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Guideline

General bone health maintenance and fracture prevention

Calcium, protein and Vitamin D

Calcium, protein and Vitamin D

Recommendation 11

Grade

For generally healthy older people:
Although the absolute benefit of calcium and vitamin D supplements in short-term (less than six years) studies for fracture reduction is low, there is good evidence adequate calcium intakes and vitamin D status are important for long-term maintenance of bone and muscle function.

C

Recommendation 12

Grade

For frail and institutionalised older people:
Calcium and vitamin D supplementation, together with adequate protein intake, are recommended for fracture prevention. Optimisation of calcium and vitamin D should be the standard of care for this group.

B

Recommendation 13

Grade

For people taking osteoporosis treatments:

  • Calcium supplements should be recommended if their dietary calcium intake is less than 1300 mg per day.
  • Vitamin D supplements should be recommended to correct low serum vitamin D levels (25-hydroxyvitamin D <50 nmol/L).

C

Recommendation 14

Grade

For most people with olive or pale brown skin, no other risk factors and who are at intermediate risk of skin cancer, a few minutes of sunlight exposure towards the middle of the day, with time depending on latitude, season and skin area exposed, followed by further sun protection measures should maintain vitamin D levels. People with dark skin at low risk of skin cancer have less need for sun protection, but require more time outdoors to avoid vitamin D deficiency. People at high risk of skin cancer need sun protection most of the year, which may limit vitamin D synthesis. The use of sunscreen, in practice, does not greatly affect vitamin D status.

B

Calcium is an important component of bone, accounting for 30–35% of its mass and much of its strength. Bone calcium also acts as a reservoir for maintaining blood calcium levels, which are needed for healthy nerve and muscle function.

Evidence for the relationship between dietary calcium intake and fracture risk reduction has been contradictory due to different methods of assessing calcium intake and the problems inherent in self-reporting of calcium intake, together with genetic, environmental, and sociological differences.

Advice on calcium consumption varies internationally. In Australia, the NHMRC recommended dietary intake (RDI) is 1300 mg per day for women aged >50 years, 1000 mg per day for men aged 50–70 years, and 1300 mg per day for men aged >70 years,3 similar to the recommendations of the Institute of Medicine in the US,8 although substantially higher than those of the National Institute for Health and Care Excellence (NICE) in the UK. Increasing calcium intake from food is recommended because, with ageing, enteric calcium absorption becomes less effective and urinary calcium loss increases.4–6 The importance of adequate calcium intake throughout life for building and maintenance of the skeleton is supported by previous Australian and New Zealand guidelines7 and those of other countries.8 Only 20–40% of the Australian adult population meet the calcium RDI. In 2011–12, the average daily intake for people aged 51–70 years was 781 mg for men and 741 mg for women, with intakes lower in people aged >70 years.9

Calcium is available from many foods. This provides consumers with a range of calcium sources to meet individual preferences and/or dietary requirements, including those with diverse cultural eating patterns. It is important to note that the calcium content in different foods varies and to focus on the foods that provide the highest content to meet RDIs. The richest sources of dietary calcium are dairy foods – milk, hard cheese, and yoghurt – and, according to current NHMRC Australian dietary guidelines, at least three serves of dairy food per day are recommended (where one serving = 250 mL milk, 200 g yoghurt or 40 g cheese).3 This adds to the approximately 300 mg of calcium in a non-calcium-rich diet. Other calcium-rich foods include firm tofu, almonds, sesame seeds, tinned fish, some green leafy vegetables, dried figs, and calcium-fortified non-diary milks.10

Protein is an important constituent of bone and muscle tissue. It provides the structural matrix of bone where calcium is the key mineral and collagen (and other non-collagenous proteins) form the organic matrix of bone. Adequate intake of dietary protein is important for bone acquisition and maintenance, as well as for maintenance of the musculoskeletal system.

