Dr Claire Bowring explains how the National Osteoporosis Society guideline for vitamin D and bone health will help to inform decisions about testing and supplementation
Osteoporosis is a long-term condition and the most common bone disorder.1 The clinically important outcomes of osteoporosis are fragility fractures—most commonly of the hip, wrist, and spine. These fractures bring significant personal and financial costs:
- for women older than 60 years of age, fragility fractures account for more days spent in hospital than many other chronic diseases2
- patients with hip fractures occupy more than 1 in 5 orthopaedic beds,2,3 and the incidence of 89,000 hip fractures a year is predicted to rise to 140,000 by 2036,4 which will result in substantial increases in morbidity and mortality
- the healthcare and social care costs associated with hip fractures are conservatively estimated to be in excess of £2.3 billion per year4
- thirty percent of patients with hip fractures die within 1 year, and more than 50% remain permanently disabled, with an impaired quality of life compounded by fear of falling.2
Vitamin D and bone health
Vitamin D is essential for musculoskeletal health. It is required for optimal mineral metabolism, and for control of calcium and phosphate homeostasis. It also promotes calcium absorption from the bowel, enables mineralisation of newly formed osteoid tissue in bone, and plays an important role in muscle function.5,6 Rickets in children and osteomalacia in adults are the main manifestations of vitamin D deficiency. Less severe vitamin D deficiency may lead to secondary hyperparathyroidism, bone loss, muscle weakness, falls, and fragility fractures in older people.7-11
Interest is growing in vitamin D, not only for its role in maintenance of bone health, but also in terms of its potential role in prevention of non-skeletal disorders, for example:
- autoimmune disease
- mental health problems
- cardiovascular disease.
Although there is no universal consensus on the biochemical criteria for vitamin D deficiency, it is common in the UK, particularly in older people. Awareness that vitamin D deficiency may contribute to the development of osteoporosis and to falls and fractures has resulted in a dramatic increase in requests for measurements of 25-hydroxyvitamin D (25OHD) in serum.
The need for a guideline
‘The sunlight campaign’ by the National Osteoporosis Society12 has been raising public awareness of the key role of
vitamin D in good bone health for more than 6 years. The National Osteoporosis Society was the first organisation in the UK to recommend that people should spend a short time outdoors in the summer sun to increase their levels of vitamin D. Bringing together a wide range of organisations with an interest in vitamin D and sun exposure, the National Osteoporosis Society was able to bring consensus13 to messages from the bone, cancer, and dermatology specialties, which agreed that safe exposure to the sun is vital for production of vitamin D.
The lack of national guidance on the indications for vitamin D measurements, on interpretation of the results, and on correction of vitamin D deficiency has resulted in confusion among patients and healthcare professionals, and a proliferation of conflicting guidelines and inconsistent practice across the UK. As a result, the National Osteoporosis Society has led the way by developing a practical clinical guideline on the management of vitamin D deficiency in adult patients with (or at risk of developing) bone disease.14
Remit of the guideline
An expert group of clinicians and scientists with expertise in vitamin D and osteoporosis was convened to develop a guideline14 with two key goals:
- to provide clear recommendations for primary, secondary, and social care health professionals on the treatment of vitamin D deficiency in relation to bone health and on the prevention of fractures
- to assist in the identification of people at risk of vitamin D deficiency and propose effective measurement techniques and reference ranges.
A number of contentious issues are covered in the guideline. Where clear-cut evidence was unavailable, the professional views of leading experts were presented in a pragmatic way.
The guideline did not set out to address the management of vitamin D deficiency in pregnancy, in patients with severe or end-stage chronic kidney disease (CKD stages 4–5), or in childhood.
(NB Vitamin D deficiency in childhood has recently been reviewed by the British Paediatric and Adolescent Bone Group,15 and the National Osteoporosis Society hopes to produce a complementary guideline, focusing on children, in the near future.)
Other potential effects of vitamin D in terms of modulation of immunity, prevention of cancer, and modulation of the risks of cardiovascular disease and multiple sclerosis16 were not within the guideline’s remit.
It is important to highlight that this is a clinical guideline intended to inform patient management, but not to influence public health policy. The latter is the remit of the Department of Health Scientific Advisory Committee on Nutrition (SACN), which is currently reviewing the dietary reference values for vitamin D.17
Who should be tested for vitamin D deficiency?
