Rheumatology Advance Access originally published online on January 6, 2006
Rheumatology 2006 45(4):486-487; doi:10.1093/rheumatology/kei273
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LETTER TO THE EDITOR |
Use of vitamin D supplements and vitamin D status in patients taking bisphosphonate drugs
Departments of Care of the Elderly and Clinical Biochemistry, North Bristol NHS Trust, Bristol, UK
Correspondence to: T. Allain, Elgar House, Southmead Hospital, Bristol BS10 5NB, UK. E-mail: theresa.allain{at}nbt.nhs.uk
SIR, Bisphosphonate drugs are widely used to treat and prevent osteoporosis. Following recent guidance from the National Institute for Clinical Excellence (NICE) on secondary fracture prevention [1], it is likely that bisphosphonate use will increase, particularly in older women. In the case of etidronate, the benefit of treatment may be attenuated by concomitant vitamin D deficiency [2]. In trials demonstrating fracture reduction with modern bisphosphonates, such as risedronate and alendronate, it was ensured that subjects were replete in calcium and vitamin D, so the effects of concomitant vitamin D deficiency are unknown. In order to replicate the results of these studies in practice, we should ensure that patients receiving bisphosphonates are replete in calcium and vitamin D.
Low vitamin D levels are common in people over the age of 65 yr without apparent risk factors for vitamin D deficiency [3]. High rates of vitamin D deficiency have been reported in women receiving treatment for osteoporosis: 52% of women with a mean age of 71 yr [4] and 17% of early postmenopausal women, mean age 56 yr [5]. Vitamin D deficiency is even more common in high-risk groups, such as falls patients (of whom 72% are deficient) [6], elderly hip fracture patients (80% deficient) [7] and middle-aged medical in-patients (57% deficient) [8]. Many of these patients will receive bisphosphonates for the treatment or prevention of osteoporosis.
It is our impression that vitamin D status is not being ascertained and supplements are not being appropriately given to patients receiving bisphosphonate drugs.
The aim of this study was to: (i) assess the proportion of people taking bisphosphonate drugs who are coprescribed a vitamin D supplement; and (ii) measure vitamin D levels and determine the prevalence of vitamin D deficiency in those people who take bisphosphonates without a vitamin D supplement. The study was approved by the research ethics committees of North Bristol NHS Trust and the primary care trusts.
Recruitment took place in two settings, primary care and secondary care, as we wanted to enrich the sample for subjects with comorbidity. It was anticipated that the clinical profile, demographic characteristics and therefore, vitamin D levels, would differ between the two groups so data were analysed separately for each group. No subject appeared in both groups, although some of the subjects recruited from primary care were attending hospital clinics elsewhere. Patients were recruited consecutively over 12 months in secondary care and 2 yr in primary care to minimize effects due to seasonal variation. A power calculation determined that a sample size of 100 vitamin D measurements in each population would provide an estimate of the true prevalence of vitamin D deficiency of 20% (95% confidence interval 11–29%) in primary care subjects and 50% (95% confidence interval 40–60%) in secondary care subjects.
General practices identified patients receiving prescriptions for bisphosphonate drugs using computerized records. Hospital in-patients taking bisphosphonates were identified by ward pharmacists during their daily drug chart reviews. A small number of subjects attending respiratory and rheumatology out-patient clinics were included in the secondary care sample.
Age, gender, indication for treatment, medications and duration of treatment were recorded. Subjects who were not taking vitamin D supplements were invited to give a blood sample for vitamin D levels. All subjects gave written informed consent according to the Declaration of Helsinki. Exclusion criteria were subjects who took bisphosphonate drugs for the treatment of malignancy or Paget's disease, those aged under 20 and those who could not consent.
Serum 25-hydroxyvitamin D was measured (since this is the major circulating form and provides an integrated assessment of both intake and stores) using a radioimmunoassay (Diasorin 25-hydroxyvitamin D; Diasorin, Stillwater MN, USA). Vitamin D deficiency was defined as a level <30 nmol/l and vitamin D insufficiency as a level <50 nmol/l [9].
