value) [18World Health Organization, United Nations Children's Fund. WHO child growth standards and the identification of severe acute malnutrition in infants and children. A joint statement 2009. Available at: http://www.who.int/nutrition/ publications/severemalnutrition/ 9789241598163/en/].

Bone mineral content (BMC) and areal bone mineral density (BMD) are valuable in determining bone strength and mineral content, and are most often measured using dual-energy X-ray absorptiometry (DXA) [19Levine MA. Assessing bone health in children and adolescents. Indian J Endocrinol Metab 2012; 16(Suppl. 2): S205-12.
[PMID: 23565379]
]. DXA uses two levels of x-ray photon energy to measure the amount of minerals in bone, and was originally developed for use in adults with osteoporosis; however great strides have been made in recent years, improving the applicability to children [20Estrada A, Ramnitz MS, Gafni RI. Bone densitometry in children and adolescents. Curr Opin Obstet Gynecol 2014; 26(5): 339-46.
[http://dx.doi.org/10.1097/GCO.0000000000000100] [PMID: 25144595]
]. In 2013, the International Society for Clinical Densitometry (ISCD) published official revised positions on reporting paediatric densitometry results, with recommendations on which skeletal sites should be measured, adjustments that should be made, and the reference databases to be used [21Crabtree NJ, Arabi A, Bachrach LK, et al. Dual-energy X-ray absorptiometry interpretation and reporting in children and adolescents: the revised 2013 ISCD Pediatric Official Positions. J Clin Densitom 2014; 17(2): 225-42.
[http://dx.doi.org/10.1016/j.jocd.2014.01.003] [PMID: 24690232]
]. According to the ISCD, the posterior-anterior spine and total-body-less-head, are the preferred skeletal sites for measurement in most paediatric subjects; the hip is not a preferred measurement site in growing children due to variability in skeletal development [22The International Society for Clinical Densitometry. The official pediatric positions. 2013. Available at: http://www.iscd.org/documents/2013/12/2013-pediatric-position-statements.pdf]. For children with short stature or growth delay, results should be adjusted using the height z-score [22The International Society for Clinical Densitometry. The official pediatric positions. 2013. Available at: http://www.iscd.org/documents/2013/12/2013-pediatric-position-statements.pdf]. However, while DXA whole-body BMC and BMD for children aged three years and above and DXA lumbar spine measurements for infants and young children aged up to 5 years were identified as feasible and reproducible, it was noted that reference data for children aged 0 to five years are currently insufficient [22The International Society for Clinical Densitometry. The official pediatric positions. 2013. Available at: http://www.iscd.org/documents/2013/12/2013-pediatric-position-statements.pdf, 23Kalkwarf HJ, Abrams SA, DiMeglio LA, Koo WW, Specker BL, Weiler H. Bone densitometry in infants and young children: the 2013 ISCD Pediatric Official Positions. J Clin Densitom 2014; 17(2): 243-57.
[http://dx.doi.org/10.1016/j.jocd.2014.01.002] [PMID: 24674638]
]. Furthermore, when evaluating DXA results in children, there are several confounding factors that should be considered, including race, gender, and pubertal status [19Levine MA. Assessing bone health in children and adolescents. Indian J Endocrinol Metab 2012; 16(Suppl. 2): S205-12.
[PMID: 23565379]
]. To date, DXA measurements of children in African countries have been mainly restricted to large research studies [24Kagura J, Feeley AB, Micklesfield LK, Pettifor JM, Norris SA. Association between infant nutrition and anthropometry, and pre-pubertal body composition in urban South African children. J Dev Orig Health Dis 2012; 3(6): 415-23.
[http://dx.doi.org/10.1017/S2040174412000475] [PMID: 25084294]
], likely due to equipment availability, costs, and lack of adequate reference data. Inconsistencies in measurement methodologies will interfere with the comparison of findings.

GROWTH IN AFRICAN CHILDREN

The prevalence of stunting of linear growth of children younger than 5 years affected at least 165 million children globally in 2011; with East (42%) and West Africa (36%) having the highest prevalence estimates [25Black RE, Victora CG, Walker SP, et al. Maternal and child undernutrition and overweight in low-income and middle-income countries. Lancet 2013; 382(9890): 427-51.
[http://dx.doi.org/10.1016/S0140-6736(13)60937-X] [PMID: 23746772]
]. On the other hand, an estimated 43 million children younger than 5 years (7%) were overweight, with most overweight children living in low-income and middle-income countries [25Black RE, Victora CG, Walker SP, et al. Maternal and child undernutrition and overweight in low-income and middle-income countries. Lancet 2013; 382(9890): 427-51.
[http://dx.doi.org/10.1016/S0140-6736(13)60937-X] [PMID: 23746772]
]. In Africa, the estimated prevalence of overweight increased from 4% in 1990 to 7% in 2011 [25Black RE, Victora CG, Walker SP, et al. Maternal and child undernutrition and overweight in low-income and middle-income countries. Lancet 2013; 382(9890): 427-51.
[http://dx.doi.org/10.1016/S0140-6736(13)60937-X] [PMID: 23746772]
]. The nutrition transition, accompanied by decreased physical activity, leads to increases in overweight and obesity. The adverse changes in dietary patterns during the nutrition transition also cause an inability to consistently meet micronutrient requirement, contributing to the “double burden” of nutrition-related diseases, a co-existence of under- and over-nutrition [26Vorster HH, Kruger A, Margetts BM. The nutrition transition in Africa: can it be steered into a more positive direction? Nutrients 2011; 3(4): 429-41.
[http://dx.doi.org/10.3390/nu3040429] [PMID: 22254104]
].

Despite this clear trend in dietary changes and growth retardation, few studies investigating growth of children up to the age of ten years have been based in South Africa. One study, carried out in white and non-white children between the ages of 0 – 10 years, indicated a slower rate of growth in the non-white children [27Cameron N. Physical growth in a transitional economy: the aftermath of South African apartheid. Econ Hum Biol 2003; 1(1): 29-42.
[http://dx.doi.org/10.1016/S1570-677X(02)00008-4] [PMID: 15463962]
]. The Ellisras Growth study [28Monyeki KD, Cameron N, Getz B. Growth and nutritional status of rural South African children 310 years old: The Ellisras growth study. Am J Hum Biol 2000; 12(1): 42-9.
[http://dx.doi.org/10.1002/(SICI)1520-6300(200001/02)12:1<42::AID-AJHB6>3.0.CO;2-0] [PMID: 11534003]
] recruited 1335 children between three and ten years of age in rural villages in the then Northern Province (now Limpopo Province) of South Africa. The children underwent anthropometric assessment to assess nutritional status, using National Health and Nutrition Examination Survey (NHANES) I and II data from the United States [29Frisancho AR. Anthropometric standards for the assessment of growth and nutritional status. Ann Arbor: University of Michigan Press 1990.
[http://dx.doi.org/10.3998/mpub.12198]
] as a historical reference. When analysed, the data for the African children indicated that height tended to follow a pattern between 3-7 years which ran parallel to the 50th percentile of US children, and within the range of 0.0-0.5 z-scores [28Monyeki KD, Cameron N, Getz B. Growth and nutritional status of rural South African children 310 years old: The Ellisras growth study. Am J Hum Biol 2000; 12(1): 42-9.
[http://dx.doi.org/10.1002/(SICI)1520-6300(200001/02)12:1<42::AID-AJHB6>3.0.CO;2-0] [PMID: 11534003]
]. After the age of seven years there was a consistent tendency for the mean height to be below the 50th percentile with the mean values for both boys and girls being below the 10th percentile at the age of ten years. Weight remained on or just below the 10th percentile from age 3-10 years [28Monyeki KD, Cameron N, Getz B. Growth and nutritional status of rural South African children 310 years old: The Ellisras growth study. Am J Hum Biol 2000; 12(1): 42-9.
[http://dx.doi.org/10.1002/(SICI)1520-6300(200001/02)12:1<42::AID-AJHB6>3.0.CO;2-0] [PMID: 11534003]
].

