Alendronate with cholecalciferol (vitamin D3) (Fosamax Plus) — Vitamin D deficiency and supplementation

Published in NPS RADAR

Date published: About this date

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This page contains additional content about the article Alendronate with cholecalciferol (vitamin D3) (Fosamax Plus) for osteoporosis, first published in NPS RADAR in August 2006, and last updated in December 2008.

Vitamin D and deficiency

Vitamin D plays a role in calcium homeostasis, which is regulated by parathyroid hormone.

Cholecalciferol (vitamin D3) is obtained from the diet and produced by the action of sunlight on skin. Vitamin D2 and D3 are hydroxylated in the liver to hydroxyvitamin D (25-OHD), the main circulating metabolite. 25-OHD is further hydroxylated in the kidneys to 1,25-dihydroxyvitamin D (1,25-OH2D), or calcitriol, the active form.1

Vitamin D deficiency: detection, treatment and prevention

While severe vitamin D deficiency manifests clinically, mild to moderate deficiency may not be obvious. Serum 25-hydroxyvitamin D (25-OHD) levels are the best indicator of vitamin D status and should be maintained at 50 nmol/L or more to prevent and treat osteoporosis in older people.2 Note that optimal levels of serum 25-OHD are not universally agreed.3,4

Risk factors for vitamin D deficiency

Deficiency is very common in institutionalised, bed-bound or housebound elderly people (50–80%5,6). Other risk factors for vitamin D deficiency include7:

  • reduced intake or synthesis due to dark skin, or dressing to cover most of the head and body (e.g. veiling)
  • malabsorption disorders
  • reduced synthesis or enhanced degradation of 25-OHD from use of drugs such as rifampicin, phenytoin or multiple anti-epileptic drug therapy, or because of chronic hepatic disorders.

Sources of vitamin D

Adequate vitamin D intake depends primarily on sun exposure, with a minor dietary contribution; recommendations describe 'adequate intake' rather than 'dietary intake', as for other nutrients. The adequate intakes shown in Box 1 assume no sun exposure. Some guidelines suggest higher supplements of at least 800 units for people with inadequate sunlight exposure8,9; and in some cases up to 2000 units per day might be necessary to prevent deficiency (e.g. institutionalised people with reduced food intake).2,8

Patients who are already vitamin D deficient need a vitamin D dosage greater than the adequate intake to replenish depleted stores. Note that vitamin D requirements for people with osteoporosis or those taking anti-resorptive therapy have not been adequately determined.

Box 1: Recommended adequate intakes for vitamin D in adults (NHMRC)*3


Daily intake

Age (years)






*Requirements assuming nil intake through sunlight


Sunlight exposure

Age, skin colour, season and geographical location (hemisphere and latitude) affect the amount of sunlight exposure required.
In Australia, around 1000 units of cholecalciferol is provided by:
  • 5–9 minutes of sun exposure at 10 am or 2 pm in summer
  • 9–12 minutes in Cairns or Townsville, or 40–47 minutes in Hobart, in winter
  • direct exposure to around 15% of body (hands, arms, face), without sunscreen and not through glass.
Older people synthesise vitamin D from sunlight more slowly and may require longer or more frequent exposure.
Advise patients to choose times of low UV activity to avoid skin cancer risk.7

For more information on sunlight exposure and vitamin D see Vitamin D and adult bone health in Australia and New Zealand: a position statement. Med J Aust 2005;182:281–5.

Dietary sources of vitamin D

  • Vitamin D is obtained in the diet from fatty fish, eggs, liver and fortified foods (some milks and margarines).3
  • Average dietary intake in Australia is estimated to be around 100 units/day.3
  • It is unlikely that adequate vitamin D concentrations can be obtained from diet alone for most Australians.7

Vitamin D supplements

Types of vitamin D supplement available in Australia are shown in Box 2.

Box 2: Types of vitamin D supplement


  • Available in 1000-unit supplements (over the counter)


  • Ergocalciferol may be less effective in increasing 1,25-OH2D concentrations than cholecalciferol10, and vitamin D2 is not reliably detected by assays11
  • Not currently available in Australia


  • The active form of vitamin D — does not require conversion in the kidneys
  • Not recommended for vitamin D deficiency, as it has a narrow therapeutic index, a high risk of hypercalcaemia and does not affect serum 25-OHD levels7,11


  1. Sahota O. Osteoporosis and the role of vitamin D and calcium-vitamin D deficiency, vitamin D insufficiency and vitamin D sufficiency. Age Ageing 2000;29:301–4. [PubMed] 
  2. eTG complete [CD-ROM]. Melbourne: Therapeutic Guidelines Ltd, July 2008.
  3.  National Health and Medical Research Council, Department of Health and Ageing. Nutrient reference values for Australia and New Zealand. Canberra: Commonwealth of Australia, 2006. (accessed 23 October 2008).
  4.  Johnson MA, Kimlin MG. Vitamin D, aging, and the 2005 Dietary Guidelines for Americans. Nutr Rev 2006;64:410–21. [PubMed] 
  5. Zochling J, Chen JS, Seibel M, et al. Calcium metabolism in the frail elderly. Clin Rheumatol 2005;24:576–82. [PubMed] 
  6. Flicker L, MacInnis RJ, Stein MS, et al. Should older people in residential care receive vitamin D to prevent falls? Results of a randomized trial. J Am Geriatr Soc 2005;53:1881–8.
  7. Vitamin D and adult bone health in Australia and New Zealand: a position statement. Med J Aust 2005;182:281–5. [PubMed] 
  8. Osteoporosis Australia. Calcium, vitamin D and osteoporosis. A Guide for GPs. 2nd edn. 2008. (accessed 28 October 2008).
  9. Compston J, Cooper A, Cooper C, et al. Guideline for the diagnosis and management of osteoporosis in postmenopausal women and men from the age of 50 years in the UK. Sheffield, UK: National Osteoporosis Guideline Group (NOGG), 2008. (accessed 23 October 2008).
  10. Armas LA, Hollis BW, Heaney RP. Vitamin D2 is much less effective than vitamin D3 in humans. J Clin Endocrinol Metab 2004;89:5387–91. [PubMed] 
  11. Australian Medicines Handbook. Adelaide: Australian Medicines Handbook Pty Ltd, 2008.