Overall 40% of subjects were receiving vitamin D supplements, in all cases as a combined calcium and vitamin D formulation (Table 1). Subjects recruited from primary care were more likely to receive a coprescription for vitamin D, even though subjects recruited from secondary care were older, had more comorbidity, and had higher rates of vitamin D deficiency and insufficiency. A small number of subjects were taking self-prescribed multivitamin or cod liver oil supplements. These subjects were included in the sample and their results did not differ from those for the overall sample. Subjects recruited in secondary care were more likely to have had their initial prescription for bisphosphonate medication from a hospital specialist rather than their general practitioner. In 40% of cases bisphosphonates were being given for the prevention or treatment of steroid-related osteoporosis. Steroid use was more frequent in the secondary care sample. There was no correlation between age and vitamin D levels; four patients from the primary care sample, aged under 50 yr, had vitamin D deficiency and one had insufficiency. Females had non-significantly lower levels of vitamin D.
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These results demonstrate that there are low levels of coprescription of vitamin D with bisphosphonates among both hospital and non-hospital attendees, and high rates of vitamin D deficiency in those that are not supplemented. On the basis of these results we advocate the widespread coprescription of vitamin D supplements when bisphosphonate drugs are used for the prevention or treatment of osteoporosis. During the study all subjects recruited in secondary care, who were not taking a vitamin D supplement prior to the study, were started on a combined calcium and vitamin D supplement once their blood sample was taken, as it is our policy to coprescribe calcium and vitamin D supplements with bisphosphonate medication. The results of the study have been fed back to participating general practices but we do not know what proportion of the subjects recruited in primary care have subsequently been started on supplements. Although calcium intake was not addressed in this study, many of these patients also require calcium supplementation, so a combined supplement is probably the easiest way of achieving this.
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The authors have declared no conflicts of interest.
References
- National Institute for Clinical Excellence. The secondary prevention of osteoporotic fracture in postmenopausal women. Technology Appraisal No. 87. London: Department of Health, 2005.
- Koster JC, Hackeng WH, Mulder H. Diminished effect of etidronate in vitamin D deficient osteopenic postmenopausal women. Eur J Clin Pharmacol 1996;51:145–7.[CrossRef][Medline]
- van der Wielen RP, Lowik MR, van den Berg H et al. Serum vitamin D concentrations among elderly people in Europe. Lancet 1995:346;207–10.[CrossRef][Web of Science][Medline]
- Holick MF, Siris ES, Binkley N et al. Prevalence of vitamin D inadequacy among postmenopausal North American women receiving osteoporosis therapy. J Clin Endocrinol Metab 2005;90:3215–24.
[Abstract/Free Full Text] - Haden ST, Fuleihan GE, Angell JE, Cotran NM, LeBoff MS. Calcidiol and PTH levels in women attending an osteoporosis program. Calcif Tissue Int 1999;64:275–9.[CrossRef][Web of Science][Medline]
- Dhesi JK, Moniz C, Close JC, Jackson SH, Allain TJ. A rationale for vitamin D prescribing in a falls clinic population. Age Ageing 2002;31:267–71.
[Abstract/Free Full Text] - Harwood RH, Sahota O, Gaynor K, Masud T, Hosking DJ; The Nottingham Neck of Femur (NONOF) Study. A randomised, controlled comparison of different calcium and vitamin D supplementation regimens in elderly women after hip fracture: The Nottingham Neck of Femur (NONOF) Study. Age Ageing 2004;33:45–51.
[Abstract/Free Full Text] - Thomas MK, Lloyd-Jones DM, Thadhani RI et al. Hypovitaminosis D in medical inpatients. N Engl J Med 1998;338:777–83.
[Abstract/Free Full Text] - Glendenning P, Vasikaran SD. Vitamin D status and redefining serum PTH reference range in the elderly. J Clin Endocrinol Metab 2002;87:946–7.
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