cholecalciferol and Pain

Sickle cell disease (SCD) is a genetic chronic haemolytic and pro-inflammatory disorder. With increased catabolism and deficits in energy and nutrient intake, individuals with SCD suffer multiple macro- and micro-nutritional deficiencies, including vitamin D deficiency. This is an update of a previous review.. To investigate the effects of vitamin D supplementation in children and adults with SCD and to compare different dose regimens. To determine the effects of vitamin D supplementation on general health (e.g. growth status and health-related quality of life), on musculoskeletal health (including bone mineral density, pain crises, bone fracture and muscle health), on respiratory health (including lung function, acute chest syndrome, acute exacerbation of asthma and respiratory infections) and the safety of vitamin D supplementation.. We searched the Cochrane Haemoglobinopathies Trials Register, compiled from electronic database searches and handsearching of journals and conference abstract books. Date of last search: 19 March 2020. We also searched database such as PubMed, clinical trial registries and the reference lists of relevant articles and reviews. Date of last search: 14 January 2020.. Randomised controlled trials (RCTs) and quasi-RCTs comparing oral administration of any form of vitamin D supplementation at any dose and for any duration to another type or dose of vitamin D or placebo or no supplementation in people with SCD, of all ages, gender, and phenotypes.. Two authors independently extracted the data and assessed the risk of bias of the included studies. They used the GRADE guidelines to assess the quality of the evidence.. Vitamin D versus placebo One double-blind RCT (n = 39) compared oral vitamin D3 (cholecalciferol) supplementation (20 participants) to placebo (19 participants) for six weeks. Only 25 participants completed the full six months of follow-up. The study had a high risk of bias due to incomplete outcome data, but a low risk of bias for randomisation, allocation concealment, blinding (of participants, personnel and outcome assessors) and selective outcome reporting; and an unclear risk of other biases. Vitamin D supplementation probably led to higher serum 25(OH)D levels at eight weeks, mean difference (MD) 29.79 (95% confidence interval (CI) 26.63 to 32.95); at 16 weeks, MD 12.67 (95% CI 10.43 to 14.90); and at 24 weeks, MD 15.52 (95% CI 13.50 to 17.54) (moderate-quality evidence). There was little or no difference in adverse events (tingling of lips or hands) between the vitamin D and placebo groups, risk ratio 3.16 (95% CI 0.14 to 72.84) (low-quality evidence). Vitamin D supplementation probably caused fewer pain days compared to the placebo group at eight weeks, MD -10.00 (95% CI -16.47 to -3.53) (low-quality evidence), but probably led to a lower (worse) health-related quality of life score (change from baseline in physical functioning PedsQL scores); at both 16 weeks, MD -12.56 (95% CI -16.44 to -8.69) and 24 weeks, MD -12.59 (95% CI -17.43 to -7.76), although this may not be the case at eight weeks (low-quality evidence). Vitamin D supplementation regimens compared Two double-blind RCTs (83 participants) compared different regimens of vitamin D. One RCT (n = 62) compared oral vitamin D3 7000 IU/day to 4000 IU/day for 12 weeks, while the second RCT (n = 21) compared oral vitamin D3 100,000 IU/month to 12,000 IU/month for 24 months. Both RCTs had low risk of bias for blinding (of participants, personnel and outcome assessors) and incomplete outcome data, but the risk of selective outcome reporting bias was high. The bias from randomisation and allocation concealment was low in one study but not in the second. There was an unclear risk of other biases. When comparing oral vitamin D 100,000 IU/month to 12,000 IU/month, the higher dose may have resulted in higher serum 25(OH)D levels at one year, MD 16.40 (95% CI 12.59 to 20.21) and at two years, MD 18.96 (95% CI 15.20 to 22.72) (low-quality evidence). There was little or no difference in adverse events between doses (low-quality evidence). There were more episodes of acute chest syndrome in the high-dose gr. We included three RCTs of varying quality. We consider that the current evidence presented in this review is not of sufficient quality to guide clinical practice. Until further evidence becomes available, clinicians should consider the relevant existing guidelines for vitamin D supplementation and dietary reference intakes for calcium and vitamin D. Well-designed RCTs of parallel design, are required to determine the effects and the safety of vitamin D supplementation as well as to assess the relative benefits of different doses in children and adults with SCD.

Topics: Administration, Oral; Anemia, Sickle Cell; Bias; Child; Cholecalciferol; Humans; Pain; Quality of Life; Randomized Controlled Trials as Topic; Time Factors; Vitamin D; Vitamin D Deficiency

We conducted a meta-analysis of RCTs to evaluate the effects of vitamin D supplementation in the prevention of symptom and structural progression of knee OA.. PubMed, Embase, and Web of Science databases were searched to identify relevant studies. Outcomes included Western Ontario and McMaster Universities Arthritis Index (WOMAC) pain, function, stiffness, tibial cartilage volume, and serum vitamin D3 levels, and adverse events. Results were expressed as weight mean difference (WMD) with 95% confidence interval (CI), and risk ratio (RR) with 95%CI.. Four RCTs involving 1136 patients were included in this study. Pooled estimates suggested that vitamin D supplementation was associated with a significant reduction in WOMAC pain, and WOMAC function, but not in WOMAC stiffness. Vitamin D supplementation increased the serum vitamin D3 level, but had no effect on tibial cartilage volume. Subgroup analysis showed that, a daily supplement of more than 2000 IU vitamin D significantly decreased the WOMAC pain and WOMAC function. There was no significant difference in incidence of adverse events between the vitamin D and placebo groups.. Vitamin D supplementation was effective in improving the WOMAC pain and function in patients with knee OA. However, it had no beneficial effect on the prevention of tibial cartilage loss. Therefore, there is currently a lack of evidence to support the use of vitamin D supplementation in preventing the progression of knee OA.

Topics: Aged; Cholecalciferol; Dietary Supplements; Disease Progression; Female; Humans; Knee Joint; Male; Middle Aged; Osteoarthritis, Knee; Pain; Pain Measurement; Randomized Controlled Trials as Topic; Tibia; Treatment Outcome; Vitamin D; Vitamins

Sickle cell disease is a genetic chronic haemolytic and pro-inflammatory disorder. The clinical manifestations of sickle cell disease result from the presence of mutations on the beta globin genes that generate an abnormal haemoglobin product (called haemoglobin S) within the red blood cell. Sickle cell disease can lead to many complications such as acute chest syndrome, stroke, acute and chronic bone complications (including painful vaso-occlusive crisis, osteomyelitis, osteonecrosis and osteoporosis). With increased catabolism and deficits in energy and nutrient intake, individuals with sickle cell disease suffer multiple macro- and micro-nutritional deficiencies, including vitamin D deficiency. Since vitamin D maintains calcium homeostasis and is essential for bone mineralisation, its deficiency may worsen musculoskeletal health problems encountered in sickle cell disease. Therefore, there is a need to review the effects and the safety of vitamin D supplementation in sickle cell disease.. To investigate the hypothesis that vitamin D supplementation increases serum 25-hydroxyvitamin D level in children and adults with sickle cell disease.To determine the effects of vitamin D supplementation on general health such as growth status and health-related quality of life; on musculoskeletal health including bone mineral density, pain crises, bone fracture and muscle health; on respiratory health which includes lung function tests, acute chest syndrome, acute exacerbation of asthma and respiratory infections; and the safety of vitamin D supplementation in children and adults with sickle cell disease.. We searched the Cochrane Haemoglobinopathies Trials Register, compiled from electronic database searches and handsearching of journals and conference abstract books. We also searched database such as PubMed, clinical trial registries and the reference lists of relevant articles and reviews.Date of last search: 15 December 2016.. Randomised controlled studies and quasi-randomised controlled studies (controlled clinical studies) comparing oral administration of any form of vitamin D supplementation to another type of vitamin D or placebo or no supplementation at any dose and for any duration, in people with sickle cell disease, of all ages, gender, and phenotypes including sickle cell anaemia, haemoglobin sickle cell disease and sickle beta-thalassaemia diseases.. Two authors independently extracted the data and assessed the risk of bias of the included study. They used the GRADE guidelines to assess the quality of the evidence.. One double-blind randomised controlled study including 46 people with sickle cell disease (HbSS, HbSC, HbSβ+thal and HbSβ0thal) was eligible for inclusion in this review. Of the 46 enrolled participants, seven withdrew before randomisation leaving 39 participants who were randomised. Only 25 participants completed the full six months of follow up. Participants were randomised to receive oral vitamin D3 (cholecalciferol) (n = 20) or placebo (n = 19) for six weeks and were followed up to six months. Two participants from the treatment group have missing values of baseline serum 25-hydroxyvitamin D, therefore the number of samples analysed was 37 (vitamin D n = 18, placebo n = 19).The included study had a high risk of bias with regards to incomplete outcome data (high dropout rate in the placebo group), but a low risk of bias for other domains such as random sequence generation, allocation concealment, blinding of participants, personnel and outcome assessors, selective outcome reporting; and an unclear risk of other biases.Compared to the placebo group, the vitamin D group had significantly higher serum 25-hydroxyvitamin D (25(OH)D) levels at eight weeks, mean difference 29.79 (95% confidence interval 26.63 to 32.95); at 16 weeks, mean difference 12.67 (95% confidence interval 10.43 to 14.90); and at 24 weeks, mean difference 15.52 (95% confidence interval 13.50 to 17.54). We determined the quality of the evidence for this outcome to be moderate. There was no significant difference of adverse events (tingling of lips or hands) between the vitamin D and placebo groups, risk ratio 3.16 (95% confidence interval 0.14 to 72.84), but the quality of the evidence was low. Regarding the frequency of pain, the vitamin D group had significantly fewer pain days compared to the placebo group, mean difference -10.00 (95% confidence interval -16.47 to -3.53), but again the quality of the evidence was low. Furthermore, the review included physical functioning PedsQL scores which was reported as absolute change from baseline. The vitamin D group had a lower (worse) health-related quality of life score than the placebo group but this was not significant at eight weeks, mean difference -2.02 (95% confidence interval -6.34 to 2.30). However, the difference was significant at both 16 weeks, mean difference -12.56 (95% confidence interval -16.44 to -8.69) and 24 weeks, mean difference -12.59 (95% confidence interval -17.43 to -7.76). We determined the quality of evidence for thi. We included only one low-quality clinical study which had a high risk of bias with regards to incomplete outcome data. Therefore, we consider that the evidence is not of sufficient quality to guide clinical practice. Until further evidence becomes available, clinicians should consider the relevant existing guidelines for vitamin D supplementation (e.g. the Endocrine Society Clinical Practice Guidelines) and dietary reference intakes for calcium and vitamin D (e.g. from the USA Institute of Medicine). Evidence of vitamin D supplementation in sickle cell disease from high quality studies is needed. Well-designed, randomised, placebo-controlled studies of parallel design, are required to determine the effects and the safety of vitamin D supplementation in children and adults with sickle cell disease.

Topics: Anemia, Sickle Cell; Cholecalciferol; Humans; Pain; Quality of Life; Randomized Controlled Trials as Topic; Time Factors; Vitamin D; Vitamin D Deficiency

Oncogenic osteomalacia (OOM) is a rare paraneoplastic syndrome induced by tumor produced phosphaturic factors, i.e. phosphatonins. The disorder is characterized by renal tubular phosphate loss, secondary to this process hypophosphatemia and defective production of active form of vitamin D. The clinical course of oncogenic osteomalacia is characterized by bone pain, pathological fractures, muscle weakness and general fatigue. Osteomalacia-associated tumors are usually located in the upper and lower limbs, with half of the lesions primarily situated in the bones. Most of them are small, slow-growing tumors. Their insignificant size and various location coupled with rare occurrence of the disease and non-specificity of clinical symptoms lead to difficulties in reaching a diagnosis, which is often time-consuming and requires a number of additional tests. The average time between the appearance of the first symptoms and the establishment of an accurate diagnosis and the beginning of treatment is over 2.5 years. The aim of this study is to discuss the pathophysiology of disease symptoms, pathomorphology of tumors, diagnostic methods and treatment of oncogenic osteomalacia.

Topics: Biopsy; Bone and Bones; Cholecalciferol; Diagnostic Imaging; Fibroblast Growth Factor-23; Fibroblast Growth Factors; Fractures, Spontaneous; Humans; Hypophosphatemia; Neoplasms, Connective Tissue; Osteomalacia; Pain; Paraneoplastic Syndromes; Somatostatin

Women have a higher prevalence than men of several clinical pain conditions and of inflammation-mediated disorders. There is also increasing evidence for sex differences in sensitivity to experimental pain and in the response to analgesics. Estrogen, progesterone, and other gonadal hormones have a complex role in inflammatory processes and the pain response. Microglia cells in the central nervous system, which have sex hormone receptors, become activated in response to inflammatory stimuli, releasing cytokines and other mediators that are pronociceptive and can amplify the pain response. Although the mechanisms underlying sex differences in pain and analgesia have not been fully elucidated, both peripheral and central nervous systems pathways may be involved. Sex differences in the opioid, dopaminergic, serotoninergic, and other pain-related systems have been documented; and some evidence suggests that differences are most pronounced during the peak reproductive years. Psychosocial factors also play an important role. Given the important role of inflammation in mediating pain, nutritional factors that modulate the inflammatory response offer a promising and exciting new avenue for the prevention and treatment of chronic pain disorders. Of particular interest is the potential role of moderate- to high-dose vitamin D and omega-3 fatty acid supplements, both of which have powerful anti-inflammatory effects. These nutritional interventions, which influence cytokine, leukotriene, and prostaglandin pathways, may be of particular benefit to women due to their higher prevalence of inflammatory chronic pain disorders. The recent launch of a new large-scale randomized trial of these nutritional supplements provides an opportunity to assess their potential antinociceptive role. Additional research is needed to clarify the mechanisms for sex differences in pain and to develop new treatment modalities that improve pain management for both men and women.

Topics: Cholecalciferol; Fatty Acids, Omega-3; Female; Gonadal Steroid Hormones; Humans; Male; Pain; Prevalence; Randomized Controlled Trials as Topic; Sex Characteristics

Osteoarthritis (OA) is a major cause of pain and disability worldwide. Despite the relatively high burden of the disease, the currently available non-surgical treatment options are directed towards symptomatic relief. Therefore, we propose the use of alendronate as a disease modifying agent to help slow and prevent OA. In addition, this study will utilize Whole-Organ Magnetic Resonance Imaging Score (WORMS) to evaluate the structural integrity of cartilage in the study population. High-quality evidence, limited to a few well-conducted randomized trials, highlights contradictory results on the effect of bisphosphonates on knee function and progression of OA. Therefore, a placebo-controlled, randomized trial is needed to evaluate the combined effect of alendronate and vit D on the structure of cartilage utilizing the WORMS score and its ability to treat knee pain in OA patients.. This multicenter, randomized, double-blinded, placebo-controlled study will evaluate the efficacy and safety of alendronate in early OA. Patients will undergo a 1:1 double-blinded randomization to receive a one-year course of either alendronate sodium vitamin D. This trial will give helpful and high-quality evidence regarding the potential therapeutic role of alendronate sodium vitamin D3, as compared to placebo, in the management of patients with knee OA regarding its role on cartilage loss, radiographic progression of OA, severity of OA, knee pain, quality of life, and inflammatory biomarkers. If proven effective, this intervention would be a great option for providing beneficial outcomes with a reduced cost in this patient population.. This trial was registered on clinicaltrials.gov (registration number: NCT04739592 ).

Topics: Alendronate; Cholecalciferol; Double-Blind Method; Humans; Knee Joint; Multicenter Studies as Topic; Osteoarthritis, Knee; Pain; Quality of Life; Randomized Controlled Trials as Topic; Tablets; Treatment Outcome; Vitamin D

Previous studies have reported that vitamin D supplement could improve fracture healing, but evidence regarding the role of vitamin D supplements in spinal fusion was limited. Thus, this study aimed to evaluate the effectiveness of oral vitamin D supplements on fusion outcomes in patients undergoing lumbar spinal fusion.. This randomized, double-blind, parallel-designed, active-control trial included the patients who planned for elective lumbar spinal fusion. Eligible patients were randomly assigned to receive either daily vitamin D3 (cholecalciferol) 800 IU and daily calcium citrate 600 mg (experimental group) or only daily calcium citrate 600 mg (control group). All supplements were given from postoperative day 1 and lasted for 3 months. Primary outcome was postoperative 1-year fusion rate, and secondary outcomes included time to fusion, Oswestry Disability Index (ODI), and visual analogue scale (VAS) for pain.. Among the included 34 patients (21 in the experimental group and 13 in the control group), baseline 25-hydroxyvitamin D (25[OHVitD) level was 26.7 (10.4) ng/ml. Preoperative prevalence of vitamin D deficiency and insufficiency were 23.5% and 47.1%, respectively. Postoperative 1-year fusion rate was not significantly different between the two groups (95.2% vs. 84.6%, P = 0.544). The experimental group had significantly shorter time to fusion (Kaplan-Meier estimated: 169 days vs. 185 days [interquartile range: 88-182 days vs. 176-324 days], log-rank test: P = 0.028), lower postoperative 6-month ODI (P < 0.001), and lower postoperative 6-month VAS (P < 0.001) than the control group. Time to fusion was significantly and negatively correlated with preoperative, postoperative 3-month, and 6-month 25(OH)VitD levels (all P < 0.01).. The patient with vitamin D supplements had shorter time to fusion, better spinal function and less pain after elective spinal fusion. Further research is warranted to identify the patients who can benefit the most from vitamin D supplements and the appropriate dose of vitamin D supplements.. ClinicalTrials.gov, NCT05023122. Registered 20 August 2021. Retrospectively registered, http://clinicaltrials.gov/ct2/show/NCT03793530 .

Topics: Calcium Citrate; Cholecalciferol; Humans; Pain; Spinal Diseases; Spinal Fusion; Vitamin D; Vitamins

Findings on the effects of vitamin D on cognitive performance have been inconsistent and no clinical trials with detailed cognitive testing in healthy older adults have been reported.. We tested whether 2000 IU is superior to 800 IU vitamin D3/d for cognitive performance among relatively healthy older adults.. We analyzed data on cognitive performance as the secondary outcome of a 2-y double-blind randomized controlled trial that originally investigated the effect of vitamin D3 on knee function and pain in seniors with osteoarthritis. Participants were randomly assigned to either 2000 or 800 IU vitamin D3/d. Capsules had identical appearances and taste. A total of 273 community-dwelling older adults aged ≥60 y were enrolled 6-8 wk after unilateral joint replacement. Inclusion required a baseline Mini Mental State Examination (MMSE) score of 24. We implemented a detailed 2-h cognitive test battery. The primary cognitive endpoint was the score achieved in the MMSE. Secondary endpoints included a composite score of 7 executive function tests, auditory verbal and visual design learning tests, and reaction times.. At baseline, mean age was 70.3 y, 31.4% were vitamin D-deficient [25(OH)D <20 ng/mL], and mean ± SD MMSE score was 28.0 ± 1.5. Although the mean ± SD 25(OH)D concentrations achieved differed significantly between treatment groups at 24-mo follow-up (2000 IU = 45.1 ± 10.2 ng/mL; 800 IU = 37.5 ± 8.8 ng/mL; P < 0.0001), none of the primary or secondary endpoints of cognitive performance differed between treatment group. Results by treatment were similar for predefined subgroups of baseline 25(OH)D status (deficient compared with replete) and age (60-69 y compared with ≥70 y).. Our study does not support a superior cognitive benefit of 2000 IU compared with 800 IU vitamin D/d among relatively healthy older adults over a 24-mo treatment period. This trial was registered at clinicaltrials.gov as NCT00599807.

Topics: Aged; Cholecalciferol; Cognition; Dietary Supplements; Dose-Response Relationship, Drug; Double-Blind Method; Female; Humans; Male; Memory; Middle Aged; Osteoarthritis, Knee; Pain; Reaction Time; Vitamin D; Vitamin D Deficiency