In 1990, a birth cohort study was initiated in the Johannesburg area, called the Birth-to-ten and later the Birth-to-twenty (Bt20) study [30Yach D, Padayachee GN, Cameron N, Wagstaff LA, Richter L. Birth to Tena study of children of the 1990s living in the Johannesburg-Soweto area. S Afr Med J 1990; 77(7): 325-6.
[PMID: 2321102]
, 31Richter L, Norris S, Pettifor J, Yach D, Cameron N. Cohort profile: Mandelas children: The 1990 birth to twenty study in South Africa. Int J Epidemiol 2007; 36(3): 504-11.
[http://dx.doi.org/10.1093/ije/dym016] [PMID: 17355979]
]. Recruitment took place between April and June of 1990, and 4034 mothers with their babies volunteered to participate. Data were collected so that growth and physical development, psychological development and social and economic conditions could be monitored. Though improvements in growth of non-white children were observed in comparison to historical data recorded in the 1970s, their growth patterns did not equal those of the white children, with white children remaining taller and heavier [27Cameron N. Physical growth in a transitional economy: the aftermath of South African apartheid. Econ Hum Biol 2003; 1(1): 29-42.
[http://dx.doi.org/10.1016/S1570-677X(02)00008-4] [PMID: 15463962]
, 31Richter L, Norris S, Pettifor J, Yach D, Cameron N. Cohort profile: Mandelas children: The 1990 birth to twenty study in South Africa. Int J Epidemiol 2007; 36(3): 504-11.
[http://dx.doi.org/10.1093/ije/dym016] [PMID: 17355979]
]. The Bt20 study also examined ethnic differences in bone mass. Despite a lower socioeconomic status, lower calcium and vitamin D intakes, and less physical activity, greater femoral neck bone mass was reported in the black children compared with white children, although both groups had similar bone mass at the spine and appendicular skeleton after adjusting for differences in stature [32Vidulich L, Norris SA, Cameron N, Pettifor JM. Differences in bone size and bone mass between black and white 10-year-old South African children. Osteoporos Int 2006; 17(3): 433-40.
[http://dx.doi.org/10.1007/s00198-005-0004-y] [PMID: 16362145]
]. Further genetic investigation was done in the Bt20 study to ascertain possible genetic factors contributing to bone health in black South African children aged around ten years [33May A, Pettifor JM, Norris SA, Ramsay M, Lombard Z. Genetic factors influencing bone mineral content in a black South African population. J Bone Miner Metab 2013; 31(6): 708-16.
[http://dx.doi.org/10.1007/s00774-013-0431-3] [PMID: 23475190]
]. Twenty-seven markers, derived from three genes, were found to be associated with either femoral neck or lumbar spine bone mineral content. The authors therefore concluded that a strong genetic effect acts at the femoral neck in black South African children, affecting bone mass. Such influences should be taken into account in any study evaluating bone health in black South African children, to ensure that genetic effects in specific skeletal areas do not mask the impact of poor nutrition elsewhere in the body.

INTERVENTIONS AGAINST STUNTING

A recent perspective on childhood growth patterns considered critical windows for interventions against stunting [34Prentice AM, Ward KA, Goldberg GR, et al. Critical windows for nutritional interventions against stunting. Am J Clin Nutr 2013; 97(5): 911-8.
[http://dx.doi.org/10.3945/ajcn.112.052332] [PMID: 23553163]
]. An analysis of the World Health Organization (WHO) global database on child growth and malnutrition revealed that early growth patterns in children from 54 resource-poor countries show a rapid fall-off in height-for-age z-scores during the first two years of life [35Victora CG, de Onis M, Hallal PC, Blössner M, Shrimpton R. Worldwide timing of growth faltering: revisiting implications for interventions. Pediatrics 2010; 125(3): e473-80.
[http://dx.doi.org/10.1542/peds.2009-1519] [PMID: 20156903]
]. This observation led to interventions and strategies to improve growth focused on the age 0-2 year age group, without consideration whether there may be an opportunity for interventions later in life. The window between nine months to two years is considered an ‘optimal window of opportunity’ within which nutritional interventions may have an effect on longitudinal growth. However, other windows of opportunity exist, and data from at least five countries show that height catch-up can take place after the age of two years, making it likely that adolescence may represent another opportunity to intervene with long lasting effects into adulthood [34Prentice AM, Ward KA, Goldberg GR, et al. Critical windows for nutritional interventions against stunting. Am J Clin Nutr 2013; 97(5): 911-8.
[http://dx.doi.org/10.3945/ajcn.112.052332] [PMID: 23553163]
, 36Hirvonen K. Measuring catch-up growth in malnourished populations. Ann Hum Biol 2014; 41(1): 67-75.
[http://dx.doi.org/10.3109/03014460.2013.827239] [PMID: 24020872]
]. However, any catch-up growth intervention should be monitored to ensure that body weight of the child does not exceed the birth percentile of the child, since overweight is associated with an increased risk for the non-communicable diseases of lifestyle later in life. As such, the approach captured by the United Nations sub-committee on nutrition through the lifecycle [37United Nations Administrative Committee on Coordination / Subcommittee on Nutrition (ACC/SCN). The world nutrition situation: Nutrition throughout the lifecycle 2000. Available at: http://www.unscn.org/layout/modules/resources/files/rwns4.pdf], which recommends adequate nutrition and interventions throughout life to improve health and well-being, is a more comprehensive approach.

IMPACT OF DAIRY PRODUCTS ON BONE GROWTH

Consumption of dairy products in childhood and adolescence is known to have a positive effect on bone mineralization in adulthood and can reduce the risk for developing osteoporosis [38Guéguen L, Pointillart A. The bioavailability of dietary calcium. J Am Coll Nutr 2000; 19(2)(Suppl.): 119S-36S.
[http://dx.doi.org/10.1080/07315724.2000.10718083] [PMID: 10759138]
]. In studies of BMC, osteoporotic women reported less milk and dairy intake when they were children or adolescents compared with non-osteoporotic controls [39Renner E. Dairy calcium, bone metabolism, and prevention of osteoporosis. J Dairy Sci 1994; 77(12): 3498-505.
[http://dx.doi.org/10.3168/jds.S0022-0302(94)77291-X] [PMID: 7699131]
-41Kalkwarf HJ, Khoury JC, Lanphear BP. Milk intake during childhood and adolescence, adult bone density, and osteoporotic fractures in US women. Am J Clin Nutr 2003; 77(1): 257-65.
[PMID: 12499350]
]. However, it has also been suggested that calcium/dairy intake can have a significant effect on bone mass in young adults. Matkovic et al. (1979) [42Matković V, Kostial K, Simonović I, Buzina R, Brodarec A, Nordin BE. Bone status and fracture rates in two regions of Yugoslavia. Am J Clin Nutr 1979; 32(3): 540-9.
[PMID: 420146]
] stated that bone mass at any age is the result of age and sex and other genetically determined factors but that nutrition has a significant effect, and two decades later, a study reported that higher milk intake during adolescence was associated with greater total body spine and radial bone mineral during development of peak bone mass [43Teegarden D, Lyle RM, Proulx WR, Johnston CC, Weaver CM. Previous milk consumption is associated with greater bone density in young women. Am J Clin Nutr 1999; 69(5): 1014-7.
[PMID: 10232644]
]. Thus, supplementation of a nutrient-poor diet with calcium or dairy products appears likely to be a beneficial strategy for improving health in deprived children.

Dietary intake of calcium and other nutrients can be assessed using dietary reference intake (DRI) values developed by the Institute of Medicine of The National Academies [44Institute of Medicine of the National Academies. Dietary Reference Intakes Tables and Application. 2010. Available at: http://www.iom.edu/Activities/Nutrition/SummaryDRIs/DRI-Tables.aspx]. The DRI values are specified on the basis of age, gender and lifestage, cover more than 40 nutrient substances, and were intended to replace the recommended dietary allowance (RDA) values. Originally produced in 1997, updated DRIs for calcium and vitamin D were released in 2010 [44Institute of Medicine of the National Academies. Dietary Reference Intakes Tables and Application. 2010. Available at: http://www.iom.edu/Activities/Nutrition/SummaryDRIs/DRI-Tables.aspx].

