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2.
J Clin Endocrinol Metab ; 107(5): 1317-1327, 2022 04 19.
Article in English | MEDLINE | ID: mdl-35018442

ABSTRACT

BACKGROUND: The role of vitamin D on muscle health is debated. METHODS: An individual participant metanalysis of 4 randomized placebo-controlled trials, investigating short-term (3-9months) effects of vitamin D3 in moderate (2800 IU) to high (7000 IU) daily oral doses on muscle health and quality of life (QoL). Inclusion criteria were either obesity (n = 52), newly diagnosed primary hyperparathyroidism (n = 41), Graves' disease (n = 86), or secondary hyperparathyroidism (n = 81). RESULTS: Overall (n = 260) as well as in a subgroup analysis including only vitamin D insufficient [25(OH)D < 50 nmol/L] individuals (n = 176), vitamin D supplementation did not affect measures of muscle health (isometric muscle strength, Timed Up and Go test, chair rising test, body composition, and balance) or QoL. However, a beneficial effect was present on QoL (physical component score) in vitamin D deficient [25(OH)D < 25 nmol/L] individuals (n = 34). Overall, relative changes in 25(OH)D inversely affected maximum muscle strength in a dose-response manner. Stratified into body mass index 30 kg/m2, vitamin D supplementation had divergent effects on isometric muscle strength, with beneficial effects in obese individuals (n = 93) at knee flexion 90° (P = 0.04), and adverse effects in nonobese individuals (n = 167) at handgrip (P = 0.02), knee extension 60° (P = 0.03) and knee flexion 60° (P < 0.01). CONCLUSION: Overall, short-term treatment with moderate to high daily doses of vitamin D did not affect muscle health or QoL. A potential beneficial effect was present on muscle strength in severely obese individuals and on QoL in vitamin D deficient individuals. Subgroup analyses, however, suggested negative effects of large relative increases in p-25(OH)D.


Subject(s)
Graves Disease , Vitamin D Deficiency , Cholecalciferol/therapeutic use , Dietary Supplements , Double-Blind Method , Graves Disease/chemically induced , Hand Strength , Humans , Muscle Strength , Muscles , Obesity/chemically induced , Obesity/drug therapy , Postural Balance , Quality of Life , Time and Motion Studies , Vitamin D , Vitamin D Deficiency/drug therapy , Vitamins
3.
BMC Endocr Disord ; 22(1): 14, 2022 Jan 06.
Article in English | MEDLINE | ID: mdl-34991581

ABSTRACT

BACKGROUND: Patients with primary hyperparathyroidism (pHPT) and impaired kidney function (estimated glomerular filtration rate (eGFR) < 60 mL/min) are offered parathyroidectomy (PTX) to protect them from further complications. Surprisingly, two recent uncontrolled cohort studies have suggested a further decrease in kidney function following PTX. We aimed to examine the effects of PTX compared to non-surgical surveillance on kidney function in pHPT patients. METHODS: Historic cohort study. From the Danish National Patient Registry (NPR) and major medical biochemistry laboratories in Denmark, we identified 3585 patients with biochemically confirmed pHPT among whom n = 1977 (55%) were treated with PTX (PTX-group) whereas n = 1608 (45%) were followed without surgery (non-PTX group). Baseline was defined as time of diagnosis and kidney function was re-assessed 9-15 months after PTX (PTX group) or 9-15 months after diagnosis (non-PTX group). RESULTS: At follow-up, eGFR had decreased significantly in the PTX- compared to the non-PTX-group (median - 4% vs. - 1%, p < 0.01). Stratification by baseline eGFR showed that the decrease was significant for those with a baseline eGFR value of 80-89 and > 90 mL/min, but not for those with lower eGFR values. Findings did not differ between patients with mild compared to moderate/severe hypercalcemia. However, after mutual adjustments, we identified baseline levels of calcium, PTH, and eGFR as well as age and treatment (PTX vs. no-PTX) as independent predictors for changes in kidney function. CONCLUSION: Compared to non-surgical surveillance, PTX is associated with a small but significant decrease in kidney function in pHPT patients with an initial normal kidney function.


