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"Effect of calcifediol treatment and best available therapy versus best available therapy on intensive care unit admission and mortality among patients hospitalized for COVID-19: A pilot randomized clinical study".
Entrenas Castillo, M, Entrenas Costa, LM, Vaquero Barrios, JM, Alcalá Díaz, JF, López Miranda, J, Bouillon, R, Quesada Gomez, JM
The Journal of steroid biochemistry and molecular biology. 2020;:105751
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Abstract
OBJECTIVE The vitamin D endocrine system may have a variety of actions on cells and tissues involved in COVID-19 progression especially by decreasing the Acute Respiratory Distress Syndrome. Calcifediol can rapidly increase serum 25OHD concentration. We therefore evaluated the effect of calcifediol treatment, on Intensive Care Unit Admission and Mortality rate among Spanish patients hospitalized for COVID-19. DESIGN Parallel pilot randomized open label, double-masked clinical trial. SETTING University hospital setting (Reina Sofia University Hospital, Córdoba Spain.) PARTICIPANTS 76 consecutive patients hospitalized with COVID-19 infection, clinical picture of acute respiratory infection, confirmed by a radiographic pattern of viral pneumonia and by a positive SARS-CoV-2 PCR with CURB65 severity scale (recommending hospital admission in case of total score > 1). PROCEDURES All hospitalized patients received as best available therapy the same standard care, (per hospital protocol), of a combination of hydroxychloroquine (400 mg every 12 h on the first day, and 200 mg every 12 h for the following 5 days), azithromycin (500 mg orally for 5 days. Eligible patients were allocated at a 2 calcifediol:1 no calcifediol ratio through electronic randomization on the day of admission to take oral calcifediol (0.532 mg), or not. Patients in the calcifediol treatment group continued with oral calcifediol (0.266 mg) on day 3 and 7, and then weekly until discharge or ICU admission. Outcomes of effectiveness included rate of ICU admission and deaths. RESULTS Of 50 patients treated with calcifediol, one required admission to the ICU (2%), while of 26 untreated patients, 13 required admission (50 %) p value X2 Fischer test p < 0.001. Univariate Risk Estimate Odds Ratio for ICU in patients with Calcifediol treatment versus without Calcifediol treatment: 0.02 (95 %CI 0.002-0.17). Multivariate Risk Estimate Odds Ratio for ICU in patients with Calcifediol treatment vs Without Calcifediol treatment ICU (adjusting by Hypertension and T2DM): 0.03 (95 %CI: 0.003-0.25). Of the patients treated with calcifediol, none died, and all were discharged, without complications. The 13 patients not treated with calcifediol, who were not admitted to the ICU, were discharged. Of the 13 patients admitted to the ICU, two died and the remaining 11 were discharged. CONCLUSION Our pilot study demonstrated that administration of a high dose of Calcifediol or 25-hydroxyvitamin D, a main metabolite of vitamin D endocrine system, significantly reduced the need for ICU treatment of patients requiring hospitalization due to proven COVID-19. Calcifediol seems to be able to reduce severity of the disease, but larger trials with groups properly matched will be required to show a definitive answer.
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Denosumab Versus Risedronate in Glucocorticoid-Induced Osteoporosis: Final Results of a Twenty-Four-Month Randomized, Double-Blind, Double-Dummy Trial.
