Short-term Administration of Alphacalcidol is Associated with More Significant Improvement of Muscular Performance in Women with Vitamin D Deficiency Compared to Native Vitamin D

Abstract

Introduction: Positive relationships between muscle function and vitamin D (VD) status, defined by serum 25-hydroxy VD (25OHD) levels have been reported and muscle strength is generally improved with VD supplementation in deficient individuals. The effects of active VD analogs have been less studied.

Aim: We aim to investigate the effect of short-term treatment with native VD (cholecalciferol) or alphacalcidol on the muscular function and physical performance in women with vitamin D deficiency.

Material and methods: We analysed 178 women with VD deficiency, defined as serum 25-hydroxyVD-25OHD concentration below 30 ng/ml. We recorded the grip-strength and the results of the chair-rise test (CRT) and timed-up-and-go test (TUG). We randomised the patients to receive cholecalciferol 1 000 IU daily or alphacalcidol 1 μg daily, for 6 months.

Results: The mean baseline 25OHD concentration was 14.47±6.57 ng/ml. After treatment the serum 25OHD level rose to 20.85±8.88 ng/ml, significantly higher in cases supplemented with cholecalciferol (22.7±8.32 ng/ml) compared to those treated with alphacalcidol (13.5±7.29 ng/ml, p=0.000). After treatment, significant improvements of TUG and CRT test results (− 6.48 and−5.05% compared to baseline, respectively, p=0.000) and gripstrength (7.85% compared to baseline, p=0.000) occurred. The benefit was more significant in cases treated with alphacalcidol for gripstrength (p=0.001), TUG (p=0.002), CRT (p=0.033). After treatment, the gripstrength increased significantly more in patients with severe baseline VD deficiency.

Conclusions: VD status improvement is associated with an increase in muscular performance in women with VD deficiency. Alphacalcidol exerts significantly better effects compared to cholecalciferol, and this can not be explained by a larger increase in serum 25OHD concentration.

Key words

vitamin D deficiency - muscle performance - cholecalciferol - alphacalcidol

^* The authors had equal contributions.