The number of vitamin D tests being requested has increased in recent years. Vitamin D testing has almost become routine in patients in some areas of the UK when the clinical indications are unclear, whereas there are difficulties obtaining tests for those who may benefit in other areas. This guideline helps to target vitamin D testing to patients for whom the outcome will alter clinical management. See Figure 1, for a schematic representation of broad groups for clinical consideration and decision making with regard to vitamin D supplementation.
Patients with bone diseases—primarily osteomalacia and osteoporosis—are the group identified as most relevant for consideration of vitamin D testing.14 Correction of vitamin D deficiency is essential for patients with osteomalacia and beneficial for those with osteoporosis. This does not mean that patients with osteoporosis should undergo routine vitamin D testing. Supplementation of calcium and vitamin D3 is common practice in individuals receiving treatment for osteoporosis, and testing vitamin D levels in patients in whom the decision to co-prescribe has already been made is unlikely to change their management.14
Although the potential adverse cardiovascular outcomes associated with calcium supplementation are outside the guideline’s remit, it does touch on these and take them into consideration.14
Patients receiving the potent antiresorptive osteoporosis treatments denosumab and zoledronate are one specific group that is highlighted for testing. Ensuring that these patients are not vitamin D deficient before starting treatment is required to avoid the development of hypocalcaemia.14
For patients presenting without musculoskeletal symptoms, routine testing of vitamin D is not recommended.14 Although public health recommendations are strictly outside the remit of this guideline, it is appropriate that the current Department of Health guidance on adult groups at risk of deficiency is reinforced (see Box 1).18
Symptoms of vitamin D deficiency are unfortunately vague and it can be difficult to ascertain whether a low serum 25OHD is causal or a surrogate marker (e.g. of poor nutrition or lack of outdoor activity). However, if patients are suspected of osteomalacia, or have chronic widespread pain, a case can be made to measure serum 25OHD.
Box 1: Department of Health guidance on vitamin D deficiency18
(Please note that references to infants and children have been omitted here as infants and children are not covered by the scope of the National Osteoporosis Society guideline on vitamin D and bone health.14)
Adults at risk of vitamin D deficiency are as follows:
- All pregnant and breastfeeding women, especially teenagers and young women
- Older people aged ≥65 years
- People who have low or no exposure to the sun—for example, those who cover their skin for cultural reasons, who are housebound, or who are confined indoors for long periods
- People who have darker skin—for example, people of African, African-Caribbean, or South Asian origin—because their bodies are not able to make as much vitamin D.
- All pregnant and breastfeeding women should take a daily supplement containing 10 µg (400 IU) vitamin D, to ensure the mother’s requirements for vitamin D are met and to build adequate fetal stores for early infancy
- People aged ≥65 years and those who are not exposed to much sun should also take a daily supplement containing 10 µg (400 IU) vitamin D.
The guideline summarises the recent publications on vitamin D from the Endocrine Society Taskforce and Institute of Medicine, as well as the rationale for their definition of deficiency based on serum 25OHD levels. The recommendations for adopting these into practice in the UK are:14
- serum 25OHD <30 nmol/l is deficient
- serum 25OHD of 30–50 nmol/l may be inadequate in some people
- serum 25OHD >50 nmol/l is sufficient for the remainder of the population.
Who should be treated for vitamin D deficiency?
Following measurement of serum 25OHD, it is recommended that patients found to be deficient (<30 nmol/l) are treated. Within the potentially inadequate range of 30–50 nmol/l, further patient groups in whom treatment is warranted are defined as those who:14
- have fragility fracture, documented osteoporosis, or high risk of fracture
- have symptoms suggestive of vitamin D deficiency
- have increased risk of developing vitamin D deficiency in the future because of reduced exposure to sunlight (e.g. due to religious dress code, dark skin)
- have raised levels of parathyroid hormone
- have conditions associated with malabsorption
- are taking antiepileptic drugs or oral glucocorticoids
- are receiving treatment with antiresorptive medication for bone disease.
In patients whose tests show they are vitamin D sufficient (>50 nmol/l), the recommendations are to give lifestyle advice on maintaining adequate vitamin D levels through safe exposure to sunlight and through diet.