Saag, KG, Pannacciulli, N, Geusens, P, Adachi, JD, Messina, OD, Morales-Torres, J, Emkey, R, Butler, PW, Yin, X, Lems, WF
Arthritis & rheumatology (Hoboken, N.J.). 2019;(7):1174-1184
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Abstract
OBJECTIVE Clinical trial results have shown that, in glucocorticoid-treated patients, treatment with denosumab 60 mg subcutaneously once every 6 months (Q6M) increased spine and hip bone mineral density (BMD) at month 12 significantly more than treatment with risedronate 5 mg orally once daily (QD). The present analysis was performed to compare efficacy and characterize safety through month 24. METHODS This phase III study enrolled men and women ≥18 years old who had received ≥7.5 mg daily prednisone or equivalent for <3 months (glucocorticoid-initiating) or for ≥3 months (glucocorticoid-continuing) before screening. All patients <50 years old had a history of osteoporotic fracture. Glucocorticoid-continuing patients ≥50 years old had T scores of -2.0 or less (or -1.0 or less with fracture history). Patients were randomized (1:1) to receive denosumab 60 mg subcutaneously Q6M or risedronate 5 mg orally QD for 24 months, with daily calcium and vitamin D. RESULTS Of 795 patients, 590 (74.2%) completed the study (in the glucocorticoid-initiating group, 109 of 145 patients treated with denosumab and 117 of 145 patients treated with risedronate; in the glucocorticoid-continuing group, 186 of 253 patients treated with denosumab and 178 of 252 patients treated with risedronate). Denosumab was superior to risedronate in increasing lumbar spine and total hip BMD at all time points assessed, among glucocorticoid-initiating patients (24-month lumbar spine: BMD increase of 6.2% versus 1.7%, respectively [P < 0.001]; 24-month total hip: BMD increase of 3.1% versus 0.0% [P < 0.001]) and among glucocorticoid-continuing patients (24-month lumbar spine: BMD increase of 6.4% versus 3.2% [P < 0.001]; 24-month total hip: BMD increase of 2.9% versus 0.5% [P < 0.001]). Adverse events, serious adverse events (including infections), and fractures were similar between treatment groups. CONCLUSION Denosumab was superior to risedronate in terms of increases in spine and hip BMD through month 24, and the safety profile was similar between treatment groups. Denosumab may offer a new osteoporosis treatment option for glucocorticoid-treated patients.
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[Comparison of the clinical effects between Dihuang Decoction and alendronate sodium in the treatment of primary osteoporosis].
Wan, JM, Zhang, JF, Huang, K, Zhang, PL, Zhu, SY
Zhongguo gu shang = China journal of orthopaedics and traumatology. 2019;(6):535-538
Abstract
OBJECTIVE To study and compare the clinical effects of Rehmannia Decoction and alendronate sodium for the treatment of primary osteoporosis. METHODS From January 2016 to December 2017, 72 patients with primary osteoporosis who took Dihuang Decoction(DHD) orally and alendronate regularly for more than one year were randomly divided into 2 groups:experimental group and control group. The experimental group consisted of 14 males and 22 females, with an average age of(63.97±3.70) years old. The patients in the experimental group took Chinese medicine DHD, one dose each time, one time in the morning and one time in the evening, twice a week. The control group consisted of 16 males and 20 females with an average age of(63.36±3.07) years old. Patients in the control group were given alendronate 70 mg orally once a week. The basic treatment for osteoporosis remained unchanged in both groups(600 mg of calcium carbonate D3 and 0.5 μg of calcitriol capsules were taken daily). Bone mineral density (BMD) of femoral neck and lumbar vertebrae was measured by dual energy X-ray absorptiometry before and after treatment for one year. The levels of serum collagen type I C-terminal peptide (beta-CTX) and serum osteoclast (SOST) were measured before and after treatment for two groups. RESULTS The age, bone mineral density, SOST and beta-CTX baseline values between the two groups before and after anti-osteoporosis treatment were compared. The difference was not statistically significant(P>0.05). Compared with the two groups, the BMD of femoral neck and lumbar vertebrae were increased after 1 year of anti-osteoporosis treatment. The differences were statistically significant (P<0.001). The value of serum beta-CTX was significantly lower than before. The t values were 52.002 and 50.071 respectively. The value of serum SOST was increased than that before treatment. The t values were -29.242 and -30.807 respectively. The differences were statistically significant (P<0.001). BMD of the femoral neck and lumbar spine was compared between the two groups after treatment. The P values were 0.294 and 0.478 respectively. The difference was not statistically significant (P>0.05). The serum beta-CTX values were compared between the two groups after treatment. The P value was 0.908. The serum SOST values were compared between the two groups after treatment. The P value was 0.888. The difference was not statistically significant (P>0.05). CONCLUSIONS In this study, traditional Chinese medicine DHD is used to treat osteoporosis. It is found that DHD and alendronate have a good effect. The DHD can be used as a choice of Chinese medicine in the treatment of primary osteoporosis.
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Changes in blood and urinary cadmium levels and bone mineral density according to osteoporosis medication in individuals with an increased cadmium body burden.