Protein intake may play a beneficial role in the prevention of bone loss and in slowing down osteoporosis, and has recently gained much attention. A 2018 expert consensus paper summarising systematic reviews and meta-analyses investigating the effects of dietary protein on bone health in adults concluded that an intake above current RDI (0.8 g/kg body weight per day), in combination with an adequate calcium intake, is associated with higher BMD, lower rate of bone loss, and modestly reduced fracture risk.11 Updated systematic reviews and meta-analyses focusing specifically on adults aged ≥65 years showed a positive trend between higher protein intake and higher femoral neck and total hip BMD, and suggested that protein intake above current RDI may reduce hip fracture risk and play a beneficial role in BMD maintenance in older adults.12,13

Older people commonly have decreased skeletal muscle mass and strength from reduced production of muscle tissue.14 Because protein intake plays an integral part in muscle and bone health, an intake of 1.0–1.2g/kg body weight per day has been recommended for older adults.15

A recent Australian study assessing the effectiveness of a nutritional intervention in institutionalised older adults by improving calcium and protein intake (<1 g/kg body weight protein per day) using dairy foods showed an 11% reduction in the risk of falls, a 48% reduction in hip fractures, and a 30% reduction in all fractures.16

Vitamin D has an important role in maintaining bone health by promoting calcium absorption and bone mineralisation.17 Epidemiological evidence using serum 25 hydroxyvitamin D (25(OH)D) as a measure of adequate vitamin D status has reported that ‘an estimated 31% of adults in Australia have inadequate vitamin D status (25(OH)D <50 nmol/L), increasing to more than 50% in women during winter–spring and in people residing in southern states’.18

A major source of vitamin D in Australia is sunlight exposure, especially in summer.19,20 However, after the age of 70 years, the skin is thinner and may be less efficient at synthesising adequate amounts of vitamin D,21 although adequate vitamin D synthesis is seen if doses of ultraviolet (UV) radiation exposure are not too high.22 A much bigger issue is a tendency for older people to avoid going, or not be able to get, outdoors.23

UV radiation from the sun has both beneficial and harmful effects on human health.24 A balance is required between excessive sun exposure that increases the risk of skin cancer and enough exposure to maintain adequate vitamin D levels. Consider a patient’s risk of skin cancer when considering sun exposure advice:

  • People with a high risk of skin cancer (those with very pale skin and/or olive/pale brown skin with other risk factors) are advised to adopt a very cautious approach to sun exposure when the UV index is ≥3.24
  • In Australia, for people with an intermediate risk of skin cancer (olive or pale brown skin with no other risk factors), sun protection is important but it should be balanced with spending sufficient time outdoors with ample skin exposed to avoid vitamin D deficiency.24 How much time outdoors depends on many factors, including skin surface area exposed, skin tone and latitude (which makes a difference, particularly in winter). As a rough guide for most people with olive or pale brown skin, exposure of approximately 15% of body surface (ie hands, face and arms) for 5–10 minutes on most days of the week in summer around mid-morning and mid-afternoon should maintain vitamin D levels.18
  • For those with constitutively dark skin, who are at low risk of skin cancer but need higher doses of UVB to make adequate vitamin D, sun protection measures are not needed unless spending extended times outdoors when the UV index is ≥3.24

 

Sun exposure in winter should be with as much skin uncovered as practical, considering external temperature, and during the middle of the day, if possible.18,24 Tables showing approximate exposure times for different seasons, skin colours, latitudes and clothing styles (shorts and T-shirt or long sleeves and long pants) are available.24 Sunscreen use blocks vitamin D synthesis in the laboratory, but does not have a major effect in practice on vitamin D status; time in the sun and surface area exposed are more important.24 Body fat is also relevant because obesity is associated with less vitamin D synthesis with vitamin D distribution into fat stores, resulting in lower blood levels of 25(OH)D.25

The current RDI of vitamin D in Australia in individuals aged >50 years is 400 IU (10 mcg) per day, rising to 600 IU (15 mcg) per day in those aged >70 years.26,27 Useful amounts of vitamin D3 can be acquired through food, such as canned salmon, which has approximately 19 mcg (770 IU) vitamin D3 per 100 g, fresh Atlantic salmon (~5 mcg [200 IU] vitamin D3 per 100 g) or fresh white fish (up to 3.5 mcg [140 IU] vitamin D3 per 100 g).3 These new data suggest that fish may be a useful source of vitamin D, particularly during winter.21

There is a large body of evidence to support the role of calcium and vitamin D in the maintenance of bone health.8,28 The role of calcium and vitamin D supplementation in the treatment of osteoporosis has also been extensively studied in clinical trials. Although calcium and vitamin D supplements have been widely used to prevent bone loss and fractures in postmenopausal women and older men, the use of these supplements continues to be controversial, with studies indicating both no significant association1 and reduced fracture risk.29 However, these studies were mostly in healthy, non-institutionalised individuals with limited participants who had low baseline vitamin D status.