There is limited evidence on effectiveness of calcium and vitamin D on dysmenorrhea. The authors aimed to determine the effect of combined calcium-vitamin D and calcium-alone on pain intensity and menstrual blood loss in women with primary dysmenorrhea.. A randomized double-blind trial.. Dormitories of Tabriz University of Medical Sciences.. 85 students with moderate or severe primary dysmenorrhea.. Participants were randomized into three groups: receiving one tablet/day of 1000 mg calcium + 5000 IU vitamin D3, calcium-alone 1000 mg, or matched placebo, from 15th cycle day until menstrual pain disappearance in the following cycle, for three cycles. Pain intensity and menstrual blood loss were assessed one cycle before, three cycles under, and one cycle following intervention using 10-cm visual analog scale and pictorial blood loss assessment chart, respectively. The groups were compared using repeated measures ANOVA.. Time after intervention and interaction of time with group had no significant effects on the outcomes. Compared to the placebo group, mean pain intensity was lower in the both calcium-vitamin D (adjusted difference -0.7, 95% confidence interval -1.6 to 0.3) and calcium-alone (-1.6, -2.6 to -0.6) groups, but the difference was statistically significant only in the calcium-alone group. Menstrual blood loss was not significantly different in the either calcium-vitamin D (-4.7, -21.9 to 12.4) or calcium-alone (-0.4, -17.4 to 16.4) groups compared to placebo.. Intake of the calcium-alone was effective in reducing menstrual pain intensity. The results could not indicate significant effects of calcium-vitamin D on the pain or any of the interventions on menstrual blood loss.. This study was approved by the Ethics committee of Tabriz University of Medical Sciences (code 92145) and registered at the Iranian Registry of Clinical Trials with IRCT201402043706N21.

Topics: Adolescent; Adult; Calcium; Cholecalciferol; Double-Blind Method; Dysmenorrhea; Female; Humans; Menstruation; Pain; Young Adult

Vitamin D deficiency has potential roles in breast cancer etiology and progression. Vitamin D deficiency has also been associated with increased toxicity from bisphosphonate therapy. The optimal dose of vitamin D supplementation is unknown, but daily sunlight exposure can generate the equivalent of a 10,000-IU oral dose of vitamin D(3). This study therefore aimed to assess the effect of this dose of vitamin D(3) in patients with bone metastases from breast cancer.. Patients with bone metastases treated with bisphosphonates were enrolled into this single-arm phase 2 study. Patients received 10,000 IU of vitamin D(3) and 1000 mg of calcium supplementation each day for 4 months. The effect of this treatment on palliation, bone resorption markers, calcium metabolism, and toxicity were evaluated at baseline and monthly thereafter.. Forty patients were enrolled. No significant changes in bone resorption markers were seen. Despite no change in global pain scales, there was a significant reduction in the number of sites of pain. A small but statistically significant increase in serum calcium was seen, as was a significant decrease in serum parathyroid hormone. Treatment unmasked 2 cases of primary hyperparathyroidism, but was not associated with direct toxicity.. Daily doses of 10,000 IU vitamin D(3) for 4 months appear safe in patients without comorbid conditions causing hypersensitivity to vitamin D. Treatment reduced inappropriately elevated parathyroid hormone levels, presumably caused by long-term bisphosphonate use. There did not appear to be a significant palliative benefit nor any significant change in bone resorption.

Topics: Adult; Aged; Aged, 80 and over; Biomarkers; Bone Neoplasms; Bone Resorption; Breast Neoplasms; Cholecalciferol; Dietary Supplements; Diphosphonates; Female; Humans; Hypoparathyroidism; Middle Aged; Pain

We aimed to compare and evaluate the efficacies of a continuous regimen of intranasal salmon calcitonin (SCT) and two cyclic regimens (different cyclic regimens from previous studies) based on alternating 15 days or on 10 days consecutively per month for 1 year in the treatment of postmenopausal osteoporosis. We performed an open-label, prospective, randomized clinical trial. A total of 120 postmenopausal osteoporotic participants between 50 and 65 years old were randomly assigned to one of three treatment groups. Patients in group 1 (n = 40) received continuously SCT nasal spray at a dose of 200 IU/day, plus continuously 500 mg/day elementary calcium and 0.25 microg/day 1-alpha hydroxyvitamin D3, for 1 year. Patients in group 2 (n = 40) received cyclically SCT nasal spray at a dose of 200 IU/day on alternating 15 days per month, plus continuously 500 mg/day elementary calcium and 0.25 microg/day 1-alpha hydroxyvitamin D3, for 1 year. Patients in group 3 (n = 40) received cyclically SCT nasal spray on 10 days consecutively per month (20 days/month rest), plus continuously 500 mg/day elementary calcium and 0.25 microg/day 1-alpha hydroxyvitamin D3, for 1 year. Data was evaluated by repeated analysis of variance (ANOVA). In addition, statistical differences between groups were assessed by the two-tailed Student's t test. After 1 year of the study, seven patients from group 1, eight patients from group 2 and five patients from group 3 withdrew from the study. No patient discontinued the study because of adverse drug effects. There was a statistically-significant improvement in pain intensity VAS scores at the end of the year to baseline scores in all three groups (p < 0.001). There was no significant difference in pain intensity VAS scores between groups at the end of the year (p > 0.05). Lumbar and femur neck BMD scores improved significantly at the end of treatment in all three groups (p < 0.05). There was no statistically-significant difference in BMD scores between groups at final (p > 0.05). Urinary DPD/Cre levels decreased significantly in all three groups by the end of the year (p < 0.05). There was no statistically-significant difference in urinary DPD/Cre final levels between groups (p > 0.05). According to the results of the present study, consecutive 10 days therapy with SCT, which is the first in the literature to our knowledge, is as effective as the other two regimens in the treatment of osteoporosis. Both cyclic regimens in our study (alternat

Topics: Administration, Inhalation; Administration, Intranasal; Aged; Bone and Bones; Bone Density; Bone Density Conservation Agents; Calcitonin; Calcium; Cholecalciferol; Drug Administration Schedule; Drug Therapy, Combination; Female; Humans; Middle Aged; Osteoporosis, Postmenopausal; Pain; Radiography

