Efficacy and safety of high dose intramuscular or oral cholecalciferol in vitamin D deficient/insufficient elderly

Abstract

Objectives

To evaluate and compare the effects and safety of high dose intramuscular (IM) or oral cholecalciferol on 25-hydroxyvitamin D [25(OH)D] levels, muscle strength and physical performance in vitamin D deficient/insufficient elderly.

Study design

Randomized prospective study.

Main outcome measures

116 ambulatory individuals aged 65 years or older living in a nursing home were evaluated. Eligible patients with 25(OH)D levels <30 ng/ml (n = 66) were randomized to IM or Oral groups according to the administration route of 600,000 IU cholecalciferol. Demographic and descriptive data were collected. Biochemical response was measured at baseline, 6th and 12th weeks. Muscle strength was measured from quadriceps by using a hand-held dynamometer and physical performance was evaluated by short physical performance battery (SPPB) at the beginning and 12th week.

Results

Among the screened ambulatory elderly only 5.2% (n = 6) had adequate vitamin D levels. 37.1% (n = 43) were vitamin D deficient and 57.7% (n = 67) were insufficient. After administration of one megadose of vitamin D, mean serum 25(OH)D levels increased significantly at 6th week (32.72 ± 9.0 ng/ml) and at 12th week (52.34 ± 14.2 ng/ml) compared with baseline (11.76 ± 7.6 ng/ml) in IM group (p < 0.0001). In Oral group levels were 47.57 ± 12.7 ng/ml, 42.94 ± 13.4 ng/ml and 14.87 ± 6.9 ng/ml, respectively (p < 0.0001). At 12th week the increase in IM group was significantly higher than Oral group (p = 0.003).

At the end of the study period, serum 25(OH)D levels were ≥30 ng/ml in all patients in IM group and in 83.3% of the patients in the Oral group. Quadriceps muscle strength and SPPB total score increased significantly in both groups and SPPB balance subscale score increased only in IM group. Six patients (9.6%) developed hypercalciuria, no significant adverse events were observed.

Conclusion

In vitamin D deficient/insufficient elderly, a single megadose of cholecalciferol increased vitamin D levels significantly and the majority of the patients reached optimal levels. Although both administration routes are effective and appear to be safe, IM application is more effective in increasing 25(OH)D levels and balance performance.

Introduction

Vitamin D deficiency is now being recognized as one of the most common medical conditions in the world [1]. Vitamin D plays an important role in skeletal development, bone health maintenance and neuromuscular functioning. Since the signs and symptoms of vitamin D deficiency are insidious or nonspecific, it often goes unrecognized and untreated [2].

Frank vitamin D deficiency is defined as 25(OH)D below 10 ng per milliliter (ng/ml) and has long been recognized as a medical condition characterized by muscle weakness, bone pain, and fragility fractures. Vitamin D insufficiency is defined as 25(OH)D between 10 and 30 ng/ml and levels equal or more than 30 ng/ml is considered as optimal [3].

The assessment of vitamin D deficiency/insufficiency prevalence is being hampered by the different threshold levels used in different studies. Vitamin D deficiency is common among community-dwelling elderly in countries at higher latitudes and very common among institutionalized elderly, geriatric patients and patients with hip fractures [4].

Older people are especially at risk of developing vitamin D deficiency due to low exposure to sunshine, decreased capacity of the older skin to synthesize vitamin D, and low dietary vitamin D intake [5]. The prevalence of vitamin D deficiency among elderly people living in residential homes has been estimated to be at least 50% [6], and prevalence up to 75% has been reported [7].

Vitamin D deficiency has been shown to be associated with myopathy in subjects of various ages, with body sway in osteoporotic and fall-prone subjects and with falls in elderly, institutionalized subjects [8]. Studies investigating the effects of vitamin D supplementation and correlation between low 25(OH)D levels and physical performance have inconsistent results. Favorable effects of Vitamin D supplementation on muscle strength, physical performance and falls are shown in some studies [9], [10], whereas other studies have failed to show an increase in muscle strength [11], [12], [13].

Compliance to oral vitamin D replacement is usually low [14], [15], [16]. Only one in two postmenopousal women with osteoporosis who take calcium and/or vitamin D have good therapeutic adherence to this treatment [14]. Patients often find large tablets difficult to swallow and effervescent tablets combined with calcium may have gastrointestinal side effects [17]. Uncertain compliance to calcium and vitamin D replacement therapy gave rise to the idea of high-dose intermittent application of vitamin D. In Turkey, the general health insurance system pays for vitamin D in the form of oral drops or megadose ampoules or as effervescent tablets combined with calcium. Considering the suggested gastrointestinal and cardiovascular side effects of calcium [18], we are reluctant to prescribe combined effervescent preparations safely in the elderly. A daily requirement for vitamin D can also be replaced with oral vitamin D drops (Devit3^® 50,000 IU/15 ml). In that case, the patients have to take approximately 8 drops per day, which they state to be unpractical and difficult to use. Therefore, it is needed to find a safe, practical and well-tolerated way of supplementation.

Several studies have investigated the pharmacokinetics, biochemical effects, efficacy and safety of a single high-dose cholecalciferol and revealed this application to be safe, well tolerated and effective [6], [11], [17], [19], [20].

The primary aim of this study is to evaluate and compare the effects and safety of high dose intramuscular (IM) or oral cholecalciferol on 25(OH)D levels in elderly patients with vitamin D deficiency or insufficiency. Besides, the clinical effects of this therapy are evaluated by muscle strength and physical performance measurements.