Eom, SY, Yim, DH, Hong, SM, Kim, YD, Kim, H, Choi, BS, Park, JD, Park, CH, Kim, GB, Yu, SD
Human & experimental toxicology. 2018;(4):350-357
Abstract
The aim of this study was to assess changes in bone mineral density (BMD) and cadmium (Cd) levels in blood and urine in individuals living in a Cd-contaminated area according to the type of osteoporosis medication over a three-year period. This follow-up study included 204 residents living in the vicinity of a closed copper refinery, who had been found to have elevated urinary or blood Cd levels. Cd levels in the blood and urine, as well as BMD, were measured every 6 months. After the first BMD measurement, individuals were prescribed antiresorptives such as alendronate or vitamin D and calcium, according to their BMD. Subjects were classified according to the type of medicine provided over the previous 6 months. General linear models controlling for other factors were used to evaluate the effects of each type of medication on the participants' Cd levels and BMD. Spinal BMD showed a significant increase in the antiresorptive group compared to the nontreatment group. Significant decreases in blood Cd levels were found in the vitamin D and calcium group, in comparison to the nontreatment group, as well as a marginally significant decrease in the antiresorptive group. The vitamin D and calcium group showed a significantly greater decrease in urinary Cd levels than the nontreatment group. In contrast, antiresorptive medication was found to have a negative effect on urinary Cd excretion. These results suggest that vitamin D and calcium treatment for osteoporosis lowers blood Cd levels more effectively and improves urinary Cd excretion.
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Whole body vibration versus magnetic therapy on bone mineral density in elderly osteoporotic individuals.
Shanb, AA, Youssef, EF, Muaidi, QI, Alothman, AA
Journal of back and musculoskeletal rehabilitation. 2017;(4):903-912
Abstract
BACKGROUND Osteoporosis usually develops gradually and progresses without significant signs and symptoms. It is one of the most common musculoskeletal conditions associated with aging. OBJECTIVES To evaluate the effects of whole body vibration (WBV) or magnetic therapy in addition to standard pharmacological treatment on bone mineral density (BMD) in elderly individuals being treated for osteoporosis. METHODS Eighty-five participants, 60-75 years of age, were randomly divided into three groups. All three groups received the same standard pharmacological treatment comprised of vitamin D, calcium, and alendronate sodium. In Group I, thirty participants were also exposed to WBV for 25 minutes in each session with two sessions per week for 4 months. In Group II, thirty participants were exposed to magnetic therapy for 50 minutes in each session with two sessions per week for 4 months. In Group III, twenty-five participants received only pharmacological treatment. Dual-energy X-ray absorptiometry was used to measure BMD of the lumbar spine and femoral heads before and after interventions. Venus blood sample was drawn for analysis of calcium and vitamin D. RESULTS An ANOVA test detected significant (p< 0.05) differences in BMD after treatment among the three groups with no significant difference was detected between patients receiving WBV and magnetic therapy. Statistical t-tests detected significant (p< 0.05) increases in BMD after application of WBV or magnetic therapy in combination with pharmacological treatment, but no significant increase after pharmacological treatment alone. CONCLUSIONS Addition of either WBV or magnetic therapy to standard pharmacological treatment for osteoporosis significantly increased BMD in elderly subjects. No significant difference in effectiveness was detected between these two alternative therapy modalities. Consequently, either WBV or magnetic therapy could be effectively applied in conjunction with pharmacological treatment to increase BMD in elderly osteoporotic patients.
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Efficacy of Alendronate for the Prevention of Bone Loss in Calcar Region Following Total Hip Arthroplasty.
Yukizawa, Y, Inaba, Y, Kobayashi, N, Choe, H, Kubota, S, Saito, T
The Journal of arthroplasty. 2017;(7):2176-2180
Abstract
BACKGROUND Bone mineral density (BMD) loss around femoral implants, particularly in the proximal femur, is a common outcome after total hip arthroplasty. Previous studies reported the prevention of postsurgical decrease in BMD with the use of osteoporosis drug therapy. This randomized study evaluated the efficacy of alendronate and alfacalcidol for preserving BMD over a long-term follow-up. METHODS Sixty consecutive patients with hip osteoarthritis who had undergone primary cementless total hip arthroplasty were randomly assigned to an alendronate (n = 20), alfacalcidol (n = 18), or control (n = 22) group. Periprosthetic BMD was measured using dual-energy X-ray absorptiometry at 1 week, 1 year, and the current follow-up (minimum 9 years after surgery). Changes in BMD are reported as mean percentages relative to the values at 1 week (baseline reference). RESULTS All groups showed a significant decrease in the BMD of the calcar at the current follow-up compared to the values at both 1 week and 1 year postoperatively (P < .001). The BMD values were significantly higher in the alendronate group than in the alfacalcidol and control groups (P < .05). The BMD values at the current follow-up were 76% ± 30% (alendronate group), 64% ± 22% (alfacalcidol group), and 59% ± 22% (control group) of the baseline values. CONCLUSION Our findings demonstrate the efficacy of early administration of alendronate for the prevention of bone loss in the calcar region.
