Vitamin D Therapy in Clinical Practice: One Dose Does Not Fit All

P. J. Ryan


Int J Clin Pract. 2007;61(11):1894-1899. 

In This Article


Vitamin D has a major role in humans to enable the absorption of calcium and phosphate for the mineralisation of the skeleton. Severe deficiency sufficient to produce rickets or osteomalacia is rare but less severe forms of vitamin D deficiency are widely appreciated as an important contributor to postmenopausal osteoporosis[1,2] and also more recently to falls.[3] Low vitamin D levels have been reported in patients admitted for hip fractures,[4] general medical admissions[5] elderly nursing home residents, normal adult populations[6] and general outpatient populations[7] in various studies.

Vitamin D treatment usually with calcium supplementation is an important component of osteoporosis therapy. It has been shown to improve vitamin D status[8] and bone mineral density (BMD).[9] The pivotal study of Chapuy et al. suggested that calcium and vitamin D was useful in elderly patients in residential care to prevent hip and other nonvertebral fracture.[10] Other studies also suggest that even in the community population there may be benefit in hip fracture prevention where patients are deficient and also show a high degree of compliance with therapy.[11,12] However, several other recent studies have indicated calcium and vitamin D or vitamin D alone may not be of value in most community dwelling patients.[13,14] More recent data suggest that vitamin D may reduce the risk of falls, strengthening its use for treatment in the frail elderly.[3] In the routine clinical management of patients with osteoporosis, calcium and vitamin D are usually given with bisphosphonates or other therapies because of the importance of deficiencies in impairing the effects of antiresorptive therapy.[15] Additionally, the benefits of bisphosphonates and strontium ranelate in osteoporosis were only effective in patients given calcium and vitamin D as part of their therapy or in those who were calcium and vitamin D replete.

Although the need for calcium and vitamin D therapy is widely appreciated the doses of treatment that should be prescribed is less clear. Guidelines usually advise standard doses of replacement - generally a minimum of 1000-1200 mg of calcium and 800 IU of vitamin D. This is based on doses used in the Chapuy trial, consensus statements and targets levels for serum 25 OH vitamin D. Definitions of deficiency and insufficiency are problematic because of large differences in results from different assay methods, varying reference populations, and uncertainty as to whether normal ranges should be established from reference populations or from biological indices such as parathyroid hormone (PTH). Using PTH to define vitamin D deficiency has been made in two ways. First the vitamin D levels above which levels do not rise in the winter has been examined. Results however vary widely from 78 nmol/l in a French study[6] to 30 nmol/l in a Dutch study.[8] Another approach has been to examine the vitamin D levels above which vitamin D supplements do not cause a fall in PTH. This level has been identified as 50 nmol/l in a study of hospital inpatients,[9] a study of 35 elderly subjects[16] and also in the MORE trial.[17] Prevalence is greater in the winter months in Europe and North America with estimates of 25-50% 25 OH vitamin D < 25 nmol/l.[6] One proposal has been to suggest that vitamin D insufficiency is a serum level < 50 nmol/l, deficiency < 25 nmol/l and severe deficiency < 12.5 nmol/l - a level below which osteomalacia is likely to develop.[18] Studies using PTH are limited by the observation that some patients with vitamin D deficiency do not mount a PTH increase which in some cases is caused by magnesium deficiency.[19] It should also be noted that there is also data to support higher threshold levels of vitamin D as being the lower limit of normal. Studies examining calcium absorption suggest that it is impaired below vitamin D levels of 80 nmol/l and this higher threshold for normal may be more appropriate.[20] A recent consensus statement has suggested that 800-1000 IU vitamin D should be sufficient to achieve a 25 OHD level of 75 nmol/l.[21] Studies comparing 25 hydroxy vitamin D levels with total hip BMD showed a positive association up to levels of 90-100 nmol/l[22] in a large population of over 13,000 men and women assessed in the NHANES 3 cohort. Previous work by Dawson-Hughes et al. has also shown that wintertime BMD losses can be prevented with supplementation that achieves serum 25 hydroxy vitamin D levels of 60-90 nmol/l.[9,23] These BMD studies support the notion of higher desirable levels of vitamin D of around 75 nmol/l.

The importance of vitamin D replacement is established but the dose required in routine practice to ensure all patients are vitamin D replete has been less widely examined. In the present study we have attempted to examine the effects of vitamin D therapy on 25 OH vitamin D values in clinical practice and tried to draw conclusions regarding vitamin D therapy.


Comments on Medscape are moderated and should be professional in tone and on topic. You must declare any conflicts of interest related to your comments and responses. Please see our Commenting Guide for further information. We reserve the right to remove posts at our sole discretion.
Post as: