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Prescribed Vitamin D and Calcium Preparations in Patients Treated With Bone Remodelling Agents in Primary Care: a Report of a Pilot Study

Posted on: Thursday, 9 February 2006, 06:00 CST

By Bayly, J R; Hollands, R D; Riordan-Jones, S E; Yemm, S J; Et al

Key words: Calcium - Osteoporosis - Therapeutics - Vitamin D

ABSTRACT

Background: Recent guidelines recommend that patients receiving treatment for osteoporosis should also receive supplementation with calcium and vitamin D unless they are calcium and vitamin D replete. Given that the majority of elderly patients have inadequate levels of vitamin D and that determining nutritional status is time- consuming and costly, it seems prudent to ensure that the majority of patients aged over 65 and receiving medication for osteoporosis should receive supplementation as a matter of course.

Objectives: To determine the level of coprescription of calcium and vitamin D in patients receiving treatment for osteoporosis with bisphosphonates, teriparatide, raloxifene or strontium.

Study design and methods: A pilot audit of nine general practices covering a population of 61202.

Results: Overall, 1.1 % (n = 662) of patients were receiving treatment for osteoporosis; of those, only 34.1% of patients were co- prescribed calcium or calcium and vitamin D. Levels of co- prescription varied considerably across practices from 74.0% to 12.2%.

Conclusions: Despite national guidelines, co-prescription of calcium and vitamin D with treatment for osteoporosis remains sub- optimal with considerable variation between practices. Strategies should be adopted to increase physician awareness of widespread vitamin D inadequacy, the rationale for supplementation and poor compliance.

Introduction

A countywide falls and fracture audit in Gloucestershire is being carried out by the Gloucestershire Primary and Community Care Audit Group (PCCAG) throughout 2005 and 2006. The audit will cover data quality, prescribing quality, whether current guidelines (National Institute for Clinical Excellence (NICE)1, and Royal College of Physicians (RCP)2,3) are being followed, falls assessment4 and management, primary prevention of fragility fracture and the management of men with prior fragility fracture. The audit will involve 84 general practices, covering a population of just under 600 000 patients.

This short report covers the level of co-prescribing of calcium and vitamin D in patients receiving treatment for osteoporosis in a pilot group of nine practices (total population 61 202).

The recent NICE guidelines1 state that adequate levels of calcium and vitamin D are needed to ensure optimum effects of the treatments for osteoporosis. Accordingly, they recommend that calcium and/or vitamin D supplementation should be provided unless clinicians are confident that patients receiving osteoporosis treatment have an adequate calcium intake and are vitamin D replete. Other earlier guidance2,5-7 recommends that older patients with osteoporosis receive an adequate intake of calcium and vitamin D.

The guidelines all base their recommendations on the evidence- base for osteoporosis treatments, primarily the bisphosphonates. All randomised controlled fracture end-point trials in osteoporosis have compared treatment (bisphosphonates, teriparatide, raloxifene and strontium) with placebo in patients who were calcium and vitamin D replete.

However, determining whether a patient is calcium and vitamin D replete can be time consuming and costly. The cost for a single vitamin D^sub 3^ assay range is 37, which includes interpretative comments with the results (personal communication). If an assay for 1,25-hydroxy-vitamin D^sub 3^ is required, the cost rises to 70. A structured dietary and life-style assessment to determine calcium intake and likely vitamin D status is, in the opinion of the authors, likely to take several minutes without a guarantee of accuracy, precision and reproducibility without training and expertise.

The recommended nutrient intakes (RNI) for patients aged over 65 years are 700mg/day of calcium and 10g/day vitamin D (equivalent to 400 IU)8. However, national guidance for patients with osteoporosis recommends higher levels of calcium of up to 1000 mg/day2,5. Data from the latest National Diet and Nutrition Survey (NDNS) demonstrate that most people aged over 65 are calcium replete9. Mean daily intake of calcium was 836 mg for men and 690mg for women, representing 119% and 99% of the RNI for men and women, respectively. People living in institutions had higher intakes of calcium. The mean intake was 136% of the RNI in men and 123% in women. However, dietary intake of vitamin D is low in older people and the majority have inadequate levels of vitamin D.

