Lifestyle risk factors and bone mineral
density of urban postmenopausal women
in the North West Province.
C. Ellis
21162859
BSc. Dietetics
Mini-dissertation submitted in partial fulfillment of the
requirements for the degree MSc. in Dietetics at the
Potchefstroom Campus of the North West University
Supervisor/Promoter: Dr HH Wright
Co-supervisor/Co-promoter: Prof. HS Kruger
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Table of contents
List of tables
... v
List of figures
... vi
Addendums
... vii
List of abbreviations
... viii
Key definitions
... xi
Acknowledgements
... xii
Summary (English)
...xiii
Opsomming (Afrikaans)
... xiv
Chapter 1: Introduction
... 1
1.1 Background to the problem
... 1
1.2 Motivation for the study
... 2
1.3 Aim
... 3
1.4 Objectives
... 3
1.5 Study design
... 4
1.6 Research team
... 4
1.7 Structure of the dissertation
... 4
1.8 Reference list
... 5
Chapter 2: Literature review
... 8
2.1 Introduction
... 8
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2.2.1 Bone physiology
... 8
2.2.2 Bone formation
... 8
2.2.3 Bone remodelling
... 10
2.2.4 Bone tissue
... 12
2.2.5 Infancy and childhood
... 13
2.2.6 Puberty and attainment of peak bone mass
... 14
2.2.7 Bone health during the peri- and postmenopausal years
... 15
2.3 Calcium metabolism and bone health
... 16
2.3.1 Vitamin D metabolism and bone health
... 18
2.4 Metabolic and hormonal regulation of bone health
... 21
2.5 Osteoporosis: a consequence of impaired bone health
... 23
2.5.1 Osteoporosis and osteopenia
... 23
2.5.2 Risk factors of osteoporosis
... 25
2.6 The role of food and nutrients in the attainment and maintenance of peak bone
mass
... 27
2.6.1 Dairy products and dietary calcium
... 28
2.6.2 Magnesium
... 34
2.6.3 Phosphate
... 36
2.6.4 Protein
... 36
2.6.5 Energy
... 37
2.6.6 Vitamin D
... 39
2.6.7 Vitamin K
... 39
2.6.8 Sodium
... 41
2.7 Diet quality scores
... 42
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3.2 Alcohol
... 43
3.3 Physical activity
... 44
4. Bone health in the South African setting
... 46
4.1 Diagnosis, treatment and prevention
... 47
4.1.1 Diagnosis
... 47
4.1.2 Treatment
... 52
4.1.3 Prevention
... 53
5. Reference list
... 55
CHAPTER 3: METHODOLOGY
... 82
3.1 Research setting
... 82
3.2 Study design
... 83
3.3 Selection of subjects
... 84
3.4 Ethical considerations
... 85
3.5 Measurements
... 86
3.6 Data collection
... 87
3.7 Statistical methods
... 90
3.8 References
... 91
CHAPTER 4: ARTICLE
... 94
Title: Lifestyle behaviors predict bone mineral density of black, urban
postmenopausal women from the North West Province.
... 94
Abstract:
... 95
Introduction
... 96
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Results
... 100
Conflict of interests, source of funding and authorship
... 114
References
... 116
CHAPTER 5: SUMMARY AND CONCLUSIONS
... 126
Objective 1: To adapt the Healthy eating index (HEI) diet quality score
... 126
Objective 2: To evaluate the quality of black urban postmenopausal women’s diet 126
Objective 3: To evaluate the bone mineral density (BMD) of black urban
postmenopausal women
... 127
Objective 4: To assess the association between diet quality score, physical activity
level and BMD
... 127
Objective 5: To identify possible predictors of BMD amongst black urban
postmenopausal women
... 127
5.1 Limitations of this study
... 128
5.2 Recommendations for future research
... 128
5.3 References
... 129
Addendum A
... 132
Addendum B
... 136
Addendum C
... 139
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List of tables
Table 1.1: Research team involved in the completion of this dissertation ………4
Table 2.1: Function of both osteoblasts and osteoclasts ………...10
Table 2.2: Factors that affect the attainment of peak bone mass ………..15
Table 2.3: Risk factors associated with osteoporosis ………...25
Table 2.4: Clinical risk factors used in the assessment of fracture risk ………27
Table 2.5: Recommended dietary allowance for calcium ………..30
Table 2.6: Calcium content of certain foods ………..31
Table 2.7: Comparison of sources of absorbable calcium with milk ………32
Table 2.8: Low vs high protein intake and the effect on kinetic measures of bone ………..….37
Table 2.9: WHO criteria for osteoporosis in women ……….48
Table 2.10: Sources of error in the diagnosis of osteoporosis by dual x-ray absorptiometry...50
Table 2.11: Most commonly used drugs in the treatment of osteoporosis and their actions....52
Table 3.1: Scoring criteria for the adapted Healthy Eating Index score ……….... 89
Table 4.1: Participant characteristics of the total group and by age group ……….101
Table 4.2: Energy and nutrient intake as well as the adapted Healthy Eating Index score of the total group and normal reporters ………....103
Table 4.3: Food portions per food group ingested for the total group and normal reporters………104
Table 4.4: Bone mineral density and T-scores for the total group and by age groups ………105
Table 4.5: Pearson correlations (adjusted for age, height, tobacco use and thiazide use) between factors affecting bone health and bone mineral density ……….105
Table 4.6: Multiple regression models for predicting left femoral neck bone mineral density………..…………....107
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List of figures
Figure 2.1: The role of osteoblasts and oseoclasts in bone remodelling ………..……12
Figure 2.2: Bone mass during the different life cycles………...14
Figure 2.3: Regulation of serum calcium levels and mechanisms increasing fracture risk through calcium and vitamin D deficiency………..…18
Figure 2.4: Metabolism of vitamin D………..19
Figure 2.5: The impact of nutrition and other aspects on various factors that influence
fracture risk. ……….………28 Figure 2.6: Potential mechanism for magnesium-induced bone loss……….35
Figure 3.1: PURE study data collection………. 83
Figure 3.2.: Subject selection for this sub-study within the PURE SA-NWP bone study………... 85
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Addendums
Addendum A: Modified Baecke questionnaire ………... 126
Addendum B: Socio-demographic questionnaire ………130
Addendum C: Quantified food frequency questionnaire ………133
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List of abbreviations
AHEI: Alternate healthy eating indexBMC: Bone mineral content BMD: Bone mineral density BMI: Body mass index
BMP: Bone morphogenetic protein BMR: Basal metabolic rate
CDT: Carbohydrate-deficient transferrin CTX: Carboxy-terminal collagen crosslink CVD: Cardiovascular disease
DDK1: Dickkopf-1
DRI: Dietary reference intake
DXA: Dual energy x-ray absorptiometry FFQ: Food frequency questionnaire FGF: Fibroblast growth factor FSH: Follicular stimulating hormone GGT: Gamma-glutamyltransferase GIT: Gastrointestinal tract
HDL: High density lipoprotein HEI: Healthy eating index
HIV: Human immunodeficiency virus IGF: Insulin-like growth factor IGF-1: Insulin-like growth factor 1
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IL-1: Interleukin-1 IL-1β: Interleukin-1Beta LBM: Lean body mass LDL: Low density lipoprotein MRC: Medical research council NTx: N-terminal telopeptide NWP: North West Province NWU: North West University OPG: Osteoprotegerin PA: Physical activity
PDGF: Platelet-derived growth factor PBM: Peak bone mass
PTH: Parathyroid hormone
PURE: Prospective Urban and Rural Epidemiology QCT: Quantified computed tomography
QFFQ: Quantified food frequency questionnaire QUS: Quantified ultrasound
RANKL: Nuclear factor-kβ ligand RDA: Recommended dietary allowance rEI: Required energy intake
RFS: Recommended food score SA: South Africa
SAFBDG: South African food-based dietary guidelines SA-NWP: South African North West Province
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SP: Substance P T3: Triiodothyronine
TGFβ: Transforming growth factor-β TNF-α: Tumour necrosis factor alpha UL: Upper level
UVB: Ultraviolet B UV: Ultraviolet
VEGF: Vascular endothelial growth factor WHO: World Health Organization
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Key definitions
Bone mineral density: Most often described as a T- or Z-score, bone mineral density refers to the amount of mineral matter per square centimetre of bone (Kanis et al., 2013).
