Build healthy bones là gì

This is a republished version of an article previously published in MJA Open

A white paper resulting from the outcomes of the Osteoporosis Australia Summit, 20 October 2011

Rationale and objectives

Acronyms

Both general practitioners and their patients often overlook bone health and, as a result, osteoporosis is often not diagnosed until fragility fractures occur. There is also a lack of an accepted strategy for osteoporosis prevention in Australia. Currently, treatment of individuals is based on either bone mineral density [BMD; see Box of acronyms] measurement and/or a prior fracture. However, more than 50% of women and 70% of men who sustain fragility fractures do not have BMD in the osteoporosis range [T score  50 nmol/L,41 although the question of whether empirical supplementation without testing would be cost-effective remains unanswered.

Vitamin D is important for bone health and muscle function throughout childhood and adolescence. Adequate vitamin D status is required to prevent rickets and to promote normal bone growth and mineralisation as peak bone mass is acquired. Based on available evidence, the recommended blood level of 25[OH]D for infants, children and adolescents for optimal bone health remains at > 50 nmol/L year round.

Vitamin D needs in healthy adults, older adults and individuals with osteoporosis

Both the recent position statement on vitamin D and health in adults from the Australian and New Zealand Bone and Mineral Society [ANZBMS], the Endocrine Society of Australia [ESA] and Osteoporosis Australia [OA]42 and the recent US Institute of Medicine [IOM] report on dietary reference intakes for calcium and vitamin D concluded that inadequate vitamin D status is defined as a 25[OH]D level  75 nmol/L, as both the Endocrine Society and the International Osteoporosis Foundation47 recommend, may require at least 1500–2000 IU [37.5–50 µg] per day of supplemental vitamin D, while for severe deficiency, doses ≤ 10 000 IU [250 µg] per day have proven to be safe.46

Other nutritional influences

There is considerable evidence of the positive influence that dietary patterns adequate in calcium, phosphorus and vitamin D have on bone health.48 However, less consistent evidence exists on the role of other vitamins and micronutrients. A large-scale study from the US showed dietary patterns that included high intakes of vegetables and fruit were associated with significantly higher bone mineral density [BMD] than those with other dietary patterns.49 Therefore, it seems prudent to encourage a variety of foods, particularly fruits and vegetables, to ensure adequate intakes of key nutrients to maintain bone health.

Exercise

Regular physical activity and exercise is recognised as one of the most effective lifestyle strategies to maximise peak bone mass during growth and prevent bone loss during ageing. However, the bone-building [osteogenic] benefits of exercise are dependent on stage of life and the relative risk of fracture. Childhood and adolescence may represent the optimal window of opportunity in which exercise can improve bone strength and protect against osteoporosis and fragility fractures in old age, particularly when these early benefits can be maintained by adopting appropriate measures in later life. A 10% higher peak bone mass can delay the development of osteoporosis by 13 years and reduce the risk of fracture by 50%.50,51

Exercise programs that combine high-impact activity with high-intensity resistance training appear most effective in augmenting BMD in premenopausal women. High-impact-alone protocols [such as jumping] are effective only on hip BMD in this group.52 Further RCTs of resistance training in premenopausal women of sufficiently long duration to provide optimum resistance-training type, intensity and volume of loading are needed.53

In frail and very elderly adults, resistance training and balance exercises in combination reduce falls and risk factors for frailty, including sarcopenia, poor balance, gait instability, depression, fear of falling and cognitive impairment.

Multimodal exercise — including weight-bearing/high-impact/high-intensity resistance exercise — may significantly reduce overall fracture risk.54 By contrast, single-modality exercise of any type does not appear to reduce fracture risk,54 with the possible exception of spinal-extensor muscle resistance training, which reduces thoracic vertebral fracture incidence.54,55

Antiresorptive and anabolic agents

In individuals at high risk of fracture, especially those who have already had previous fractures, specific anti-osteoporosis therapy reduces vertebral fracture risk by 40%–70% and non-vertebral fractures by about 25%.56,57,58,59,60,61,62,63,64,65,66 The various anti-osteoporosis treatments have been separately evaluated in placebo-controlled RCTs with fracture end points; however, a corresponding head-to-head comparison has not been conducted. In Australia, these treatments are covered by the Pharmaceutical Benefits Scheme [PBS] for men and women after fragility fracture as well as for those at high risk, without prior fracture, on the basis of age [≥ 70 years] and low BMD T-score [≤ − 2.5 or ≤ − 3.0].67

Recently, it has been suggested that a temporary cessation of treatment [“drug holiday”] can be offered to patients after 3–5 years of treatment with antiresorptive therapy. Currently, there is no evidence to support a drug holiday in individuals with continuing osteoporosis [T score ≤ − 2.5 at femoral neck].68 If a drug holiday is considered appropriate, a plan must also be put in place to review the patient regularly. It seems prudent to reinstate therapy if there is any further bone density decline, which is usually preceded by an increase in bone turnover marker levels.

Bone density testing

The current ideal test to assess fracture risk is the dual energy x-ray absorptiometry [DXA] to measure lumbar spine and proximal femoral BMD in all high-risk individuals.69 In addition, the use of DXA to screen asymptomatic individuals may be worthwhile at age 65 or 70 years.70,71 Currently, Australian Medicare funds this approach in people over the age of 70.

Recommendations

Final recommendations for this paper were developed through the process of consultation, review and discussion at the Osteoporosis Australia Summit meeting on 20 October 2011.

