How Should GPs Assess Vitamin D Deficiency?

New National vitamin D guidelines from the National Osteoporosis Society

(New guidelines on vitamin D supplementation have been published by the National Osteoporosis Society. These have been endorsed by the Royal College of Nursing, Bone Research Society, British Dietetic Association, Paget's Association., International Osteoporosis Foundation, UK Clinical Pharmacology Association, Primary Care Rheumatology Society, Royal Pharmaceutical Society, British Orthopaedic Association, Society for Endocrinology)

Vitamin D and Bone Health: A Practical Clinical Guideline for Patient Management

These guidelines do not address supplementation in pregnant women, although this is covered in NICE guidance.

The importance of vitamin D guidelines

Guidelines to ensure adequate vitamin D levels are important because in the UK we become vitamin D deficient every year between October and April. Many high-risk frail people are also housebound throughout the year. People who have had a previous skin cancer will have been advised not to sunbathe, and others may be on medications (such as amiodarone) that are a contra-indication to sunbathing.

Rickets, a disease associated with Victorian times, is now returning so efforts to combat the condition are needed. Furthermore, vitamin D repletion is important to ensure efficacy of bone-strengthening treatments in our aging population, as is calcium repletion.

Most elderly patients have dietary deficiency of calcium either because they are trying to cut down their cholesterol, or are too poor on a pension to eat properly. The housebound /residential care home patients rarely get out, even when the sun occasionally shines. For drugs like Denosumab and zoledronate it is often part of agreed protocols that the vitamin D level has to be >50 nmol/L to give the drug. Simply by correcting vitamin D deficiency you can make people feel better, sometimes relieve myalgia (especially in patients on aromatase inhibitors), and improve muscle strength reducing risk of falls and fracture, as well as ensuring the efficacy of the active treatment.

The British National Formulary (BNF) now lists a variety of vitamin D formulations: alone or in combination with calcium. Most people don't like taking calcium + vitamin D tablets because they are too gritty, 'taste like chalk', 'are too sweet',or give constipation and/or headaches. Some patients stopped taking calcium + vitamin D supplements after publication of Prof Ian Reid's Meta analysis. This showed that if you had enough calcium in your diet (>700 mg calcium/day) and you took calcium and vitamin D supplements, you had a 40% increased risk of heart attack and stroke ( There is still huge controversy about calcium supplementation versus dietary intake, which this guideline neatly sidesteps.

There are some new high-dose vitamin D (cholecalciferol or vitamin D3) listed in the BNF so that GPs can prescribe vitamin D3 alone on an FP10, to correct vitamin D deficiency (InVita D3 50,000 IU once a week for 6-8 weeks and re-check, or the 3,200 IU Fultium once daily for 6-8 weeks and recheck) or a maintenance dose (Fultium 800 IU once daily, or Invita D3 25,000 IU once a month): the advantage of this for our frail elderly population is the medication can go in the Nomad, so improving concordance, rather than an over the counter preparation which will be forgotten about.

It should be noted that Fultium contains peanut oil so is not suitable for people with peanut allergies. InVita D3 contains olive oil. It should also be noted that BOTH preparations are made from irradiation of lanolin from sheep's wool so may be unacceptable to vegans.

How should GPs assess vitamin D deficiency?

Vitamin D is essential for musculoskeletal health. It is required for optimal mineral metabolism and the control of calcium and phosphate homeostasis, it promotes calcium absorption from the bowel, enables mineralisation of newly formed osteoid tissue in bone and plays an important role in muscle function. 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.

Who to test for vitamin D deficiency

Vitamin D testing should be prioritised to those patients where the outcome will alter clinical management:

1. Patients with bone diseases that may be improved with vitamin D treatment

Correcting vitamin D deficiency is essential for patients with osteomalacia and is beneficial for patients with osteoporosis. This does not mean that patients with osteoporosis should undergo routine vitamin D testing. calcium and vitamin D3 supplementation is common practice in those on treatment for osteoporosis, and testing vitamin D levels in patients where the decision has been made to co-prescribe is unlikely to change patient management.

2. Patients with bone diseases, prior to specific treatment where correcting vitamin D deficiency is appropriate

Ensuring patients receiving potent antiresorptive osteoporosis treatments (denosumab or zoledronate) are not vitamin D deficient before starting treatment is required to avoid the development of hypocalcaemia.