Subject(s)
Glomerular Filtration Rate , Hyperparathyroidism, Primary/physiopathology , Hyperparathyroidism, Primary/surgery , Parathyroidectomy , Watchful Waiting , Aged , Biomarkers/analysis , Denmark , Female , Humans , Kidney Function Tests , Male , Middle Aged , Registries , Retrospective Studies
4.
J Bone Miner Res ; 36(9): 1651-1660, 2021 09.
Article in English | MEDLINE | ID: mdl-34405916

ABSTRACT

The objective of this study was to investigate the effects of vitamin D supplementation versus placebo on muscle health. For this systematic review and trial-level meta-analysis of placebo-controlled trials, a systematic search of randomized controlled trials published until October 2020 was performed in Medline, Embase, and Google Scholar. We included studies in humans (except athletes) on supplementation with vitamin D2 or D3 versus placebo, regardless of administration form (daily, bolus, and duration) with or without calcium co-supplementation. The predefined endpoints were physical performance reported as timed up and go test (TUG; seconds), chair rising test (seconds), 6-minute walking distance (m), and Short Physical Performance Battery (SPPB; points). Furthermore, endpoints were maximum muscle strength (Newton) measured at handgrip, elbow flexion, elbow extension, knee flexion, and knee extension, as well as muscle (lean tissue) mass (kg). Falls were not included in the analysis. Cochrane Review Manager (version 5.4.1.) calculating mean difference (MD) using a random effect model was used. In total, 54 randomized controlled trials involving 8747 individuals were included. Vitamin D versus placebo was associated with a significantly longer time spent performing the TUG (MD 0.15 [95% confidence interval (CI) 0.03 to 0.26] seconds, N = 19 studies, I2  = 0%, n = 5223 participants) and a significant lower maximum knee flexion strength (MD -3.3 [-6.63 to -0.03] Newton, N = 12 studies, I2  = 0%, n = 765 participants). Total score in the SPPB showed a tendency toward worsening in response to vitamin D compared with placebo (MD -0.18 [-0.37 to 0.01] points, N = 8 studies, I2  = 0%, n = 856 participants). Other measures of muscle health did not show between-group differences. In subgroup analyses, including studies with low vitamin D levels, effects of vitamin D supplementation did not differ from placebo. Available evidence does not support a beneficial effect of vitamin D supplementation on muscle health. Vitamin D may have adverse effects on muscle health, which needs to be considered when recommending vitamin D supplementation. © 2021 American Society for Bone and Mineral Research (ASBMR).


Subject(s)
Postural Balance , Vitamin D , Cholecalciferol , Dietary Supplements , Hand Strength , Humans , Muscles , Randomized Controlled Trials as Topic , Time and Motion Studies
5.
Nutrients ; 12(5)2020 May 04.
Article in English | MEDLINE | ID: mdl-32375334

ABSTRACT

Recently, we demonstrated negative effects of vitamin D supplementation on muscle strength and physical performance in women with vitamin D insufficiency. The underlying mechanism behind these findings remains unknown. In a secondary analysis of the randomized placebo-controlled trial designed to investigate cardiovascular and musculoskeletal health, we employed NMR-based metabolomics to assess the effect of a daily supplement of vitamin D3 (70 µg) or an identically administered placebo, during wintertime. We assessed the serum metabolome of 76 postmenopausal, otherwise healthy, women with vitamin D (25(OH)D) insufficiency (25(OH)D < 50 nmol/L), with mean levels of 25(OH)D of 33 ± 9 nmol/L. Compared to the placebo, vitamin D3 treatment significantly increased the levels of 25(OH)D (-5 vs. 59 nmol/L, respectively, p < 0.00001) and 1,25(OH)2D (-10 vs. 59 pmol/L, respectively, p < 0.00001), whereas parathyroid hormone (PTH) levels were reduced (0.3 vs. -0.7 pmol/L, respectively, p < 0.00001). Analysis of the serum metabolome revealed a significant increase of carnitine, choline, and urea and a tendency to increase for trimethylamine-N-oxide (TMAO) and urinary excretion of creatinine, without any effect on renal function. The increase in carnitine, choline, creatinine, and urea negatively correlated with muscle health and physical performance. Combined with previous clinical findings reporting negative effects of vitamin D on muscle strength and physical performance, this secondary analysis suggests a direct detrimental effect on skeletal muscle of moderately high daily doses of vitamin D supplements.