This trial aimed to determine the possible therapeutic and immunomodulatory effects of vitamin D3 in patients with knee OA. In this open-label clinical trial, symptoms were assessed over 3 months in patients with primary knee OA receiving oral vitamin D3 4000 IU/day. Clinical response was evaluated at baseline and 3 months using WOMAC subscores and VAS. Serum levels of cytokines IL-1β, TNF-α, IL-13, IL-17, IL-33, IL-4, and IL-10 were determined by ELISA method. Eighty patients with knee OA were included. All 80 completed the study; the median 25(OH)D3 level was 23.1 ng/ml at baseline and increased by 12.3 ng/ml after treatment. Vitamin D3 after 3 months of supplementation induced a significant reduction in VAS pain and WOMAC subscores. Using OMERACT-OARSI criteria, 86.7% of patients treated with vitamin D3 responded to treatment. At the end of 3 months, systemic values of IL-1β (p < 0.01), IL-23 (p < 0.01), and IL-33 (p < 0.01) were significantly increased, values of TNF-α (p < 0.01), IL-13 (p < 0.01), and IL-17 (p < 0.01) were significantly decreased, while value of IL-4 was not significantly changed. No adverse events were detected. Treatment with vitamin D is associated with improvement in pain, as well as stiffness and physical function. Vitamin D supplementation increased systemic values of IL-33. Our results indicate that vitamin D3 supplementation may be used as a novel therapeutic in knee OA. Future studies are needed to investigate a potential role of IL-33 in the pathogenesis of knee OA.

Topics: Cholecalciferol; Dietary Supplements; Double-Blind Method; Humans; Inflammation; Inflammation Mediators; Interleukin-13; Interleukin-17; Interleukin-33; Osteoarthritis, Knee; Pain; Tumor Necrosis Factor-alpha; Vitamin D

Vitamin D deficiency is now recognized as an independent risk factor and is involved in the pathogenesis of carpal tunnel syndrome (CTS). The purpose of this study was to evaluate the effects of vitamin D. A total of 42 patients were analyzed. At 3 months posttreatment, there was a significant reduction in the severity of pain (VAS score) from baseline (. Vitamin D

Topics: Carpal Tunnel Syndrome; Cholecalciferol; Humans; Pain; Prospective Studies; Vitamin D Deficiency

Topics: Adolescent; Ascorbic Acid; Chest Pain; Cholecalciferol; Dietary Supplements; Echocardiography; Gingiva; Hemorrhage; Humans; Hypertension, Pulmonary; Iron; Leg; Male; Pain; Scurvy; Wounds and Injuries

Osteoarthritis (OA) is the most common type of arthritis and proinflammatory cytokines have been considered as the main etiologic factor in the pathogenesis of the disease. Serum levels of cytokines, that are associated with innate immunity and TH1 cells, have been analyzed in OA patients, however, there is limited research that profiles cytokines associated with Th17 cells and their relation to vitamin D3 and pain.. The sera from 131 patients with OA and 262 healthy controls were evaluated for serum levels of IL-17A, IL-21, IL-23 and vitamin D3 using ELISA.. Serum levels of IL-17A, and IL-23 were statistically higher in OA patients than in healthy controls, while IL-21 and vitamin D3 were significantly lower in OA patients when compared to controls. A significant positive correlation was found between the serum levels of IL-17A and IL-23 using WOMAC pain scores and vitamin D3 serum levels.. The results suggest that IL-17A plays a significant role in OA pathogenesis and the induction of pain. Decreased serum levels of vitamin D3 may reflect a positive role played by the factor in the regulation of immune responses in OA patients.

Topics: Adult; Case-Control Studies; Cholecalciferol; Cross-Sectional Studies; Female; Humans; Interleukin-17; Interleukin-23; Interleukins; Male; Osteoarthritis; Pain

The human glycine receptors (hGlyRs) are chloride-selective ion channels that mediate inhibitory neurotransmission in the brain stem and spinal cord. They are also targets for compounds of potential use in analgesic therapies. Here, we develop a strategy to discover analgesic drugs via structure-based virtual screening based on the recently published NMR structure of the hGlyR-α1 transmembrane domain (PDB ID: 2M6I ) and the critical role of residue S296 in hGlyR-α1 potentiation by Δ(9)-tetrahydrocannabinol (THC). We screened 1549 FDA-approved drugs in the DrugBank database on an ensemble of 180 hGlyR-α1 structures generated from molecular dynamics simulations of the NMR structure of the hGlyR-α1 transmembrane domain in different lipid environments. Thirteen hit compounds from the screening were selected for functional validation in Xenopus laevis oocytes expressing hGlyR-α1. Only one compound showed no potentiation effects; seven potentiated hGlyR-α1 at a level greater than THC at 1 μM. Our virtual screening protocol is generally applicable to drug targets with lipid-facing binding sites.

