Vitamin D Deficiency, hypocalcemia, and increased skeletal muscle degradation in rats.

Wassner, Steven J.; Li, Jeanne B.; Sperduto, A.; Norman, Michael E.

doi:10.1172/jci110947

Cited by 65 publications

(35 citation statements)

References 36 publications

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“…This results in marked declines in circulating levels of 1,25(OH) 2 D. Studies in humans show that vitamin D deficiency is associated with muscle weakness and atrophy [16,28,29]. At the cellular level, vitamin D deficiency impairs intracellular calcium kinetics and muscle cell contractility [8,9], mitochondrial metabolism [10,11] and protein synthesis [12,13]. Treatment with vitamin D corrects these impairments [14,30] as well as restoring strength and improving balance in vitamin D deficient humans [16,29,31].…”

Section: Discussionmentioning

confidence: 99%

“…Treatment with vitamin D corrects these impairments [14,30] as well as restoring strength and improving balance in vitamin D deficient humans [16,29,31]. Despite the fact that vitamin D deficiency is associated with muscle loss [12,13] and weakness [16,28,29], which may contribute to the significant muscle atrophy, weakness, and widespread disability experienced by patients with ESRD, the current focus of vitamin D treatment for the control of SHPT, as outlined in the current K/DOQI guidelines [5], is on measuring its effects on bone metabolism and tissue calcification.…”

Section: Discussionmentioning

confidence: 99%

“…Numerous studies in animals and humans have demonstrated the effects of vitamin D deficiency on various aspects of muscle cell function [8][9][10][11]. Vitamin D deficiency is associated with decreased muscle size [12][13][14] and strength [15,16], particularly of the large extensor and flexor muscles of the lower limbs [16], essential for functional mobility, and with reduced physical function and increased falls in the elderly [15]. There is evidence that these deficits can be improved by vitamin D supplementation [16].…”

Section: Introductionmentioning

confidence: 99%

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Relationship Between Vitamin D and Muscle Size and Strength in Patients on Hemodialysis

Gordon

Sakkas

Doyle

et al. 2007

Journal of Renal Nutrition

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OBJECTIVE-Vitamin D has various actions in skeletal muscle. The purpose of this study was to compare lower limb muscle size and strength in hemodialysis (HD) patients being treated with 1,25-dihydroxyvitamin D (calcitriol) or a 1,25-dihydroxyvitamin D analog (paricalcitol) to HD patients who were receiving none.DESIGN-This was a retrospective cross-sectional study. SETTING-Outpatient hemodialysis centers.PATIENTS-HD patients receiving calcitriol or paricalcitol (active vitamin D) for control of secondary hyperparathyroidism (VitD, n = 49) were compared to HD patients who were not (n = 30).MAIN OUTCOME MEASURES-Cross-sectional areas (CSA) of thigh and tibialis anterior muscles by magnetic resonance imaging (MRI), and three measures of strength; three-repetition maximum (3RM) for knee extension (isotonic), peak torque of knee extensors (isokinetic), and maximal voluntary contraction (MVC) of the ankle dorsiflexor muscles (isometric).RESULTS-There were no differences in age, weight, dialysis vintage, or intact parathyroid hormone levels between the groups, although serum albumin was higher in the VitD group (p <0.05). Patients in the VitD group had larger thigh muscle CSA (p < 0.05) and were stronger across all strength measures (p< 0.05) after controlling for age and gender (ANCOVA). When all analyses were subsequently adjusted for serum albumin concentration, only the difference in 3RM knee extension strength lost significance. There were no significant differences in any measurements between patients who received calcitriol or paricalcitol.CONCLUSION-Treatment with active vitamin D was associated with greater muscle size and strength in this cohort of HD patients.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Relationship Between Vitamin D and Muscle Size and Strength in Patients on Hemodialysis

Gordon

Sakkas

Doyle

et al. 2007

Journal of Renal Nutrition

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“…This is especially pertinent for skeletal muscle; because it is a major source of NGF, because there is evidence for a physiological role for vitamin D in other aspects of muscle physiology and because of the cross-talk between neuropathies and myopathies in diabetes mellitus. Degradation of skeletal muscle in vitamin D deficiency is an old observation [31] 2+ uptake and DNA synthesis in myocytes, such that structural modification of these molecules appears to increase their therapeutic potential for the treatment of myopathies [35]. Altered vitamin D metabolism has been shown in both short-term and long-term diabetes [36,37] and decreased concentrations of 1,25-(OH) 2 D 3 are commonly observed, despite the different calcium balances.…”