Recommendations

Bone health is often overlooked as a serious public health problem and as a result, osteoporosis is often not diagnosed until fragility fractures occur. Based on a large population-based study of bone mineral density [BMD] measurements in Australian adults, it is estimated that 1.2 million Australians have osteoporosis and a further 6.3 million are at risk with osteopenia [low BMD].2

For many individuals, taking simple osteoporotic preventive actions with calcium, vitamin D and exercise throughout life will enable them to continue to enjoy an active and independent lifestyle that is associated with good bone health. The mandate of the 2011 Osteoporosis Australia Summit Building healthy bones throughout life was to develop clear evidence-informed recommendations about calcium, vitamin D and exercise requirements in children, healthy adults, and older adults and individuals with osteopenia and osteoporosis. The recommendations that follow describe calcium, vitamin D and exercise needs relevant to all stages of life, and also highlight specific needs during childhood, midlife and old age.

Recommendations for all stages of life

Calcium

1. Eat sufficient and nutritious foods for growth and development.
   1.  Daily dietary calcium intakes should be consistent with the Australian and New Zealand guidelines for an adequate calcium intake.4
   2.  It is agreed that a diet low in calcium increases the risk of bone loss and fracture. The Australian and New Zealand guidelines for an adequate calcium intake are shown in Box 1.
   3.  Calcium needs are increased during the adolescent growth spurt.
   4.  Practically, people should aim to include 3–5 serves of calcium-rich foods daily [eg, dairy or calcium-fortified foods], as the preferred means of achieving an adequate calcium intake. Box 2 provides the calcium content of key foods.
   5. Individuals who dislike or are intolerant of dairy products and wish to achieve their required calcium intake from diet will need to have more serves of other high-calcium-containing foods [eg, specific vegetables, fish, nuts] or calcium-fortified foods [eg, soy milk].
   6.  For people with inadequate dietary calcium intake [below the estimated average requirement [EAR]/recommended dietary intake [RDI]], calcium supplements are recommended and are as effective as dietary sources. Under these circumstances, calcium supplementation with 500–600 mg per day is indicated.
2. Achieve and maintain a healthy body weight to maintain muscle mass, particularly guarding against underweight and overweight.
   1.  In population studies, fracture risk is increased in females with low BMI and body fat, especially if body weight is sufficiently low to impair sex hormone production.
   2.  Population studies also show that obesity is not protective against fractures in some individuals.72,73
   3.  Sarcopenia is associated with low BMD and an increased risk of fracture.74,75,76,77

Vitamin D

1. Ensure adequate vitamin D levels.
   1.  Sun exposure is the primary source of vitamin D. Encourage regular and safe sunlight exposure [avoiding burning], in accordance with current Australian and New Zealand Bone and Mineral Society [ANZBMS], Endocrine Society of Australia [ESA] and Osteoporosis Australia [OA] recommendations.42 However, there is a need for more research in this area. Box 3 provides guidance on recommended sun exposure from the vitamin D position statement supported by the ANZBMS, the ESA and OA.42
   2.  Maintaining adequate vitamin D is critical for calcium absorption and is also important for optimal bone health and muscle function.
   3.  There is general agreement that serum levels of 25-hydroxyvitamin D [25[OH]D] in the general population should be above 50 nmol/L at the end of winter or in early spring for optimal bone health.
   4.  Most adults will not receive more than 5%–10% of their vitamin D requirements from dietary sources. In healthy adults, the main contributor to circulating vitamin D levels is vitamin D produced in the skin in response to sunlight exposure.
   5.  Current evidence does not support a case for food fortification with vitamin D. More evidence on whether there is widespread vitamin D deficiency is required before such a case can be supported.
   6. If sun exposure is limited or there are other risk factors for vitamin D deficiency [dark skin, clothing covering the skin, conditions affecting vitamin D metabolism, breastfed babies with other risk factors], it is important to measure the serum 25[OH]D level and take vitamin D supplements in doses that will maintain serum 25[OH]D levels over 50 nmol/L year round.
   7.  For people who do not get adequate exposure to sunlight, vitamin D supplements provide a means of increasing vitamin D intake. To treat moderate to severe deficiency, it would be reasonable to use 3000–5000 IU [75–125 µg] of vitamin D supplements per day for at least 6–12 weeks, with most patients requiring ongoing treatment at a maintenance dose of around 1000–2000 IU [25–50 µg] per day. Higher doses of 2000–4000 IU [50–100 µg] per day may be required in some individuals [eg, if obese].

Exercise

1. Undertake regular weight-bearing physical activity, muscle-strengthening exercises and challenging balance/mobility activities in a safe environment and promote a healthy lifestyle.
   1. Encourage regular participation in a variety of weight-bearing activities, including dynamic impact-loading sports [eg, basketball, netball, hockey, football, soccer], school-based physical education classes and regular outside play, for at least 30 minutes 3–5 days per week.
   2.  For healthy individuals [without osteoporosis] with few risk factors for fracture, the key focus of exercise and physical activity is to improve or maintain bone density, muscle mass, strength and functional capacity [balance, gait]. A combination of weight-bearing and resistance training is recommended.
   3.  Some examples of the impact of particular exercises on bone health are shown in Box 4.
2. For individuals with osteoporosis and/or at increased risk of falling, challenging balance and mobility exercises are recommended.
3. Exercise offers greater skeletal benefits when undertaken with a diet containing an adequate intake of calcium [equivalent to the EAR/RDI].
4. Avoid prolonged periods of sedentary behaviours [sitting], due to detrimental effects on bone and cardiovascular health.

Other

1. Encourage health promotion models to reduce uptake of smoking, dieting behaviours and alcohol use.
   1. If alcohol is consumed, it should be consumed in moderation — up to one standard drink per day for women and two standard drinks per day for men.
   2.  Excessive alcohol intake is a cause of fracture, because of an increased propensity to fall.
   3.  Excessive alcohol also impairs bone formation.
   4.  Do not smoke. Smoking is associated with a reduction in bone structure and strength.
2. Maintain normal sex hormone levels for the stage of life, and correct levels as appropriate in premenopausal women and men.
3. Test for bone health.
   1.  Population-based vitamin D testing using a blood sample is not recommended.
   2.  Vitamin D testing is not recommended in otherwise healthy individuals who do not have risk factors or disorders predisposing to osteoporosis and minimal trauma fracture.
   3.  If sunlight exposure is very low or there are other risk factors for vitamin D deficiency [dark skin, absence of skin exposure], testing may be recommended. If vitamin D testing is recommended, it should be done at the end of winter or in early spring.
   4.  Consider bone density testing, using dual energy x-ray absorptiometry, in the presence of risk factors or at age ≥ 70 years in the absence of risk factors.