Subject(s)
Dietary Supplements/adverse effects , Muscle Strength/drug effects , Physical Functional Performance , Randomized Controlled Trials as Topic , Vitamin D Deficiency/physiopathology , Vitamin D/administration & dosage , Vitamin D/adverse effects , Carnitine/blood , Choline/blood , Female , Humans , Methylamines/blood , Parathyroid Hormone/blood , Postmenopause , Vitamin D/analogs & derivatives , Vitamin D/blood
6.
Calcif Tissue Int ; 105(6): 642-650, 2019 Dec.
Article in English | MEDLINE | ID: mdl-31522253

ABSTRACT

Independently of plasma 25-hydroxyvitamin D (P-25(OH)D) levels, elevated parathyroid hormone (PTH) levels may exert an adverse effect on muscle health, postural stability, well-being, and quality of life. Using a cross-sectional design, we investigated 104 healthy postmenopausal women with low P-25(OH)D (< 50 nmol/l) levels, who had either secondary hyperparathyroidism (SHPT) with elevated PTH levels (> 6.9 pmol/l, n = 52) or normal PTH levels (n = 52). The average PTH value in women with SHPT was 8.5 (interquartile range 7.5-9.7) pmol/l and 5.3 (4.4-6.3) pmol/l in women with normal PTH (p < 0.001). Plasma phosphate was significantly lower in women with SHPT than in women with normal PTH (1.01 ± 0.14 vs. 1.09 ± 0.13 mmol/l; p < 0.01). In the total cohort, average level of 25(OH)D were 38 (31-45) nmol/l, with no differences between groups. SHPT was associated with impaired muscle strength as assessed by both maximum muscle strength and maximum force production at knee flexion with the knee fixed at 60° and 90° (pall < 0.05). Postural stability was impaired during semi tandem standing (p = 0.001). However, the two groups did not differ in terms of self-reported physical activity, muscle-related symptoms, quality of life, or lean muscle mass as assessed by dual-energy X-ray absorptiometry. Independently of 25(OH)D levels, mild to moderately elevated PTH levels are associated with adverse effects on muscle strength and postural stability. Why some individuals respond to vitamin D insufficiency with an elevated PTH and others do not need further elucidation, but elevated PTH itself seems to affect muscle function and postural stability.


Subject(s)
Muscle Strength/physiology , Parathyroid Hormone/blood , Quality of Life , Vitamin D Deficiency/blood , Aged , Bone Density/physiology , Cross-Sectional Studies , Female , Humans , Hyperparathyroidism, Secondary/complications , Middle Aged , Vitamin D/blood
7.
Calcif Tissue Int ; 104(2): 160-170, 2019 02.
Article in English | MEDLINE | ID: mdl-30293198

ABSTRACT

Vitamin D supplementation is often used in the prevention and treatment of osteoporosis, but the role of vitamin D has lately been questioned. We aimed to investigate the effect of 3 months of daily vitamin D3 supplementation (70 µg [2800 IU] vs. placebo) initiated in winter months on bone health. This study is a double-blinded placebo-controlled randomized trial. Bone health was assessed by bone turnover markers, DXA, HRpQCT, and QCT scans. The participants were 81 healthy postmenopausal women with low 25(OH)D (< 50 nmol/l) and high PTH levels (> 6.9 pmol/l) at screening. Vitamin D3 supplementation significantly increased levels of 25(OH)D and 1,25(OH)2D by 59 nmol/l and 19 pmol/l, respectively, whereas PTH was reduced by 0.7 pmol/l (all p < 0.0001). Compared with placebo, vitamin D3 did not affect bone turnover markers, aBMD by DXA or trabecular bone score. Vitamin D3 increased trabecular vBMD (QCT scans) in the trochanter region (0.4 vs. - 0.7 g/cm3) and the femoral neck (2.1 vs. - 1.8 g/cm3) pall < 0.05. HRpQCT scans of the distal tibia showed reduced trabecular number (- 0.03 vs. 0.05 mm-1) and increased trabecular thickness (0.001 vs. - 0.005 mm), as well as an improved estimated bone strength as assessed by failure load (0.1 vs. - 0.1 kN), and stiffness (2.3 vs. - 3.1 kN/mm pall ≤ 0.01). Changes in 25(OH)D correlated significantly with changes in trabecular thickness, stiffness, and failure load. Three months of vitamin D3 supplementation improved bone strength and trabecular thickness in tibia, vBMD in the trochanter and femoral neck, but did not affect aBMD.