Osteopenia: This can be defined as a reduction of the amount of calcium and phosphate found in the bone. It is also associated with a decrease in bone mineral density (Escott-Stump, 2008:600). It is usually characterised by bone density below 2 standard deviations of the normal mean (Lennkh et al., 1999) or it can be defined as a BMD T-score between -1 and -2.5 (WHO, 1994).
Osteoporosis: According to the World Health Organization (WHO), osteoporosis can be defined as a disease characterised by low bone mass and micro-architectural deterioration of bone tissue. This leads to increased bone fragility and fracture risk (WHO, 1994).
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Acknowledgements
To my supervisor Dr H Wright and co-supervisor Prof. HS Kruger:
I would like to express my deepest appreciation and gratitude. With your collective guidance, wisdom, assistance and leadership I was able to complete this dissertation successfully.
To all of the other members at the Centre of Excellence for Nutrition (CEN):
I would like to thank you for making me part of a family. I would also like to extend my heartfelt gratitude for everyone’s support and encouragement throughout the year.
To my parents, family members and friends:
Thank you for the constant encouragement, sympathy, motivation, support and unconditional love. All of this contributed to my being able to complete my dissertation successfully.
To the Lord:
Thank you for giving me the strength to overcome any obstacle and for the necessary guidance and wisdom to complete this dissertation to the best of my abilities.
“I can do all things through Christ who strengthens me.” Philippians 4:13
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Summary (English)
Background: Osteoporosis and the resultant fractures are increasing globally, making the disease
an emerging public health concern. Over the last few decades osteoporosis has been recognised as a disease with a high incidence in urbanised areas in developing countries, including South Africa (SA). In the past it was believed that black people had greater protection against the development of osteoporosis than Caucasians owing to greater bone mineral densities (BMD). Emerging evidence indicates that black, urban postmenopausal women are at an increased risk for the development of low bone mass, decreased bone formation and bone turnover, as well as increased bone degradation because of inadequate dietary intake, reduced physical activity (PA), and low vitamin D status. The current study will therefore aim to explore the role of diet quality and PA as possible contributing factors to BMD in urban black women from the North West Province (NWP).
Methods: For this study, a representative sub-sample of urban black Setswana-speaking women
(n=325) was recruited, from the first follow-up in 2010 of the PURE SA-NWP study. Inclusion criteria were women > 45 years, not pregnant or lactating, HIV negative, not menstruating and/or have a follicle stimulating hormone (FSH) level of ≥ 40 IU/L, which resulted in a sample size of 171 women. Habitual PA level was assessed with the use of the modified Baecke questionnaire. A socio-demographic questionnaire including questions on contraception use, number of children, medical history, history of alcohol and tobacco use was completed. Dietary data were obtained through a culturally sensitive validated quantified food frequency questionnaire (QFFQ). Under- and over-reporters were identified with the Goldberg cut-off. The Healthy Eating Index (HEI) diet quality score was adapted to explore associations between BMD and diet quality. Femoral neck (FN), total hip and lumbar spine BMD were measured with dual energy x-ray absorptiometry (DXA).
Results: The total group had a low level of PA (mean WPA = 2.99); 45.6% reported tobacco use,
56.1% were hypertensive and 25.7% used thiazides. Women ≤60 years had significantly higher BMD at all measured sites (FN BMD = 0.743g/cm2 vs 0.689g/cm2, p = <0.01) compared to women
>60 years. Osteoporosis was identified amongst 40.4% of the women. The average dietary calcium intake of the group was inadequate [488(344;633)mg] and the adapted HEI diet quality score were low [2(2;3)]. No associations were found between PA, diet and/or BMD. Multiple regression analysis showed that age, height, postmenopausal status, dietary calcium, vitamin D status, alcohol and tobacco use, as well as waist circumference predicted 32% of the variance in femoral neck BMD (r2 =
0.324, p<0.001).
Conclusion: Lifestyle behaviours associated with urbanisation and age-related bone loss increase
the risk of osteoporosis in black postmenopausal SA women from the NWP. In order to decrease the incidence of osteoporosis and its associated fractures, prevention strategies should include education on the importance of reduced alcohol and increased calcium intakes in this group of women.
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Opsomming (Afrikaans)
Agtergrond: Osteoporose en gepaardgaande frakture neem wêreldwyd toe, wat die siekte ‘n
opkomende publieke gesondheidsprobleem maak. Oor die laasste paar dekades is osteoporose herken as ‘n siekte met ‘n hoë voorkoms in stedelike areas in ontwikkelende lande, insluitende Suid-Afrika (SA). In die verlede was die mening dat swartmense meer beskerm is teen die ontwikkeling van osteoporose as Kaukasiërs as gevolg van groter beenmineraaldigthede (BMD). Opkomende bewyse dui daarop dat swart stedelike postmenopousale vroue ‘n verhoogde risiko het vir die ontwikkeling van lae beenmassa, verlaagde beenvorming en beenomset asook verhoogde beendegradasie as gevolg van ontoereikende dieetinname, verlaagde fisiese aktiwiteit (FA), asook lae vitamien D. Die huidige studie het daarom te doel om die rol van dieetkwaliteit en FA as moontlike bydraende faktore tot BMD in stedelike swart vroue van die Noordwes-Provinsie (NWP) te ondersoek.
Metodes: ‘n Verteenwoordigende sub-steekproef van stedelike swart Setswana-sprekende vroue
(n=325) van die eerste opvolg in 2010 van die PURE SA-NWP studie is vir hierdie studie gewerf. Insluitingskriteria was vroue > 45 jaar, nie-swanger of lakterend, MIV-negatief, nie-menstruerend en/of ‘n follikelstimulerende hormoon (FSH)-vlak ≥ 40 IU/L, wat gelei het tot ‘n steekproefgrootte van 171 vroue. Gewoontelike FA-vlak is met die gebruik van die gemodifiseerde Baecke-vraelys gemeet. ‘n Sosio-demografiese vraelys insluitende vrae oor kontrasepsie gebruik, die aantal kinders, mediese geskiedenis, alkohol en tabak gebruik is ingevul. Dieetdata is verkry deur ‘n kultuursensitiewe gekwantifiseerde voedselfrekwensievraelys (QFFQ). Onder- en oorrapporteerders is met die Goldberg-afsnypunt geïdentifiseer. Die “Healthy Eating Index (HEI)”-dieetkwaliteittelling is aangepas om verbande tussen BMD en dieetkwaliteit te ondersoek. Femorale nek (FN), totale heup en lumbale rug BMD is gemeet met dubbel-energie x-straal-absorpsiometrie (DXA).
Resultate: Die totale groep het ‘n lae vlak van FA gehad (WPA = 2.99); 45.6% het tabakgebruik
gerapporteer, 56.1% was hipertensief en 25.7% het thiazied gebruik. Vroue ≤60 jaar het betekenisvol hoër BMD op alle meetplekke gehad (FN BMD = 0.743g/m2 vs. 0.689g/cm2, p = <0.01). Osteoporose
is onder 40.4% vroue geïdentifiseer. Die gemiddelde dieetkalsiuminname was onvoldoende [488(344;633)mg] en die aangepasde HEI-dieetkwaliteittelling was laag [2(2;3)]. Geen verbande is gevind tussen FA, dieet en/of BMD nie. Veelvoudige regressie-analise het getoon dat ouderdom, lengte, postmenopausale status, dieetkalsium, vitamien D status, alkohol en tabakgebruik asook middelomtrek in hierdie groep 32% van die variasie van FN BMD voorspel (r2 = 0.324; p<0.001). Gevolgtrekking: Leefstylfaktore geassosieer met verstedeliking asook ouderdomverwante
beenverlies verhoog die risiko vir osteoporose in swart menopousale SA vroue van die NWP. Ten einde die insidensie van osteoporose en die geassosieerde frakture te verlaag, moet voorkomingstrategieë onderrig oor die belangrikheid van verlaagde alkohol, tabak en verhoogde
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Chapter 1: Introduction
1.1 Background to the problem
The growing interest in bone-related health issues is due to the increased prevalence of osteoporosis and fractures globally, making this disease an emerging public health concern (Chen & Ho, 2010; Kaneki et al., 2006). Various factors have been shown to affect bone health; these include age, sex, ethnicity, race, family history and diet, as well as certain lifestyle factors, including physical activity, smoking and alcohol intake. These factors are known to influence the attainment of peak bone mass (PBM) during the premenopausal years as well as the rate of bone loss during the postmenopausal years (Marcason, 2010). The achievement and maintenance of optimal bone health is important not only for increased quality of life but also to decrease the costs associated with fractures (Shi et al., 2009). It has been found that patients over the age of 60 years who sustain a hip fracture and are treated surgically have mortality rates of 14–36% annually (Ions & Stevens, 1987; White et al., 1987). Advancing age is associated with increased risk of mortality after a hip fracture. A study by Navarrete et al. (2009) found that patients over the age of 83 years had an increased mortality risk during the first year following the fracture. Furthermore, the hospitalisation and medical costs associated with osteoporotic fractures are significant. A cost analysis done in the United States on a national level estimated that 2.05 million fractures occur annually, resulting in a cost of more than $16.9 billion. By the year 2025 it is expected that fractures occurring annually will have increased to more than 3 million, resulting in a cost of $25.3 billion each year (Budhia et al., 2012). In the United Kingdom, fracture costs are expected to range from £144 to £10 760 depending on the fracture site (Stevenson et al., 2006). A cost analysis done for 2010 calculated that the direct costs in the five largest European countries (France, Germany, Italy, Spain and the United Kingdom) amounted to €29 billion (Kanis et al., 2013). In South Africa (SA) the acute care costs of hip fractures amounted to R50 000 per patient in 2000 (Hough, 2000; Kanis et al., 2002).
If PBM is attained during the premenopausal years the risk of the development of osteoporosis during the postmenopausal years is lower (Zagarins et al., 2012). During menopause an oestrogen deficiency is the main reason for increased bone loss as it leads to the disruption of the bone micro-architecture and increased bone resorption, resulting in overall bone loss (Shuster et al., 2010). Caucasian women can lose up to 10.5% of their spine bone mineral density (BMD) during the menopause (Recker et al., 2000).
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Physical activity and nutrition are two important lifestyle behaviour factors that can influence BMD. A positive relationship has been found between BMD and physical activity (Suleiman et al., 1997). Therefore physical activity is recommended for both the treatment as well as possible prevention of the development of osteoporosis (Kohrt et al., 2004). BMD can be increased in both men and women through weight-bearing exercise and impact-loading exercise through its mechanical load on bone tissue, thereby decreasing the risk of fractures. Additional exercise can reduce the risk of injurious falls as muscle strength is preserved (Kohrt et al., 2004). Nutrition, on the other hand, can affect bone health directly and indirectly. Bone metabolism and structure are indirectly influenced by nutrition through its effect on the achievement of PBM and bone quality (Zanker & Cooke, 2004). The latter, in turn, influences the risk of osteoporosis and fractures. Dietary intake can also directly influence bone health as it provides substrates for the synthesis of bone tissue and influences the levels of circulating hormones that have an effect on bone metabolism (Zanker & Cooke, 2004). The following nutrients have been shown to play key roles in bone health: vitamin K, vitamin D, calcium, magnesium, phosphate and protein (Prentice, 1997; Tucker et al., 1999; Marcason, 2010). Deficiencies in these nutrients are associated with an adverse effect on bone health as well as contributing to the development of osteoporosis (Rude, 1998).
1.2 Motivation for the study
Osteoporosis has attracted little attention in efforts to address the problem, in developing countries, despite being a common metabolic bone disease. Several reasons have been suggested for this lack of attention. These include acceptance of osteoporosis as an inevitable part of the ageing process, the belief that osteoporosis is a problem only in developed countries, limited diagnostic facilities and a paucity of epidemiological data regarding population-specific normative data for bone density amongst minority groups (Handa et al., 2008). However, over the last few decades osteoporosis has been recognised as a disease with a high incidence in urbanised areas in developing countries, including SA (Kruger et al., 2004).
South Africa is experiencing rapid urbanisation, resulting in populations moving from rural to urban areas because of increased work availability as well as enhanced opportunities for a better lifestyle (Kruger et al., 2011). However, the accompanying lifestyle changes that take place during urbanisation have been associated with various health consequences, including reduced bone health (Kruger et al., 2011). In the past it was believed that black people had greater protection than Caucasians against the development of osteoporosis owing to greater BMDs (Aloia et al., 1996; Handa et al., 2008). Emerging evidence indicates that black, urban postmenopausal women are at increased risk of the development of low bone mass, decreased bone formation and bone turnover, and increased bone degradation resulting from inadequate
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dietary intake, reduced physical activity and low vitamin D status (Kruger et al., 2004; Kruger et al., 2011).