Recommendations for building healthy bones in children

In addition to the above general recommendations, these recommendations are designed to provide advice to parents and carers relating to steps they can take to promote healthy bone growth in children. They are also intended to provide public health recommendations during pregnancy and lactation, childhood, and the teenage years.

Peak bone mass is acquired during late adolescence and early adulthood and sets the stage for vulnerability to fracture and other bone disorders later in life. The 2 years around puberty is a particularly important period to maintain adequate calcium and engage in weight-bearing exercise, as about 40% of adult peak bone mass is acquired during this period.78

1. Ensure adequate calcium intake.
   1.  Encourage and support breast feeding. Breast milk is an important source of calcium. Infants should be exclusively breastfed to 6 months of age and continue to be breastfed, with complementary foods, until 12 months.
   2.  Reduced-fat milk products are not suitable for children under 2 years of age.
2. Ensure adequate vitamin D.
   1.  Promote adequate maternal vitamin D status during pregnancy.
   2.  Breastfed babies from women at risk of vitamin D deficiency require supplementation.
   3.  Children with chronic illness or disability warrant special consideration of their vitamin D status and bone health.
3. Engage in regular weight-bearing activity and promote a healthy lifestyle.
   1.  Encourage schools to incorporate a diverse and enjoyable battery of weight-bearing activities and sports into their school physical education programs. This could include participation in short periods [5–10 minutes] of daily, targeted, multidirectional, moderate- to high-impact activities, such as jumping, skipping and hopping.

Building healthy bones in healthy adults

These recommendations are designed to augment the general recommendations and provide specific advice to healthy adult individuals relating to steps they can take themselves to reduce the risk of fracture in the future. They also include public health recommendations for the prevention of fracture in adults who have achieved peak bone mass and are at low risk of fracture. Because fracture risk increases with age, these recommendations are particularly important for individuals who wish to maintain their bone strength into old age, and especially for postmenopausal women and older individuals to maintain their bone strength.

The needs of adults with specific disorders affecting the skeleton [eg, osteoporosis, coeliac disease] are not addressed in these recommendations; these individuals should seek specific medical advice appropriate to the condition.

1. Ensure adequate vitamin D levels [see Recommendation 3 for all stages of life].
2. Be habitually physically active and undertake regular weight-bearing and/or muscle-strengthening exercises.
   1. Encourage regular participation in moderate-impact weight-bearing physical activity, high-impact training [eg, 50–100 jumps] or related impact-loading sports for at least 30 minutes 3–5 days per week.
   2.  Include muscle-strengthening exercises on at least 2 days per week. For maximum benefits, the program should be high intensity [60%–80% of peak capacity], become progressively more challenging over time, and target the major muscles around the hip and spine.
   3.  Where possible, encourage participation in a multimodal exercise regimen [including weight-bearing/high-impact/high-intensity resistance exercise] at least three times per week.

Building healthy bones in older adults and individuals with osteopenia and osteoporosis

These recommendations are designed to supplement the general recommendations and provide specific advice to individuals relating to steps they can take themselves to reduce fracture risk, and to provide them with information on how best to access appropriate health advice. They are public health recommendations for the prevention of fracture in adults > 50 years of age who are at higher risk of fracture, defined as having a 5-year absolute risk of fracture over 5%.

Adults with specific disorders [such as coeliac disease or conditions for which they take oral corticosteroids] that may be responsible for their low bone density should also seek specific medical advice appropriate to the condition.

Adults with a 5-year absolute risk of fracture over 10% should also seek specific advice on the management of osteoporosis, if present, which is well covered in the Royal Australian College of General Practitioners' Clinical guideline for the prevention and treatment of osteoporosis in postmenopausal women and older men.79

1. Dietary calcium intakes should be consistent with the Australian and New Zealand guidelines for an adequate calcium intake.4
   1.  Calcium intake by diet is strongly recommended, but calcium supplements at doses of 500–600 mg per day may be required in some individuals when calcium from dietary sources is not possible.
   2.  Current concerns over the potential for an increased risk of myocardial infarction with calcium supplements are still being debated but should not alter acceptance of the recommendation. Mortality has not been increased in any study of calcium supplements.
2. Vitamin D plays an important role in bone health.
   1.  In addition to the general recommendations made in Recommendation 10 for all stages of life, vitamin D level should be established by measuring vitamin D levels in the blood in the following situations:
      • osteoporosis when diagnosed by bone density testing;
      • after falling;
      • following a minimal trauma fracture.
   2.  If 25[OH]D levels are below the desirable level, the following doses are recommended:
      • supplementation with vitamin D capsules or tablets is recommended in doses of 1000–2000 IU [25–50 µg] per day;
      • higher dose intermittent therapy, eg, 50 000 IU [1250 µg] per month, is an alternative, although more data on the safety of monthly dosing are required.
   3.  The desired outcome of vitamin D supplementation is:
      • a reduced risk of fractures if serum 25[OH]D levels are above 75 nmol/L;
      • a reduced risk of falls if serum concentrations are above 60 nmol/L;
      • individuals with serum 25[OH]D levels above 50 nmol/L at the end of winter or in early spring are likely to have levels of 60–75 nmol/L for much of the remainder of the year.
3. For older adults, the elderly and those with or at risk of osteoporosis, falls and fracture, the key focus of exercise should be to not just slow bone loss, but to increase or maintain muscle mass and muscle strength, and to improve muscle function, gait and mobility to reduce the risk of falls and fractures.
   1.  Encourage participation in a multimodal and supervised exercise program that includes weight-bearing activities, progressive resistance training and high challenging balance and functional activities at least three times per week.
   2.  It is important that muscle groups connected to bones of relevance to osteoporotic fracture be emphasised in such programs [eg, spinal extensor muscles, hip abductors, hip extensors, knee extensors/flexors] and those related to gait and balance [ankle plantar flexors and dorsiflexors, inverters and everters, hip abductors].
   3.  Regular leisure-time walking should be encouraged for its benefits on weight control and cardiovascular health. For skeletal health benefits, it is recommended that individuals progress to brisk or hill walking and then to other forms of moderate-impact weight-bearing exercises.
   4.  Elderly people with osteoporosis and a history of fracture should avoid exercises or activities that involve forward flexion of the spine, particularly while carrying weights.
   5.  Maintain safe environments to avoid falls and encourage falls education. Elderly individuals should consider and address risk factors for falls [vision problems, use of sedatives, postural hypotension, environmental hazards].

