combined calcium and vitamin D supplements in osteoporosis

Last edited 03/2024

  • combined calcium and vitamin D supplements - 400-800 units vitamin D and upto 1 gram of elemental calcium per day - has been shown to be effective in preventing hip fractures in the frail elderly aged 75 years and over
  • serum calcium should be checked before starting supplementation, but it is not necessary to routinely check calcium afterwards (2)
  • groups that have been recommended to have combined calcium and vitamin D supplementation (2):
    • over 70s in residential care
    • patients with a history of recurrent falls
    • a patient who has a history of a fragility fracture
    • older patients with significant oral steroid use e.g. prednisolone 5mg or higher daily for three months
    • patients taking bisphosphonates - in the major trials where efficacy of bisphosphonates has been demonstrated also gave calcium, and in all studies patients were vitamin D replete

A review commentary (3) stated that "..calcium plus vitamin D remains the cornerstone of prevention of fractures in elderly people and patients with osteoporosis". The doses of calcium and vitamin D were suggested as calcium >= 500mg per day and vitamin D >= 800 IU per day.

However the evidence about the effectiveness of calcium and vitamin D has been conflicting and there have been some negative studies (4,5,6) concerning the effectiveness of calcium and vitamin D supplementation in patients at risk of fractures.

There are more conflicts in the evidence base seen in meta-analysis data:

Meta-analysis by Bischoff-Ferrari concluded that oral vitamin D prevents non-vertebral and hip fractures in patients >= 65 years of age (7)

  • Vitamin D supplementation in patients >= 65 years of age
    • a meta-analysis by Bischoff-Ferrari (7) et al revealed that oral vitamin D prevents non-vertebral and hip fractures in a dose dependent manner in patients >= 65 years of age
      • the study authors identify that vitamin D dose is the most important factor and emphasise that only studies that assess 25-hydroxyvitamin D concentractions can be considered reliable. This point applies equally well to clinical practice - poor adherence or malabsorption can be detected by this simple precaution.
      • the overall conclusion is that 400 IU is the minimum daily dose likely to benefit individuals >= 65 years of age
      • the findings suggest that it is more effective and economical to prescribe cholecalciferol (unhydroxylated form for vitamin D3) than ergocalciferol (vitamin D2)
      • the authors note that it is difficult to assess the value of calcium prescribed with vitamin D supplements
        • note also that the analysis included persons living independently and in institutions - this makes it difficult to determine the extent which increased physical activity might reduce the need for vitamin D supplementation
          • a study also concluded that findings do not support routine oral supplementation with calcium and vitamin D3, either alone or in combination, for the prevention of further fractures in previously mobile elderly people (6)

A further meta-analysis examined the association between calcium or Vitamin D supplementation and fracture incidence in community-dwelling older adults and found

  • no evidence of reduced fracture incidence associated with calcium and/or vitamin D supplementation(8):
    • meta-analysis of 33 randomized clinical trials that included 51145 participants, the use of supplements that included calcium, vitamin D, or both was not associated with a significant difference in the risk of hip fractures compared with placebo or no treatment (risk ratio, 1.53, 1.21, and 1.09, respectively)
      • randomized clinical trials comparing calcium, vitamin D, or combined calcium and vitamin D supplements with a placebo or no treatment for fracture incidence in community-dwelling adults older than 50 years
    • use of supplements that included calcium, vitamin D, or both compared with placebo or no treatment was not associated with a lower risk of fractures among community-dwelling older adults
    • the authors state that these findings do not support the routine use of these supplements in community-dwelling older people
    • note though that there are potential limitations to this meta-analysis including:
      • the study is that it did not consider adherence to supplementation, which could affect fracture incidence. Some of the primary studies had adherence rates as low as 55% to 60%
      • control patients may have received supplementation outside of their studies, thereby reducing the difference between the control and intervention groups
      • duration of most studies used in meta-analsysis were 1-2 years duration which may be too short to reveal reduction in fracture outcomes

Long-Term Effect of Randomization to Calcium and Vitamin D Supplementation on Health in Older Women

  • in post-hoc analysis of 7-year RCT (n=36,282 postmenopausal) (9):
    • supplementation (400mg elemental calcium + 400 IU vitamin D vs placebo) seemed to reduce cancer mortality (HR 0.93, 95%CI 0.87-0.99) & increase CVD mortality (1.06, 1.01-1.12) after more than 20 years of follow-up
      • there was no effect on all-cause mortality

SIGN guidance states (10):

  • calcium and vitamin D treatment either alone or in combination are not recommended for prevention of fractures among community-dwelling postmenopausal women and older men
  • calcium and vitamin D treatment may be considered for frail older people, for example nursing care residents, who are at high risk of vitamin D deficiency to reduce the risk of non-vertebral fractures
  • is not necessary to measure an individual’s serum vitamin D level unless there is a clinical concern of osteomalacia
  • is important to ensure patients taking antiresorptive therapy have sufficient calcium and vitamin D intake, through assessment of diet and supplementation with calcium/vitamin D or vitamin D alone accordingly

Notes:

  • although the BNF states that pharmacological doses of vitamin D require monitoring, supplementation with 1-1.2g of elemental calcium and 800 iu of vitamin D, as suggested by many regimes for osteoporosis does not usually require routine monitoring of serum calcium levels. However patients receiving pharmacological doses of vitamin D should have the plasma-calcium concentration whenever nausea or vomiting are present (9). Also caution should be taken on the use of calcium and vitamin D supplementation with thiazide diuretics (which may themselves cause hypercalcaemia)

Reference:

Related pages:

calcium supplementation in osteoporosis

osteoporosis

vitamin D

cholecalciferol

ergocalciferol

dietary calcium and risk of fracture in osteoporosis