Most recent studies have investigated the relationship of diet with bone health by focusing on individual nutrients and their association with bone health (Bronner & Pansu, 1999; Zagarins et al., 2012; Czeczelewski et al., 2012). Limited data are available, however, on the association of diet quality and dietary patterns with bone health. Zagarins and co-workers (2012) investigated the relationship between whole-body BMD in young, healthy premenopausal women nearing PBM and established indices of overall diet quality. Diet quality was assessed with the Alternate Healthy Eating Index (AHEI) as well as the recommended food score (RFS). However, no association was found between overall diet quality and BMD. It was concluded by the authors that current diet quality scores are not appropriate for exploring associations between diet quality and BMD as a health outcome. It is recommended that diet quality scores should be adapted to include more foods that are rich in nutrients known to play an important role in bone health in order to investigate the possible association between diet quality and bone health appropriately (Zagarins et al., 2012).
The current study will therefore aim to explore the role of diet quality with an adapted score and physical activity as possible contributing factors to BMD in urban black women from the North West Province (NWP).
1.3 Aim
The aim of this study is to explore possible lifestyle risk factors contributing to BMD in urban black postmenopausal women from the NWP.
1.4 Objectives
To adapt the Healthy Eating Index (HEI) diet quality score to include more foods that are rich in nutrients known to play an important role in bone health.
To evaluate the quality of the diets of black, urban postmenopausal women
To access the physical activity of black, urban postmenopausal women
To evaluate the BMD of black, urban postmenopausal women.
To assess the association between the adapted HEI diet quality score, physical activity level, and BMD.
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1.5 Study design
This bone study is a sub-study nested within the Prospective Urban and Rural Epidemiology (PURE) bone study of the South African North West Province (SA-NWP) arm and will have a cross-sectional observational study design. The methodology and study design are described in detail in Chapter 3.
1.6 Research team
Table 1.1: Research team involved in the completion of this dissertation
Study leader: The study leader gave guidance on
the planning of the dissertation, statistical analysis, and writing up of the data.
Dr Hattie H. Wright
Co-supervisor: The co-supervisor provided assistance to the supervisor on the planning of the dissertation, statistical analysis and writing up of the data.
Prof H. Salome Kruger
Principal investigator PURE bone sub-study: Dr.
Kruger provided assistance in the provision of and writing up of the data
.
Dr Lanthé Kruger
Assistant supervisor on the analysis of dietary data: Dr. Dolman provided assistance in the
adaptation of the existing HDI score and calculating the adapted HDI score to measure diet quality.
Dr Robin C. Dolman
Student: Miss Ellis completed the dissertation for her
Master’s degree in Dietetics and assisted in the collection of anthropometric data.
Miss Christa Ellis
1.7 Structure of the dissertation
Chapter 1 of this dissertation provides the background to and the motivation for the research study. Chapter 2 reviews normal bone metabolism as well as the development, diagnosis, risk factors, management and prevention of osteoporosis. The methodology of the study is discussed in Chapter 3, and the results are presented in article format in Chapter 4, which will be submitted to the Journal of Human Nutrition and Dietetics. In Chapter 5 a short summary is given regarding the main conclusions of this dissertation with reference to the set objectives.
This dissertation is written in South African English, with the exception of Chapter 4, which follows American English usage.
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1.8 Reference list
ALOIA J.F., VASWANI A., YEH J.K. & FLASTER E. 1996. Risk for osteoporosis in black women. Calcified tissue international, 59(6): 415-423.
BRONNER F. & PANSU D. 1999. Nutritional aspects of calcium absorption. Journal of nutrition, 129:9-12.
BUDHIA S., MIKYAS Y., TANG M. & BADAMGARAV E. 2012. Osteoporotic fractures: a systematic review of the US healthcare costs and resource utilization. Pharmacoeconomics, 30(2): 147-170. CHEN Y.M. & HO S.C. 2010. Fruit, vegetables and bone health. Bioactive foods in promoting health: fruits and vegetables, 173-188.
CZECZELEWSKI J., DLUGOLECKA B., CZECZELEWSKA E. & RACZYNSKA B. 2012. Intakes of selected nutrients, bone mineralisation and density of adolescent female swimmers over a three-year period. Biology of sport, 30(1): 17-20.
HANDA R., KALLA A.A. & MAALOUF G. 2008. Osteoporosis in developing countries. Best practice & research clinical rheumatology, 22(4): 693-708.
HOUGH S. 2000. Osteoporosis clinical guideline. South African medical association, osteoporosis working group. South African medical journal, 90: 907-944.
IONS G.K. & STEVENS J. 1987. Prediction of survival in patients with femoral neck fractures. Journal of bone and joint surgery, 69: 384-387.
KANENKI M., HOSOI T., OUCHI Y. & ORIMO H. 2006. Pleiotropic actions of vitamin k: protector of bone health and beyond? Nutrition, 22: 845-852.
KANIS J.A., JOHNELL O., ODEN A., DE LAET C., OG LESBY A. & JONSSON B. 2002. Intervention thresholds for osteoporosis. Bone, 31: 26-31.
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KANIS J.A., McCLOSKEY E.V., JOHANSSON H., COOPER C., RIZOLLI R. & REGINSTER JY. 2013. European guidance for the diagnosis and management of osteoporosis in postmenopausal women. Osteoporosis international, 24:23-57.
KOHRT W.M., BLOOMFIELD S.A., LITTLE K.D., NELSON M.E. & YINGLING V.R. 2004. American college of sports medicine position stand; physical activity and bone health. Medicine and science in sports and exercise, 36(11):1985-1996.
KRUGER M.C., DE WINTER R.M., BECKER P.J. & VORSTER H.H. 2004. Changes in markers of bone turnover following urbanisation of black South African women. Journal of endocrinology, metabolism and diabetes of South Africa, 9(1): 103-108.
KRUGER M.C., KRUGER I.M., WENTZEL-VILJOEN E. & KRUGER A. 2011. Urbanization of black South African women may increase risk of low bone mass due to low vitamin D status, low calcium intake, and high bone turnover. Nutrition research, 31: 748-758.
MARCASON W. 2010. What is the effect of a high protein diet on bone health? Journal of American dietetic association, 3:34
NAVARRETE F.E., BAIXAULI F., FENOLLOSA B. & JOLIN T. 2009. Hip fractures in the elderly: mortality predictive factors at one year from surgery. Revista Española decirugia ortopédicay, 53(4): 237-241.
PRENTICE A. 1997. Is nutrition important in osteoporosis? Proceedings of the nutrition society, 56:357-367.
RECKER R., LAPPE J., DAVIES K. & HEANEY R. 2000. Characterization of perimenopausal bone loss: a prospective study. Journal of bone and mineral research, 15(10): 1965-1973.
RUDE R.K. 1998. Magnesium deficiency: a cause of heterogenous disease in humans. Journal of bone and mineral research, 13(4): 749-758.
SHI N., FOLEY K., LENHART G. & BADAMGARAV E. 2009. Direct healthcare cost of hip, vertebral, and non-hip, non-vertebral fractures. Bone, 45:1084-1090.
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SHUSTER L.T., RHODES D.J., GOSTOUT B.S., GROSSARDT B.R. & ROCCA W.A. 2010. Premature menopause or early menopause: long term health consequences. Journal of maturitas, 65:161-166.