• References

• 1 Richy F, Schacht E, Bruyere O et al. Vitamin D analogs versus native vitamin D in preventing bone loss and osteoporosis-related fractures: a comparative meta-analysis. Calcif Tissue Int 2005; 76: 176-186
• 2 Bischoff-Ferrari HA, Dietrich T, Orav EJ et al. Higher 25-hydroxyvitamin D concentrations are associated with better lower-extremity function in both active and inactive persons aged>or =60 y. Am J Clin Nutr 2004; 80: 752-758
• 3 Bischoff HA, Stahelin HB, Urscheler N et al. Muscle strength in the elderly: its relation to vitamin D metabolites. Arch Phys Med Rehabil 1999; 80: 54-58
• 4 Houston DK, Tooze JA, Neiberg RH et al. 25-hydroxyvitamin D status and change in physical performance and strength in older adults: the Health, Aging, and Body Composition Study. Am J Epidemiol 2012; 176: 1025-1034
• 5 von Hurst PR, Conlon C, Foskett A. Vitamin D status predicts hand-grip strength in young adult women living in Auckland, New Zealand. J Steroid Biochem Mol Biol 2013; 136: 330-332
• 6 Mathei C, Van Pottelbergh G, Vaes B et al. No relation between vitamin D status and physical performance in the oldest old: results from the Belfrail study. Age Ageing 2013; 42: 186-190
• 7 Kuchuk NO, Pluijm SM, van Schoor NM et al. Relationships of serum 25-hydroxyvitamin D to bone mineral density and serum parathyroid hormone and markers of bone turnover in older persons. J Clin Endocrinol Metab 2009; 94: 1244-1250
• 8 Wicherts IS, van Schoor NM, Boeke AJ et al. Vitamin D status predicts physical performance and its decline in older persons. J Clin Endocrinol Metab 2007; 92: 2058-2065
• 9 Visser M, Deeg DJ, Lips P. Low vitamin D and high parathyroid hormone levels as determinants of loss of muscle strength and muscle mass (sarcopenia): the Longitudinal Aging Study Amsterdam. J Clin Endocrinol Metab 2003; 88: 5766-5772
• 10 Muir SW, Montero-Odasso M. Effect of vitamin D supplementation on muscle strength, gait and balance in older adults: a systematic review and meta-analysis. J Am Geriatr Soc 2011; 59: 2291-2300
• 11 Dukas L, Schacht E, Runge M et al. Effect of a six-month therapy with alfacalcidol on muscle power and balance and the number of fallers and falls. Arzneimittelforschung 2010; 60: 519-525
• 12 WHO press. WHO scientific group on the assessment of osteoporosis at primary health care level – Summary Meeting Report. 2004; 8-9
• 13 Bohannon RW, Peolsson A, Massy-Westropp N et al. Reference values for adult grip strength measured with a Jamar dynamometer: a descriptive meta-analysis. Physiotherapy 2006; 92: 11-15
• 14 Stockton KA, Mengersen K, Paratz JD et al. Effect of vitamin D supplementation on muscle strength: a systematic review and meta-analysis. Osteoporos Int 2011; 22: 859-871
• 15 Hagenau T, Vest R, Gissel TN et al. Global vitamin D levels in relation to age, gender, skin pigmentation and latitude: an ecologic meta-regression analysis. Osteoporos Int 2009; 20: 133-140
• 16 Barker T, Martins TB, Hill HR et al. Different doses of supplemental vitamin D maintain interleukin-5 without altering skeletal muscle strength: a randomized, double-blind, placebo-controlled study in vitamin D sufficient adults. Nutr Metab (Lond) 2012; 9: 16
• 17 Knutsen KV, Madar AA, Lagerlov P et al. Does vitamin D improve muscle strength in adults? A randomized, double-blind, placebo-controlled trial among ethnic minorities in Norway. J Clin Endocrinol Metab 2014; 99: 194-202
• 18 Bischoff HA. Effects of vitamin D and calcium supplementation on falls: a randomized controlled trial. J Bone Miner Res 2003; 18: 343-351
• 19 Pfeifer M. Effects of a long-term vitamin D and calcium supplementation on falls and parameters of muscle function in community-dwelling older individuals. Osteoporos Int 2009; 20: 315-322
• 20 Schacht E, Richy F, Reginster JY. The therapeutic effects of alfacalcidol on bone strength, muscle metabolism and prevention of falls and fractures. J Musculoskelet Neuronal Interact 2005; 5: 273-284
• 21 Dukas L. Alfacalcidol reduces the number of fallers in a community-dwelling elderly population with a minimum calcium intake of more than 500 mg daily. J Am Geriatr Soc 2004; 52: 230-236
• 22 Schacht E, Ringe JD. Alfacalcidol improves muscle power, muscle function and balance in elderly patients with reduced bone mass. Rheumatol Int 2012; 32: 207-215
• 23 Verhaar HJ, Samson MM, Jansen PA et al. Muscle strength, functional mobility and vitamin D in older women. Aging (Milano) 2000; 12: 455-460
• 24 Bouillon R, Bischoff-Ferrari H, Willett W. Vitamin D and health: perspectives from mice and man. J Bone Miner Res 2008; 23: 974-979
• 25 Wang Y, DeLuca HF. Is the vitamin d receptor found in muscle?. Endocrinology 2011; 152: 354-363
• 26 Pojednic RM, Ceglia L, Olsson K et al. Effects of 1,25-dihydroxyvitamin D3 and vitamin D3 on the expression of the vitamin d receptor in human skeletal muscle cells. Calcif Tissue Int 2015; 96: 256-263
• 27 Castelo-Branco C, Cortes X, Ferrer M. Treatment persistence and compliance with a combination of calcium and vitamin D. Climacteric 2010; 13: 578-584
• 28 Hollis BW. Circulating 25-hydroxyvitamin D levels indicative of vitamin D sufficiency: implications for establishing a new effective dietary intake recommendation for vitamin D. J Nutr 2005; 135: 317-322
• 29 Holick MF, Binkley NC, Bischoff-Ferrari HA et al. Evaluation, treatment, and prevention of vitamin D deficiency: an Endocrine Society clinical practice guideline. J Clin Endocrinol Metab 2011; 96: 1911-1930
• 30 Rix M, Eskildsen P, Olgaard K. Effect of 18 months of treatment with alfacalcidol on bone in patients with mild to moderate chronic renal failure. Nephrol Dial Transplant 2004; 19: 870-876
• 31 Chesney RW, Zimmerman J, Hamstra A et al. Vitamin D metabolite concentrations in vitamin D deficiency. Are calcitriol levels normal. Am J Dis Child 1981; 135: 1025-1028
• 32 Olsson K, Saini A, Stromberg A et al. Evidence for Vitamin D Receptor Expression and Direct Effects of 1alpha,25(OH)2D3 in Human Skeletal Muscle Precursor Cells. Endocrinology 2016; 157: 98-111
• 33 Hosseinpour F, Wikvall K. Porcine microsomal vitamin D(3) 25-hydroxylase (CYP2D25). Catalytic properties, tissue distribution, and comparison with human CYP2D6. J Biol Chem 2000; 275: 34650-34655