Early studies conducted in Caucasian [45Bonjour JP, Carrie AL, Ferrari S, et al. Calcium-enriched foods and bone mass growth in prepubertal girls: a randomized, double-blind, placebo-controlled trial. J Clin Invest 1997; 99(6): 1287-94.
[http://dx.doi.org/10.1172/JCI119287] [PMID: 9077538]
-47Cadogan J, Eastell R, Jones N, Barker ME. Milk intake and bone mineral acquisition in adolescent girls: randomised, controlled intervention trial. BMJ 1997; 315(7118): 1255-60.
[http://dx.doi.org/10.1136/bmj.315.7118.1255] [PMID: 9390050]
] and Gambian children [48Dibba B, Prentice A, Ceesay M, Stirling DM, Cole TJ, Poskitt EM. Effect of calcium supplementation on bone mineral accretion in gambian children accustomed to a low-calcium diet. Am J Clin Nutr 2000; 71(2): 544-9.
[PMID: 10648270]
] showed that supplementing the diet with calcium or milk to increase nutrient intake may enhance bone accretion. In one study, girls who had their diet supplemented with milk had higher circulating IGF-1 concentrations, which may affect bone growth [47Cadogan J, Eastell R, Jones N, Barker ME. Milk intake and bone mineral acquisition in adolescent girls: randomised, controlled intervention trial. BMJ 1997; 315(7118): 1255-60.
[http://dx.doi.org/10.1136/bmj.315.7118.1255] [PMID: 9390050]
]. When extra phosphorus was provided, bone area as well as vertebral height increased and total BMC also increased [45Bonjour JP, Carrie AL, Ferrari S, et al. Calcium-enriched foods and bone mass growth in prepubertal girls: a randomized, double-blind, placebo-controlled trial. J Clin Invest 1997; 99(6): 1287-94.
[http://dx.doi.org/10.1172/JCI119287] [PMID: 9077538]
]. In another study, the diet of eleven year old white girls was supplemented with dairy products to the level of 1200 mg calcium per day for 12 months [49Chan GM, Hoffman K, McMurry M. Effects of dairy products on bone and body composition in pubertal girls. J Pediatr 1995; 126(4): 551-6.
[http://dx.doi.org/10.1016/S0022-3476(95)70348-9] [PMID: 7699532]
]. The increased intake of dairy provided not only calcium but protein and other minerals plus additional vitamin D. After one year the intervention group had significantly greater increases in lumbar spine bone density and total body mineralisation [49Chan GM, Hoffman K, McMurry M. Effects of dairy products on bone and body composition in pubertal girls. J Pediatr 1995; 126(4): 551-6.
[http://dx.doi.org/10.1016/S0022-3476(95)70348-9] [PMID: 7699532]
].

More recent data also support an association between dairy consumption, growth, and bone health. In children in Kenya, physical growth, cognitive function and school performance were all improved when meat and milk were added to the normal daily diet [50Neumann CG, Murphy SP, Gewa C, Grillenberger M, Bwibo NO. Meat supplementation improves growth, cognitive, and behavioral outcomes in Kenyan children. J Nutr 2007; 137(4): 1119-23.
[PMID: 17374691]
]. Milk supplementation improved linear growth, and the meat and milk supplemented groups had improved weight gain, suggesting chronic energy deficits resulting from the unsupplemented diet. In another study, bone changes over two years in young children with a history of milk avoidance were evaluated, and results demonstrated persistent height reduction, obesity and low bone density at the ultradistal radius and lumbar spine [51Rockell JE, Williams SM, Taylor RW, Grant AM, Jones IE, Goulding A. Two-year changes in bone and body composition in young children with a history of prolonged milk avoidance. Osteoporos Int 2005; 16(9): 1016-23.
[http://dx.doi.org/10.1007/s00198-004-1789-9] [PMID: 15565350]
]. In contrast, other authors have suggested that dairy or calcium intake may only be beneficial to specific subpopulations of children, or may actually fail to provide any benefit to children at all. In a meta-analysis on the relationship between dairy and calcium intake and BMC, a review of 21 studies concluded that increased dairy/calcium intake with or without vitamin D improved spine and whole body mineral content, but only in children with low baseline intakes of dairy or calcium [52Huncharek M, Muscat J, Kupelnick B. Impact of dairy products and dietary calcium on bone-mineral content in children: results of a meta-analysis. Bone 2008; 43(2): 312-21.
[http://dx.doi.org/10.1016/j.bone.2008.02.022] [PMID: 18539555]
]. Lanou et al. (2005) [53Lanou AJ, Berkow SE, Barnard ND. Calcium, dairy products, and bone health in children and young adults: a reevaluation of the evidence. Pediatrics 2005; 115(3): 736-43.
[http://dx.doi.org/10.1542/peds.2004-0548] [PMID: 15741380]
] reviewed the evidence for the effects of calcium and dairy products on bone health of children and adolescents, and found no consistent benefits of increasing dairy consumption for child or young adult bone health.

Wiley (2012) [54Wiley AS. Cow milk consumption, insulin-like growth factor-I, and human biology: a life history approach. Am J Hum Biol 2012; 24(2): 130-8.
[http://dx.doi.org/10.1002/ajhb.22201] [PMID: 22121110]
] recently presented an interesting perspective on cow milk consumption and human biology; posing the question of whether drinking cow milk accelerates linear growth and maturation or affects size in adulthood. The results presented were drawn from new analyses of NHANES data collected between 1999-2004, and other published studies in the US [54Wiley AS. Cow milk consumption, insulin-like growth factor-I, and human biology: a life history approach. Am J Hum Biol 2012; 24(2): 130-8.
[http://dx.doi.org/10.1002/ajhb.22201] [PMID: 22121110]
]. Overall, children aged 24-59 months with the highest quartile of milk intake (>2 cups per day), attained a greater height percentile compared with those in the lower quartiles of intake. These results are in line with a previous study in New Zealand, which reported that children who avoided milk were shorter than milk-drinking controls [55Black RE, Williams SM, Jones IE, Goulding A. Children who avoid drinking cow milk have low dietary calcium intakes and poor bone health. Am J Clin Nutr 2002; 76(3): 675-80.
[PMID: 12198017]
]. However, data on prepubertal children (5-11 years) were more variable. An older study done in the UK [56Leighton G, Clark ML. Milk consumption and the growth of school children: Second preliminary reports on tests to the Scottish Board of Health. BMJ 1929; 1(3548): 23-5.
[http://dx.doi.org/10.1136/bmj.1.3548.23] [PMID: 20774373]
] reported greater growth in children receiving milk over a duration of seven months compared with children receiving a biscuit or no supplement. While some more recent studies support this result, others have produced data indicating no effects of milk on growth, and the NHANES data did not support an effect linked with drinking milk daily [54Wiley AS. Cow milk consumption, insulin-like growth factor-I, and human biology: a life history approach. Am J Hum Biol 2012; 24(2): 130-8.
[http://dx.doi.org/10.1002/ajhb.22201] [PMID: 22121110]
]. However, it should be noted that in addition to increasing calcium availability, milk also provides energy and contributes to macronutrient intake, which may also impact on height and growth. Since few trials correct for energy and macronutrient intake, the question of whether milk does affect growth in prepubertal children remains to be confirmed.

