The role of vitamin D in the management of osteoporosis came under the spotlight recently after a study reviewed the results of 81 research trials of people aged 18 or over taking vitamin D supplements. It found no reduction in fractures or falls and no improvement in bone density in people taking the supplements and recommeded guidelines were adapted.
Leading osteoporosis experts recently issued a statement with the National Osteoporosis Society (NOS) stressing that the current advice for vitamin D in bone health has not changed after a review concluded that vitamin D supplements do not strengthen bones or prevent broken bones.
The new meta-analysis of 81 randomised trials was published in The Lancet Diabetes & Endocrinology journal1 and found no differences in the effects of higher versus lower doses of vitamin D.
In the study, the authors pooled data from 81 randomised controlled trials. The majority of the trials studied vitamin D alone (ie, not prescribed in conjunction with calcium supplements) and were of one year or less. Most included women aged over the age of 65 (77% of trials) who lived in the community and who received daily doses of more than 800 IU per day (68% of trials).
In addition, more than half of the trials were done in populations with baseline concentrations of 25-hydroxyvitamin D (25OHD) of less than 50nmol/L (a cut-off often considered to indicate low vitamin D levels), but only 6% were done in populations with vitamin D deficiency (a baseline 25OHD of less than 25nmol/L). The majority of trials (91%) reported achieving 25OHD concentrations of 50nmol/L or more, and about half reported achieving 25OHD concentrations of 75nmol/L or more.
There was no clinically meaningful effect of vitamin D supplementation on total fracture, hip fracture, or falls. There was evidence that vitamin D does not reduce total fractures, hip fractures, or falls by 15%—a clinically meaningful threshold. Even when lower thresholds were assessed, there was still reliable evidence that vitamin D does not reduce falls by 7.5% and total fractures by 5%.
In secondary analyses looking at bone density, there were small differences for lumbar spine, femoral neck, and for total body, but none of these were clinically relevant. In addition, the authors conducted more than 60 subgroup analyses to verify their findings.
The authors concluded that there is therefore little justification to use vitamin D supplements to maintain or improve musculoskeletal health, except for the prevention of rare conditions such as rickets and osteomalacia in high-risk groups, which can occur due to vitamin D deficiency after a prolonged lack of exposure to sunshine.
They said: “Our findings suggest that vitamin D supplementation does not prevent fractures or falls, or have clinically meaningful effects on bone mineral density. There were no differences between the effects of higher and lower doses of vitamin D. There is little justification to use vitamin D supplements to maintain or improve musculoskeletal health. This conclusion should be reflected in clinical guidelines.”
Leading osteoporosis experts have questioned the significance of the findings and reiterated it does not change current guidance, advising that people at risk of vitamin D deficiency should continue to take their supplements.2
They said that a large number of subjects included in the review had what are considered to be normal levels of vitamin D in the UK, so only 6% of subjects were actually considered deficient in vitamin D with the majority being generally healthy and mobile adults at very low risk of breaking bones.
It said that these findings were not really applicable to people who are at high risk of fracture, for whom it is especially important to get the vitamin D they need.
The NOS was quick to point out that although there is an increasing consensus that taking supplements of calcium and vitamin D alone does not reduce falls and fracture risk, there are also some people who are at risk of vitamin D deficiency, including those who don’t get out in the sunlight very often, who may benefit from a vitamin D supplement—especially during the winter months.
It added that where people are at high risk of fracture, drugs are recommended that have evidence demonstrating fracture prevention. Calcium and vitamin D supplements are also commonly prescribed ‘to be on the safe side’ and make sure people with osteoporosis are getting everything they need to promote strong bones.
What is vitamin D?
Vitamin D helps to control the amount of calcium and phosphate in our bodies. Both are needed for healthy bones, teeth and muscles.
Vitamin D is found naturally in a small number of foods, including oily fish, red meat, liver and egg yolks. It’s also found in fortified foods like breakfast cereals and fat spreads. However, it’s difficult for us to get the recommended amount of vitamin D from food alone. Our main source of vitamin D is from the action of sunlight on our skin.3
The National Osteoporosis Society recently launched updated practical clinical guidelines on vitamin D to provide clarity for healthcare professionals. Key recommendations are:
Measurement of plasma 25(OH)D is the best way of estimating vitamin D status.
Plasma 25(OH)D measurement is recommended for:
patients with musculoskeletal symptoms that could be attributed to vitamin D deficiency
patients suspected of having bone diseases that may be improved with vitamin D treatment
patients with bone diseases, prior to specific treatment where correcting vitamin D deficiency may be necessary.
In most cases, routine vitamin D testing is unnecessary in patients with osteoporosis or fragility fracture, who may be co-prescribed vitamin D supplementation with an oral antiresorptive treatment.
Following review of the Scientific Advisory Committee on Nutrition (SACN) and Institute of Medicine (IOM) reports, it proposed that the following vitamin D thresholds are adopted by UK practitioners in respect to bone health:
- plasma 25(OH)D <25nmol/L is deficient
- plasma 25(OH)D of 25–50nmol/L may be inadequate in some people
- plasma 25(OH)D > 50nmol/L is sufficient for almost the whole population.
- Oral vitamin D3 is the treatment of choice in vitamin D deficiency.
- Where rapid correction of vitamin D deficiency is required, such as in patients with symptomatic disease or about to start treatment with a potent antiresorptive agent (zoledronate or denosumab or teriparatide), the recommended treatment regimen is based on fixed loading doses followed by regular maintenance therapy:
- a loading regimen to provide a total of approximately 300,000 IU vitamin D, given either as separate weekly or daily doses over six to ten weeks
- maintenance therapy comprising vitamin D in doses equivalent to 800–2,000 IU daily (occasionally up to a maximum of 4,000 IU daily), given either daily or intermittently at higher doses.
- Where correction of vitamin D deficiency is less urgent and when co-prescribing vitamin D supplements with an oral antiresorptive agent, maintenance therapy may be started without the use of loading doses.
- Adjusted plasma calcium is recommended to be checked one month after completing the loading regimen or after starting lower dose vitamin D supplementation in case primary hyperparathyroidism has been unmasked.
- Routine monitoring of plasma 25(OH)D is generally unnecessary but may be appropriate in patients with symptomatic vitamin D deficiency or malabsorption and where poor compliance with medication is suspected.
- Considering optimisation of bone health and the public health agenda, it is important to promote the relevance of adequate dietary calcium intake and consider use of ‘calcium calculators’ to help patients and primary-care clinicians.
- Bolland M, Grey, A, Avenell A. Effects of vitamin D supplementation on musculoskeletal health: a systematic review, meta-analysis, and trial sequential analysis. Lancet Endocrinology 2018; 6(11): 847–58
Managing editor, GM