Topics: Analgesics, Non-Narcotic; Animals; Binding Sites; Cannabinoids; Drug Evaluation, Preclinical; Female; Lipids; Molecular Dynamics Simulation; Molecular Targeted Therapy; Nuclear Magnetic Resonance, Biomolecular; Oocytes; Pain; Protein Conformation; Protein Structure, Tertiary; Receptors, Glycine; Reproducibility of Results; Xenopus laevis

To assess the effect of active vitamin D3 on quality of life (QOL) and pain in raloxifene-treated Japanese women with postmenopausal osteoporosis.. This is a post hoc analysis of a previous prospective postmarketing observational study conducted without a comparator group. This study was conducted in 60 Japanese hospitals from September 2007 to February 2009. We compared changes from baseline in QOL and pain in patients receiving raloxifene plus active vitamin D3 with those in patients receiving raloxifene monotherapy at 8 and 24 weeks after treatment.. Japan Pharmaceutical Information Center (JapicCTI-070465).. QOL and pain were assessed using Short Form-8 (SF-8), European Quality of Life Instrument 5 Dimensions (EQ-5D), Japanese Osteoporosis Quality of Life Questionnaire (JOQOL), visual analogue pain scales (VAS pain), and pain frequency scores.. A total of 506 patients were included in the post hoc analysis. Both raloxifene monotherapy (RLX, n = 354) and active vitamin D3 cotreatment (COMBI, n = 152) significantly improved QOL and reduced pain from the baseline at Week 8 and Week 24. The COMBI group had significantly greater improvements in JOQOL total score and activity of daily living (total) domain at Week 24 and last observation carried forward (LOCF) than the RLX group. The COMBI group also had significantly greater improvements in SF-8 domains of general health (at Week 8, Week 24, and LOCF), role physical (at Week 24 and LOCF), and mental health (at LOCF) than the RLX group. The COMBI group also had significantly greater reduction in VAS pain at LOCF than the RLX group (mean [SD]: RLX = -0.99 [2.72], COMBI = -1.54 [2.21], P = 0.042).. Active vitamin D3 supplementation to raloxifene treatment for 24 weeks may have additional benefits in improving QOL and relieving pain in Japanese women with postmenopausal osteoporosis.

Topics: Aged; Bone Density Conservation Agents; Cholecalciferol; Drug Therapy, Combination; Female; Humans; Japan; Middle Aged; Osteoporosis, Postmenopausal; Pain; Pain Measurement; Product Surveillance, Postmarketing; Prospective Studies; Quality of Life; Raloxifene Hydrochloride; Surveys and Questionnaires

Nursing home residents have severe vitamin D deficiency and increased risk of falls and fractures. These individuals may need 125 μg of vitamin D3 to achieve desirable 25-hydroxyvitamin D [25(OH)D] concentrations to improve overall health. We evaluated health-related quality of life (HRQoL) in 45 nursing home residents (28 women and 17 men, aged 58-89 years) with 25(OH)D concentrations <50 nM who consumed daily one bun that had been fortified with 125 μg vitamin D3. The Romanian version of Questionnaire of the European Foundation for Osteoporosis (QUALEFFO-41) was applied at baseline and after 12 months. Data were analyzed using repeated measures analyses of variance (ANOVA). After one year supplementation, serum 25(OH)D reached optimal status (>75 nM) and bone health has improved significantly. Nursing home residents who consumed daily bread fortified with 125 μg vitamin D3 reported significant (P=.02 for the effect of time) improvement in HRQoL (total score of QUALEFFO-41). The interaction time x treatment was also statistically significant on pain (P=.04), daily activities (P=.02), and locomotion (P=.04). To ensure the serum concentrations of 25(OH)D recommended by medical groups for bone- and general-health in the older nursing residents, the practical experience shows that much higher amounts of vitamin D3 are required. Fortification of bread and cereals is a feasible way to improve vitamin D nutrition.

Topics: Activities of Daily Living; Aged; Aged, 80 and over; Bone Density; Bread; Calcium, Dietary; Cholecalciferol; Female; Food, Fortified; Frail Elderly; Humans; Male; Middle Aged; Nursing Homes; Osteoporosis; Osteoporotic Fractures; Pain; Quality of Life; Surveys and Questionnaires; Vitamin D; Vitamin D Deficiency

Aromatase inhibitors have recently been proposed for the treatment of endometriosis; however, no previous study examined the effects of these agents on pain and urinary symptoms of premenopausal women with bladder endometriosis.. Two premenopausal patients with bladder endometriosis were treated with letrozole (2.5 mg/day), norethisterone acetate (2.5 mg/day), elemental calcium and vitamin D3 for 6 months. The double-drug regimen quickly improved pain and urinary symptoms in both patients. One patient had no significant adverse effect and continued the therapy for 14 months. The other patient developed myalgia and severe arthralgia; pain and urinary symptoms recurred few months after the interruption of the 6-month treatment and the patient underwent laparoscopic partial cystectomy.. Aromatase inhibitors improve pain and urinary symptoms in patients with bladder endometriosis; however, severe side effects of treatment may occur. These agents should be administered only to patients who refuse surgery and fail to respond to other therapies.