Overview of bone health in Australia

Potential economic impact if bone health is not effectively addressed

Burden of disease — osteoporosis in Australia

Osteoporosis and osteopenia affect 1.2 million and 6.3 million Australians, respectively.2 Without preventive intervention, the number of osteoporosis sufferers is expected to increase to 3 million by 2021 as the population ages.3 For people over the age of 60 years, one in two postmenopausal women and one in three older men will suffer an osteoporosis-related fracture.3 Mortality is increased after all fragility fractures, particularly hip fractures.80 Over one in four people who suffer a hip fracture will die during the first year and less than one-third will regain their prefracture level of mobility.81 Thus, the risk of mortality among women with a hip fracture is similar to or higher than that in women with breast cancer.81 Based on the 2001 Access Economics report commissioned by Osteoporosis Australia, the total direct care cost of osteoporosis is estimated to be over $1.9 billion per year in Australia, with an additional $5.6 billion expended in indirect costs.82

Doctor-reported osteoporosis and Indigenous Australians

An estimated 692 000 Australians [3.4% of the total population] had doctor-diagnosed cases of osteoporosis in 2007–08 based on data from the Australian Institute of Health and Welfare.83 Women accounted for the majority of cases [81.9%].

Although the disease occurs mainly in people aged 55 years and over [84.0%], osteoporosis is a condition without overt symptoms and is known to be underdiagnosed. While the extent of this is difficult to establish, the prevalence of doctor-diagnosed osteoporosis is almost certainly an underestimate. The diagnosis of osteoporosis is more prevalent among those who live in major cities than in rural and remote locations, but this may relate to lack of access to the diagnostic test, bone densitometry, in the latter locations.84

In 2004–05, 0.74% of Indigenous men and 1.11% of Indigenous women reported having doctor-diagnosed cases of osteoporosis. The age-standardised prevalence rates show that osteoporosis was more common among Indigenous men [1.8 times] but less common among Indigenous women [0.5 times] than in their non-Indigenous counterparts.83 Osteoporosis is not more common in those born overseas or those from a low socioeconomic class.83

The hip and pelvis [40.5%] and wrist and forearm [17.1%] were the most common sites of minimal trauma fractures in 2007–08. Interestingly, the age-related rates of hospital separations for minimal trauma hip fracture decreased between 1998–99 and 2007–08, a trend that is consistent with reports from North America and Scandinavia.83 In Australia, the age-related incidence of hip fracture decreased by 15% and 8% in women and men, respectively, between 1998–99 and 2007–08. However, the total number of minimal trauma hip fractures rose from 14 671 to 17 192 over the same period.83

Osteoporosis was managed at a rate of 1 in 100 GP–patient encounters in 2007–08, double the rate seen in 1998–99. Advice and the prescription and supply of medications were the mainstays in these encounters. In hospital settings, both surgical procedures and allied health services were provided to treat fractures.83 Osteoporotic fractures, particularly minimal trauma hip fractures, can lead to premature deaths among the elderly; mortality is increased for at least 5 years even after minor minimal trauma fractures.80

Risk factors

Some risk factors for osteoporosis are non-modifiable, such as female sex, menopause, age, other metabolic disorders, and a genetic predisposition to poor skeletal health. These are useful markers to identify people at increased risk of developing osteoporosis. However, several other risk factors for osteoporosis are readily modifiable:

• lack of weight-bearing exercise
• poor calcium intake
• vitamin D deficiency [serum 25-hydroxyvitamin D [25[OH]D] level  50 years, the combination of vitamin D with calcium, but not vitamin D alone, had a modest effect in preventing fractures [relative-risk reductions of 13%–24%], particularly in those with long-term compliance rates ≥ 80%.11 According to this study, the daily dose of vitamin D and calcium should be at least 800 IU [20 µg] and 1200 mg, respectively. These values are somewhat different to those recommended in the Australian guidance for vitamin D when sun exposure is minimal, at 600 IU [15 µg] per day for those aged ≤ 70 years and 800 IU [20 µg] per day for people aged > 70 years.42 These recommendations appear conservative, and those with substantial sun avoidance may require higher doses.

  Swedish data show the combination of calcium and vitamin D is cost-effective in 70-year-old women at an efficacy as low as 67% of that seen in clinical trial data. Treatment was also cost-effective in 50–60-year-old women with osteoporosis or a family history of maternal hip fracture.90 A Markov model using the efficacy rate in an important hip fracture prevention trial88,89 and prevalence data for osteoporosis in Sweden91 show the costs of treating all 70–79-year-old women and 25% of women 70 years or older in Sweden with calcium and vitamin supplementation would be offset by savings from reductions in fracture rates. Another study shows that increasing the serum 25-hydroxyvitamin D [25[OH]D] level of all Europeans to 80 nmol/L has the potential to reduce the total direct economic burden of diseases related to vitamin D deficiency by 11.4% or €105 000 million,92 depending on the effects of vitamin D on chronic diseases.

