Vitamin D supplementation in musculoskeletal health: what's new?

Although vitamin D plays a significant role in musculoskeletal health, evidence does not support the use of vitamin D supplementation for healthy people.

Vitamin D supplementation in musculoskeletal health: what's new?

Despite an abundance of sunshine in Australia, more than one in five Australian adults do not get enough vitamin D, which is vital for musculoskeletal health. For those with confirmed deficiency, vitamin D supplementation is the recommended treatment. But what about people who have not been diagnosed as vitamin D deficient? 

 

Practice points

  • Vitamin D is essential for musculoskeletal health. The association between vitamin D deficiency and bone disease is well established.
  • Serum vitamin D testing should only be considered for people at increased risk of deficiency.
  • Supplementation is recommended only for people who are vitamin D deficient (with serum 25-hydroxyvitamin D levels < 50 nmol/L).
  • Meta-analyses investigating effects of vitamin D supplementation on fracture risk have found mixed results. Improvements are more likely if vitamin D and calcium supplements are taken together.
  • There is limited high quality evidence to support vitamin D supplementation for people with non-musculoskeletal health conditions.
 

Vitamin D overview

Vitamin D (or ‘calciferol’) is a fat-soluble vitamin essential for musculoskeletal health.1,2

In the liver, vitamin D is metabolised to 25-hydroxyvitamin D (25[OH]D), the major circulating form of vitamin D measured in most assays.3

In the kidneys, further hydroxylation takes place to form 1,25-dihydroxyvitamin D, the active form of vitamin D, which promotes the absorption of calcium and phosphate from the gut and facilitates bone mineralisation.3,4

How much vitamin D is needed?

Assuming no or minimal sunlight exposure, the recommended daily adequate intake (AI) of vitamin D in Australia is 5 micrograms (200 IU) for children, adolescents and adults aged 19–50 years, 10 micrograms (400 IU) for adults aged 51–70 years, and 15 micrograms (600 IU) for adults over 70 years of age.5

Vitamin D is found in small amounts in animal-sourced foods, such as oily fish, eggs and meat. Vitamin D is also added to fortified foods such as fortified milk and margarine.5,6

The Food and Nutrient Database for Dietary Studies (FNDDS) Nutrient Values Database (accessible via FoodData Central) can be used as a guide to see how much vitamin D is found in different food sources.

However, for most Australians, vitamin D intake through dietary sources alone is insufficient.5,6

The main source of vitamin D in humans is vitamin D3 (cholecalciferol), which is formed through the action of ultraviolet B (UVB) radiation on 7-dehydrocholestrol in the skin.5,6

How much sun is needed?

The amount of sun needed to produce enough vitamin D depends on the time of day, a person’s skin type and the amount of skin exposed.3

Considerable variation in vitamin D levels can also result from geographical differences and seasonal changes in sun exposure, making it difficult to recommend an amount of sun applicable to the population as a whole.3

The Cancer Council website has more information on vitamin D production and sun exposure.

 

Vitamin D deficiency

In Australia, 23% of people are estimated to have vitamin D deficiency.7

Older adults are particularly at risk, due to the age-related decline in the skin’s ability to synthesise vitamin D3 from the sun.3

The association between vitamin D deficiency and bone disease is well established.2,3 Vitamin D deficiency can cause osteomalacia and rickets (softening of the bones) in children and contribute to osteoporosis and fragility fractures.2,3

An association between vitamin D deficiency and other health conditions has also been identified, including cancer and cardiovascular, respiratory, gastrointestinal, neurological, metabolic and skin conditions.2

Vitamin D deficiency is typically diagnosed by measuring circulating 25[OH]D levels.4 However, measuring vitamin D status consistently can be difficult and results from different immunoassays can be highly variable.8,9

This has contributed to some controversy regarding the appropriate level of vitamin D required to maintain optimum health.9,10

To support health professionals in their clinical decision making, Australian Therapeutic Guidelines recommend the following serum 25[OH]D concentrations to classify vitamin D deficiency:4

  • mild = 30 to 49 nmol/L
  • moderate = 12.5 to 29 nmol/L
  • severe = lower than 12.5 nmol/L.
 

Who should be tested for vitamin D deficiency?

Australian Therapeutic Guidelines on disorders of bone and calcium homeostasis only recommend vitamin D testing for people at heightened risk of vitamin D deficiency.4

This includes people who have:4

  • limited skin exposure to UVB radiation from sunlight (due to lifestyle factors, chronic illness or hospitalisation)
  • dark skin
  • fat malabsorption conditions (such as coeliac disease or inflammatory bowel disease)
  • medical conditions (such as obesity, end-stage liver disease or kidney disease) or take medicines (such as rifampicin or antiepileptics) that affect vitamin D metabolism and storage.

Routine testing of people who are not at risk is likely to identify people with low vitamin D levels who are otherwise healthy, potentially leading to vitamin D supplementation without evidence to support its benefits for this population.8

Vitamin D testing higher than expected

A 2014 Department of Health MBS review reported that the number of MBS claims for vitamin D testing increased each year over the 10 years between 2003–4 and 2012–13.11

Although, testing volumes initially decreased following the introduction of new items with specific appropriate use criteria in 2014, a report for the MBS Review Taskforce by the Diagnostic Medicine Clinical Committee in 2018 found that the overall use of vitamin D testing was still higher than expected.12

As a result, the Committee has recommended that the MBS make a a number of key changes to vitamin D testing.12

  • Reserve vitamin D testing for patients who have, or are at risk of having, both vitamin D deficiency and bone disease.
  • Create an explanatory note that details the various conditions and circumstances that may place a patient at risk of bone disease or vitamin D deficiency, therefore warranting testing.
  • Apply a 12-month frequency restriction on the testing of 25-hydroxyvitamin D.
  • Create a new item to allow for additional vitamin D testing for patients with confirmed vitamin D deficiency and bone disease, with a 3-month frequency restriction.
 

Who should receive vitamin D supplementation?

Australian Therapeutic Guidelines recommend supplementation only for people who have confirmed vitamin D deficiency (serum 25[OH]D below 50 nmol/L).4

This includes asymptomatic people with vitamin D deficiency. Clinical features of osteomalacia may be absent in adults and may not appear until serum 25(OH)D levels fall below 20 nmol/L.4

In Australia, guidelines recommend vitamin D3 supplementation at 25–50 micrograms (1000–2000 IU) per day for people with mild vitamin D deficiency.4

For moderate to severe deficiency, vitamin D3 supplementation is recommended at 75–125 micrograms (3000–5000 IU) per day for 6–12 weeks, or 1250 micrograms (50,000 IU) once a month for 3–6 months.4

All patients are recommended to maintain a total daily calcium intake of 1300 mg.4

Serum 25(OH)D concentrations should be maintained at 50 nmol/L or more at the end of winter or early spring in the general population, and 75 nmol/L or more in people diagnosed with osteoporosis.4

Supplementation in healthy people

Australian Therapeutic Guidelines advise that people with serum 25(OH)D concentrations of 50–75 nmol/L are not vitamin D-deficient.4

Vitamin D supplementation is not warranted in this population as there is insufficient evidence that it prevents long-term disease.4

In 2017, Osteoporosis Australia and the Royal Australian College of General Practitioners published updated guidelines on osteoporosis prevention, diagnosis and management in post-menopausal women and men over 50 years of age.13

They recommend against routine vitamin D (and calcium) supplementation in non-institutionalised older people, as the absolute benefit in terms of fracture reduction is low.13

However, they recommend that there is evidence of significant benefit of supplementation in people at risk of deficiency, particularly those who are institutionalised.13

Vitamin D supplementation for older people in care facilities is recommended, to reduce the rate of falls.13 Vitamin D supplementation may reduce the risk of falls by improving muscle strength and functioning.14

 

Vitamin D supplementation: evidence of benefit?