A normal diet supplies only around 10% of a person’s vitamin D; useful food sources include certains types of fish (herring, salmon, pilchards, sardines), some breakfast cereals, and eggs. Fuller details can be found in the NOS leaflet, Healthy living for strong bones (see www.nos.org.uk/~/document.doc?id=981).
How to treat vitamin D deficiency
The key aims of treatment are to:14
- use adequate doses to ensure correction of vitamin D deficiency (>50 nmol/l)
- bring about timely reversal of the clinical consequences of vitamin D deficiency
- avoid toxicity.
A number of factors need to be considered when deciding on the appropriate treatment for vitamin D deficiency, including preparation type, dosing strategy, and monitoring.
Vitamin D3 is the recommended treatment of choice, but guidance is given for supplementation with vitamin D2, as well as vitamin D3. The importance of adherence to treatment is emphasised, and the impact of a person’s personal and religious beliefs on choice of preparation is also addressed. A link to Which vitamin D preparations are suitable for a vegetarian or vegan diet?,19 a document published by UK Medicines Information, is provided alongside the guideline on the National Osteoporosis Society’s website; this document is an excellent resource for information about the available vitamin D preparations, including their licensing, excipients used, and the presence of gelatine. Intramuscular injection of vitamin D may be perceived to be a good choice with respect to adherence, but the guideline recommends oral preparations because of problems with bioavailability among other formulations.14
Example regimens for rapid correction of vitamin D deficiency are provided within the guideline. These are based on fixed loading doses followed by maintenance therapy:14
- a loading regimen to provide a total dose of about 300,000 IU vitamin D should be given as separate weekly or daily doses over 6–10 weeks
- maintenance therapy comprising vitamin D in doses equivalent to 800–2000 IU daily (occasionally up to 4000 IU daily) should be given after the loading regimen—or intermittently if higher doses are to be used.
A month after a loading dose of vitamin D has been given, a calcium blood test is recommended to make sure a patient does not have primary hyperparathyroidism.14,20 This condition causes hypercalcaemia, which would be exacerbated by high-dose vitamin D supplementation.
Routine follow-up tests for vitamin D are generally unnecessary unless symptoms of vitamin D deficiency continue, a patient has malabsorption problems, or if it is likely that they have not been taking the prescribed supplements.
For primary care practitioners who are treating or advising patients, especially those working without local specialist guidance, this guideline will make an important contribution and ensure more confident, competent, and consistent practice. In addition, the guideline provides clarification on a number of issues that can now be communicated to patients: not everyone needs a blood test for vitamin D deficiency, and if you are likely to be deficient, taking vitamin D tablets is a sensible preventative measure. However, in specific situations, appropriate testing will be useful to target more particular regimens to those who need them.
Debates about vitamin D will continue, and alternative international guidelines, with a tendency to target serum 25OHD at more than 75 nmol/l, will continue to give conflicting advice. However the publication of the National Osteoporosis Society’s guideline on vitamin D and bone health provides an opportunity to reflect on, and adapt local procedures to a consistent UK approach, and presents clinically useful information on the current assessment and treatment of vitamin D-associated musculoskeletal disease.
Vitamin D and bone health: a practical clinical guideline for patient management14 has been endorsed by Arthritis Research UK, Bone Research Society, British Dietetic Association, British Geriatric Society, British Orthopaedic Association, International Osteoporosis Foundation, Paget’s Association, Primary Care Rheumatology Society, Royal College of Nursing, Royal Pharmaceutical Society, Royal Society of Medicine, Society for Endocrinology, and United Kingdom Clinical Pharmacy Association.
The National Osteoporosis Society is grateful to the following authors for giving their time and expertise to develop this guideline: Professor Roger Francis (Chair), Dr Terry Aspray, Professor William Fraser, Dr Neil Gittoes, Dr Kassim Javaid, Professor Helen Macdonald, Dr Sanjeev Patel, Professor Peter Selby, Dr Nuttan Tanna, and Dr Claire Bowring.