  Summary

  Osteoporosis affects 1.2 million Australians,2 many of whom are unaware they have the disease. Without preventive intervention, this number is expected to increase to 3 million by 2021 as the population ages.3 The total direct care cost of osteoporosis is estimated to be over $1.9 billion per year in Australia, with an additional $5.6 billion expended in indirect costs.82 While many risk factors for osteoporosis are modifiable, the evidence of the skeletal benefits of risk factor mitigation is limited. The best evidence is for adequate calcium intake and adequate vitamin D levels. Vitamin D replacement for primary fracture prevention is effective in those who have inadequate serum levels of 25[OH]D, particularly in institutionalised patients, and when combined with calcium supplements. Such a strategy of increasing serum 25[OH]D concentrations > 50–60 nmol/L and ensuring an adequate calcium intake is likely to significantly reduce fracture rates. There is also emerging evidence that this strategy will also be cost-effective, particularly in individuals aged > 50 years who are at increased risk of osteoporosis.

  The role of calcium

  The history of dietary recommendations on calcium

  The first Australian recommended dietary intakes [RDIs] were issued by the National Health and Medical Research Council [NHMRC] in 1954. These RDIs have been subject to several revisions since, with the most recent revision being released in 2006.4

  Before 1997 in the United States and 2006 in Australia, dietary recommendations were based on criteria where RDIs met the following definition:

  Recommended Dietary Intakes [RDIs] are the levels of intake of essential nutrients considered … on the basis of available scientific knowledge to be adequate to meet the known nutritional needs of practically all healthy people. The RDIs are derived from estimates of requirements for each age/sex category and incorporate generous factors to accommodate variations in absorption and metabolism. They therefore apply to group needs. RDIs exceed the actual nutrient requirements of practically all healthy people and are not synonymous with requirements.93

  Accordingly, earlier RDIs were not designed to evaluate the dietary adequacy of individuals, although they were often used or, indeed, misused for this purpose. In 1997, the US Institute of Medicine [IOM] developed a more complex framework for dietary recommendations that included the concept of adequate intakes [AIs], as well as estimated average requirements [EARs], recommended dietary allowances [RDAs] or intakes [RDIs, as used in Australia] and tolerable upper intake levels [ULs].94 These measures allowed for the evaluation of an individual's dietary adequacy. Not all nutrients have both an EAR and AI; the AI is used when there is not enough evidence to set an EAR. It is important to note that intakes below the RDI cannot be assumed to be inadequate because the RDI by definition exceeds the actual requirements of all but 2%–3% of the population.

  The 1997 revision of the dietary reference intakes [DRIs] for calcium, phosphorus, magnesium, vitamin D, and fluoride in the US set an AI for calcium.94 This revision was based on a different approach in response to expanded uses of the values and newer understandings of the role of nutrients. The concept of “optimal health” was introduced on account of the increasing acceptance that DRIs needed to extend beyond the prevention of deficiencies into the range of disease prevention. From 1997, a paradigm shift occurred with acknowledgement of the involvement of calcium in the aetiology of osteoporosis.95 Although reduced bone formation may aggravate the bone loss process in elderly people, particularly men, bone resorption is a major contributor to osteoporosis in women.96,97,98 As bone resorption is related to inadequate calcium intake, RDIs for calcium have risen steadily over the past 30 years. In the 2006 revision of nutrient reference values [NRVs], Nutrient reference values for Australia and New Zealand including recommended dietary intakes, the working party retained the concept of the avoidance of deficiency states as the concept used to set EARs and RDIs.4 Additional reference values were introduced to address chronic disease prevention. In setting the calcium requirements, the NRVs were based on calcium balance studies rather than changes in bone mineral density [BMD] or factorial estimates as used in the US DRIs, as this was considered to be problematic.4

  In 2010, the US IOM released new recommendations for calcium,99 and set EARs and RDAs for calcium, rather than AIs.94 Box 5 provides a comparison of the revised recommendations from the US IOM with the current recommendations from the NHMRC. At the time of writing, the Australian Government has put to tender a scoping exercise to assess if a review is required of the current 2006 NRVs.

  Food versus nutritional supplements for bone health

  Food or food components may differ in their effects on bone compared with a single nutrient. Current thinking has moved towards examining associations with whole foods and food groups rather than single nutrients. This is based on the recognition that dietary components in food may interact.100,101 Additionally, most countries use a food-based approach to dietary guidelines, as this provides the best approach to inform dietary advice. However, a food-based approach presents issues when interpreting evidence relating to bone health:

  • Many interventions have used a dietary calcium supplement, either with or without vitamin D.
  • When a food-based intervention is undertaken, it is impossible to avoid changing the diet without altering the nutrient profile of the participant's food intake.
  • Milk studies are complicated by differences in composition [eg, in the US, vitamin D is routinely added to milk, whereas this is not the case in Australia].
  • Few studies have been designed to address if food has a more favourable effect on bone compared with single nutrients.

  There is a strong biological rationale for the importance of certain food groups in the maintenance of bone health. Grains, fruits and vegetables, meat and dairy, nuts and seeds supply a range of essential nutrients, including vitamins A, C, D and K, calcium, phosphorus, potassium, magnesium, and zinc, which have key roles in bone metabolism. There is considerable evidence of the positive influence that dietary patterns adequate in calcium, phosphorus and vitamin D have on bone health.48 Less consistent evidence exists on the role of other vitamins and micronutrients. Vitamin C is essential for production of collagen, the main protein in the bone matrix. Vitamin K is essential for the formation of the bone matrix protein, osteocalcin. While biochemical mechanisms associate these vitamins with bone mass, reduced intakes have been associated with low bone mass, increased bone loss and fracture,102 but the evidence for supplementation is limited or confusing.48

  Potassium is considered to be important in achieving optimal bone health, due to its influence on calcium homoeostasis, particularly in the conservation and excretion of calcium, and may counter the negative effect of sodium on hypercalciuria.48 Only one supplementation study has shown the benefit of potassium citrate in older women consuming a high-salt diet compared with a placebo.103 However, many vegetables, fruits and dairy foods are good sources of potassium, and dietary patterns rich in these foods have been associated with reduced bone turnover in adults.104,105 Other minerals important for skeletal enzyme reactions include zinc and magnesium, which are present in legumes, vegetables and fruits. A large-scale US study has demonstrated that dietary patterns are related to BMD and, specifically, dietary patterns that include high intakes of vegetables and fruits result in significantly higher BMDs than those found with other dietary patterns.49 Therefore it seems prudent to encourage a varied diet, particularly including fruits and vegetables, to ensure adequate intakes of key nutrients to maintain bone health.