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Nasal Levels of Antimicrobial Peptides in Allergic Asthma Patients and Healthy Controls: Differences and Effect of a Short 1,25(OH)2 Vitamin D3 Treatment.
Thijs, W, Janssen, K, van Schadewijk, AM, Papapoulos, SE, le Cessie, S, Middeldorp, S, Melissant, CF, Rabe, KF, Hiemstra, PS
PloS one. 2015;(11):e0140986
Abstract
BACKGROUND Allergy is often accompanied by infections and lower levels of antimicrobial peptides (AMPs). Vitamin D has been shown to increase expression of selected AMPs. In this study we investigated whether antimicrobial peptide levels in nasal secretions of allergic asthma patients are lower than in healthy controls, and whether administration of the active form of vitamin D (1,25(OH)2D3) affects these antimicrobial peptide levels. METHODS The levels of antimicrobial peptides in nasal secretions were compared between 19 allergic asthma patients and 23 healthy controls. The effect of seven days daily oral treatment with 2 μg 1,25(OH)2D3 on antimicrobial peptides in nasal secretions was assessed in a placebo-controlled cross-over clinical study. RESULTS Levels of neutrophil α-defensins (human neutrophil peptides 1-3; HNP1-3) and lipocalin 2 (LCN2; also known as NGAL) were significantly lower in asthmatics, but no differences in LL-37 and SLPI were detected. Treatment with a short-term 1,25(OH)2D3 caused a small increase in HNP1-3, but not when the asthma and control groups were analyzed separately. LL-37, LCN2 and SLPI did not change after treatment with 1,25(OH)2D3. CONCLUSION Levels of the antimicrobial peptides HNP1-3 and LCN2 are lower in nasal secretions in asthmatics and are not substantially affected by a short-term treatment with active vitamin D.
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Successful knowledge translation intervention in long-term care: final results from the vitamin D and osteoporosis study (ViDOS) pilot cluster randomized controlled trial.
Kennedy, CC, Ioannidis, G, Thabane, L, Adachi, JD, Marr, S, Giangregorio, LM, Morin, SN, Crilly, RG, Josse, RG, Lohfeld, L, et al
Trials. 2015;:214
Abstract
BACKGROUND Few studies have systematically examined whether knowledge translation (KT) strategies can be successfully implemented within the long-term care (LTC) setting. In this study, we examined the effectiveness of a multifaceted, interdisciplinary KT intervention for improving the prescribing of vitamin D, calcium and osteoporosis medications over 12-months. METHODS We conducted a pilot, cluster randomized controlled trial in 40 LTC homes (21 control; 19 intervention) in Ontario, Canada. LTC homes were eligible if they had more than one prescribing physician and received services from a large pharmacy provider. Participants were interdisciplinary care teams (physicians, nurses, consultant pharmacists, and other staff) who met quarterly. Intervention homes participated in three educational meetings over 12 months, including a standardized presentation led by expert opinion leaders, action planning for quality improvement, and audit and feedback review. Control homes did not receive any additional intervention. Resident-level prescribing and clinical outcomes were collected from the pharmacy database; data collectors and analysts were blinded. In addition to feasibility measures, study outcomes were the proportion of residents taking vitamin D (≥800 IU/daily; primary), calcium ≥500 mg/day and osteoporosis medications (high-risk residents) over 12 months. Data were analyzed using the generalized estimating equations technique accounting for clustering within the LTC homes. RESULTS At baseline, 5,478 residents, mean age 84.4 (standard deviation (SD) 10.9), 71% female, resided in 40 LTC homes, mean size = 137 beds (SD 76.7). In the intention-to-treat analysis (21 control; 19 intervention clusters), the intervention resulted in a significantly greater increase in prescribing from baseline to 12 months between intervention versus control arms for vitamin D (odds ratio (OR) 1.82, 95% confidence interval (CI): 1.12, 2.96) and calcium (OR 1.33, 95% CI: 1.01, 1.74), but not for osteoporosis medications (OR 1.17, 95% CI: 0.91, 1.51). In secondary analyses, excluding seven nonparticipating intervention homes, ORs were 3.06 (95% CI: 2.18, 4.29), 1.57 (95% CI: 1.12, 2.21), 1.20 (95% CI: 0.90, 1.60) for vitamin D, calcium and osteoporosis medications, respectively. CONCLUSIONS Our KT intervention significantly improved the prescribing of vitamin D and calcium and is a model that could potentially be applied to other areas requiring quality improvement. TRIAL REGISTRATION ClinicalTrials.gov: NCT01398527 . Registered: 19 July 2011.