STEVENSON M.D., DAVIS S.E. & KANIS J.A. 2006. The hospitalization costs and out-patient costs of fragility fractures. Women’s health medicine, 3(4): 149-151.
SULEIMAN S., NELSON M., LI F., BUXTON-THOMAS M. & MONIZ C. 1997. Effect of calcium intake and physical activity level on bone mass and turnover in healthy, white, postmenopausal women. American journal of clinical nutrition, 66: 937-943.
TUCKER K.L., HANNAN M.T., CHEN H., CUPPLES L.A., WILSON P.W.F. & KIEL D.P. 1999. Potassium, magnesium, and fruit and vegetable intakes are associated with greater bone mineral density in elderly men and women. American journal of clinical nutrition, 69: 727-736.
WHITE B.L., FISHEER W.D. & LAUREN C.A. 1987. Rate of mortality for the elderly patients after fracture of the hip in the 1980s. Journal of bone and joint surgery, 69: 1335-1339.
ZAGARINS S.E., RONNENBERG A.G., GEHLBACH S.H., LIN R. & BERTONE-JOHNSON E.R. 2012. Are existing measures of overall diet quality associated with peak bone mass in young premenopausal women? Journal of human nutrition and dietetics, 25: 172-179.
ZANKER C.L. & COOKE C.B. 2004. Energy balance, bone turnover, and skeletal health in physically active individuals. American college of sports medicine, 1372-1381.
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Chapter 2: Literature review
2.1 Introduction
Osteoporosis is considered to be the primary bone disease worldwide. The general public often considers osteoporosis to be a normal and unavoidable part of the ageing process. However, osteoporosis is a detectable and preventable disease (Shuler et al., 2012). The prevalence of osteoporosis continues to increase with progressively ageing populations. It is estimated that over 200 million people worldwide have osteoporosis (Cooper, 1999). Advancing age is considered to be one of the best predictors of osteoporosis. However, other factors, such as early menopause, a fracture after the age of 40 years, maternal history of hip fractures and low body weight, as well as specific diseases and treatment options, can increase the risk of developing fractures. All fractures are associated with a decreased quality of life as well as morbidity and mortality (Anon, 2001).
There is a variety of nutritional factors that play an important role in the maintenance of optimal bone health (Tucker et al., 1999), as well as certain lifestyle factors which can have either a positive or a negative effect on bone health. This literature review will focus on the skeletal system through the life cycle, the role of food and nutrition in bone health and the role of lifestyle behaviours in bone health.
2.2 The skeletal system
2.2.1 Bone physiology
Mature bone consists of inflexible connective tissue that includes bone cells, fibres, ground substance and crystallised minerals such as calcium, which lends to bone its inflexibility. The ground substance found in bone is a gelatinous material that consists primarily of proteoglycans and hyaluronic acid secreted by chondroblasts (Crowther, 2008:1004). Bone cells allow bone to grow, repair, change shape and endlessly synthesise new bone tissue and digest old tissue. The fibres in bone are made primarily of collagen. The diffusion of nutrients, oxygen, biochemicals, metabolic waste and minerals between bone and blood vessels occurs with the help of ground substance (Crowther, 2008:1004).
2.2.2 Bone formation
Bone formation occurs in two steps: osteoblasts lay down the components of the organic matrix and collagen fibres, after which mineralisation occurs (Theobald, 2005).
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Bone formation starts during foetal development with the growth of cartilage. The development of an organic matrix (osteoid) by bone cells is the start of the development of new bone tissue, which results in mature bone (Crowther, 2008:1004). The organic matrix consists primarily of collagen fibres. In the organic matrix, deposition of calcium and phosphate salts occur in combination with hydroxyl ions. Hydroxyl ions are deposited as crystals of hydroxyapatite. Bone strength is influenced by the pliant strength of collagen and the hardness of the hydroxyapatite. Osteocalcin, osteopontin and a variety of other proteins can be found in the bone matrix (Mahan & Escott-Stump, 2008: 615). The next step in bone formation is termed calcification. In this step minerals are deposited and then crystallised, and minerals then attach to collagen fibres (Crowther, 2008: 1004).
Osteoblasts are responsible for both the production as well as the formation of bone tissue, while osteoclasts are responsible for the breakdown and resorption of bone. Osteoblasts give rise to the development of osteocytes and bone lining cells (Mahan & Escott-Stump, 2008:616). Osteogenic mesenchymal stromal cells give rise to the development of osteoblast cells. These cells produce type I collagen and play an important role in bone formation (Crowther, 2008:1005). The hematopoietic monocyte-macrophage lineage gives rise to the development of osteoclasts. These are typically large with multinucleated cells (Crowther, 2008:1005). Osteocytes are modified osteoblasts. The osteoblast cells that are surrounded in osteoid as it hardens, as a result of minerals entering the calcification process, result in modification of the osteoblast cell. Osteocytes can be found within the lacuna, which is a space within the hardened bone matrix. It should be noted that the exact function of osteocytes is not fully known. They do, however, play an important role in the synthesis of matrix molecules and are therefore thought to have a supporting role in bone calcification. They also play a role in the concentration of nutrients within the matrix (Crowther, 2008:1007).
In Table 2.1 the functions of both osteoblasts and osteoclast are given. Both these cells give rise to the development of different processes such as mineralisation and communication, and enhance the production of certain elements such as type 1 collagen. Osteoblasts and osteoclasts aid in a variety of other mechanisms that will enhance either bone formation (osteoblasts) or bone resorption (osteoclasts) (Mahan & Escott-Stump, 2008:616).
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Table 2.1: Function of both osteoblasts and osteoclasts (Mahan & Escott-Stump, 2008:616).
Osteoblasts Osteoclasts
Bone formation Bone resorption
Synthesis of matrix proteins Degradation of bone tissue via enzymes and acid secretion
Type I collagen production Cross-linked telopeptides of type I collagen (NTX2, CTX3)
Osteocalcin production Osteoclast enzymes:
Tartrate-resistant acid phosphatase (TRACP 5b)
Cathepsin K Mineralisation
Secretion of cytokines (RANKL)1- activates
osteoclast differentiation
1RANKL=nuclear factor-kb ligand; 2NTX= N-terminal telopeptide; 3CTX=carboxy-terminal collagen crosslink 2.2.3 Bone remodelling
Bone remodelling refers to growth of the skeleton until a mature height is achieved. It represents the complete volume of bone that is reabsorbed and formed over a period of time (Parfitt, 2002). The process of formation of new bone tissue will occur first, followed by the digestion of old tissue. In girls, bone remodelling is usually completed by the age of 16–18 years and in boys, by the age of 18–20 years. After the growth period is completed, bone tissue can continue to intensify through the act of consolidation. During the early stages of development such as infancy and childhood the skeleton is associated with growth but as the skeleton ages later in adulthood, bone loss occurs (Mahan & Escott-Stump, 2008:617).