  Dairy foods provide the major sources of calcium in the Australian diet, contributing 52% of the total calcium intake in men and 53% in women.106 In addition to its high calcium content, the other components of milk, including protein, lactose, magnesium and potassium, either alone or in combination with calcium, could also play an important role in bone growth and bone health. Intervention studies using milk in girls have reported positive effects on total body bone mineral accretion.107,108 A study of normally active boys with adequate calcium intakes found that additional exercise and calcium supplementation resulted in a 2%–3% greater increase in bone mineral content [BMC].109 A similar study in girls reported BMC increases of 2%–4% when short bouts of moderate exercise were combined with increased dietary calcium.110

  Milk intervention studies in adults are limited, but have been evaluated in the following populations:

  • Premenopausal women: Milk supplementation was effective in slowing bone loss.111
  • Postmenopausal women: The rate of bone loss was slowed with milk supplementation in Chinese postmenopausal women with low calcium intakes.112 Another study directly compared calcium obtained from milk powder with calcium supplementation through tablets and reported equal effectiveness with both in slowing the rate of bone loss at the hip.113
  • Middle aged and older men: A study of calcium- and vitamin D-fortified milk in older men found that the fortified milk stopped or slowed bone loss at the hip and spine and reduced cortical bone loss at the femur.114

  The positive effects of milk consumption on fracture prevention have not been established.115

  The effect of dietary protein on bone metabolism has long been debated. A recent systematic review and meta-analysis assessing dietary acid load and bone disease116 and several short-term controlled-feeding studies showed that a high-protein diet did not have adverse effects on calcium retention and bone metabolism.117,118,119 The positive effect of protein on bone health has been recently reviewed and the benefits to children and adults outlined.120 Notably, the provision of protein not only has an anabolic effect on bone, especially during periods of growth, but also improves calcium absorption.121 A recent systematic review showed that in older subjects, protein intake could explain 1%–2% of the variation in BMD,122 reduced bone loss over time,123,124,125 and reduced risk of hip fracture,126,127 although a recent placebo-controlled trial in older women did not show benefit to hip bone density with the addition of whey protein [30 g/day] to diet.128 However, it is important to note that benefits of protein on bone are greatest when calcium intake is in accordance with the recommended levels.129

  Evidence of the benefits of a high fruit and vegetable intake in relation to bone density and osteoporotic fracture incidence is currently equivocal.105,130,131,132,133,134

  Current calcium intake in Australia

  The median dietary intake of calcium in the last Australian National Nutrition Survey was 827 mg per day for older men and 619 mg per day for older women [≥ 65 years].4 Thus, the median intake for men is close to the EAR of 840 mg per day, but for women the median intake needs to increase significantly in the oldest age group [EAR, 840–1100 mg per day].

  In a random sample of Australian women with a similar median calcium intake of 631 mg per day, calcium intake from food sources alone was higher among those who also took a multivitamin supplement;135 only 7% of the women reported current use of calcium supplements. Inclusion of calcium derived from supplements increased the cohort's mean total calcium intake by 6%. Calcium intake was not influenced by country of birth.

  The 1995 National Nutrition Survey reported that 50%–66% of calcium intake was provided by milk products, with 30%–45% from dairy milk, about 10% from cheese and about 5% from frozen milk products.106 People who avoid dairy products need to ensure substitute food products are calcium-fortified. To achieve a daily intake of 1000–1300 mg calcium, at least three servings of dairy are recommended, with at least one of those servings being calcium-fortified. Studies suggest that the optimal level for calcium intake is higher when vitamin D status is low.8,44

  A large randomised controlled trial [RCT] has demonstrated that long-term calcium intake in older women can be increased by providing an annual estimate of average daily calcium intake to the individual and her doctor.136 Strategies such as this feedback on dietary calcium intakes may become valuable tools in promoting increased calcium intake from food. Calcium and vitamin D supplementation have moderate to poor long-term adherence.16,137 These supplements are frequently perceived by patients as an excessive medication, and lack of motivation is the most common reason for non-adherence.138 Furthermore, calcium carbonate supplements are associated with gastrointestinal side effects such as bloating and constipation.139 Calcium citrate supplements have a lower proportion of elemental calcium, but the biological availability is higher; these supplements offer a good alternative with fewer gastrointestinal side effects, particularly in the elderly or those taking proton pump inhibitor drugs, which cause an elevation in gastric pH.

  Benefits versus risks of calcium

  Calcium plays an essential role in many physiological processes, including muscular, neural and metabolic functions, as well as bone mechanical properties. Studies suggest that a chronically negative calcium balance may contribute to suboptimal bone mass accrual in children, and to bone loss in adults.140,141,142,143 While potential side effects of calcium supplementation such as kidney stones, abdominal pain, hypercalcaemia and milk-alkali syndrome have been recognised for a long time, recent data on the cardiovascular safety of oral calcium supplements may challenge any recommendations, at least with regards to their use in the primary prevention of osteoporotic fractures.

