1,25-Dihydroxyvitamin D<sub>3</sub>and Muscle Strength in the Elderly: A Randomized Controlled Trial*

Grady, Deborah; Halloran, Bernard P.; Cummings, Steve; Leveille, Suzanne G.; Wells, Lauren; Black, Dennis M.; Byl, Nancy N.

doi:10.1210/jcem-73-5-1111

Cited by 101 publications

(114 citation statements)

References 39 publications

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“…If this is correct, it could explain some negative results found by others, e.g. Grady et al [43] , who did not find any increase in muscle strength in elderly women 1 69 years after calcitriol treatment, probably because initial serum 25(OH)D levels exceeded 60 nmol/l. Kenny et al [44] also reported that vitamin D supplementation in healthy older community-dwelling men showing average serum 25(OH)D levels of 65 nmol/l did not improve their functional abilities.…”

Section: Discussionmentioning

confidence: 89%

Treatment of Vitamin D Deficiency Increases Lower Limb Muscle Strength in Institutionalized Older People Independently of Regular Physical Activity: A Randomized Double-Blind Controlled Trial

et al. 2009

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Aims: To investigate the effects of a 6-month supplementation with calcium and cholecalciferol on biochemical parameters and muscle strength of institutionalized elderly. Methods: This prospective, double-blind, placebo-controlled, randomized trial included Brazilian institutionalized people ≥60 years of age receiving a 6-month supplementation (December to May) of daily calcium plus monthly placebo (calcium/placebo group) or daily calcium plus oral cholecalciferol (150,000 IU once a month during the first 2 months, followed by 90,000 IU once a month for the last 4 months; calcium/vitamin D group). Fasting blood samples for 25(OH)D, PTH and calcium determination were collected (n = 56) and muscle tests were performed (n = 46) to measure the strength of hip flexors (SHF) and knee extensors (SKE) before (baseline) and after the 6-month intervention (6 months). Results: Due to seasonal variations, serum 25(OH)D significantly enhanced in both groups after treatment, but the calcium/vitamin D group had significantly higher 25 (OH)D levels than the calcium/placebo group (84 vs. 33%, respectively; p < 0.0001). No cases of hypercalcemia were observed. While the calcium/placebo group showed no improvement in SHF and SKE at 6 months (p = 0.93 and p = 0.61, respectively), SHF was increased in the calcium/vitamin D group by 16.4% (p = 0.0001) and SKE by 24.6% (p = 0.0007). Conclusions: The suggested cholecalciferol supplementation was safe and efficient in enhancing 25(OH)D levels and lower limb muscle strength in the elderly, in the absence of any regular physical exercise practice.

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Section: Discussionmentioning

confidence: 89%

Treatment of Vitamin D Deficiency Increases Lower Limb Muscle Strength in Institutionalized Older People Independently of Regular Physical Activity: A Randomized Double-Blind Controlled Trial

et al. 2009

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“…Serum levels of 25OHD among the participants were, however, above 460 nmol/l [60]. If 25OHD is the primary in vivo mediator, no hypovitaminosis D myopathy could be expected among these participants, and consequently no effect of treatment with calcitriol should be expected.…”

Section: Therapeutic Implicationsmentioning

confidence: 85%

“…In another treatment study, Grady et al [60] failed to demonstrate any muscular effects of treatment with 0.5 mg calcitriol daily in 98 men and women volunteers over 69 years old. Serum levels of 25OHD among the participants were, however, above 460 nmol/l [60].…”

Section: Therapeutic Implicationsmentioning

confidence: 95%

Vitamin D and Muscle Function

Pfeifer¹,

Begerow²,

Minne³

2002

Osteoporos Int

438

267

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The aim of this review is to summarize current knowledge on the relation between vitamin D and muscle function. Molecular mechanisms of vitamin D action on muscle tissue have been known for many years and include genomic and non-genomic effects. Genomic effects are initiated by binding of 1,25-dihydroxyvitamin D3 (1,25(OH)2D) to its nuclear receptor, which results in changes in gene transcription of messenger RNA and subsequent protein synthesis. Non-genomic effects of vitamin D are rapid and mediated through a membrane-bound vitamin D receptor (VDR). Genetic variations in the VDR and the importance of VDR polymorphisms in the development of osteoporosis are still a matter of controversy and debate. Most recently, VDR polymorphisms have been described to affect muscle function. The skin has an enormous capacity for vitamin D production and supplies the body with 80-100% of its requirements of vitamin D. Age, latitude, time of day, season of the year and pigmentation can dramatically affect the production of vitamin D in the skin. Hypovitaminosis D is a common feature in elderly people living in northern latitudes and skin coverage has been established as an important factor leading to vitamin D deficiency. A serum 25-hydroxyvitamin D level below 50 nmol/l has been associated with increased body sway and a level below 30 nmol/l with decreased muscle strength. Changes in gait, difficulties in rising from a chair, inability to ascend stairs and diffuse muscle pain are the main clinical symptoms in osteomalacic myopathy. Calcium and vitamin D supplements together might improve neuromuscular function in elderly persons who are deficient in calcium and vitamin D. Thus 800 IU of cholecalciferol in combination with mg of elemental calcium reduces hip fractures and other non-vertebral fractures and should generally be recommended in individuals who are deficient in calcium and vitamin D. Given the strong interdependency of vitamin D deficiency, low serum calcium and high levels of parathyroid hormone, however, it is difficult to identify exact mechanisms of action.