Evidence indicates that the absolute benefit of these treatments in terms of short-term (less than five years) fracture prevention for non-institutionalised individuals is relatively low and considerably less than that seen with licensed osteoporosis treatments, such as bisphosphonates or denosumab.8,29 The US Preventive Services Task Force has recommended against routine calcium and vitamin D supplementation in non-institutionalised older people.30 However, there is reasonable evidence of benefit for those who may be deficient, particularly institutionalised individuals or frail older people.31

Based mainly on calcium balance studies, the target calcium intake from dietary sources and supplements should be 1000 mg per day for adults, rising to 1300 mg per day for women aged >50 years and men aged >70 years.3,8,32 Vitamin D from sunlight exposure (with more sun protection and limited time outdoors for people at high risk of skin cancer and less protection and more time outdoors for those with dark skin at low risk of skin cancer24) or, if sun exposure is very limited, supplements should ensure serum 25(OH)D concentrations >50 nmol/L.8 Although the middle of the day has the highest UV overall, so skin damage may occur in a very short time, it is also when the ratio of UVB (needed for vitamin D synthesis) to UVA (which damages the skin and does not produce vitamin D) is highest.17,24

If vitamin D supplements are required to achieve target serum 25(OH)D concentrations of >50 nmol/L as recommended,8 a dose of 800–1000 IU per day is usually sufficient, although higher doses are needed in some people.17,18,28 Dietary calcium intake is often suboptimal in older people, especially institutionalised individuals.

Calcium and vitamin D supplements work together by reducing secondary hyperparathyroidism and bone turnover. BMD is also increased by calcium and vitamin D, but this effect appears modest. Calcium and vitamin D are not available on the PBS, but are recommended for people likely to have insufficient intakes. This is particularly important for those taking other osteoporosis therapies.

Calcium supplements are available in two common forms: calcium carbonate and calcium citrate. Calcium tablets typically contain 250–600 mg of elemental calcium. The most commonly available type of vitamin D supplement is vitamin D3 or cholecalciferol. Vitamin D3 elevates serum 25(OH)D concentrations more than vitamin D2 or ergocalciferol and is more reliably measured by commercially available assays. Currently available doses of vitamin D range from 400 to 1000 IU, available as capsules, tablets or liquid formulations.

Calcium supplements modestly increase the risk of renal calculi.39 Calcium supplements can also cause abdominal bloating and constipation.39 It has been reported there could be an increased risk of myocardial infarction with calcium supplements,40 but not all studies support this conclusion.41 Calcium and vitamin D supplements do not increase the risk of death and some studies suggest a small reduction in the risk of death.41

Clinical toxicity is uncommon with vitamin D, even at high doses. Single doses of up to 500,000 IU are tolerated without causing hypercalcemia or hypercalciuria. However, the use of higher-dose formulations of vitamin D in older people has been associated with an increased risk of falls. Overall, daily, or at most, weekly vitamin D supplements are preferred.31

Evidence Statement

The benefit of vitamin D and/or calcium supplementation on fracture prevention has been extensively assessed in numerous clinical trials with varying protocols, with a significant number of systematic reviews and meta-analyses reporting different conclusions.29,33–35 A Cochrane review of vitamin D in postmenopausal women and older men,36 as well as several other reviews,29,31,33,34,37 concluded that although vitamin D alone is unlikely to prevent fractures in the doses and formulations tested so far in older people, supplements of vitamin D with calcium may prevent hip or other type of fracture. A 2022 comprehensive umbrella review assessing reasons for the discrepancies among systematic reviews/meta-analyses of trials (generally of less than five years) on vitamin D supplementation concluded that although calcium and vitamin D supplements together reduce the risk of hip and other fractures, this seemed largely due to data from institutionalised individuals, despite there being no significant differences in relation to residency in subgroup analyses.31 Overall, the reductions in fracture risk with vitamin D and calcium from these trials are small in absolute terms with relatively large numbers of people needed to be treated to prevent fractures. Only the Cochrane review37 was deemed by the umbrella review to be of moderate quality.31