  Benefits of calcium

  There have been numerous studies on the effect of calcium, with or without vitamin D supplementation, on bone turnover and BMD, both in healthy people and in patients with osteoporosis. Key findings include:

  • Bone turnover and parathyroid hormone levels: Calcium supplementation alone appears to reduce parathyroid hormone [PTH] levels and bone turnover, particularly in people with low dietary calcium intake.144,145,146,147,148,149,150,151,152,153,154,155
  • Bone mineral density [BMD]: Inconsistent results have been observed in younger postmenopausal women in clinical studies.113,156,157,158,159 The same is true to an extent in studies of older people, although one larger study has described improved hip and whole body BMD.16 Additionally, a study of older Chinese women with low calcium intake reported reduced bone loss at the hip.160 A meta-analysis of smaller calcium-only trials concluded that calcium supplementation has a moderate but consistently positive effect on BMD in postmenopausal women.10 A recent meta-analysis found that supplementation with calcium, or calcium in combination with vitamin D, maintains or increases BMD at the spine and reduces bone loss at the hip.11 These effects seemed to be more pronounced in specific groups: in those with low baseline BMD or osteoporosis; in people with low dietary calcium intake or low vitamin D levels [ 75 nmol/L may be more appropriate.200 At the very least, if the 25[OH]D level is measured around the end of summer, allowance needs to be made for a subsequent drop during winter, so that a higher target of at least 60 nmol/L may be advisable.42 Box 3 represents the current scientific findings from the vitamin D position statement supported by the ANZBMS, the ESA, and OA.42

    Since vitamin D receptors are present in all nucleated cells examined and many cells have the capacity to produce the active hormone, 1,25-dihydroxyvitamin D [1,25[OH]2D], there is considerable interest in the possible extraskeletal effects of this hormone. There are extensive laboratory experimental data over many years supporting these proposed effects — one of the first demonstrations that 1,25[OH]2D was important for insulin secretion was published in 1980.201 There is also a relatively large body of supporting data from studies of autoimmune diseases, cancer studies and models of innate immunity in animals. The human studies, however, are mostly limited to epidemiological studies showing, with moderate consistency, that high sunlight exposure or other indices of replete vitamin D status are associated with reduced risk of certain cancers and autoimmune diseases, such as type 1 diabetes and multiple sclerosis, as well as being involved in a range of other health parameters. Although such observations have been made since 1937,202 evidence supporting a role for vitamin D in these non-skeletal health outcomes from well conducted randomised controlled trials [RCTs] is mostly lacking. The trials that have been conducted have mostly not had extraskeletal health effects as a primary outcome, while the trials that have had extraskeletal health effects as a primary outcome have tended to be small, short and have had dose or compliance problems. Large-scale trials, such as the Vitamin D and Omega-3 Trial [VITAL], are underway, but will take some time to report. There are also ethical issues in undertaking the trials. Ideally, the enrolled subjects should be vitamin D deficient/insufficient [by defined criteria], as increasing vitamin D levels beyond some optimal concentration may produce no further benefit; however, this poses a problem for the placebo group.

    Some indicators have started to appear in the literature that high 25[OH]D concentrations, mostly > 100 nmol/L but sometimes > 75 nmol/L, may be associated with adverse health outcomes.203,204,205 The data are surprising, considering that the 25[OH]D levels of people living in high ambient ultraviolet [UV] environments average around 130 nmol/L.206 The nature of the studies showing these negative effects is similar to that of the epidemiological association studies showing better health outcomes from higher 25[OH]D levels.

    Some of the discrepancies in the literature may be due to genetic influences on vitamin D status and response to therapy. Polymorphisms of the genes encoding vitamin D binding protein, 7-dehydrocholesterol reductase, which affects substrate levels in skin, and the putative 25-hydroxylase have been shown to affect vitamin D status.207 More recently, the effect of vitamin D on tuberculosis seroconversion has been reported to be dependent on polymorphisms of the vitamin D receptor,208 while infantile hypercalcaemia in response to moderate supplemental vitamin D has been shown to be a consequence of mutations in the 24-hydroxylase gene.209

    Vitamin D storage and metabolism

    There is little understanding of vitamin D storage. The secosteroid, 25[OH]D, has a half-life in blood of 15–50 days, much greater than most steroids and much greater than that of its binding protein.210,211 Little is known about the factors which affect half-life, except that low calcium intake and/or high parathyroid hormone [PTH] levels markedly shorten this.210,212 Vitamin D can be given as a yearly dose, with reasonable maintenance of 25[OH]D levels over most of the year.213,214 Some vitamin D goes into fat, where it appears to be trapped.215 Some 25[OH]D goes into muscle,216 but meat is a poor source of vitamin D.

    Many of the physiological effects of vitamin D, though not all, are better related to circulating 25[OH]D levels than to 1,25[OH]2D concentrations. The latter are poor indicators of vitamin D status.217 This may be explained in part by the ability of many tissues, including bone, macrophages and probably parathyroid gland, to convert 25[OH]D to 1,25[OH]2D locally. Indeed, in laboratory studies of bone cell function, endogenously produced 1,25[OH]2D caused different functional effects from exogenously added hormone.218