3. Patients with musculoskeletal symptoms that could be attributed to vitamin D deficiency

Symptoms of vitamin D deficiency are unfortunately vague and it can be difficult to ascertain whether a low serum 25OHD level is causal or a surrogate marker (e.g. of poor nutrition or a lack of outdoor activity). Nonetheless, if patients are suspected of having symptoms caused by osteomalacia, or have chronic widespread pain, a case can be made to measure vitamin D as part of their clinical and laboratory evaluation.

Who to treat

The recommended definition of deficiency made for adopting into UK practice is:

•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 almost the whole population.

Following measurement of serum 25OHD it is recommended that patients found to be deficient (<30 nmol/L) are treated. Within the potentially inadequate range (30-50 nmol/L) further patient groups are defined that would warrant treatment:

•fragility fracture, documented osteoporosis or high fracture risk

•treatment with antiresorptive medication for bone disease

•symptoms suggestive of vitamin D deficiency

•increased risk of developing vitamin D deficiency in the future because of reduced exposure to sunlight, religious dress code, dark skin, etc

•raised parathyroid hormone levels

•medication with antiepileptic drugs or oral glucocorticoids

•conditions associated with malabsorption.

In patients whose tests show they have sufficient vitamin D levels (>50 nmol/L) the recommendations are to give lifestyle advice on maintaining adequate vitamin D levels through safe sunlight exposure and diet. For more information, see What advice should nutrition and exercise? within the Initiationsection of this resource

How to treat vitamin D deficiency

The key aims of treatment are:

•using adequate doses to ensure correction of vitamin D deficiency (to > 50 nmol/L)

•timely reversal of the clinical consequences of vitamin D deficiency

•avoiding toxicity.

Oral vitamin D3 is recommended as 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), 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 6 to 10 weeks

•maintenance therapy comprising vitamin D in doses equivalent to 800-2000 IU daily (occasionally up to 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.

Monitoring patients after treatment

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. This causes hypercalcaemia which would be exacerbated by the high-dose vitamin D supplement.

Routine follow-up vitamin D blood tests are generally unnecessary unless vitamin D deficiency symptoms continue, a patient has malabsorption problems or it is likely they have not been taking the prescribed supplements.

How Should GPs Assess Fracture Risk?

The 'gold standard' for diagnosing osteoporosis is by measuring bone mineral density (BMD) using dual X-ray absorptiometry (DXA) and comparing the patient's result with that of a young adult of the same sex. In terms of standard deviations relative to the young adult normal, this is known as the T-score. BMD measurement is an important part of clinical decision-making and more information about the role of DXA scanning is given in 'How should GPs use bone densitometry?'. Bone density, however, is not the only indicator for fracture risk and 25% of women suffering a hip fracture do not have a T-score in the osteoporotic range. Age, previous history of fragility fracture and family history are risk factors for future fractures, independent of BMD. When using a fracture risk assessment tool, the National Osteoporosis Society recommends assessing BMD before commencing treatment.

There are several fracture risk assessment tools, including FRAX(r) and QFracture, in the NICE short clinical guideline CG146 - Osteoporosis: Assessing the risk of fragility fracture, published in August 2012. Those at risk should be identified opportunistically, either because they have already suffered a fracture or because they have a clinical risk factor or disease associated with a low BMD. FRAX(r) is likely to overestimate fracture risk in patients who are already taking an osteoporosis treatment and fracture risk may be underestimated in patients with clinically apparent vertebral fracture, who have had multiple fragility fractures or where there has been high exposure to corticosteroids, alcohol or smoking. More information on the limitations of FRAX(r) is given by the International Society for Clinical Densitometry. As with any assessment tool or guidance, clinical judgement should always be used. The following table, taken from CG146, summarises the risk factors included in both tools (as of April 2012):

  QFracture FRAX
Age 30-84 years 40-90 years
Sex Yes Yes
BMI Yes Yes
Weight Yes Yes
Height Yes Yes
Previous fracture No Yes
Parental history of hip fracture Yes Yes
Smoking Yes Yes
Alcohol Yes


Hormone replacement therapy Yes No
Menopause symptoms Yes No
Endocrine disorders Yes No
Glucocorticoid use Yes Yes
Secondary osteoporosis* No Yes
Asthma Yes No
Cardiovascular disease Yes No
History of falls Yes No
GI malabsorption Yes No
Chronic liver disease Yes No
Rheumatoid arthritis Yes Yes
Type 2 diabetes Yes No
Tricyclic anti-depressants Yes No
BMD (femoral neck T-score/absolute risk No Yes (optional)

*e.g. type 1 diabetes, chronic hyperthyroidism, premature menopause, chronic liver disease, chronic malnutrition, chronic liver disease

Treatment thresholds have been proposed by the National Osteoporosis Guideline Group (NOGG) for use with the FRAX(r) calculated 10-year risks. These are based on fracture risks in the previous Royal College of Physicians guidelines. For more information on the NOGG guideline are available within the Initiation section. QFracture proposes thresholds based on the top 10% at highest risk:

- For women, the cut off for the top 10% at highest risk is 10-year risk of 11.1%

- For men, the cut off for the top 10% at highest risk is 2.6%

How Should GPs Use Bone Densitometry?