A recent ancillary study of the randomised controlled Vitamin D and Omega-3 Trial (VITAL) involving 28,871 participants with mean age of 67 years reported that vitamin D3 supplementation (2000 IU per day) alone did not result in a significantly lower risk of fractures than placebo among generally healthy mid-life and older adults with generally good vitamin D status.38 These recent findings importantly question the health benefits of vitamin D supplements alone in the general population of older adults, although as the authors of the VITAL study state, the study was not designed to investigate people with low vitamin D status and there were not enough participants with low vitamin D to draw any conclusions for them.38 RCTs are necessarily conducted over a few years only and with limited exceptions, such as those involving subjects in aged care facilities, generally enrol people of good enough health and mobility to participate in the trial process. Vitamin D and calcium are both threshold ‘nutrients’, meaning that giving more to people who already have enough, however defined, cannot be expected to have a benefit.28

A recent study regarding improving nutrition in aged care settings that included increasing calcium and protein intake levels in people who were vitamin D replete have shown benefits such as fall and fracture reduction.16

A very large body of evidence, including the 662-page 2011 Institute of Medicine report8 and other reviews,28 points to a causal role of vitamin D and calcium for bone health. Severe vitamin D and/or calcium deficiency is the cause of most cases of rickets and osteomalacia.8,28 Deficiency of either calcium or vitamin D can accelerate bone loss and osteoporosis in older people due to increases in parathyroid hormone and secondary hyperparathyroidism.8,17,28

The safety of calcium and/or vitamin D supplements has also been examined in several meta-analyses.37,39,40 In a Cochrane review, the risk of renal insufficiency or calculi was found to be increased by vitamin D and calcium supplements (RR 1.17; 95% CI: 1.03–1.34).39 That review also found an increased risk of gastrointestinal symptoms with vitamin D and calcium supplements (RR 1.04; 95% CI: 1.00–1.08).39 The risk of cardiac events has also been examined, but despite being based on datasets from the same RCTs, different meta-analyses have drawn different conclusions. One meta-analysis found an increased risk of myocardial infarction (RR 1.24; 95% CI: 1.07–1.45) and stroke (RR 1.15; 95% CI: 1.00–1.32) in people taking calcium supplements with or without vitamin D;40 another meta-analysis found no association with myocardial infarction (RR 1.08; 95% CI: 0.92–1.26) or coronary heart disease in general.37 Meta-analyses generally indicate that calcium supplements with or without vitamin D have no effect on overall mortality, but the combination of calcium and vitamin D has been found to reduce the risk of death in one meta-analysis.41

RCTs have evaluated the effectiveness of higher-dose intermittent vitamin D supplements to reduce the risk of falls in individuals at high risk of falling. The use of high-dose oral vitamin D increased the risk of falls rather than reduced it.42,43 One trial that compared the effect of 24,000 IU vitamin D once per month to 60,000 IU vitamin D once per month found that the higher dose was associated with a significantly increased incidence of falls.43