Bone undergoes continuous remodelling after the growth period, the greatest portion of which occurs in trabecular bone (Mahan & Escott-Stump, 2008:617). Bone volume is affected through changes that occur during bone remodelling. These changes cause alterations in the degree of mineralisation and trabecular micro-architecture. Each remodelling event is associated with the formation of a temporary cavity (Jaworski, 1976). Bone remodelling is considered to be a three-step process: i) the activation phase, which occurs in a localised area and leads to the formation of osteoclasts when a stimulus such as hormones, drugs or vitamins activates bone cell
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precursors; ii) the resorption phase, when osteoclasts steadily absorb bone, which results in a lengthened cavity named a resorption cavity; and iii) the formation phase, when the deposition of new bone, known as secondary bone, occurs. This process occurs through osteoblasts that line the resorption cavity. The process continues until the resorption cavity is narrowed and a haversian canal forms around a blood vessel. During this process old haversian canals are destroyed and new canals are formed. The total remodelling process occurs over a period of three to four months (Crowther, 2008:1010).
Biochemical markers of bone remodelling can predict fracture risk, suggesting that the amount of bone remodelling that occurs in the skeleton can have a biomechanical effect that is independent of bone mass (Garnero et al., 1996; Garnero, 2000; Cummings et al., 2002).
As can be seen in Figure 2.1, bone mass is maintained through a balance between the activity of osteoblasts (right), which play a role in the formation of bone, and osteoclasts (left), which break down bone. Under normal circumstances, bone formation and bone resorption are closely related processes that involve the remodelling of bone. Osteoblasts are involved in the formation of bone through the production of a matrix that becomes mineralised. Osteoblasts also play a role in the regulation of osteoclast activity through the expression of cytokines such as receptor activator of nuclear factor-kβ ligand (RANKL), which activates osteoclast differentiation as well as osteoprotegerin (OPG), which inhibits RANKL. There are a variety of factors that will stimulate osteoblast proliferation or differentiation, including bone morphogenetic protein (BMP), transforming growth factor-β (TGFβ), insulin-like growth factor (IGF), fibroblast growth factor (FGF), platelet-derived growth factor (PDGF), vascular endothelial growth factor (VEGF) and Wnt group of proteins. The Wnt antagonist Dickkopf-1 (DDK1) blocks osteoblast proliferation (Logothetis & Lin, 2005).
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Osteoclast
Bone remodelling
Osteoblast
RANKL
Osteoprotegerin
BMP, TGFβ,
IGF, FGF,
PDGF, VEGF,
Wnt
DDK1
BMP: bone morphogenetic protein; DDK1: Dickkopf-1; FGF: fibroblast growth factor; IGF: insulin-like growth factor; PDGF: platelet-derived growth factor; RANKL: nuclear kβ ligand; TGFβ: transforming growth factor-β; VEGF: vascular endothelial growth factor
Figure 2.1: The role of osteoblasts and osteoclasts in bone remodelling (Adapted from Logothetis & Lin, 2005).
2.2.4 Bone tissue
A large portion of the skeleton consists of either compact or cortical bone tissue. Shafts of the long bone contain primarily cortical bone (Mahan & Escott-Stump, 2008:615). Cortical bone consists of osteons that undergo continuous but slow remodelling. The rest of the skeleton is made up of trabecular or cancellous bone tissue, which occurs in the knobby ends of the long bones, the iliac crest of the pelvis, wrists, scapula and vertebrae, as well as the sections of bone that surround the marrow. Trabecular bone is considered to be less dense than cortical bone tissue (Mahan & Escott-Stump, 2008:615). Trabecular bone is an open structure of interconnecting bony spicules. These interconnecting spicules found in trabecular bone tissue add support to the cortical bone tissue. They also provide a large surface area that is exposed to circulating fluids from the marrow (Mahan & Escott-Stump, 2008:615). The loss of trabecular
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bone during the later stages of life is considered to be responsible for the increased risk of fractures (Mahan & Escott-Stump, 2008:615).
2.2.5 Infancy, childhood and adolescence
Osteoporosis and fractures in both children and adolescents are becoming an important public health problem. This is due to increased health care costs associated with osteoporotic and childhood fractures as well as the morbidity associated with these fractures (Piscitelli et al., 2007; Heaney, 1995). Bone mass accumulation during the different stages of childhood and adolescence is a primary determinant of peak bone mass (PBM) and fracture risk in the later stages of life (Heaney, 1995). It is therefore important to achieve a high bone mass as skeletal maturity is often considered the best protection against age-related bone loss (Newton-John & Morgan, 1970; Gam, 1970; Matkovic et al., 1977). PBM is achieved only when maturity is reached. However, the period of maturity is also associated with bone loss. If optimal PBM is not achieved and maintained, bone loss will surpass bone deposition, resulting in decreased bone mass and increased fracture risk (Peck et al., 1987).
The human skeleton continuously develops throughout the different life stages of infancy, childhood and adolescence. It will reach full size and density during the first three decades of life. However, the rate of bone remodeling will vary, depending on the different developmental stages of infancy, childhood, adolescence and young adulthood (Matkovic, 1991).
During the period of infancy and childhood physical growth continues to occur. Growth during childhood is not a uniform process; it occurs in a sigmoid curve between birth and adulthood. Characteristic periods of acceleration and deceleration can be seen. Soon after birth the maximal growth tempo for length is developed. A rapid deceleration in this tempo of growth in length can be seen during the second year of life in comparison with the first year. A progressive decrease in this tempo to one third of the tempo of the first year will continue until the age of 10 years in females and 12 years in males (Matkovic et al., 1994). The following few years are characterised primarily by accelerated growth rate, also known as the pre-pubertal growth spurt. Peak growth rate is achieved at the age of 12 years in females and 14 years in males. After this period, deceleration occurs until adult stature is achieved. A variety of factors such as gender, ethnicity, socio-economic status, genetics and diet also influences bone growth (Matkovic et al., 1994).
As can be seen in Figure 2.2, active growth will occur during the first stages and continue throughout puberty until PBM has been reached around the mid-twenties, after which, slow and
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gradual bone loss will start occurring. Rapid bone loss can be experienced from the mid-thirties and continue throughout the remaining life span (Shuler et al., 2012).
Osteopenia Osteoporosis Puberty Menopause 0 10 20 30 40 50 60 70 80 Age (yrs)
Bo
ne
m
as
s
PBMPBM: peak bone mass
Figure 2.2: Bone mass during the different life cycles (Adapted from Shuler et al., 2012).
2.2.6 Puberty and attainment of peak bone mass
Bone mass will continue to accumulate until a peak has been reached (Weaver, 2000). PBM can be defined as the highest level of bone mass that has been achieved through normal growth. Women, however, will achieve a PBM of the lumbar spine and femur only in late adolescence to early adulthood, while bone mass of the hip will be achieved only during the mid-thirties (Matkovic et al., 1994). In general, however, the thickness, density and strength of bones continue to accumulate until one reaches one’s mid-thirties, when PBM is achieved (Theobald, 2005). This achievement of an optimal PBM can help in the prevention of osteoporosis, as this disease usually develops only in the later stages of adulthood (Zagarins et al., 2012). Factors affecting the attainment of PBM are listed in Table 2.2. Bone mineral density (BMD) can therefore be used as a parameter for the assessment fracture risk in any age group (Rizolli et al., 2010).
After PBM has been achieved, bone deposition continues but the rate is considerably decreased and also slower than bone resorption (Theobald, 2005). It should be noted that the age at which
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BMD acquisition will cease depends largely on dietary intake and physical activity (Mahan & Escott-Stump, 2008:620).