CALCIUM SUPPLEMENTATION

In several studies, calcium supplementation, rather than overall dairy intake, has formed the basis of research into possible associations between growth and diet. In one study, providing only calcium as a supplement increased BMC but not bone area [48Dibba B, Prentice A, Ceesay M, Stirling DM, Cole TJ, Poskitt EM. Effect of calcium supplementation on bone mineral accretion in gambian children accustomed to a low-calcium diet. Am J Clin Nutr 2000; 71(2): 544-9.
[PMID: 10648270]
], while in another, providing calcium as a supplement in boys and girls aged nine years improved bone density and mineralisation but not longitudinal growth, bone area and width, or body weight [46Johnston CC Jr, Miller JZ, Slemenda CW, et al. Calcium supplementation and increases in bone mineral density in children. N Engl J Med 1992; 327(2): 82-7.
[http://dx.doi.org/10.1056/NEJM199207093270204] [PMID: 1603140]
]. Data from a 4-year randomized controlled trial supplementing ten year old females with calcium citrate-malate suggested that bone accretion in the supplemented group was significantly higher than the control group after 4 years. However, after a three year extension of the trial, the positive effects had largely disappeared, with the exception of the metacarpals and the forearms of taller subjects [57Matkovic V, Goel PK, Badenhop-Stevens NE, et al. Calcium supplementation and bone mineral density in females from childhood to young adulthood: a randomized controlled trial. Am J Clin Nutr 2005; 81(1): 175-88.
[PMID: 15640478]
].

A recent meta-analysis of calcium supplementation trials in children aged between six years and 18 years, reported no significant effect on bone density at the femoral neck and lumbar spine, with a small effect on total BMC [58Winzenberg T, Shaw K, Fryer J, Jones G. Effects of calcium supplementation on bone density in healthy children: meta-analysis of randomised controlled trials. BMJ 2006; 333(7572): 775.
[http://dx.doi.org/10.1136/bmj.38950.561400.55] [PMID: 16980314]
]. However, previous research indicated that calcium supplementation may need to be combined with exercise for the full beneficial effects to be observed [59Iuliano-Burns S, Saxon L, Naughton G, Gibbons K, Bass SL. Regional specificity of exercise and calcium during skeletal growth in girls: a randomized controlled trial. J Bone Miner Res 2003; 18(1): 156-62.
[http://dx.doi.org/10.1359/jbmr.2003.18.1.156] [PMID: 12510818]
]. In an earlier review on the role of physical activity and calcium intake for bone mass growth in children, French et al. (2000) [60French SA, Fulkerson JA, Story M. Increasing weight-bearing physical activity and calcium intake for bone mass growth in children and adolescents: a review of intervention trials. Prev Med 2000; 31(6): 722-31.
[http://dx.doi.org/10.1006/pmed.2000.0758] [PMID: 11133340]
] reported that weight-bearing physical activity and calcium supplementation both improved bone mass gain in children and adolescents, with the consistent sites being the lumbar spine and total bone mass. However, the continuing benefit and durability of these effects was not known until recently, when this question was addressed in a long-term calcium supplementation trial in Gambian children [61Prentice A, Dibba B, Sawo Y, Cole TJ. The effect of prepubertal calcium carbonate supplementation on the age of peak height velocity in Gambian adolescents. Am J Clin Nutr 2012; 96(5): 1042-50.
[http://dx.doi.org/10.3945/ajcn.112.037481] [PMID: 22990031]
]. Participating children, aged 8-12 years, received calcium 1000 mg/day for 12 months, and were subsequently followed to the age of 21-25 years with height measurements occurring every six-months, or annually. In calcium-supplemented boys peak height velocity was accelerated by 7 months and they reached greater stature at a mean age of 15.5 years. But at mean age 23.5 years, the calcium supplemented group was 3.5 cm shorter than their counterparts. No significant effect was observed in girls [61Prentice A, Dibba B, Sawo Y, Cole TJ. The effect of prepubertal calcium carbonate supplementation on the age of peak height velocity in Gambian adolescents. Am J Clin Nutr 2012; 96(5): 1042-50.
[http://dx.doi.org/10.3945/ajcn.112.037481] [PMID: 22990031]
].

Overall, it would appear that providing dairy or calcium supplementation could improve growth and bone mineralisation in children [62USDA Nutrition Evidence Library. What is the relationship between the intake of milk and milk products and bone health? 2012. Available at: http://www.nel.gov/evidence.cfm?evidence_summary_id=250369]. However, while these types of studies are feasible in growing children in developing countries, they do not address possible deficiencies in other minerals and some vitamins.

IMPACT OF MICRONUTRIENTS

More than 20 years ago, it was suggested that although providing calcium as a supplement alone or with phosphorus did not improve height or weight gain in children of developing countries, providing calcium in combination with other micronutrients could potentially enhance growth [63Prentice A, Bates CJ. Adequacy of dietary mineral supply for human bone growth and mineralisation. Eur J Clin Nutr 1994; 48(Suppl. 1): S161-76.
[PMID: 8005083]
]. The Bt20 study conducted longitudinal food frequency analyses and consistently found that calcium, iron, zinc and biotin fell below 65% of the recommended daily allowance. In addition, vitamin A, riboflavin, nicotinic acid and pantothenic acid fell below the RDA in 2003, and from 2000 to 2003 there was an increase in the percentage of children falling below the recommended intakes for most micronutrients [31Richter L, Norris S, Pettifor J, Yach D, Cameron N. Cohort profile: Mandelas children: The 1990 birth to twenty study in South Africa. Int J Epidemiol 2007; 36(3): 504-11.
[http://dx.doi.org/10.1093/ije/dym016] [PMID: 17355979]
]. Addition of micronutrients such as zinc to the daily diet may help to overcome problems of poor absorption of macronutrients, thus indirectly improving physical and mental growth and well-being. However, while food supplementation and fortification with micronutrients have been shown to be both efficacious and cost-effective [64Bhutta ZA, Salam RA, Das JK. Meeting the challenges of micronutrient malnutrition in the developing world. Br Med Bull 2013; 106: 7-17.
[http://dx.doi.org/10.1093/bmb/ldt015] [PMID: 23645843]
], there is currently no consensus on the timing or methodology for such improvements to be implemented in developing countries.

There have been several studies in children evaluating the effect of single micronutrient supplementation on linear growth. According to a meta-analysis of more than 30 randomized controlled trials, the most conclusive evidence exists for the addition of zinc to the diet [1Ramakrishnan U, Aburto N, McCabe G, Martorell R. Multimicronutrient interventions but not vitamin a or iron interventions alone improve child growth: results of 3 meta-analyses. J Nutr 2004; 134(10): 2592-602.
[PMID: 15465753]
]. Zinc has been found to have a small but significant effect on growth in children aged 0-13 years, by reducing the incidence of diarrhoea and pneumonia, which were two factors affecting growth. In contrast, iron supplementation only improved linear growth in anaemic children, while vitamin A had little or no benefit on linear growth [1Ramakrishnan U, Aburto N, McCabe G, Martorell R. Multimicronutrient interventions but not vitamin a or iron interventions alone improve child growth: results of 3 meta-analyses. J Nutr 2004; 134(10): 2592-602.
[PMID: 15465753]
]. These data are supported by other publications, although the conclusions must be interpreted with caution due to the inclusion of non-randomized trials and community-based studies in the analyses [11Rivera JA, Hotz C, González-Cossío T, Neufeld L, García-Guerra A. The effect of micronutrient deficiencies on child growth: a review of results from community-based supplementation trials. J Nutr 2003; 133(11)(Suppl. 2): 4010S-20S.
[PMID: 14672304]
, 65Bhandari N, Bahl R, Taneja S. Effect of micronutrient supplementation on linear growth of children. Br J Nutr 2001; 85(Suppl. 2): S131-7.
[http://dx.doi.org/10.1079/BJN2000305] [PMID: 11509101]
]. One limitation of the meta-analysis is that reports on the relationship between iron and growth in children are sparse and not convincing, making it difficult to draw definitive conclusions [1Ramakrishnan U, Aburto N, McCabe G, Martorell R. Multimicronutrient interventions but not vitamin a or iron interventions alone improve child growth: results of 3 meta-analyses. J Nutr 2004; 134(10): 2592-602.
[PMID: 15465753]
]. Furthermore, the response to vitamin A appeared to be linked to the season, with a response in the summer months; thus the non-response recorded for vitamin A supplementation and growth could result from the fact in an intervention lasting for a year, any small effect taking place in a specific season is likely to be diluted out in the overall data [1Ramakrishnan U, Aburto N, McCabe G, Martorell R. Multimicronutrient interventions but not vitamin a or iron interventions alone improve child growth: results of 3 meta-analyses. J Nutr 2004; 134(10): 2592-602.
[PMID: 15465753]
]. The other consideration mentioned was that none of the children in the supplemented groups were vitamin A deficient which could limit the response. The results of single micronutrient supplementation are therefore limited, and since it seems likely that multiple nutrient deficiencies exist, it may be expected that supplementation with individual micronutrients will have a limited impact on growth.