  • In otherwise healthy non-institutionalised individuals, the relative reduction in fracture risk with calcium and/or vitamin D supplementation alone is small and may be associated with some adverse events. As such, these should not be considered routinely in healthy people or as first-line treatments for people with osteoporosis.
  • Nevertheless, in adults, adequate calcium intakes of around 1000 mg per day from dietary sources and vitamin D from sunlight exposure, except in people with a high risk of skin cancer, to maintain 25(OH)D concentrations above 50 nmol/L should be encouraged. Short, frequent exposures are efficient for most people, with longer exposures for those with dark skin.
  • In frail or institutionalised older individuals, target calcium intake should be 1300 mg per day in postmenopausal women and men aged >70 years, ideally from dietary sources. Where this cannot be achieved, a calcium supplement of 500–600 mg per day is suggested.23
  • In frail or institutionalised older individuals, some sunlight exposure (with short, frequent exposures being more efficient for most people and longer exposures for those with dark skin) if practical and/or supplements should ensure that serum 25(OH)D concentrations are above 50 nmol/L.23
  • A protein target intake of 1.0–1.2 g/kg body weight per day could be considered for frail and institutionalised people. Increased dairy intake could help achieve calcium and protein targets.
  • Calcium citrate does not need to be taken after meals like calcium carbonate because it does not require an acid environment to be optimally absorbed. Calcium and vitamin D supplements may be taken at any time of the day.
  • Calcium and vitamin D supplements are more likely to be effective in reducing fracture risk when given in combination to individuals who are deficient. Most studies demonstrating efficacy of other osteoporosis treatments have been conducted in the setting of concurrent calcium and vitamin D supplementation (i.e., in calcium- and vitamin D-replete people).
  1. Cosman F, de Beur SJ, LeBoff MS, et al. Clinician’s guide to prevention and treatment of osteoporosis. Osteoporos Int 2014;25(10):2359–81.
  2. Scottish Intercollegiate Guidelines Network (SIGN). Management of osteoporosis and the prevention of fragility fractures. SIGN, 2021 [Accessed 30 October 2023]
  3. National Health and Medical Research Council (NHMRC). Australian dietary guidelines. NHMRC, 2013 [Accessed 21 November 2023]
  4. Nordin BE, Need AG, Morris HA, O’Loughlin PD, Horowitz M. Effect of age on calcium absorption in postmenopausal women. Am J Clin Nutr 2004;80(4):998–1002.
  5. Nordin BE, Morris HA. Recalculation of the calcium requirement of adult men. Am J Clin Nutr 2011;93(2):442–45.
  6. Prince R, Devine A, Dick I, et al. The effects of calcium supplementation (milk powder or tablets) and exercise on bone density in postmenopausal women. J Bone Miner Res 1995;10(7):1068–75.
  7. Ebeling PR, Daly RM, Kerr DA, Kimlin MG. Building healthy bones throughout life: An evidence-informed strategy to prevent osteoporosis in Australia. Med J Aust 2013;199(S7):S1–46.
  8. Institute of Medicine (US) Committee to Review Dietary Reference Intakes for Vitamin D and Calcium; Ross AC, Taylor CL, Yaktine AL, Del Valle HB, editors. Dietary reference intakes for calcium and vitamin D. National Academies Press, 2011 [Accessed 31 October 2023]
  9. Australian Bureau of Statistics (ABS). Australian health survey: Nutrition first results – food and nutrients, 2011–2012. ABS, 2014 [Accessed 31 October 2023]
  10. Food Standards Australia & New Zealand. Australian food composition database. 2022 [Accessed 31 October 2023]
  11. Rizzoli R, Biver E, Bonjour JP, et al. Benefits and safety of dietary protein for bone health-an expert consensus paper endorsed by the European Society for Clinical and Economical Aspects of Osteopororosis, Osteoarthritis, and Musculoskeletal Diseases and by the International Osteoporosis Foundation. Osteoporos Int 2018;29(9):1933–48.
  12. Groenendijk I, den Boeft L, van Loon LJC, de Groot LCPGM. High versus low dietary protein intake and bone health in older adults: A systematic review and meta-analysis. Comput Struct Biotechnol J 2019;17:1101–12.
  13. Darling AL, Manders RJF, Sahni S, et al. Dietary protein and bone health across the life-course: An updated systematic review and meta-analysis over 40 years. Osteoporos Int 2019;30(4):741–61.
  14. Truswell AS. Dietary guidance for older Australians. Nutr Diet 2009;66(4):243–48.
  15. Mithal A, Bonjour JP, Boonen S, et al. Impact of nutrition on muscle mass, strength, and performance in older adults. Osteoporos Int 2013;24(5):1555–66.
  16. Iuliano S, Poon S, Robbins J, et al. Effect of dietary sources of calcium and protein on hip fractures and falls in older adults in residential care: Cluster randomised controlled trial. BMJ 2021;375:n2364.
  17. Pike JW, Christakos S. Biology and mechanisms of action of the vitamin D hormone. Endocrinol Metab Clin North Am 2017;46(4):815–43.