PBM is usually greater in men than in women since men have a larger frame size. Bone mineral content (BMC) is, under normal conditions, lower in women than in men. The difference that is seen in bone mass is largely contributed to by the differences in lean and fat mass between men and women. Hereditary factors such as family history will also play an important role in the accumulation and attainment of PBM (Mahan & Escott-Stump, 2008:620).
Table 2.2: Factors that affect the attainment of peak bone mass (Philips, 2004)
Genetics Family history (heredity)
Genetic polymorphisms
Some ethnic groups may have stronger bones than others
Gender Men tend to have a greater bone mass than women
Diet Supply of calcium and vitamin D in particular,
also protein and energy, influences bone mass
Physical activity Regular weight-bearing exercise is important for strong bones
Body weight Heavier people have stronger bones
Hormones In women irregular menstrual cycles or their absence can cause bone loss
2.2.7 Bone health during the peri- and postmenopausal years
Menopause is defined as the time when a woman has experienced more than 12 consecutive months of amenorrhea without other intervening causes such as exogenous hormone use, surgery or dietary deficiencies (Francucci et al., 2008).
Menopause will lead to increased bone loss (Shuster et al., 2010) and is therefore considered to be an important risk factor for the development of osteoporosis. This is mainly due to oestrogen deficiency that will not only cause rapid bone loss but also lead to disruption of the bone micro-architecture (Shuster et al., 2010).
Menopause can be divided into perimenopause and postmenopause. Early menopause can be defined as the occurrence of menopause before the age of 45 years (Torgerson et al., 1994), and can be either spontaneous or induced. Induced early menopause can be due to a variety of factors such as surgical interventions or chemotherapy. Perimenopause is associated with
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progressive bone loss that occurs over a period of several years after the occurrence of menopause. Bone loss is considered to assume a two-phase pattern, with a fast phase that is followed by a prolonged slow phase period (Nordin et al., 1992; Okano et al., 1998). Women who experience lowered oestrogen levels before the median age of natural menopause are considered to be at increased risk of premature morbidity and mortality as well as the development of osteoporosis (Shuster et al., 2010). In a study conducted by Ahlborg and co-workers, (2001), it was found that women with a lowered premenopausal BMD had an increased risk of maintaining this decreased BMD for the remainder of their lives. Adjustments in lifestyle and nutritional intake should be made early in life to ensure an optimal PBM (Kruger et al., 2006).
The greatest amount of bone loss, occurring during the first two years after menopause, is also associated with the biggest increase in bone turnover. This period is also characterised by increased bone resorption in comparison with bone formation (Mazzuoli et al., 2000). Oestrogen-dependent bone loss, however, occurs over a prolonged period of time (Mazzuoli et al., 2000).
2.3 Calcium metabolism and bone health
Calcium is considered the primary extracellular divalent cation in the body. It is involved in a variety of functions such as muscle contraction, blood coagulation, neurotransmitter release, and neuronal excitability (Theobald, 2005). Phosphate, magnesium and calcium are the primary minerals in bone, of which calcium forms the largest part (Theobald, 2005). During the growth period an adequate intake of dietary calcium (see recommended intake in Table 4) is required for the achievement of optimal PBM (Anderson et al., 1993; Sowers & Galuska, 1993).
The three primary sites at which calcium homeostasis occurs include the bone, kidneys and gastrointestinal tract (GIT). Parathyroid hormone (PTH) has a direct or indirect effect on calcium homeostasis at each of these sites. There are three primary calciotrophic hormones involved in calcium homeostasis, namely calcitonin, calcitriol and PTH. Serum calcium concentration influences both the production and secretion of PTH. A decrease in calcium concentration will increase the secretion of PTH whereas an increase in serum calcium will inhibit the secretion of PTH. There are four primary mechanisms through which PTH regulates serum calcium concentrations: i) PTH increases calcium reabsorption within the kidneys, thus leading to a decrease in urinary calcium excretion; ii) PTH decreases phosphate reabsorption, resulting in increased urinary phosphate excretion and reduced plasma phosphate levels; iii) PTH causes the secretion of both calcium and phosphate from the bones in order to maintain serum calcium
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and phosphate levels. Phosphate also encourages the deposition of calcium and phosphate on bone; and iv) PTH increases calcitriol formation within the kidney, which improves calcium absorption from the GIT. Once serum calcium levels are restored, PTH secretion is inhibited (Theobald, 2005).
Even though calcitonin is not directly involved in calcium homeostasis, it is still important to note that bone resorption is inhibited through the action of calcitonin. Calcitonin protects the skeleton during periods of stress such as growth or pregnancy. The primary function of calcitriol is to govern calcium homeostasis. Calcium homeostasis is also regulated by vitamin D since it influences calcium absorption from the GIT (Theobald, 2005).
It is important to note that both testosterone and oestrogen play a role in the intestinal absorption of calcium. When intestinal absorption of calcium is decreased, calcium from the cancellous and compact bone will be used to raise the serum calcium levels back to normal. A larger quantity of calcium will be absorbed from bone than can be replaced and this will then lead to a reduction in bone mass. Oestrogen levels will decrease during menopause; this will increase the sensitivity of bone to PTH, decreasing bone mass. At the point of menopause rapid bone loss can be seen and it will remain high during the perimenopausal period (Cheung et al., 2011).
Figure 2.3 depicts the proposed mechanism by which a calcium and vitamin D deficiency can contribute to increased bone loss and fracture risk. A lowered intake of calcium and insufficient vitamin D status as well as insufficient sunlight exposure will lead to decreased intestinal absorption of calcium. This causes lowered levels of circulating calcium in the blood, leading to both decreased bone formation and increased PTH production. This, in effect, will cause increased bone remodelling and the combination of this with decreased bone formation will result in a net loss of bone and increased fracture risk. A decreased dietary intake and synthesis of vitamin D has also been linked with an increased risk of falling (Rizolli, 2008).
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Decreased calcium
intake Decreased intake & synthesis of vitamin D
Decreased serum calcium Decreased intestinal absorption Increased PTH production
Increased falling risk
Increased bone remodeling ( ↑ bone resorption); Increased urinary excretion
of phosphate; Increased renal tubular calcium reabsorption; Decreased renal
tubular phosphate reabsorption
Decreased bone formation
Bone
loss
Fracture risk Increased 1,25(OH)2-D3 Increased serum calcium Increased GIT absorption(calcium & phosphate); Increased mineralization
of bone
Decreased PTH
GIT: Gastrointestinal tract; PTH: parathyroid hormone
Synthesis Suppression
Figure 2.3: Regulation of serum calcium levels and mechanisms increasing fracture risk through calcium and vitamin D deficiency (Adapted from Berglunda et al., 2000; Rizolli, 2008).
