Hypophosphatemia is responsible for skeletal muscle weakness of vitamin D deficiency

Abstract Beyond its established role in bone and mineral homeostasis, there is emerging evidence that vitamin D exerts a range of effects in skeletal muscle. Reports of profound muscle weakness and changes in the muscle morphology of adults with vitamin D deficiency have long been described. These reports have been supplemented by numerous trials assessing the impact of vitamin D on muscle strength and mass and falls in predominantly elderly and deficient populations. At a basic level, animal models have confirmed that vitamin D deficiency and congenital aberrations in the vitamin D endocrine system may result in muscle weakness. To explain these effects, some molecular mechanisms by which vitamin D impacts on muscle cell differentiation, intracellular calcium handling, and genomic activity have been elucidated. There are also suggestions that vitamin D alters muscle metabolism, specifically its sensitivity to insulin, which is a pertinent feature in the pathophysiology of insulin resistance and type 2 diabetes. We will review the range of human clinical, animal, and cell studies that address the impact of vitamin D in skeletal muscle, and discuss the controversial issues. This is a vibrant field of research and one that continues to extend the frontiers of knowledge of vitamin D's broad functional repertoire.

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Exogenous parathyroid hormone attenuates ovariectomy-induced skeletal muscle weakness in vivo

Bone ◽

10.1016/j.bone.2021.116029 ◽

2021 ◽

pp. 116029

Author(s):

Taro Fujimaki ◽

Takashi Ando ◽

Takanori Hata ◽

Yoshihiro Takayama ◽

Tetsuro Ohba ◽

...

Keyword(s):

Skeletal Muscle ◽

Parathyroid Hormone ◽

Muscle Weakness ◽

Skeletal Muscle Weakness

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Association between vitamin D deficiency and exercise capacity in patients with CKD, a cross-sectional analysis

10.1101/2020.10.26.350546 ◽

2020 ◽

Author(s):

Emma L Watson ◽

Thomas J Wilkinson ◽

Tom F O’Sullivan ◽

Luke A Baker ◽

Douglas W Gould ◽

...

Keyword(s):

Skeletal Muscle ◽

Vitamin D ◽

Vitamin D Deficiency ◽

Exercise Capacity ◽

Muscle Mass ◽

Ex Vivo ◽

Muscle Size ◽

Cross Sectional ◽

Cross Sectional Analysis ◽

Sectional Analysis

AbstractEvidence is growing for a role of vitamin D in regulating skeletal muscle mass, strength and functional capacity. Given the role the kidneys play in activating total vitamin D, and the high prevalence of vitamin D deficiency in Chronic Kidney Disease (CKD), it is possible that deficiency contributes to the low levels of physical function and muscle mass in these patients. This is a secondary cross-sectional analysis of previously published interventional study, with ex vivo follow up work. 34 CKD patients at stages G3b-5 (eGFR 25.5 ± 8.3ml/min/1.73m2; age 61 ± 12 years) were recruited, with a sub-group (n=20) also donating a muscle biopsy. Vitamin D and associated metabolites were analysed in plasma by liquid chromatography tandem-mass spectroscopy and correlated to a range of physiological tests of muscle size, function, exercise capacity and body composition. The effects of 1α,25(OH)2D3 supplementation on myogenesis and myotube size was investigated in primary skeletal muscle cells from vitamin D deficient donors. In vivo, there was no association between total or active vitamin D and muscle size or strength, but a significant correlation with was seen with the total form. Ex vivo, 1α,25(OH)2D3 supplementation reduced IL-6 mRNA expression, but had no effect upon proliferation, differentiation or myotube diameter. This early preliminary work suggests that vitamin D deficiency is not a prominent factor driving the loss of muscle mass in CKD, but may play a role in reduced exercise capacity.

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Waddling Gait: A complication of valproate therapy and a thought beyond vitamin D deficiency

Sultan Qaboos University Medical Journal [SQUMJ] ◽

10.18295/squmj.2020.20.01.016 ◽

2020 ◽

Vol 20 (1) ◽

pp. 104 ◽

Cited By ~ 1

Author(s):

Amit Sharma ◽

Siddhartha Sinha ◽

Amit Narang ◽

Dushyant K. Chouhan ◽

Sumit Gupta

Keyword(s):