Vitamin D is obtained through the diet, but the majority is obtained through the action of ultraviolet light on the skin. With ageing there is a decline in the skin content of 7- dehydrocholesterol (the precursor to vitamin D) and a consequent reduction in vitamin D production. Optimum dietary intake therefore becomes more important. Data from the NDNS found a mean daily intake of 4.07g/day in men and 2.92g/day in women9. Almost all elderly people living independently (97%) had a vitamin D intake below 10g/ day. 99% of elderly people living in residential and nursing care homes had levels below 10g/day.

Given that dietary intake is not the sole source of vitamin D and that sunlight plays a role in vitamin D generation, at least during the summer months in the UK, measurement of serum vitamin D levels gives a better indication of vitamin D status. There are no generally accepted criteria for vitamin D deficiency. Levels below 20 nmol/L indicate severe deficiency, clinically associated with rickets and osteomalacia10. Recent publications suggest that the optimal level of vitamin D for bone health should be between 50 nmol/ L (=20ng/ml) and 80 nmol/L (32ng/ml)n or higher, and at least 80nmol/ L12.

Data from the Health Survey for England 2000 demonstrate that levels of vitamin D are low in people aged over 65 regardless of their osteoporosis status13. Mean levels of vitamin D in people living independently were 56.2 nmol/L in men aged over 65 and 48.4nmol/L in women aged over 65. The corresponding figures for people living in residential and nursing care homes were 38.1 nmol/ L and 36.7 nmol/L.

Patients with fragility fracture have still lower levels of vitamin D. A recent audit carried out in Glasgow found mean vitamin D levels of 24.7nmol/L in 548 patients with hip fracture and 44.1 nmol/L in 50 patients with non-vertebral fracture14. The prevalence of inadequacy at the 80 nmol/L level was 98.9% in the hip fracture patients and 90% in the patients with nonvertebral fracture. A further audit of 103 patients with hip fracture in London revealed mean vitamin D levels of 32.1 nmol/L and a prevalence of inadequacy of 99% at the 80 nmol/L threshold15.

Given that vitamin D levels are generally low in the elderly and especially so in patients with fragility fracture, particularly at the hip, it would seem prudent to ensure all patients aged over 65 receiving medication for osteoporosis receive supplementation as a matter of course, rather than determining each individual's calcium and vitamin D status. Indeed, it has been recommended that most patients with prior fragility fracture receiving treatment with bisphosphonates or strontium should also receive obligatory supplementation with vitamin D with or without calcium16.

However, there is some controversy over the value of calcium and/ or vitamin D in reducing fracture risk.

Two recently published large-scale studies17,18 did not demonstrate a reduction in fracture rate with supplementation with calcium and/or vitamin D in the absence of treatment with anti- resorptive or other bone remodelling agents. The RECORD trial compared treatment with calcium alone (1000mg/day), vitamin D alone (800IU/day), calcium and vitamin D or placebo in 5292 patients aged over 70 years with fragility fracture17. A further trial compared daily supplementation with calcium (1000 mg) and vitamin D (800 IU) together with a leaflet on falls prevention and dietary advice with the leaflet alone in 3314 women aged over 70 years with risk factors for hip fracture18. A further study of 9440 elderly men and women randomised to an annual injection of vitamin D (300 000 IU) or placebo found an increased risk of hip fracture in those patients in the vitamin D group (relative hazard = 1.48)19.