Section: Discussionmentioning

confidence: 99%

A vitamin D 3 derivative (CB1093) induces nerve growth factor and prevents neurotrophic deficits in streptozotocin-diabetic rats

et al. 1999

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Deficiencies in nerve growth factor (NGF) expression have been reported in skin and muscle [1,2] in diabetic rats and in skin biopsy specimens of patients, with an association of this deficiency with neuropathy [3]. There are also deficits in expression of neuronal genes that form targets for NGF which correlate with the NGF deficits [4] and which are reduced by NGF treatment [5]. This latter observation gives rationale to treatment of patients with NGF to prevent biochemical and functional aspects of neuropathy in those fibres, whose phenotypes are maintained by NGF [6]. Such treatment, however, is not without problems. Diabetologia (1999) AbstractAims/hypothesis. Streptozotocin-diabetic rats show impaired neurotrophic support by deficient nerve growth factor (NGF) in muscle and skin. We, therefore, examined a novel agent (CB1093; 1(S),3(R)-Dihydroxy-20(R)-(1-ethoxy-5-ethyl-5-hydroxy-2-heptyn-1-yl)-9,10-seco-pregna-5(Z),7(E),10(19)-triene), which induces expression of endogenous nerve growth factor. Methods. We gave CB1093 orally followed by measurements of mechanical nociception, nerve growth factor, neuropeptides (immunoassay) and nerve growth factor receptors (western blots).Results. In non-diabetic rats CB1093 caused dose-dependent increases in nerve growth factor production (140 % in soleus muscle and 190 % in sciatic nerve) and a mechanical hyperalgesia in the foot. There was also increased sciatic nerve expression of neuronal NGF target gene products, substance P (16 %) and calcitonin gene-related peptide (CGRP; 52 %). Depletions of nerve growth factor, substance P and CGRP in sciatic nerves of diabetic rats were prevented by CB1093, which also increased soleus nerve growth factor concentrations to 30 % over those seen in non-diabetic rats and increased its mRNA expression in skin. The CB1093 did not affect expression of nerve growth factor receptors (trkA and p75 NTR ) in dorsal root ganglia in control or diabetic rats, though the p75 NTR expression was reduced by diabetes. The mechanical hyperalgesia seen in diabetic rats treated with vehicle was not exacerbated by CB1093. Conclusion/interpretation. These findings show that in animal models of diabetes it is possible to prevent depletions of nerve growth factor and the products of its neuronal target genes by oral treatment of a highly potent inducer of NGF gene expression. Pain is a possible side-effect, though this was a function of dose and was manifest more in controls than in diabetic rats. [Diabetologia (1999)

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“…The latter two effects are probably mediated via the interaction of vitamin D with the vitamin D receptor (VDR) as VDR knock-out mice suffer from abnormal muscle development and deregulated expression of myogenic regulatory factors [8]. The impact of vitamin D on muscle is also reflected by the increase in muscle mass and decreased rate of myofibrillar protein degradation after vitamin D administration to deficient rats [9]. Also, in humans, vitamin D administration in vitamin D-deficient people induces increases in muscle size and strength, and an increased proportion and size of type II fibres [10].…”

Section: Introductionmentioning

confidence: 99%

Effects of alfacalcidol on circulating cytokines and growth factors in rat skeletal muscle

et al. 2011

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Supra-physiological levels of vitamin D induce skeletal muscle atrophy, which may be particularly detrimental in already sarcopaenic elderly. Neither the cause nor whether the atrophy is fibre type specific are known. To obtain supraphysiological levels of circulating vitamin D (1,25(OH) 2 D 3 ) 27.5-month-old female Fischer 344 9 Brown Norway F1 rats were orally treated for 6 weeks with vehicle or the vitamin D analogue alfacalcidol. Alfacalcidol treatment induced a 22% decrease in body mass and 17% muscle atrophy. Fibre atrophy was restricted to type IIb fibres in the low-oxidative part of the gastrocnemius medialis only (-22%; P \ 0.05). There was a concomitant 1.6-fold increase in mRNA expression of the ubiquitin ligase MuRF-1 (P \ 0.001), whereas those of insulin-like growth factor 1 and myostatin were not affected. Circulating IL-6 was unaltered, but leptin and adiponectin were decreased (-39%) and increased (64%), respectively. The treated rats also exhibited a reduced food intake. In conclusion, supraphysiological levels of circulating 1,25(OH) 2 D 3 cause preferential atrophy of type IIb fibres, which is associated with an increased expression of MuRF-1 without evidence of systemic inflammation. The atrophy and loss of body mass in the presence of supra-physiological levels of vitamin D are primarily due to a reduced food intake.

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Vitamin D Deficiency, hypocalcemia, and increased skeletal muscle degradation in rats.

Cited by 65 publications

References 36 publications

Relationship Between Vitamin D and Muscle Size and Strength in Patients on Hemodialysis

Relationship Between Vitamin D and Muscle Size and Strength in Patients on Hemodialysis

A vitamin D 3 derivative (CB1093) induces nerve growth factor and prevents neurotrophic deficits in streptozotocin-diabetic rats

Effects of alfacalcidol on circulating cytokines and growth factors in rat skeletal muscle

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