In addition to evaluating the impact of single micronutrient supplementation, the same meta-analysis reported that multi-micronutrient interventions do improve growth in children [1Ramakrishnan U, Aburto N, McCabe G, Martorell R. Multimicronutrient interventions but not vitamin a or iron interventions alone improve child growth: results of 3 meta-analyses. J Nutr 2004; 134(10): 2592-602.
[PMID: 15465753]
]. This outcome could be due to interactions between nutrients [66Dujkhuizen MA, Wieringa FT, West CE, Martuti S. Muhilal. Effects of iron and zinc supplementation in Indonesian infants on micronutrient status and growth. J Nutr 2001; 13: 2860-5.] as well as direct effects by single nutrients in the mixture. A recent systematic review of 18 trials in which young children in developing countries were given multinutrient-fortified milk and cereal products indicated that correcting multiple micronutrient deficiencies may be beneficial in improving an overall poor diet and reducing common health problems, although information on long-term functional outcomes remains scarce [67Eichler K, Wieser S, Rüthemann I, Brügger U. Effects of micronutrient fortified milk and cereal food for infants and children: a systematic review. BMC Public Health 2012; 12: 506.
[http://dx.doi.org/10.1186/1471-2458-12-506] [PMID: 22770558]
].

While there have been many studies on single or multiple micronutrient supplementation in infants and young children [11Rivera JA, Hotz C, González-Cossío T, Neufeld L, García-Guerra A. The effect of micronutrient deficiencies on child growth: a review of results from community-based supplementation trials. J Nutr 2003; 133(11)(Suppl. 2): 4010S-20S.
[PMID: 14672304]
, 67Eichler K, Wieser S, Rüthemann I, Brügger U. Effects of micronutrient fortified milk and cereal food for infants and children: a systematic review. BMC Public Health 2012; 12: 506.
[http://dx.doi.org/10.1186/1471-2458-12-506] [PMID: 22770558]
-69Ramakrishnan U, Nguyen P, Martorell R. Effects of micronutrients on growth of children under 5 y of age: meta-analyses of single and multiple nutrient interventions. Am J Clin Nutr 2009; 89(1): 191-203.
[http://dx.doi.org/10.3945/ajcn.2008.26862] [PMID: 19056559]
], there is a paucity of data on micronutrient supplementation and growth in older children, and specifically in South African children aged between 9 and 12 years. One study in South African schoolchildren aged 6-11 years (mean age eight years) reported that while a multi-micronutrient-fortified beverage was able to improve cognition, it had no effect on height [70Taljaard C, Covic NM, van Graan AE, et al. Effects of a multi-micronutrient-fortified beverage, with and without sugar, on growth and cognition in South African schoolchildren: a randomised, double-blind, controlled intervention. Br J Nutr 2013; 110(12): 2271-84.
[http://dx.doi.org/10.1017/S000711451300189X] [PMID: 23823584]
]. Furthermore, the impact of the micronutrients on cognition was attenuated by the addition of sugar to the beverage, indicating that nutrient interactions can add an additional level of complexity to supplementation research, and may significantly influence study outcomes [70Taljaard C, Covic NM, van Graan AE, et al. Effects of a multi-micronutrient-fortified beverage, with and without sugar, on growth and cognition in South African schoolchildren: a randomised, double-blind, controlled intervention. Br J Nutr 2013; 110(12): 2271-84.
[http://dx.doi.org/10.1017/S000711451300189X] [PMID: 23823584]
]. Authors of studies in other countries have reported varying results [71Hyder SM, Haseen F, Khan M, et al. A multiple-micronutrient-fortified beverage affects hemoglobin, iron, and vitamin A status and growth in adolescent girls in rural Bangladesh. J Nutr 2007; 137(9): 2147-53.
[PMID: 17709456]
-74Abrams SA, Mushi A, Hilmers DC, Griffin IJ, Davila P, Allen L. A multinutrient-fortified beverage enhances the nutritional status of children in Botswana. J Nutr 2003; 133(6): 1834-40.
[PMID: 12771326]
]. In Bangladesh, a trial in 989 girls (mean age 12 years) receiving multinutrient supplementation reported that mean height, weight and mean upper arm circumference increased significantly more in the supplemented group over the first six months compared with the control group [71Hyder SM, Haseen F, Khan M, et al. A multiple-micronutrient-fortified beverage affects hemoglobin, iron, and vitamin A status and growth in adolescent girls in rural Bangladesh. J Nutr 2007; 137(9): 2147-53.
[PMID: 17709456]
]. Significant improvement was also found in haemoglobin concentration, iron status and vitamin A status over the first six months in the supplemented group, with no further improvement over the second six months of the study. Despite these improvement, the girls did not appear to gain significant height during the supplementation period [71Hyder SM, Haseen F, Khan M, et al. A multiple-micronutrient-fortified beverage affects hemoglobin, iron, and vitamin A status and growth in adolescent girls in rural Bangladesh. J Nutr 2007; 137(9): 2147-53.
[PMID: 17709456]
]. In contrast, children in Tanzania aged between 6-11 years, supplied with a beverage containing three minerals and seven vitamins delivering between 30-120% of the RDA during week days for six months, showed improvements in both linear growth and weight gain [72Latham MC, Ash DM, Makola D, Tatala SR, Ndossi GD, Mehansho H. Efficacy trials of a micronutrient dietary supplement in schoolchildren and pregnant women in Tanzania. Food Nutr Bull 2003; 24(4)(Suppl.): S120-8.
[http://dx.doi.org/10.1177/15648265030244S209] [PMID: 17016954]
, 73Ash DM, Tatala SR, Frongillo EA Jr, Ndossi GD, Latham MC. Randomized efficacy trial of a micronutrient-fortified beverage in primary school children in Tanzania. Am J Clin Nutr 2003; 77(4): 891-8.
[PMID: 12663288]
]. Similarly, children in Botswana aged 6-11 years, who were supplemented with an experimental beverage which was fortified with 12 micronutrients, gained significantly more weight over the eight weeks of supplementation [74Abrams SA, Mushi A, Hilmers DC, Griffin IJ, Davila P, Allen L. A multinutrient-fortified beverage enhances the nutritional status of children in Botswana. J Nutr 2003; 133(6): 1834-40.
[PMID: 12771326]
]. While these studies show promise, the variability in results between countries suggest that low energy and protein intake may still limit growth even in the presence of adequate micronutrients.

CONCLUSION

Dietary supplementation in previously undernourished children may improve growth and development, and ultimately produce a healthier workforce and society. Although considerable attention has been focused on the early months and years of life as the optimal time to effect change, there may be other windows of opportunity throughout childhood and adolescence to reverse, to at least some degree, the impact of poor maternal diet and foetal underdevelopment. Furthermore, although many studies have evaluated dairy and calcium supplementation, it seems likely that maximum benefit is gained only when the diet includes sources of energy, protein, and micronutrients, which can act together to reduce deficits and boost physical and cognitive development. In South Africa, societal changes during the past few decades have radically altered a traditional diet which sustained the population for centuries, introducing cheap but nutrient-poor, fast-food alternatives which has resulted in a generation of undernourished children. Further studies are required to explicitly identify the role for the specific nutrients affecting bone growth, the optimal timing of supplementation and the dosage thereof, and the method by which multinutrients can be made available to these children and future generations, to reverse the tide of stunting and poor health which currently threatens to engulf them. The efficacy and efficiency of supplementation vs. food based approaches should be determined.

CONFLICT OF INTEREST

The authors confirm that this article content has no conflict of interest.

ACKNOWLEDGEMENTS

The authors devised, researched, and wrote the article. The authors would like to thank Sally Mitchell, PhD (Massey University, NZ), for editorial assistance with the preparation and formatting of this manuscript.