Selecting Patients for DXA Scan

BMD, a prior fracture and age are the most powerful contributors to future fracture risk. Consider a scan in any patient at risk of osteoporosis in whom knowledge of BMD may influence management. Your local DXA service is likely to have locally agreed referral criteria to follow and there is also advice from bodies such as NICE (primary and secondary fracture prevention in postmenopausal women), SIGN (management of osteoporosis) and the Royal College of Physicians (corticosteroid guidance). More information about the national guidance available is given in the Initiation section.

It may be helpful to use the FRAX(r) tool to estimate the patient's 10-year fracture probability and the associated NOGG guidance to decide whether DXA referral would be helpful. Even if the fracture risk is very high and the patient definitely requires treatment, it still may be helpful to know their BMD in order to assess the severity of their osteoporosis and as a baseline to monitor their progress.

In many cases, it is clinically appropriate and feasible to send a patient over the age of 75 for a DXA scan, although NICE guidance allows for a diagnosis to be assumed in this age group where this is not the case.

When referring a patient for a DXA scan, the National Osteoporosis Society leaflet Scans and Tests may be helpful.

Repeating DXA Scans in Patients at Risk of Osteoporosis

Most DXA services provide information about the interpretation of the BMD result for an individual patient. If this is not available, it is important to remember that there are other risk factors for fracture that should also be taken into account when interpreting the BMD result. BMD of the femoral neck can be entered into the FRAX(r) probability assessment for a patient who has not already been treated for osteoporosis.

Good practice for reporting DXA scans is outlined in the National Osteoporosis Society Practical Guide Reporting Dual Energy Absorbtiometry Scans in Adult Fracture Risk Assessment.

Repeating DXA Scans in Patients at Risk of Osteoporosis

The decision as to whether and when to repeat a DXA scan will depend on the initial results and the individual patient's circumstances. Factors to take into account are whether the patient has risk factors for accelerated bone loss, such as corticosteroid therapy, medical conditions or treatment predisposing the patient to bone loss, such as inflammatory disease, malabsorption, aromatase inhibitor therapy or recent menopause. It is rarely helpful to repeat DXA scans within 2 years. Repeat measurements should be guided by local service agreements and the advice given at the time of the baseline scan.

Using Follow-up Scans to Monitor Treatment

There is a lack of consensus on this issue. DXA scans are of limited value in assessing response to treatment and a treatment response can rarely be demonstrated in less than 2 years. This is because the changes in BMD in response to treatment are small and slow and similar in magnitude to the error of the DXA measurement. However, repeat measurement of BMD can provide positive reinforcement to encourage continued compliance with treatment and is helpful in identifying patients who are not responding adequately to treatment.

What Other Investigations are Important?

As well as a DXA scan, the following additional tests should be carried out routinely to exclude secondary causes of osteoporosis:

•History and physical examination

•Blood cell count, sedimentation rate or C-reactive protein, serum calcium, albumin, creatinine, phosphate, alkaline phosphatase, liver transaminases

•Thyroid function test

How Should GPs Assess Falls Risk?

Ask opportunistically - annually if possible - about the number and characteristics of any falls in older patients, especially those aged over 75 years.

Patients with a fragility fracture who present with a fall are at highest risk of subsequent falls and should undergo a falls risk assessment. Those at highest risk are those with two or more falls in the previous year or a single fall plus a disorder of gait and/or balance (such as a postural instability, a failed 'get up and go' test, regular use of a walking aid, a history of stroke or Parkinson's disease), and those with a fall resulting in injury (such as a fracture). These should be offered a falls service referral but many will decline and the GP may have to pragmatically address the obvious risk factors for falls noted in the initiation section of this website. Another group that should be offered specialist assessment are those with a falls associated with syncope or with loss of consciousness to exclude underlying cardiac or neurological causes.

The key components of falls risk assessment in general practice would include medication review, visual acuity, vitamin D status, cognitive function, exercise recommendations, environmental check, check for postural hypotension and mobility assessment e.g. timed 'get up and go' test.

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