2.3.1 Vitamin D metabolism and bone health
Vitamin D is classified as a fat-soluble vitamin that can be produced in the body through sun exposure or can be consumed in the diet (Schulman et al., 2011; Zittermann, 2003). It is important that the metabolism of vitamin D is understood, in order to highlight the importance of adequate sunlight exposure and sufficient dietary intake. As illustrated in Figure 2.4, vitamin D, both dietary and endogenous, is transported to the liver, where it is transformed into 25-hydroxyvitamin D (25(OH)D). The liver releases the 25(OH)D into the blood stream, where it circulates with a biological half-life of 12–19 days. In the kidney the 25(OH)D is transformed into vitamin D hormone 1,25-dihydroxyvitamin D (calcitriol) through enzymatic action. PTH homeostatically controls the renal synthesis of cacitriol, and serum concentrations of both calcium and phosphate influence PTH synthesis. Renal 24-hydroxylase can also transform 25(OH)D into 24,25-dihydroxyvitamin D (Trang et al., 1998; Zitterman, 2003).
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Sun
Pro-D3 → Pre- D3 U.V.B Skin Vitamin D3 Liver 25-Hydroxyvitamin D Kidney Calcitriol 24,25 (OH)2D Low serum PTH High serum PTHLow serum phosphate
Intestine Diet
Vitamin D3 Vitamin D2
Target tissue
U.V.B: Ultraviolet B; PTH: parathyroid hormone
Figure 2.4: Metabolism of vitamin D (Adapted from Norman, 1998; Zitterman, 2003).
There are a number of review articles that indicate that vitamin D deficiency is at an epidemic level globally (Holick, 2004; Willis et al., 2008; Zitteman, 2003). Vitamin D deficiency is considered to be an important risk factor for the development of osteoporosis. The deficiency will result in decreased intestinal absorption of calcium, impaired mineralisation, enhanced bone resorption and hyperparathyroidism. This deficiency is especially predominant in the elderly age group, owing to lack of sun exposure and inadequate dietary intake and reduction in the functional capacity of the skin to synthesise vitamin D3 (Lips, 2001; van Schoor et al., 2008; Perez-Lopez et al., 2011). In America, it is estimated that around 90% of adults aged 51–70 years do not consume adequate amounts of dietary vitamin D (Moore et al., 2004).
Vitamin D deficiency is characterised by an increased rate of fractures and frailty (Perez-Lopez et al., 2011), weakened muscle function, increased risk of falls (Bischoff-Ferrari et al., 2004) and impaired muscular performance (Bartoszewska et al., 2010). Other adverse effects associated with a vitamin D deficiency include diseases such as cancer, hypertension and autoimmune diseases (Canell et al., 2008; Holick, 2004; Zitterman, 2003). In children, a deficiency in vitamin
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D results in the development of rickets, Which is characterised by skeletal deformities, increased risk of fractures and delayed skeletal growth. In adults, a vitamin D deficiency results primarily in osteomalacia and resulting muscle weakness. With the progression of the disease, it leads to osteoporosis (Yuen & Jablonski, 2010).
Sunlight is considered to be the primary source of circulating vitamin D in humans (Canell & Hollis, 2008). Lighter skin is associated with optimal vitamin D production (Murray, 1934; Loomis, 1967). In areas away from the equator, light skin is required for the sufficient production of vitamin D as the ultra-violet (UV) radiation is weaker in these areas (Murray, 1934). However, people who use sunscreen or who have pigmented skin have lower levels of 25(OH)D. Pigmented skin increases the risk of vitamin D deficiency because the pigmentation reduces the effectiveness of sunlight exposed vitamin D production (Zittermann, 2003). Sun exposure of the face, arms, hands or back twice a week for 5–15 minutes between 10am and 3pm during the spring, summer and autumn months is considered to be sufficient. This level of sun exposure is enough for most skin populations in order to maintain sufficient levels of vitamin D (Holick, 2004). However, people with increased melanin-pigmented skin require increased sun exposure time in order to maximise vitamin D formation (Zittermann, 2003). It is important to note that adequate and regular exposure to sunlight, as well as sufficient dietary intake, is required to prevent deficiency during winter months (Brot et al., 2001).
Lack of sun exposure is not often the cause of a vitamin D deficiency in South Africa (SA), however, frail and bedridden patients can develop a vitamin D deficiency if not exposed to an adequate amount of sunlight (Zittermann, 2003).
2.3.1.1 Vitamin D and calcium relationship to bone health
One of the main functions of vitamin D is to maintain normal calcium levels and to increase intestinal calcium absorption. Studies indicate that only 10–15% of dietary calcium will be absorbed when there is a vitamin D deficiency, in comparison with 30–35% dietary calcium absorption when there is an adequate level of vitamin D (Heaney et al., 2003; Holick, 2004). Adequate levels of both vitamin D and calcium are necessary to achieve optimum bone health (Panda et al., 2004). Reduced bone density as well as increased risk of stress fractures is associated with decreased calcium (Myburgh et al., 1990) and vitamin D (Ruohola et al., 2006) levels in amenorrhoeic athletes (Wolman et al.,1992).
Vitamin D plays a primary role in the regulation of both calcium and phosphorous levels in the blood. This occurs through the promotion of absorption from dietary intake in the intestines and
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re-absorption of calcium in the kidneys. Vitamin D is essential for bone formation and mineralisation and is considered to be important in the development of a strong skeleton (Yuen & Jablonski, 2010).
Calcium can enter the body through the intestine by means of an active, vitamin D-dependent transporter across the proximal duodenum. Calcium can also enter through facilitated diffusion which occurs throughout the small intestine. The absorption of calcium from the GIT is reciprocally related to dietary calcium intake. A low dietary intake of calcium will cause a compensatory increase in the fractional absorption of calcium in the intestine due to activation of vitamin D. However, it should be noted that this mechanism will decrease with advancing age (Caroli et al., 2011). It is therefore important to maintain adequate levels of vitamin D for optimal calcium absorption. The precise amount that is considered to be an adequate quantity of vitamin D is difficult to determine because circulating vitamin D levels are derived from both dietary intake and exposure to sunlight. The liver will convert dietary and sunlight-derived vitamin D into 25(OH)D and then the kidney will convert this into calcitriol, the active form of vitamin D (Caroli et al., 2011).
2.4 Metabolic and hormonal regulation of bone health
Bone is a living organ and continuously undergoes bone remodelling. Remodelling ensures maintenance of the micro-architecture and repair of bone tissue in response to physical trauma. Bone remodelling is regulated through local physiological processes as well as metabolic and hormonal regulation (Bayliss et al., 2011).
Decreased energy intake resulting in energy deficiency has been associated with disruptions in metabolic hormones that are known to play an important role in bone turnover, such as decreased leptin and insulin-like growth factor-1 (IGF-1) (Grinspoon et al., 1996; Welt et al., 2004). As with anorexia nervosa, starvation is also associated with a decreased intake of total daily energy and this will result in a decrease in fat stores, leading to lowered leptin levels (Schulman et al., 2011). The reduction in leptin levels eventually leads to a decrease in IGF-1 production, a lowered triiodothyronine (T3) state, as well as to hypercortisolemia. These changes are associated with adverse effects on bone health, as they promote bone resorption and reduced bone formation (Usdan et al., 2008).
Even milder forms of energy restriction have been shown to affect bone health negatively (Schulman et al., 2011). Only a few days of fasting are associated with decreased bone formation markers (Grinspoon et al., 1995). A study by Ihle and Loucks, (2004) indicated the