REFERENCES

[1] Ramakrishnan U, Aburto N, McCabe G, Martorell R. Multimicronutrient interventions but not vitamin a or iron interventions alone improve child growth: results of 3 meta-analyses. J Nutr 2004; 134(10): 2592-602.
[PMID: 15465753]
[2] UNICEF. Facts for life. 2010. Available at: http://www.factsforlifeglobal.org
[3] Muthayya S, Rah JH, Sugimoto JD, Roos FF, Kraemer K, Black RE. The global hidden hunger indices and maps: an advocacy tool for action. PLoS One 2013; 8(6): e67860.
[http://dx.doi.org/10.1371/journal.pone.0067860] [PMID: 23776712]
[4] Shenkin A. Micronutrients in health and disease. Postgrad Med J 2006; 82(971): 559-67.
[http://dx.doi.org/10.1136/pgmj.2006.047670] [PMID: 16954450]
[5] Christian P. Micronutrients and reproductive health issues: an international perspective. J Nutr 2003; 133(6): 1969S-73S.
[PMID: 12771347]
[6] Ramakrishnan U. Prevalence of micronutrient malnutrition worldwide. Nutr Rev 2002; 60(5 Pt 2): S46-52.
[PMID: 12035858]
[7] Weaver CM. The role of nutrition on optimizing peak bone mass. Asia Pac J Clin Nutr 2008; 17(Suppl. 1): 135-7.
[PMID: 18296321]
[8] Giustina A, Mazziotti G, Canalis E. Growth hormone, insulin-like growth factors, and the skeleton. Endocr Rev 2008; 29(5): 535-59.
[http://dx.doi.org/10.1210/er.2007-0036] [PMID: 18436706]
[9] Loveridge N, Noble BS. Control of longitudinal growth: the role of nutrition. Eur J Clin Nutr 1994; 48(2): 75-84.
[PMID: 8194496]
[10] Estívariz CF, Ziegler TR. Nutrition and the insulin-like growth factor system. Endocrine 1997; 7(1): 65-71.
[http://dx.doi.org/10.1007/BF02778066] [PMID: 9449035]
[11] Rivera JA, Hotz C, González-Cossío T, Neufeld L, García-Guerra A. The effect of micronutrient deficiencies on child growth: a review of results from community-based supplementation trials. J Nutr 2003; 133(11)(Suppl. 2): 4010S-20S.
[PMID: 14672304]
[12] Bailey DA, McKay HA, Mirwald RL, Crocker PR, Faulkner RA. 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; 14(10): 1672-9.
[http://dx.doi.org/10.1359/jbmr.1999.14.10.1672] [PMID: 10491214]
[13] Hawkes CP, Grimberg A. Measuring growth hormone and insulin-like growth factor-I in infants: what is normal? Pediatr Endocrinol Rev 2013; 11(2): 126-46.
[PMID: 24575549]
[14] World Health Organization. Training course on child growth assessment. 2010. Available at: http://www.who.int/ childgrowth/training/ module_b_measuring_growth.pdf
[15] Darteh EK, Acquah E, Kumi-Kyereme A. Correlates of stunting among children in Ghana. BMC Public Health 2014; 14: 504.
[http://dx.doi.org/10.1186/1471-2458-14-504] [PMID: 24884653]
[16] World Health Organization. WHO child growth standards. 2006. Available at: http://www.who.int/childgrowth/standards/en/
[17] WHO Multicentre Growth Reference Study Group. WHO Child Growth Standards based on length/height, weight and age. Acta Paediatr Suppl 2006; 450: 76-85.
[PMID: 16817681]
[18] World Health Organization, United Nations Children's Fund. WHO child growth standards and the identification of severe acute malnutrition in infants and children. A joint statement 2009. Available at: http://www.who.int/nutrition/ publications/severemalnutrition/ 9789241598163/en/
[19] Levine MA. Assessing bone health in children and adolescents. Indian J Endocrinol Metab 2012; 16(Suppl. 2): S205-12.
[PMID: 23565379]
[20] Estrada A, Ramnitz MS, Gafni RI. Bone densitometry in children and adolescents. Curr Opin Obstet Gynecol 2014; 26(5): 339-46.
[http://dx.doi.org/10.1097/GCO.0000000000000100] [PMID: 25144595]
[21] Crabtree NJ, Arabi A, Bachrach LK, et al. Dual-energy X-ray absorptiometry interpretation and reporting in children and adolescents: the revised 2013 ISCD Pediatric Official Positions. J Clin Densitom 2014; 17(2): 225-42.
[http://dx.doi.org/10.1016/j.jocd.2014.01.003] [PMID: 24690232]
[22] The International Society for Clinical Densitometry. The official pediatric positions. 2013. Available at: http://www.iscd.org/documents/2013/12/2013-pediatric-position-statements.pdf
[23] Kalkwarf HJ, Abrams SA, DiMeglio LA, Koo WW, Specker BL, Weiler H. Bone densitometry in infants and young children: the 2013 ISCD Pediatric Official Positions. J Clin Densitom 2014; 17(2): 243-57.
[http://dx.doi.org/10.1016/j.jocd.2014.01.002] [PMID: 24674638]
[24] Kagura J, Feeley AB, Micklesfield LK, Pettifor JM, Norris SA. Association between infant nutrition and anthropometry, and pre-pubertal body composition in urban South African children. J Dev Orig Health Dis 2012; 3(6): 415-23.
[http://dx.doi.org/10.1017/S2040174412000475] [PMID: 25084294]
[25] Black RE, Victora CG, Walker SP, et al. Maternal and child undernutrition and overweight in low-income and middle-income countries. Lancet 2013; 382(9890): 427-51.
[http://dx.doi.org/10.1016/S0140-6736(13)60937-X] [PMID: 23746772]
[26] Vorster HH, Kruger A, Margetts BM. The nutrition transition in Africa: can it be steered into a more positive direction? Nutrients 2011; 3(4): 429-41.
[http://dx.doi.org/10.3390/nu3040429] [PMID: 22254104]
[27] Cameron N. Physical growth in a transitional economy: the aftermath of South African apartheid. Econ Hum Biol 2003; 1(1): 29-42.
[http://dx.doi.org/10.1016/S1570-677X(02)00008-4] [PMID: 15463962]
[28] Monyeki KD, Cameron N, Getz B. Growth and nutritional status of rural South African children 310 years old: The Ellisras growth study. Am J Hum Biol 2000; 12(1): 42-9.
[http://dx.doi.org/10.1002/(SICI)1520-6300(200001/02)12:1<42::AID-AJHB6>3.0.CO;2-0] [PMID: 11534003]
[29] Frisancho AR. Anthropometric standards for the assessment of growth and nutritional status. Ann Arbor: University of Michigan Press 1990.
[http://dx.doi.org/10.3998/mpub.12198]
[30] Yach D, Padayachee GN, Cameron N, Wagstaff LA, Richter L. Birth to Tena study of children of the 1990s living in the Johannesburg-Soweto area. S Afr Med J 1990; 77(7): 325-6.
[PMID: 2321102]
[31] Richter L, Norris S, Pettifor J, Yach D, Cameron N. Cohort profile: Mandelas children: The 1990 birth to twenty study in South Africa. Int J Epidemiol 2007; 36(3): 504-11.
[http://dx.doi.org/10.1093/ije/dym016] [PMID: 17355979]
[32] Vidulich L, Norris SA, Cameron N, Pettifor JM. Differences in bone size and bone mass between black and white 10-year-old South African children. Osteoporos Int 2006; 17(3): 433-40.
[http://dx.doi.org/10.1007/s00198-005-0004-y] [PMID: 16362145]
[33] May A, Pettifor JM, Norris SA, Ramsay M, Lombard Z. Genetic factors influencing bone mineral content in a black South African population. J Bone Miner Metab 2013; 31(6): 708-16.
[http://dx.doi.org/10.1007/s00774-013-0431-3] [PMID: 23475190]
[34] Prentice AM, Ward KA, Goldberg GR, et al. Critical windows for nutritional interventions against stunting. Am J Clin Nutr 2013; 97(5): 911-8.
[http://dx.doi.org/10.3945/ajcn.112.052332] [PMID: 23553163]
[35] Victora CG, de Onis M, Hallal PC, Blössner M, Shrimpton R. Worldwide timing of growth faltering: revisiting implications for interventions. Pediatrics 2010; 125(3): e473-80.
[http://dx.doi.org/10.1542/peds.2009-1519] [PMID: 20156903]
[36] Hirvonen K. Measuring catch-up growth in malnourished populations. Ann Hum Biol 2014; 41(1): 67-75.
[http://dx.doi.org/10.3109/03014460.2013.827239] [PMID: 24020872]
[37] United Nations Administrative Committee on Coordination / Subcommittee on Nutrition (ACC/SCN). The world nutrition situation: Nutrition throughout the lifecycle 2000. Available at: http://www.unscn.org/layout/modules/resources/files/rwns4.pdf
[38] Guéguen L, Pointillart A. The bioavailability of dietary calcium. J Am Coll Nutr 2000; 19(2)(Suppl.): 119S-36S.
[http://dx.doi.org/10.1080/07315724.2000.10718083] [PMID: 10759138]
[39] Renner E. Dairy calcium, bone metabolism, and prevention of osteoporosis. J Dairy Sci 1994; 77(12): 3498-505.
[http://dx.doi.org/10.3168/jds.S0022-0302(94)77291-X] [PMID: 7699131]
[40] Stracke H, Renner E, Knie G, Leidig G, Minne H, Federlin K. Osteoporosis and bone metabolic parameters in dependence upon calcium intake through milk and milk products. Eur J Clin Nutr 1993; 47(9): 617-22.