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“…The acute effects of these agents on the calcium balance are variable and are better judged by long-term responses in bone mass (discussed below). In contrast to the use of these derivatives in chronic renal failure and in osteomalacia, no effect is observed on muscle strength in the elderly [21].…”

Section: Vitamin D Analoguesmentioning

confidence: 82%

Treatment of osteoporosis with vitamin D

et al. 1997

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There are probably few more controversial areas in the pathophysiology and therapeutics of osteoporosis than that concerning the role of vitamin D and its derivatives. It has been argued that osteoporosis is in part related to defective production of calcitriol, and low values for calcitriol have been reported in postmenopausal women [1]. It is suggested that this gives rise to intestinal malabsorption of calcium, secondary hyperparathyroidism which accelerates bone turnover and thereby induces skeletal losses. Since oestrogens may stimulate the synthesis of calcitriol, at least in vitro, oestrogen withdrawal has been considered to be the signal for decreased production of calcitriol. This is, however, not the sole merchanism that could account for calcium malabsorption. It is equally plausible that oestrogen deficiency directly causes bone loss which in turn infuses the extracellular fluid with calcium, and that this in turn decreases the secretion of parathyroid hormone (PTH) and the synthesis of calcitriol. Thus, the intestinal malabsorption is a consequence of bone loss and not its cause [2].A more convincing role of disturbed metabolism of vitamin D arises in the elderly. With advancing years low values for calcitriol and increased secretion of PTH are consistently reported [1,3]. The administration of physiologically appropriate doses of parent vitamin D reverses these abnormalities [3,4]. For this reason it is probable that hyperparathyroidism is in part due to inadequacies in the nutriitional status of the elderly. Although florid osteomalacia due to vitamin D deficiency is rare [5], milder vitamin D insufficiency may be common, particularly in the institutionalized elderly. Over and above there is circumstantial evidence that abnormalities in the production of calcitriol occur due to the decline in renal function that occurs with age, which would also induce secondary hyperparathyroidism [6].In view of these uncertainties, the role of vitamin D, its analogues and metabolites in therapeutics cannot be argued from considerations of pathophysiology, but must Correspondence and offprint requsts to: Professor J. A. Kanis, WHO be judged from a pharmacodynamic perspective. From this viewpoint the principal action of vitamin D and related compounds is to increase intestinal absorption of calcium irrespective of the underlying pathophysiology and thereby to increase serum calcium, suppress PTH, suppress the turnover of bone and thus to decrease the rate of bone loss in bone-losing states [2]. Whether vitamin D has additional anabolic effects on the formation of bone is uncertain. Even if not, vitamin D treatment could be viewed as a means for the sustained delivery of calcium.The agents most widely used are the parent vitamins, calcitriol and alfacalcidol. Alfacalcidol is a synthetic .analogue of calcitriol that is metabolized to calcitriol by its 25-hydroxylation in the liver. Dihydrotachysterol (DHT) has a similar structural configuration with a pseudo-Iz-hydroxyl in the 3ß position ot the A ring. Like alfacalc...

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1,25-Dihydroxyvitamin D₃and Muscle Strength in the Elderly: A Randomized Controlled Trial*

Cited by 101 publications

References 39 publications

Treatment of Vitamin D Deficiency Increases Lower Limb Muscle Strength in Institutionalized Older People Independently of Regular Physical Activity: A Randomized Double-Blind Controlled Trial

Treatment of Vitamin D Deficiency Increases Lower Limb Muscle Strength in Institutionalized Older People Independently of Regular Physical Activity: A Randomized Double-Blind Controlled Trial

Vitamin D and Muscle Function

Treatment of osteoporosis with vitamin D

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1,25-Dihydroxyvitamin D3and Muscle Strength in the Elderly: A Randomized Controlled Trial*

Cited by 101 publications

References 39 publications

Treatment of Vitamin D Deficiency Increases Lower Limb Muscle Strength in Institutionalized Older People Independently of Regular Physical Activity: A Randomized Double-Blind Controlled Trial

Treatment of Vitamin D Deficiency Increases Lower Limb Muscle Strength in Institutionalized Older People Independently of Regular Physical Activity: A Randomized Double-Blind Controlled Trial

Vitamin D and Muscle Function

Treatment of osteoporosis with vitamin D

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1,25-Dihydroxyvitamin D₃and Muscle Strength in the Elderly: A Randomized Controlled Trial*