Meta-analyses investigating the effects of vitamin D supplementation on fracture risk reduction have found mixed results.15-18

The most comprehensive meta-analysis to date included 81 randomised controlled trials (53,537 participants) that investigated bone fracture, falls or bone mineral density.15

Most trials in the analysis included community-dwelling women aged 65 years or older who were taking daily vitamin D supplements of more than 800 IU/day.15

The authors concluded that vitamin D supplementation did not prevent fractures or falls, or have clinically meaningful effects on bone mineral density.15

They also found no difference between trials comparing the effect of low-dose (described as ≤ 800 IU/day) and high-dose (> 800 IU/day) vitamin D supplementation on fractures and falls.15

However, most of the trials included in the analysis studied vitamin D supplementation as monotherapy.15 Fracture risk reduction is more likely in people with vitamin D deficiency if vitamin D and calcium supplements are taken together.10,16-21

Furthermore, the majority of trials included people with baseline 25(OH)D levels of less than 50 or 75 nmol/L. The authors acknowledged that only four trials (6%) reported mean baseline 25(OH)D concentrations of less than 25 nmol/L and additional trials in populations with lower baseline levels may have produced different results.15

Non-musculoskeletal health outcomes

There is limited high quality evidence to support vitamin D supplementation for people with non-musculoskeletal health conditions.22,23

Results from randomised controlled trials are inconsistent and most of the evidence is drawn from observational studies.23

Therefore, associations between vitamin D levels and musculoskeletal health outcomes may be due to reverse causality (that is, low vitamin D levels are a consequence rather than a cause of disease) as well as other confounding variables, such as obesity, physical activity and smoking.23

 

Adverse effects of supplementation

Too much vitamin D can cause toxicity. Hypercalcaemia is the most common adverse effect resulting from excess vitamin D intake. It is characterised by nausea, dehydration, constipation and hypercalciuria.24

However, vitamin D toxicity is generally associated with large doses of vitamin D (10,000 IU/day) when taken for prolonged periods in patients with normal gut absorption or in those with concurrent excessive intakes of calcium.24

In randomised controlled trials, high-dose oral vitamin D supplements increased, rather than decreased, the risk of falls.13,25,26

 

Conclusions

Although vitamin D plays a significant role in the maintenance of musculoskeletal health, evidence does not support the use of vitamin D supplementation to maintain musculoskeletal health for healthy people.

Current recommendations are:

  • to reserve vitamin D supplementation only for people with confirmed vitamin D deficiency, and 
  • to undertake vitamin D testing only for people at increased risk of deficiency.


Based on the current evidence, these recommendations are appropriate.

Health professionals should consider concurrent calcium supplementation to reflect current evidence and recommendations.

 

Information for consumers

  • Vitamin D has an important role helping the body absorb calcium from the diet. Calcium keeps our bones and muscles healthy and strong.
  • Low levels of vitamin D (vitamin D deficiency) can lead to bones becoming more fragile and prone to breaking.
  • Some people are more at risk of vitamin D deficiency than others, including those who don’t leave the house, have naturally dark skin, wear clothing that covers most of their bodies, or have medical conditions such as obesity, end-stage liver disease or kidney disease.
  • If you are at risk of vitamin D deficiency, a vitamin D test may help your doctor decide whether supplements are needed. If you are not at risk, a test is not usually recommended.
  • Most people can get adequate vitamin D by exposing their skin to sunlight. In the summer, most adults will get adequate vitamin D by doing day-to-day outdoor activities, such as walking, gardening and cycling.
  • Small amounts of vitamin D can be obtained from eating foods like oily fish and eggs. However, people are unlikely to get their recommended amount of vitamin D through diet alone.
 