[PMID: 8243426]
[41] Kalkwarf HJ, Khoury JC, Lanphear BP. Milk intake during childhood and adolescence, adult bone density, and osteoporotic fractures in US women. Am J Clin Nutr 2003; 77(1): 257-65.
[PMID: 12499350]
[42] Matković V, Kostial K, Simonović I, Buzina R, Brodarec A, Nordin BE. Bone status and fracture rates in two regions of Yugoslavia. Am J Clin Nutr 1979; 32(3): 540-9.
[PMID: 420146]
[43] Teegarden D, Lyle RM, Proulx WR, Johnston CC, Weaver CM. Previous milk consumption is associated with greater bone density in young women. Am J Clin Nutr 1999; 69(5): 1014-7.
[PMID: 10232644]
[44] Institute of Medicine of the National Academies. Dietary Reference Intakes Tables and Application. 2010. Available at: http://www.iom.edu/Activities/Nutrition/SummaryDRIs/DRI-Tables.aspx
[45] Bonjour JP, Carrie AL, Ferrari S, et al. Calcium-enriched foods and bone mass growth in prepubertal girls: a randomized, double-blind, placebo-controlled trial. J Clin Invest 1997; 99(6): 1287-94.
[http://dx.doi.org/10.1172/JCI119287] [PMID: 9077538]
[46] Johnston CC Jr, Miller JZ, Slemenda CW, et al. Calcium supplementation and increases in bone mineral density in children. N Engl J Med 1992; 327(2): 82-7.
[http://dx.doi.org/10.1056/NEJM199207093270204] [PMID: 1603140]
[47] Cadogan J, Eastell R, Jones N, Barker ME. Milk intake and bone mineral acquisition in adolescent girls: randomised, controlled intervention trial. BMJ 1997; 315(7118): 1255-60.
[http://dx.doi.org/10.1136/bmj.315.7118.1255] [PMID: 9390050]
[48] Dibba B, Prentice A, Ceesay M, Stirling DM, Cole TJ, Poskitt EM. Effect of calcium supplementation on bone mineral accretion in gambian children accustomed to a low-calcium diet. Am J Clin Nutr 2000; 71(2): 544-9.
[PMID: 10648270]
[49] Chan GM, Hoffman K, McMurry M. Effects of dairy products on bone and body composition in pubertal girls. J Pediatr 1995; 126(4): 551-6.
[http://dx.doi.org/10.1016/S0022-3476(95)70348-9] [PMID: 7699532]
[50] Neumann CG, Murphy SP, Gewa C, Grillenberger M, Bwibo NO. Meat supplementation improves growth, cognitive, and behavioral outcomes in Kenyan children. J Nutr 2007; 137(4): 1119-23.
[PMID: 17374691]
[51] Rockell JE, Williams SM, Taylor RW, Grant AM, Jones IE, Goulding A. Two-year changes in bone and body composition in young children with a history of prolonged milk avoidance. Osteoporos Int 2005; 16(9): 1016-23.
[http://dx.doi.org/10.1007/s00198-004-1789-9] [PMID: 15565350]
[52] Huncharek M, Muscat J, Kupelnick B. Impact of dairy products and dietary calcium on bone-mineral content in children: results of a meta-analysis. Bone 2008; 43(2): 312-21.
[http://dx.doi.org/10.1016/j.bone.2008.02.022] [PMID: 18539555]
[53] Lanou AJ, Berkow SE, Barnard ND. Calcium, dairy products, and bone health in children and young adults: a reevaluation of the evidence. Pediatrics 2005; 115(3): 736-43.
[http://dx.doi.org/10.1542/peds.2004-0548] [PMID: 15741380]
[54] Wiley AS. Cow milk consumption, insulin-like growth factor-I, and human biology: a life history approach. Am J Hum Biol 2012; 24(2): 130-8.
[http://dx.doi.org/10.1002/ajhb.22201] [PMID: 22121110]
[55] Black RE, Williams SM, Jones IE, Goulding A. Children who avoid drinking cow milk have low dietary calcium intakes and poor bone health. Am J Clin Nutr 2002; 76(3): 675-80.
[PMID: 12198017]
[56] Leighton G, Clark ML. Milk consumption and the growth of school children: Second preliminary reports on tests to the Scottish Board of Health. BMJ 1929; 1(3548): 23-5.
[http://dx.doi.org/10.1136/bmj.1.3548.23] [PMID: 20774373]
[57] Matkovic V, Goel PK, Badenhop-Stevens NE, et al. Calcium supplementation and bone mineral density in females from childhood to young adulthood: a randomized controlled trial. Am J Clin Nutr 2005; 81(1): 175-88.
[PMID: 15640478]
[58] Winzenberg T, Shaw K, Fryer J, Jones G. Effects of calcium supplementation on bone density in healthy children: meta-analysis of randomised controlled trials. BMJ 2006; 333(7572): 775.
[http://dx.doi.org/10.1136/bmj.38950.561400.55] [PMID: 16980314]
[59] Iuliano-Burns S, Saxon L, Naughton G, Gibbons K, Bass SL. Regional specificity of exercise and calcium during skeletal growth in girls: a randomized controlled trial. J Bone Miner Res 2003; 18(1): 156-62.
[http://dx.doi.org/10.1359/jbmr.2003.18.1.156] [PMID: 12510818]
[60] French SA, Fulkerson JA, Story M. Increasing weight-bearing physical activity and calcium intake for bone mass growth in children and adolescents: a review of intervention trials. Prev Med 2000; 31(6): 722-31.
[http://dx.doi.org/10.1006/pmed.2000.0758] [PMID: 11133340]
[61] Prentice A, Dibba B, Sawo Y, Cole TJ. The effect of prepubertal calcium carbonate supplementation on the age of peak height velocity in Gambian adolescents. Am J Clin Nutr 2012; 96(5): 1042-50.
[http://dx.doi.org/10.3945/ajcn.112.037481] [PMID: 22990031]
[62] USDA Nutrition Evidence Library. What is the relationship between the intake of milk and milk products and bone health? 2012. Available at: http://www.nel.gov/evidence.cfm?evidence_summary_id=250369
[63] Prentice A, Bates CJ. Adequacy of dietary mineral supply for human bone growth and mineralisation. Eur J Clin Nutr 1994; 48(Suppl. 1): S161-76.
[PMID: 8005083]
[64] Bhutta ZA, Salam RA, Das JK. Meeting the challenges of micronutrient malnutrition in the developing world. Br Med Bull 2013; 106: 7-17.
[http://dx.doi.org/10.1093/bmb/ldt015] [PMID: 23645843]
[65] Bhandari N, Bahl R, Taneja S. Effect of micronutrient supplementation on linear growth of children. Br J Nutr 2001; 85(Suppl. 2): S131-7.
[http://dx.doi.org/10.1079/BJN2000305] [PMID: 11509101]
[66] Dujkhuizen MA, Wieringa FT, West CE, Martuti S. Muhilal. Effects of iron and zinc supplementation in Indonesian infants on micronutrient status and growth. J Nutr 2001; 13: 2860-5.
[67] Eichler K, Wieser S, Rüthemann I, Brügger U. Effects of micronutrient fortified milk and cereal food for infants and children: a systematic review. BMC Public Health 2012; 12: 506.
[http://dx.doi.org/10.1186/1471-2458-12-506] [PMID: 22770558]
[68] Allen LH, Peerson JM, Olney DK. Provision of multiple rather than two or fewer micronutrients more effectively improves growth and other outcomes in micronutrient-deficient children and adults. J Nutr 2009; 139(5): 1022-30.
[http://dx.doi.org/10.3945/jn.107.086199] [PMID: 19321586]
[69] Ramakrishnan U, Nguyen P, Martorell R. Effects of micronutrients on growth of children under 5 y of age: meta-analyses of single and multiple nutrient interventions. Am J Clin Nutr 2009; 89(1): 191-203.
[http://dx.doi.org/10.3945/ajcn.2008.26862] [PMID: 19056559]
[70] Taljaard C, Covic NM, van Graan AE, et al. Effects of a multi-micronutrient-fortified beverage, with and without sugar, on growth and cognition in South African schoolchildren: a randomised, double-blind, controlled intervention. Br J Nutr 2013; 110(12): 2271-84.
[http://dx.doi.org/10.1017/S000711451300189X] [PMID: 23823584]
[71] Hyder SM, Haseen F, Khan M, et al. A multiple-micronutrient-fortified beverage affects hemoglobin, iron, and vitamin A status and growth in adolescent girls in rural Bangladesh. J Nutr 2007; 137(9): 2147-53.
[PMID: 17709456]
[72] Latham MC, Ash DM, Makola D, Tatala SR, Ndossi GD, Mehansho H. Efficacy trials of a micronutrient dietary supplement in schoolchildren and pregnant women in Tanzania. Food Nutr Bull 2003; 24(4)(Suppl.): S120-8.
[http://dx.doi.org/10.1177/15648265030244S209] [PMID: 17016954]
[73] Ash DM, Tatala SR, Frongillo EA Jr, Ndossi GD, Latham MC. Randomized efficacy trial of a micronutrient-fortified beverage in primary school children in Tanzania. Am J Clin Nutr 2003; 77(4): 891-8.
[PMID: 12663288]
[74] Abrams SA, Mushi A, Hilmers DC, Griffin IJ, Davila P, Allen L. A multinutrient-fortified beverage enhances the nutritional status of children in Botswana. J Nutr 2003; 133(6): 1834-40.
[PMID: 12771326]