  18. Nowson CA, McGrath JJ, Ebeling PR, et al. Vitamin D and health in adults in Australia and New Zealand: A position statement. Med J Aust 2012;196(11):686–87.
  19. Pasco JA, Henry MJ, Nicholson GC, Sanders KM, Kotowicz MA. Vitamin D status of women in the Geelong Osteoporosis Study: Association with diet and casual exposure to sunlight. Med J Aust 2001;175(8):401–05.
  20. Fayet-Moore F, Brock KE, Wright J, et al. Determinants of vitamin D status of healthy office workers in Sydney, Australia. J Steroid Biochem Mol Biol 2019;189:127–34.
  21. MacLaughlin J, Holick MF. Aging decreases the capacity of human skin to produce vitamin D3. J Clin Invest 1985;76(4):1536–38.
  22. Davie M, Lawson DE. Assessment of plasma 25-hydroxyvitamin D response to ultraviolet irradiation over a controlled area in young and elderly subjects. Clin Sci (Lond) 1980;58(3):235–42.
  23. Sambrook PN, Cameron ID, Chen JS, et al. Does increased sunlight exposure work as a strategy to improve vitamin D status in the elderly: A cluster randomised controlled trial. Osteoporos Int 2012;23(2):615–24.
  24. Australian Skin and Skin Cancer Research Centre. Position Statement Balancing the Harms and Benefits of Sun Exposure. 2023 [Accessed 23 September 2024]
  25. Wortsman J, Matsuoka LY, Chen TC, Lu Z, Holick MF. Decreased bioavailability of vitamin D in obesity. Am J Clin Nutr 2000;72(3):690–93.
  26. Vitamin D, calcium, or combined supplementation for the primary prevention of fractures in community-dwelling older adults: Recommendation statement. Am Fam Physician 2018;98(4):Online [Accessed 31 October 2023]
  27. National Health and Medical Research Council (NHMRC). Nutrient reference values for Australia and New Zealand including recommended dietary intakes. NHMRC, 2017 [Accessed 16 January 2024]
  28. Bouillon R, Marcocci C, Carmeliet G, et al. Skeletal and extraskeletal actions of vitamin D: Current evidence and outstanding questions. Endocr Rev 2019;40(4):1109–51.
  29. Yao P, Bennett D, Mafham M, et al. Vitamin D and calcium for the prevention of fracture: A systematic review and meta-analysis. JAMA Netw Open 2019;2(12):e1917789.
  30. Moyer VA; U.S. Preventive Services Task Force. Vitamin D and calcium supplementation to prevent fractures in adults: U.S. Preventive Services Task Force recommendation statement. Ann Intern Med 2013;158(9):691–96.
  31. Chakhtoura M, Bacha DS, Gharios C, et al. Vitamin D supplementation and fractures in adults: A systematic umbrella review of meta-analyses of controlled trials. J Clin Endocrinol Metab 2022;107(3):882–98.
  32. National Institutes of Health, Office of Dietary Supplements. Calcium fact sheet for health professionals [Accessed 29 September 2023]
  33. Zhao JG, Zeng XT, Wang J, Liu L. Association between calcium or vitamin D supplementation and fracture incidence in community-dwelling older adults: A systematic review and meta-analysis. JAMA 2017;318(24):2466–82.
  34. Bolland MJ, Grey A, Avenell A. Effects of vitamin D supplementation on musculoskeletal health: A systematic review, meta-analysis, and trial sequential analysis. Lancet Diabetes Endocrinol 2018;6(11):847–58.
  35. Meyer HE, Smedshaug GB, Kvaavik E, Falch JA, Tverdal A, Pedersen JI. Can vitamin D supplementation reduce the risk of fracture in the elderly? A randomized controlled trial. J Bone Miner Res 2002;17(4):709–15.
  36. Avenell A, Mak JC, O’Connell D. Vitamin D and vitamin D analogues for preventing fractures in post-menopausal women and older men. Cochrane Database Syst Rev 2014;2014(4):CD000227.
  37. Lewis JR, Radavelli-Bagatini S, Rejnmark L, et al. The effects of calcium supplementation on verified coronary heart disease hospitalization and death in postmenopausal women: A collaborative meta-analysis of randomized controlled trials. J Bone Miner Res 2015;30(1):165–75.
  38. LeBoff MS, Chou SH, Ratliff KA, et al. Supplemental vitamin D and incident fractures in midlife and older adults. N Engl J Med 2022;387(4):299–309.
  39. Mazess RB, Bischoff-Ferrari HA, Dawson-Hughes B. Vitamin D: Bolus is bogus – a narrative review. JBMR Plus 2021;5(12):e10567.
  40. Bolland MJ, Grey A, Avenell A, Gamble GD, Reid IR. Calcium supplements with or without vitamin D and risk of cardiovascular events: Reanalysis of the Women’s Health Initiative limited access dataset and meta-analysis. BMJ 2011;342:d2040.
  41. Rejnmark L, Avenell A, Masud T, et al. Vitamin D with calcium reduces mortality: Patient level pooled analysis of 70,528 patients from eight major vitamin D trials. J Clin Endocrinol Metab 2012;97(8):2670–81.
  42. Sanders KMSA, Stuart AL, Williamson EJ, et al. Annual high-dose oral vitamin D and falls and fractures in older women: A randomized controlled trial. JAMA 2010;303(18):1815–22.
  43. Bischoff-Ferrari HA, Dawson-Hughes B, Orav EJ, et al. Monthly high-dose vitamin D treatment for the prevention of functional decline: A randomized clinical trial. JAMA Intern Med 2016;176(2):175–83.
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