Topics: Adult; Aromatase Inhibitors; Calcium; Cholecalciferol; Cystectomy; Drug Therapy, Combination; Endometriosis; Female; Humans; Letrozole; Nitriles; Norethindrone; Pain; Treatment Outcome; Triazoles; Urinary Bladder Diseases

Topics: Adrenal Cortex Hormones; Adult; Aspirin; Cholecalciferol; Colitis, Ulcerative; Cyclosporine; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Knee Joint; Male; Mesalamine; Osteonecrosis; Pain; Platelet Aggregation Inhibitors; Radiography; Simvastatin; Vitamins

Hypovitaminosis D is well known in different populations, but may be under diagnosed in certain populations. We aim to determine the first diagnosis considered, the duration and resolution of symptoms, and the predictors of response to treatment in female asylum seekers suffering from hypovitaminosis D.. A pre- and post-intervention observational study.. A network comprising an academic primary care centre and nurse practitioners.. Consecutive records of 33 female asylum seekers with complaints compatible with osteomalacia and with hypovitaminosis D (serum 25-(OH) vitamin D < 21 nmol/l). Treatment intervention: The patients received either two doses of 300,000 IU intramuscular cholecalciferol as well as 800 IU of cholecalciferol with 1000 mg of calcium orally, or the oral treatment only.. We recorded the first diagnosis made by the physicians before the correct diagnosis of hypovitaminosis D, the duration of symptoms before diagnosis, the responders and non-responders to treatment, the duration of symptoms after treatment, and the number of medical visits and analgesic drugs prescribed 6 months before and 6 months after diagnosis.. Two-sample t-tests, chi-squared tests, and logistic regression analyses were performed. Analyses were performed using SPSS 10.0.. Prior to the discovery of hypovitaminosis D, diagnoses related to somatisation were evoked in 30 patients (90.9%). The mean duration of symptoms before diagnosis was 2.53 years (SD 3.20). Twenty-two patients (66.7%) responded completely to treatment; the remaining patients were considered to be non-responders. After treatment was initiated, the responders' symptoms disappeared completely after 2.84 months. The mean number of emergency medical visits fell from 0.88 (SD 1.08) six months before diagnosis to 0.39 (SD 0.83) after (P = 0.027). The mean number of analgesic drugs that were prescribed also decreased from 1.67 (SD 1.5) to 0.85 (SD 1) (P = 0.001).. Hypovitaminosis D in female asylum seekers may remain undiagnosed, with a prolonged duration of chronic symptoms. The potential pitfall is a diagnosis of somatisation. Treatment leads to a rapid resolution of symptoms, a reduction in the use of medical services, and the prescription of analgesic drugs in this vulnerable population.

Topics: 25-Hydroxyvitamin D 2; Administration, Oral; Adult; Analgesics; Calcium; Chi-Square Distribution; Cholecalciferol; Drug Prescriptions; Emergencies; Female; Humans; Injections, Intramuscular; Logistic Models; Osteomalacia; Pain; Primary Health Care; Prospective Studies; Radioimmunoassay; Spectrophotometry; Time Factors; Vitamin D Deficiency

Hepatitis C-Associated Osteosclerosis (HCAO) is characterized by a marked increase in bone mass with deep bone pain. Since 1992, eleven cases of HCAO have been reported. This report describes an elderly Japanese man with HCAO, whose clinical course we followed for 3 years. A 68-year-old man developed pain in both pretibial regions in June 2000, and he had frequent episodic loss of muscular strength in his hands. He had recieved blood transfusion for a bleeding ulcer 43 years before and was seropositive for hepatitis C virus. His serum alkaline phosphatase (ALP) level was markedly increased, while his serum calcium was slightly decreased and serum phosphate was normal. Skeletal radiographs of the lower extremities showed a progressive increase in skeletal density, but did not show any apparent deformity. Administration of nonsteroidal anti-inflammatory drugs led to a reduction in bone pain. Treatment with vitamin D3 and calcium decreased the number of episodes of sudden muscular weakness and maintained serum calcium within the normal range. Three years after the onset of the disease, bone mineral density of his lumbar vertebrae and left hip rose from 0.963 g/cm2 to 1.096 g/cm2, and from 0.938 g/cm2 to 1.383 g/cm2, respectively. His serum ALP level decreased from 2889 to 277 IU/L (normal range: 104-338) and serum calcium normalized. These findings were accompanied by a decrease in bone pain. This case and previous reports suggest that the skeletal tissue of this disease appears to be of good quality.

Topics: Aged; Alanine Transaminase; Alkaline Phosphatase; Anti-Inflammatory Agents, Non-Steroidal; Asian People; Aspartate Aminotransferases; Bone and Bones; Bone Density; Calcium; Cholecalciferol; Hepatitis C; Humans; Male; Osteosclerosis; Pain; Parathyroid Hormone; Phosphorus; Radiography; Whole Body Imaging

Topics: Adult; Afghanistan; Bosnia and Herzegovina; Cholecalciferol; Ethiopia; Female; Humans; Middle Aged; Osteomalacia; Pain; Refugees; Somalia; Vitamin D Deficiency

In rats, vitamin D-deficiency increases basal pain threshold and the analgesic effect of morphine (hot plate test). Cholecalciferol (1000 I.U./Kg/day s.c.x 5 days) restores pain sensitivity in vitamin D-deficient rats and brings the analgesic effect of morphine back to normal. On the other hand, tolerance to morphine develops faster in vitamin D-deficient rats, this effect too being prevented by cholecalciferol treatment. These data suggest a role for vitamin D status in pain sensitivity and opiate activity.

Topics: Animals; Calcium; Cholecalciferol; Drug Tolerance; Morphine; Pain; Rats; Rats, Inbred Strains; Sensory Thresholds; Vitamin D Deficiency