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The effect of calcium supplementation on blood pressure in non-pregnant women with previous pre-eclampsia: An exploratory, randomized placebo controlled study.
Hofmeyr, GJ, Seuc, AH, Betrán, AP, Purnat, TD, Ciganda, A, Munjanja, SP, Manyame, S, Singata, M, Fawcus, S, Frank, K, et al
Pregnancy hypertension. 2015;(4):273-9
Abstract
BACKGROUND Epidemiological findings suggest that the link between poverty and pre-eclampsia might be dietary calcium deficiency. Calcium supplementation has been associated with a modest reduction in pre-eclampsia, and also in blood pressure (BP). METHODS This exploratory sub-study of the WHO Calcium and Pre-eclampsia (CAP) trial aims to determine the effect of 500mg/day elemental calcium on the blood pressure of non-pregnant women with previous pre-eclampsia. Non-pregnant women with at least one subsequent follow-up trial visit at approximately 12 or 24weeks after randomization were included. RESULTS Of 836 women randomized by 9 September 2014, 1st visit data were available in 367 women of whom 217 had previously had severe pre-eclampsia, 2nd visit data were available in 201 women. There was an overall trend to reduced BP in the calcium supplementation group (1-2.5mmHg) although differences were small and not statistically significant. In the subgroup with previous severe pre-eclampsia, the mean diastolic BP change in the calcium group (-2.6mmHg) was statistically larger than in the placebo group (+0.8mmHg), (mean difference -3.4, 95% CI -0.4 to -6.4; p=0.025). The effect of calcium on diastolic BP at 12weeks was greater than in those with non-severe pre-eclampsia (p=0.020, ANOVA analysis). CONCLUSIONS There is an overall trend to reduced BP but only statistically significant in the diastolic BP of women with previous severe pre-eclampsia. This is consistent with our hypothesis that this group is more sensitive to calcium supplementation, however results need to be interpreted with caution.
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Effect of VDRA on survival in incident hemodialysis patients: results of the FARO-2 observational study.
Messa, P, Cozzolino, M, Brancaccio, D, Cannella, G, Malberti, F, Costanzo, AM, di Luzio Paparatti, U, Festa, V, Gualberti, G, Mazzaferro, S, et al
BMC nephrology. 2015;:11
Abstract
BACKGROUND Mortality rate among patients with stage five chronic kidney disease (CKD) maintained on hemodialysis (HD) is high. Although evidence suggests that use of Vitamin D Receptor Activators (VDRA) in CKD patients increases survival, few studies have examined the effect of VDRA in incident HD patients. The FARO-2 study evaluated the clinical outcome of VDRA therapy on mortality in incident HD patients. METHODS FARO-2 was a longitudinal epidemiological study performed on 568 incident HD patients followed prospectively from 26 dialysis centers over a 3-year period. Data were collected every 6 months using a questionnaire, obtaining clinical, biochemical and therapeutic parameters. Kaplan-Meier curves and Cox proportional hazard regression models were used to determine cumulative probability of time-to-death and adjusted hazard ratios. RESULTS 568 patients (68% male) with an average age of 65.5 years were followed up. Mean dialysis duration at study entry was 3 months. VDRA use increased from 46% at 6 months to 54.7% at 36 months of follow-up (p = 0.08). No difference was observed in the presence of comorbid diseases at baseline in patients with and without VDRA therapy. Cumulative probability of survival at 24 months was 74.5% (95% CI: 70.2-78.3). Patients receiving VDRA therapy showed a significant increase in survival at 24 months (80.7%; 95% CI: 75.7-84.8) compared to those without (63.3%; 95% CI: 54.8-70.7, p <0.01). The presence of vascular disease, decreased hemoglobin, increased P and lack of VDRA treatment were significantly associated with an increased risk of mortality. Lack of VDRA treatment still remained significant as a predictor of mortality after adjusting for levels of PTH, P and Ca (HR = 2.16, 95% CI: 1.09-4.30, p = 0.03). CONCLUSIONS Findings from FARO-2 indicate that in incident HD patients VDRA therapy was associated with increased survival.