A study published earlier this year compared treatment with clodronate (a bisphosphonate unlicensed in the UK for osteoporosis) with placebo over 3 years in women with osteoporosis (t-score < - 2.5) and/or at least one vertebral fracture receiving a calcium supplement of 500mg/day but no vitamin D supplement. The study demonstrated a significant reduction in vertebral fracture of 46% and significant increases in bone mineral density at the spine without co-prescription of vitamin D20. However, this study was smaller than the bisphosphonate trials (n = 593 versus n = 2027 in the vertebral fracture arm of the Fracture Intervention Trial with alendronate21) and patients in the clodronate trial were younger (mean age < 70 years) than those in the FIT trial (mean age > 70 years), and potentially less likely to be vitamin D deficient. Furthermore, the clodronate trial did not demonstrate a reduction in nonvertebral fractures, which may be relevant in view of the importance of vitamin D in optimising neuromuscular reflexes and reducing the likeliho\od of falls22. The fact that a vertebral fracture risk reduction is seen in the absence of vitamin D supplementation does not in itself mean that supplementation is not necessary.

Likewise, the fracture risk reduction in the absence of both vitamin D and calcium co-prescription in the Women's Health Initiative23study was seen in a younger age group and again would not necessarily imply that a replete calcium and vitamin D status is unnecessary for optimal benefit. However, this study is concerned with the co-prescription of calcium and vitamin D preparations in patients who have been judged to need definitive treatment for osteoporosis. In this situation, NICE guidance1 recommends that calcium and vitamin D preparations are prescribed unless the clinician is confident that the patient is replete. Since the majority of patients are likely to require supplementation, particularly of vitamin D, it would be expected that optimal treatment would see the majority of patients receiving such a supplement.

Study design

Nine demographically representative practices from the 84 within Gloucestershire were approached to take part in a pilot. The practices were chosen to reflect a variety of different clinical systems and IT skill levels. Structured Query Language sets were drafted in a database enquiry engine known as Morbidity QUery Information Export SynTax (MIQUEST) that is commonly used within NHS Primary Care. The relevant clinical codes were largely selected from the subset published on the website of the National Osteoporosis Society (www.nos.org.uk). The comma-separated value (CSV) files generated were run through an analysis and reporting tool written utilising macros embedded in Microsoft Excel spreadsheet software.

The three data quality facilitators visited the practices to provide training in running and interpreting the queries. The output was stripped of patient-identifiable data except for age and sex information. The extracted files were imported into the spreadsheet and analysis was performed by the countywide audit advisor.

The pilot audit was carried out in nine practices with a total population of 61 202 patients. The mean number of patients per practice was 6800 (SD = 2876). The largest practice list size was 13688 and the smallest 3875. Overall, patients were split evenly into men and women. Age/sex demographics are shown in Table 1. Variance in age/sex split from the overall Gloucestershire profile was minimal, although there were more patients aged under 45 years and slightly fewer patients aged over 65 years in the nine pilot practices. This was mainly due to Practice 6, which provides medical services to 3300 university students. These have been removed from the denominator group to reflect the normal practice population.

Results

Overall 662 patients (1.1% of total population) were receiving osteoporosis treatment (defined as bisphosphonates, teriparatide, raloxifene or strontium). Of the patients receiving osteoporosis treatment, 83.7% (n = 554) were women and 16.3% (n = 108) were men. Of the women, 2.0% (n = 11) were aged under 45 years, 19.7% (H = 109) were aged 45-64 years, 29.1% (n = 161) were aged 65-74 years and 49.3% (n = 273) were aged 75 and over. The corresponding figures for men were 2.8% (n = 3), 33.3% (n = 36), 27.8% (n = 30) and 36.1% (n = 39).

Table 1. Demographic data from pilot practices and Gloucestershire practices overall

The percentage of patients receiving osteoporosis treatment ranged from 1.6% (77/4687) to 0.7% (49/6773 and 55/7640) of the total practice population (Figure 1).

Overall 34.1% of the patients on osteoporosis treatment were also prescribed calcium alone or calcium and vitamin D. At an individual practice level there was considerable variation in co-prescribing: the percentage of patients receiving a co-prescription ranged from 74.3% (55/77) to 12.2% (6/49) (Figure 2). The majority of patients received both calcium and vitamin D (30.8%, n = 204), although 3.3% (n = 22) received calcium alone.