Endorsements



"Open access will revolutionize 21st century knowledge work and accelerate the diffusion of ideas and evidence that support just in time learning and the evolution of thinking in a number of disciplines."


Daniel Pesut
(Indiana University School of Nursing, USA)

"It is important that students and researchers from all over the world can have easy access to relevant, high-standard and timely scientific information. This is exactly what Open Access Journals provide and this is the reason why I support this endeavor."


Jacques Descotes
(Centre Antipoison-Centre de Pharmacovigilance, France)

"Publishing research articles is the key for future scientific progress. Open Access publishing is therefore of utmost importance for wider dissemination of information, and will help serving the best interest of the scientific community."


Patrice Talaga
(UCB S.A., Belgium)

"Open access journals are a novel concept in the medical literature. They offer accessible information to a wide variety of individuals, including physicians, medical students, clinical investigators, and the general public. They are an outstanding source of medical and scientific information."


Jeffrey M. Weinberg
(St. Luke's-Roosevelt Hospital Center, USA)

"Open access journals are extremely useful for graduate students, investigators and all other interested persons to read important scientific articles and subscribe scientific journals. Indeed, the research articles span a wide range of area and of high quality. This is specially a must for researchers belonging to institutions with limited library facility and funding to subscribe scientific journals."


Debomoy K. Lahiri
(Indiana University School of Medicine, USA)

"Open access journals represent a major break-through in publishing. They provide easy access to the latest research on a wide variety of issues. Relevant and timely articles are made available in a fraction of the time taken by more conventional publishers. Articles are of uniformly high quality and written by the world's leading authorities."


Robert Looney
(Naval Postgraduate School, USA)

"Open access journals have transformed the way scientific data is published and disseminated: particularly, whilst ensuring a high quality standard and transparency in the editorial process, they have increased the access to the scientific literature by those researchers that have limited library support or that are working on small budgets."


Richard Reithinger
(Westat, USA)

"Not only do open access journals greatly improve the access to high quality information for scientists in the developing world, it also provides extra exposure for our papers."


J. Ferwerda
(University of Oxford, UK)

"Open Access 'Chemistry' Journals allow the dissemination of knowledge at your finger tips without paying for the scientific content."


Sean L. Kitson
(Almac Sciences, Northern Ireland)

"In principle, all scientific journals should have open access, as should be science itself. Open access journals are very helpful for students, researchers and the general public including people from institutions which do not have library or cannot afford to subscribe scientific journals. The articles are high standard and cover a wide area."


Hubert Wolterbeek
(Delft University of Technology, The Netherlands)

"The widest possible diffusion of information is critical for the advancement of science. In this perspective, open access journals are instrumental in fostering researches and achievements."


Alessandro Laviano
(Sapienza - University of Rome, Italy)

"Open access journals are very useful for all scientists as they can have quick information in the different fields of science."


Philippe Hernigou
(Paris University, France)

"There are many scientists who can not afford the rather expensive subscriptions to scientific journals. Open access journals offer a good alternative for free access to good quality scientific information."


Fidel Toldrá
(Instituto de Agroquimica y Tecnologia de Alimentos, Spain)

"Open access journals have become a fundamental tool for students, researchers, patients and the general public. Many people from institutions which do not have library or cannot afford to subscribe scientific journals benefit of them on a daily basis. The articles are among the best and cover most scientific areas."


M. Bendandi
(University Clinic of Navarre, Spain)

"These journals provide researchers with a platform for rapid, open access scientific communication. The articles are of high quality and broad scope."


Peter Chiba
(University of Vienna, Austria)

"Open access journals are probably one of the most important contributions to promote and diffuse science worldwide."


Jaime Sampaio
(University of Trás-os-Montes e Alto Douro, Portugal)

"Open access journals make up a new and rather revolutionary way to scientific publication. This option opens several quite interesting possibilities to disseminate openly and freely new knowledge and even to facilitate interpersonal communication among scientists."


Eduardo A. Castro
(INIFTA, Argentina)

"Open access journals are freely available online throughout the world, for you to read, download, copy, distribute, and use. The articles published in the open access journals are high quality and cover a wide range of fields."


Kenji Hashimoto
(Chiba University, Japan)

"Open Access journals offer an innovative and efficient way of publication for academics and professionals in a wide range of disciplines. The papers published are of high quality after rigorous peer review and they are Indexed in: major international databases. I read Open Access journals to keep abreast of the recent development in my field of study."


Daniel Shek
(Chinese University of Hong Kong, Hong Kong)

"It is a modern trend for publishers to establish open access journals. Researchers, faculty members, and students will be greatly benefited by the new journals of Bentham Science Publishers Ltd. in this category."


Jih Ru Hwu
(National Central University, Taiwan)


Browse Contents



Webmaster Contact: info@benthamopen.net
Copyright © 2019 Bentham Open