    Protocols for vitamin D administration

    Assuming there is a need to improve a patient's vitamin D status and that advice to increase sun exposure is impractical or inadvisable, what is an appropriate protocol? Most vitamin D supplements in Australia are vitamin D3. This means the controversies about whether vitamin D2 raises 25[OH]D levels as effectively as vitamin D3 [even if the assay measures both adequately] and, more importantly, whether vitamin D2 is less effective functionally [on which there are very few recent data] are not major issues in this country.219,220 There is insufficient appreciation of data that show that standard 1000 IU [25 µg] doses of vitamin D per day can be expected to raise 25[OH]D levels by only 10–20 nmol/L.221,222 Major issues are cost and compliance, particularly in refugee communities and the elderly. For these reasons, weekly, monthly, 3-monthly or yearly doses of vitamin D have been advocated. Generally available vitamin D supplements are usually 1000 IU [25 µg] oral tablets or capsules, liquid vitamin D [1000 IU/0.2 mL], and preparations imported with permission or made by compounding chemists. Intermittent, high-dose vitamin D [eg, 50 000 IU per month] is cheaper, effective in improving vitamin D status quickly,223 produces average 25[OH]D levels consistent with the equivalent daily dose224 and does not seem to cause undue problems with hypercalciuria or hypercalcaemia.213,223 However, while dosing of 100 000 IU [2500 µg] every 4 months was shown to reduce fractures in a community study in the UK,86 a 500 000 IU [12 500 µg] yearly dose of vitamin D3 in winter in Victoria resulted in increased falls and a tendency to increased fracture rates in the first 3 months following the dose.214

    Even if optimal-dosing protocols for vitamin D could be established, most meta-analyses of RCTs examining falls and fractures [and a recent one on overall mortality] report that improved outcomes are generally the result of combined treatment with vitamin D and calcium, rather than either agent alone.11,225,226 Calcium supplements are normally given daily and are often combined with vitamin D.

    Vitamin D deficiency in Australia

    The definition of vitamin D sufficiency has varied among the studies conducted in Australia. Regardless, as a population, it is evident that Australians are not as vitamin D sufficient as might be expected for residents of a “sunny country”. A study combining results from mostly normal populations in south-east Queensland, Victoria and Tasmania reported a prevalence of vitamin D deficiency [defined as  50 nmol/L. Current understanding of the complex interaction of genetic, behavioural and environmental factors that influence the production of vitamin D within human skin is limited. While UVR exposure is an effective means of increasing vitamin D status, deliberate UVR exposure for durations sufficient to increase vitamin D status may increase the risk of other adverse health outcomes. Accordingly, daily oral supplementation remains the most safe, reliable and effective method to increase vitamin D levels.

    Vitamin D fortification in food

    Few foods contain significant amounts of vitamin D. Small amounts of vitamin D3 are found in the fat of animals and, as such, full-cream milk and butter contains vitamin D, but the amount is dependent on the season of production. A rich source is fish, especially high-fat fish such as salmon, herring and mackerel from the North Sea. It should be noted that farmed salmon contains only one-quarter of the amount of vitamin D found in wild salmon, and vitamin D can be lost in the cooking process. For many countries, foods fortified with vitamin D are the major dietary sources of vitamin D. In Australia, all margarines are mandatorily fortified with small amounts of vitamin D. Small amounts of vitamin D are permitted to be added to dried milk,287 modified milk, cheese, yoghurt, dairy desserts, butter, various analogues derived from legumes and their products, certain beverages derived from cereals, and formulated beverages, but few milks are fortified in Australia. UV-irradiated mushrooms also contain vitamin D. It is not permitted to add vitamin D to breakfast cereals or fruit juices in Australia, in contrast with many other developed countries.

    The intake of vitamin D in Australia is less than the intakes recorded in countries that either mandate vitamin D fortification of milk at levels higher than those allowed in Australia and/or permit extensive voluntary vitamin D fortification of a number of food products. Under these circumstances, the mean vitamin D intake for adults can be almost double the Australian intake, at about 192 IU [4.8 µg] per day.288

    The only country to employ mandatory vitamin D fortification of milk at a level twice that allowed by Australia is Canada [~ 80 IU [2 µg] per 200 mL]. The mean vitamin D intake from food in Canada is 232 IU [5.8 µg] per day in adults, with higher intakes seen in children; median intakes of 1–3-year-olds and 4–8-year-olds are 252 IU [6.3 µg] per day and 224 IU [5.6 µg] per day, respectively.288 Vitamin D fortification at this level appears to have some positive impact on the rates of severe deficiency and rickets. A recent analysis of a representative sample of Canadians indicated that, in winter, 25% were classified as deficient [ 50 nmol/L [without other infant supplementation].335,336 A trial in breastfeeding women used maternal vitamin D doses of 6400 IU [160 µg] per day in one arm to ensure infant levels > 50 nmol/L.337 Breast milk is a poor source of vitamin D338 and, like other age groups, breastfed infants are dependent on skin synthesis for their vitamin D stores.339

    There is limited evidence for the effect of vitamin D on maternal bone health during lactation and after weaning, and inadequate evidence to recommend a higher target level for breastfeeding mothers than the current target level for healthy adults of > 50–60 nmol/L. There is also currently inadequate evidence to support maternal vitamin D supplementation as a single strategy to treat low vitamin D levels in exclusively breastfed neonates.

    Vitamin D needs in infants, children and adolescents

    Vitamin D is important for bone health and muscle function throughout childhood and adolescence. Adequate vitamin D status is required to prevent rickets and to promote normal bone growth and mineralisation as peak bone mass is acquired.

    Rickets is a generalised disruption of skeletal mineralisation [osteomalacia], together with abnormal growth plate mineralisation and development during periods of linear growth. Rickets occurs most commonly in infancy, although it is also seen in adolescents.340 Most rickets in childhood is due to low vitamin D, although there is no absolute 25[OH]D level associated with rickets. Low calcium and/or phosphate intake or increased losses of phosphate and/or calcium may be additional contributors, or the primary cause. Case series of children with rickets from Australia,341,342,343 the US344,345,346,347,348 and Canada349,350,351 have noted almost all affected children have dark skin and prolonged breastfeeding. In the three Australian series, 75%–95% of the affected children were migrants or born to immigrant parents.341,342,343 In New South Wales, reported cases doubled from 17 cases in 2002 to 35 cases in 2003 and were almost exclusively in recently immigrated children, or first-generation offspring of immigrant parents, from the Indian subcontinent, Africa and the Middle East.343

    Seventeen studies of cohorts of infants and young children with rickets [sample size, 5–129] have reported a mean/median level of 25[OH]D