Figure 1. Percentage of patients with a prescription for osteoporosis medication (bisphosphonates, teriparatide, raloxifene or strontium) by practice and overall population

Figure 2. Percentage of patients with a prescription for osteoporosis medication (bisphosphonates, teriparatide, raloxifene or strontium) also (co-)prescribed calcium or calcium and vitamin D by practice and overall population

Discussion

This pilot audit demonstrates that only around onethird of patients receiving osteoporosis medication in a primary care setting also receive a prescription for calcium and vitamin D. This low level of co-prescription is confirmed by prescribing data from the Mediplus database which shows a similar level of co-prescription for bisphosphonates and calcium and vitamin D at 35%24. A prospective study of 164 patients in a secondary care setting (70% in-patients and 30% outpatients) taking bisphosphonates for the prevention or treatment of osteoporosis found that 32% were receiving supplementation with calcium and vitamin D25. Of the patients not receiving supplements, vitamin D status was available for 98 patients and 79% (n = 77) had vitamin D levels below 50nmol/L.

There is considerable variation in co-prescribing across practices. It is possible that the decision to co-prescribe may be influenced by the age of the patient or their residential status. It might be assumed that patients aged under 65 years are less likely to be deficient in calcium and vitamin D. Therefore, demographic differences between the practices could account for the variation in co-prescribing. However, in this study there were no significant differences between the nine pilot practices in terms of age/sex breakdown. Furthermore, on analysis of the data, we found that there was no significant inverse correlation between the percentage of patients aged under 65 years receiving a prescription for an osteoporosis medication and co-prescribing of calcium and vitamin D. Furthermore, it is conceivable that housebound patients or those in residential care would be more likely to receive a co-prescription - unfortunately, however, reliable electronically retrievable data is not available on residential or mobility status or indeed recorded routinely in general practice. This study was therefore unable to determine whether this could have led to the marked inter-practice variation.

It is well established that there is considerable variation in data quality in general practice, and specifically in the field of osteoporosis26. A study of 78 practices in England found a 100-fold variation in data recording in osteoporosis between practices. However, the pilot audit on which we report used prescribing data which is extremely well recorded and reflects genuine activity.

The practice with the highest level of co-prescription had previously taken part in a collaborative case-finding project27, and staff had received input and mentoring to raise disease awareness and knowledge as part of the project. Practice 9, with the second highest coprescription rate, has a partner with a special interest in osteoporosis. The knowledge, experience and enthusiasm of individual practices may impact on co-prescribing. Practices without such advantages may benefit from the feedback and education which is provided by effective clinical audit.

Estimates of the number of women in the UK with a fragility fracture suggest that around 1.3 million postmenopausal women have a prior fragility fracture and around 0.2 million experience a new fragility fracture each year28. Given that the population of the UK is 59.6 million, we can estimate that over 2.2% of the patients in the audit population will have a prior fracture. Although this estimate does not include men with fragility fracture, patients experiencing a new fracture or patients treated for osteoporosis without fragility fracture, it does provide an approximate indication of the proportion of patients requiring treatment for osteoporosis. The audit found that 1.1% of the population was on treatment for osteoporosis, revealing a possible shortfall in the identification and management of patients with osteoporosis or the recording of such patients.

Although only approximately one-half of the expected number of patients with osteoporotic fracture were on anti-resorptive treatment in this study, this represents a considerable improvement on earlier work from elsewhere in the UK. A small questionnaire survey carried out in the late 1990s in 82 patients with recent fragility fracture revealed that only 15% were receiving treatment with a bisphosphonate and onethird had been given advice regarding diet and calcium supplementation29. An audit of 160 patients with nonvertebral fragility fracture, published in 2000, found that only 3.8% of patients were receiving anti-resorptive agents after their fracture and that 19% were taking the minimum audit standard of calcium and/or vitamin D30. A study using prescribing data from the General Practice Research Database carried out in 1994-1996 revealed that less than 5% of patients with hip or Colle's fracture were receiving treatment with anti-resorptive treatment31.