Vitamin D ◽

Vitamin D Deficiency ◽

Sodium Valproate ◽

Muscle Weakness ◽

Serum Alkaline Phosphatase ◽

Elevated Serum ◽

Drug Induced ◽

Childhood Disorders ◽

Abnormal Gait ◽

Proximal Myopathy

Proximal muscle weakness is a common presentation in paediatric-orthopaedic clinics and is frequently paired with a vitamin D deficiency diagnosis. Recently, side effects of the extensive use of antiepileptic and antipsychotic drugs such as sodium valproate in childhood disorders are being documented. Sodium valproate causes a time-dependent, drug-induced proximal myopathy. We report a 13-year-old female patient who presented at the Orthopaedic Outpatient Department at Lady Hardinge Medical College, New Delhi, India, in 2019 with an abnormal gait. The patient was taking a combination therapy of sodium valproate, risperidone and trihexyphenidyl for absence seizures and a mood disorder. Following clinical investigations, the patient was diagnosed with proximal myopathy. As a result of elevated serum alkaline phosphatase and creatine kinase myocardial band levels, sodium valproate was replaced with ethosuximide and a carnitine supplementation was prescribed. The patient fully recovered and regained full mobility. Proximal myopathy had been incorrectly managed and assumed to be caused by a vitamin D deficiency.Keywords: Muscle Weakness; Carnitine; Myopathy; Valproic Acid; Vitamin D Deficiency; Gait; Case Report; India.

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Vitamin D Deficiency Promotes Skeletal Muscle Hypersensitivity and Sensory Hyperinnervation

Journal of Neuroscience ◽

10.1523/jneurosci.3637-11.2011 ◽

2011 ◽

Vol 31 (39) ◽

pp. 13728-13738 ◽

Cited By ~ 72

Author(s):

S. E. Tague ◽

G. L. Clarke ◽

M. K. Winter ◽

K. E. McCarson ◽

D. E. Wright ◽

...

Keyword(s):

Skeletal Muscle ◽

Vitamin D ◽

Vitamin D Deficiency

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Exercise and Dietary-Protein as a Countermeasure to Skeletal Muscle Weakness: Liverpool Hope University – Sarcopenia Aging Trial (LHU-SAT)

Frontiers in Physiology ◽

10.3389/fphys.2019.00445 ◽

2019 ◽

Vol 10 ◽

Cited By ~ 17

Author(s):

Ben Kirk ◽

Kate Mooney ◽

Farzad Amirabdollahian ◽

Omid Khaiyat

Keyword(s):

Skeletal Muscle ◽

Muscle Weakness ◽

Dietary Protein ◽

Skeletal Muscle Weakness

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Prevalence and Correction of 25(OH) Vitamin D Deficiency in Peritoneal Dialysis Patients

Peritoneal Dialysis International ◽

10.1177/089686080502500411 ◽

2005 ◽

Vol 25 (4) ◽

pp. 362-366 ◽

Cited By ~ 61

Author(s):

Nirav Shah ◽

Judith Bernardini ◽

Beth Piraino

Keyword(s):

Vitamin D ◽

Peritoneal Dialysis ◽

Calcium Phosphate ◽

Vitamin D Deficiency ◽

Muscle Weakness ◽

Serum Calcium ◽

Bone Pain ◽

Vitamin D Levels ◽

Before And After ◽

25 Oh Vitamin D

Background Peritoneal dialysis (PD) patients are at risk for 25(OH) vitamin D deficiency due to effluent loss in addition to traditional risk factors. Objectives To measure 25(OH) vitamin D deficiency in prevalent PD patients, to evaluate a replacement dose, and to determine the effects of correction. Methods 25(OH) vitamin D levels were drawn on prevalent PD patients. Patients deficient in 25(OH) vitamin D were given ergocalciferol, 50 000 IU orally once per week for 4 weeks. Patients scored muscle weakness, bone pain, and fatigue on a scale of 0 (none) to 5 (severe). Serum calcium, phosphate, parathyroid hormone (PTH), and 25(OH) vitamin D, and 1,25(OH)2 vitamin D levels were obtained before and after treatment. Results 25(OH) vitamin D levels were measured in 29 PD patients. Deficiency (<15 ng/mL) was found in 28/29 (97%); 25/29 (86%) had undetectable levels (<7 ng/mL). One course of ergocalciferol corrected the deficiency in all but 1 patient, who required a second course. Scores for muscle weakness and bone pain fell from pre- to posttreatment ( p < 0.001). 1,25(OH)2 vitamin D levels rose post ergocalciferol (from 20 to 26 pg/mL, n = 20, p = 0.09). Serum calcium, phosphate, and PTH levels did not change with ergocalciferol. Conclusions Most PD patients had marked 25(OH) vitamin D deficiency, which was readily and safely corrected with one course of 50000 IU ergocalciferol, having no effect on serum calcium, phosphorus, or PTH, but complaints of muscle weakness and bone pain decreased. A prospective, placebo-controlled double-blinded study is needed to determine whether replacement of 25(OH) vitamin D is beneficial in PD patients.

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