References

  1. Osteoporosis Australia Medical and Scientific Advisory Committee. Supplementation. Sydney: Osteoporosis Australia, 2014 (accessed 28 March 2019).
  2. Sahota O. Understanding vitamin D deficiency. Age Ageing 2014;43:589-91.
  3. Joshi D, Center JR, Eisman JA. Vitamin D deficiency in adults. Aust Prescr 2010;33:103-6.
  4. Endocrinology Expert Group. Therapeutic Guidelines: Bone and metabolism: Vitamin D deficiency. West Melbourne: Therapeutic Guidelines Ltd, 2014 (accessed 30 January 2019).
  5. National Health and Medical Research Council. Nutrient reference values for Australia and New Zealand: Vitamin D. Canberra: Commonwealth of Australia, 2019 (accessed 28 March 2019).
  6. Nowson C, McGrath J, Ebeling P, et al. Vitamin D and health in adults in Australian and New Zealand: A position statement. Med J Aust 2012;196:686-7.
  7. Australian Bureau of Statistics. Australian Health Survey: Biomedical results for nutrients, 2011-12. Canberra: Commonwealth of Australia, 2013 (accessed 8 February 2019).
  8. Royal College of Pathologists of Australasia. Position statement: Use and interpretation of vitamin D testing. Sydney: RCPA, 2013 (accessed 6 February 2019).
  9. Spector TD and Lewis L. Should healthy people take a vitamin D supplement in winter months? BMJ 2016;355:i6183.
  10. Winzenberg T, Mei I, Mason R, et al. Vitamin D and the musculoskeletal health of older adults. Aust Fam Physician 2012;41:92-9.
  11. Australian Government Department of Health. MBS Reviews: Vitamin D testing. Canberra: Department of Health, 2014 (accessed 2 May 2019).
  12. Medicare Benefits Schedule Review Taskforce. Report from the Diagnostic Medicine Clinical Committee. Canberra: Department of Health, 2018 (accessed 13 February 2019).
  13. Royal Australian College of General Practitioners and Osteoporosis Australia. Osteoporosis prevention, diagnosis and management in postmenopausal women and men over 50 years of age. East Melbourne: RACGP, 2017 (accessed 5 February 2019).
  14. Kalyani R, Stein B, Valiyil R, et al. Vitamin D treatment for the prevention of falls in older adults: Systematic review and meta-analysis. J Am Geriatr Soc 2010.
  15. Bolland M, 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;6:847-58.
  16. Avenell A, Mak J, O'Connell D. Vitamin D and vitamin D analogues fo preventing fractures in post-menopausal women and older men. Cochrane Database Syst Rev 2014;Apr 14:CD000227.
  17. Tang B, Eslick G, Nowson C, et al. Use of calcium or calcium in combination with vitamin D supplementation to prevent fractures and bone loss in people aged 50 years and older: A meta-analysis. Lancet 2007;370:657-66.
  18. Boonen S, Lips P, Bouillon R, et al. Need for additional calcium to reduce the risk of hip fracture with vitamin D supplementation: Eevidence from a comparative metaanalysis of randomized controlled trials. J Clin Endocrinol Metab 2007;92:1415-23.
  19. The DIPART (viamin D Individual Patient Analysis of Randomized Trials) Group. Patient level pooled analysis of 68 500 patients from seven major vitamin D fracture trials in US and Europe. BMJ 2010;340:b5463.
  20. Avenell A, Gillespie W, Gillespie L, et al. Vitamin D and vitamin D analogues for preventing fractures associated with involutional and post-menopausal osteoporosis. Cochrane Database Syst Rev 2005;Jul 20:CD000227.
  21. Ewald D. Osteoporosis: Prevention and detection in general practice. Aust Family Physician 2012;41:104-8.
  22. Gandini S, Boniol M, Haukka J, et al. Meta-analysis of observational studies of serum 25-hydroxyvitamin D levels and colorectal, breast and prostate cancer and colorectal adenoma. Int J Cancer 2011;128:1414-24
  23. Scientific Advisory Committee on Nutrition. Vitamin D and health. London: Public Health England, 2016 (accessed 7 February 2019).
  24. Kennel K, Drake M, Hurley D. Vitamin D deficiency in adults: Who to test and how to treat. Mayo Clin Proc 2010;85:752-8.
  25. Sanders K, Stuart A, Williamson E, et al. Annual high-dose oral vitamin D and falls and fractures in older women: a randomized controlled trial. JAMA 2010;18:1815-22.
  26. 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;176:175-83.