Stop at One campaign
From October 2013, the National Osteoporosis Society will be launching a UK-wide campaign called Stop at One to raise public awareness of fractures caused by osteoporosis in people aged over 50 years (particularly women, who are most at risk). The charity’s goal is to reduce secondary fractures caused by undiagnosed osteoporosis. The campaign will encourage people who have sustained a fragility fracture to speak to their GP about assessment of their future fracture risk. More information is available on the society’s website: www.nos.org.uk/stopatone
- A.D.A.M. Medical Encyclopedia. Atlanta: A.D.A.M Inc. Osteoporosis—overview: thin bones; low bone density. Available at: www.ncbi.nlm.nih.gov/pubmedhealth/PMH0001400/
- Osteoporosis Resources for Primary Care website. What is the impact of osteoporosis? Available at: www.osteoporosis-resources.org.uk/introduction/3-what-is-the-impact-of-osteoporosis (accessed 28 August 2013).
- Lindsay R. The burden of osteoporosis: cost. Am J Med 1995; 98 (2A); 9S–11S.
- National Osteoporosis Society. 25th anniversary report—a fragile future. Bath: NOS, 2011. Available at: www.nos.org.uk/document.doc?id=904
- Holick M. Vitamin D deficiency. N Engl J Med 2007; 357 (3): 266–281.
- Francis R, Anderson F, Patel S et al. Calcium and vitamin D in the prevention of osteoporotic fractures. QJM 2006; 99 (6): 355–363.
- Bischoff-Ferrari H, Giovannucci E, Willett W et al. Estimation of optimal serum concentrations of 25-hydroxyvitamin D for multiple health outcomes. Am J Clin Nutr 2006; 84 (1): 18–28.
- Bischoff-Ferrari H. Optimal serum 25-hydroxyvitamin D levels for multiple health outcomes. Adv Exp Med Biol 2008; 624: 55–71.
- Lips P. Vitamin D deficiency and secondary hyperparathyroidism in the elderly: consequences for bone loss and fractures and therapeutic implications. Endocr Rev 2001; 22 (4): 477–501.
- Sahota O, Mundey M, San P et al. The relationship between vitamin D and parathyroid hormone: calcium homeostasis, bone turnover, and bone mineral density in postmenopausal women with established osteoporosis. Bone 2004; 35 (1): 312–319.
- Sahota O, Gaynor K, Harwood R, Hosking D. Hypovitaminosis D and ‘functional hypoparathyroidism’—the NoNoF (Nottingham Neck of Femur) study. Age Ageing 2001; 30 (6): 467–472.
- National Osteoporosis Society website. The sunlight campaign. www.nos.org.uk/page.aspx?pid=535 (accessed 26 August 2013).
- National Osteoporosis Society. Consensus vitamin D position statement. Bath: NOS, 2010. Available at: www.nos.org.uk/document.doc?id=945
- National Osteoporosis Society. Vitamin D and bone health: a practical clinical guideline for patient management. Bath: NOS, 2013. Available at: www.nos.org.uk/document.doc?id=1352
- Arundel P, Ahmed S, Allgrove J et al. British Paediatric and Adolescent Bone Group’s position statement on vitamin D deficiency. BMJ 2012; 345: e8182.
- Rosen C, Adams J, Bikle D et al. The nonskeletal effects of vitamin D: an Endocrine Society scientific statement. Endocr Rev 2012; 33 (3): 456–492.
- Scientific Advisory Committee on Nutrition website. Call for evidence—SACN review of vitamin D. www.sacn.gov.uk/news_press_releases/latest_news/call_for_evidence_-_sacn_review_of_vitamin_d.html (accessed 26 August 2013).
- Department of Health. Vitamin D—advice on supplements for at risk groups—letter from UK Chief Medical Officers. London: DH, 2012. Available at: www.gov.uk/government/publications/vitamin-d-advice-on-supplements-for-at-risk-groups
- UK Medicines Information. Which vitamin D preparations are suitable for a vegetarian or vegan diet? London: London Medicines Information Service, 2011. Available at: www.medicinesresources.nhs.uk/upload/NHSE%20QA%20Vitamin%20D%20-%20vegetarians%20and%20vegans%20387.2%20FINAL.doc
- Hannan F, Fairney A, Johnston D. Vitamin D deficiency masking primary hyperparathyroidism. Ann Clin Biochem 2004; 41 (5): 405–407.
- van Staa T, Dennison E, Leufkens H, Cooper C. Epidemiology of fractures in England and Wales. Bone 2001; 299 (6): 517–522. G