Compliance with calcium and vitamin D preparations has been shown to be poor17,18. At present calcium and vitamin D is prescribed as calcium salts (carbonate, lactate or phosphate) and vitamin D3 (colecalciferol) packaged together as tablets (chewable and nonchewable) and effervescent granules to be taken daily. Doses for individual preparations vary as follows:

* Calcium 97mg/vitamin D g (400 IU)

* Calcium 500mg/vitamin D 11 g (440 IU)

* Calcium 500mg/vitamin D 5 g (200IU)

* Calcium 600 mg/vitamin D g (400 IU)

* Calcium 1200 mg/vitamin D 20 g (800 IU)

Less commonly, vitamin D alone can be administered as an intravenous injection of 500ng/day loc-hydroxyvitamin D3, adjusted to avoid hypercalcaemia or as capsules of 1,25-dihydroxy-vitamin D\1 (250ng b.d.).

The recent RECORD study17 demonstrated that 75.5%, 80.8%, 77.7% and 79.8% of patients were taking oral calcium and vitamin D (1000mg/ day and 800IU/day), oral vitamin D alone (800 IU), oral calcium alone (1000mg) or placebo respectively, on more than 80% of days 24 months into the trial. Taking calcium (either alone or with vitamin D) was associated with more frequent decisions to stop therapy because of gastrointestinal symptoms or difficulties in taking the tablets. Another study18 comparing the effect of treatment with oral supplementation with calcium (1000mg) and vitamin D (800 IU) and patient information with patient information alone on fracture prevention, demonstrated self-reported compliance of around 63% at 12 months.

Therefore, even if all patients on osteoporosis treatments were co-prescribed calcium and vitamin D, it is likely that around 30% of patients would not adhere to treatment. It is clear that strategies need to be adopted to increase physician awareness of the high rates of vitamin D inadequacy in the population at risk of fragility fracture and to improve concordance with supplementation.

This study reports on the results of a pilot audit in nine practices. Roll out of the audit to all 84 practices is planned during 2006, and will cover all aspects of osteoporosis and falls management. With respect to the nine pilot practices, it would be valuable to complete the audit cycle and repeat the audit in 12 months to determine whether there has been a change in clinical practice. It would also be interesting to determine whether there is a difference in fracture rates between patients receiving a bone- remodelling agent alone or in combination with calcium and vitamin D.

The study is limited by the small numbers involved, although this will be addressed when the overall audit is completed. The study does not determine why levels of co-prescribing are so low and the considerable variation between practices.

Conclusion

Only around one-third of patients receiving a prescription for an osteoporosis medication also receive a prescription for calcium and vitamin D. There is considerable variation between practices.

Acknowledgements

This work was supported by a Higher Education Innovation Fund (HEIF-2) grant from the University of Derby and an unrestricted educational grant from Merck Sharp & Dohme Limited. The views expressed in this paper are those of the authors and not necessarily those of the publisher or sponsor.

The authors would like to thank the pilot practices who co- operated with the project in providing data, and Rosemary Clifford, Audit Manager at the PCCAG, for her invaluable guidance.

References

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CrossRef links are available in the online published version of this paper: http://www.cmrojournal.com

Paper CMRO-3193_4, Accepted for publication: 01 November 2005

Published Online: 30 November 2005

doi: 10.1185/030079906X80288

J. R. Bayly(a,b), R. D. Hollandsc, S. E. Riordan-Jones(a), S. J. Yemm(a), I. Brough-Williams(a), M. Thatcher(a), N. M. Woodman(a) and T. Dixon(d)

a Gloucestershire Primary and Community Care Audit Group, Gloucester, UK

b Faculty of Education Health and Sciences, University of Derby, Derby, UK

c Underwood Surgery, Cheltenham, UK

d JB Medical Ltd, Sudbury, UK

Address for correspondence: Dr J. R. Bayly, 4 Vale View, Field Road, Whiteshill, Stroud, Gloucestershire GL6 6AG, UK. Tel.: +44 (0)1453-764993; Fax: +44 (0)1453-766325; email: jonathan@bayly.org

Copyright Librapharm Jan 2006

Source: Current Medical Research and Opinion

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