Subject(s)
Bone Density/drug effects , Bone and Bones/drug effects , Bone and Bones/ultrastructure , Cholecalciferol/therapeutic use , Hyperparathyroidism, Secondary/drug therapy , Vitamin D Deficiency/drug therapy , Aged , Bone and Bones/chemistry , Dietary Supplements , Double-Blind Method , Female , Humans , Hyperparathyroidism, Secondary/blood , Hyperparathyroidism, Secondary/complications , Middle Aged , Osteoporosis, Postmenopausal/blood , Osteoporosis, Postmenopausal/prevention & control , Placebos , Seasons , Vitamin D Deficiency/blood , Vitamin D Deficiency/complications
8.
Endocrine ; 62(1): 182-194, 2018 10.
Article in English | MEDLINE | ID: mdl-30043092

ABSTRACT

PURPOSE: Emerging data supports an association between parathyroid hormone (PTH) and aldosterone. It has been speculated, that potential adverse cardiovascular effects of vitamin D insufficiency may partly be caused by the development of secondary hyperparathyroidism with increased activity of the renin-angiotensin-aldosterone system (RAAS). We aimed to investigate the effect of normalizing vitamin D status and/or reducing PTH levels on RAAS activity and other markers of cardiovascular health. METHODS: In a double-blinded study during wintertime, we randomized 81 healthy postmenopausal women with secondary hyperparathyroidism (PTH > 6.9 pmol/l) and 25-hydroxy-vitamin D (25(OH)D) levels < 50 nmol/l to 12 weeks of treatment with vitamin D3 70 µg/day (2800 IU/day) or identical placebo. Markers of cardiovascular health were defined as changes in the plasma RAAS, glycated hemoglobin, lipids, and lipoproteins, blood pressure, vascular stiffness, heart rate, and cardiac conductivity. RESULTS: Compared to placebo, vitamin D3 treatment significantly increased plasma levels of 25(OH)D and 1,25(OH)2D by 230% (95% CI: 189-272%) and 58% (190-271%), respectively. Vitamin D3 treatment reduced PTH by 17% (11-23%), but did not reduce RAAS activity. Compared to placebo, vitamin D3 treatment increased plasma levels of high-density lipoproteins (HDL) by 4.6% (0.12-9.12%), but did not affect other measured indices. CONCLUSIONS: Vitamin D3 supplementation normalized vitamin D levels and reduced PTH. The supplement increased levels of HDL, but had no effects on RAAS activity or other indices of cardiovascular health.


Subject(s)
Cardiovascular System/drug effects , Cholecalciferol/therapeutic use , Hyperparathyroidism/complications , Vitamin D Deficiency/drug therapy , Aged , Aged, 80 and over , Blood Pressure/drug effects , Blood Pressure/physiology , Cardiovascular System/physiopathology , Cholecalciferol/administration & dosage , Double-Blind Method , Female , Heart Rate/drug effects , Heart Rate/physiology , Hormone Replacement Therapy , Humans , Hyperparathyroidism/physiopathology , Middle Aged , Treatment Outcome , Vascular Stiffness/drug effects , Vascular Stiffness/physiology , Vitamin D Deficiency/complications , Vitamin D Deficiency/physiopathology
9.
Calcif Tissue Int ; 103(5): 483-493, 2018 11.
Article in English | MEDLINE | ID: mdl-29931459

ABSTRACT

Vitamin D insufficiency and hyperparathyroidism have been associated with reduced muscle strength, physical performance, postural stability, well-being, and quality of life. In a double-blinded, randomized placebo-controlled trial, we aimed to investigate effects of vitamin D3 supplementation on above-mentioned outcomes in healthy community-dwelling postmenopausal women with plasma levels of 25-hydroxyvitamin D (25(OH)D) below < 50 nmol/l and high parathyroid hormone (PTH) levels. Participants (N = 81) were 1:1 treated with vitamin D3, 70 µg (2800 IU)/day or identical placebo for three months during wintertime (56°N). Vitamin D3 supplementation increased levels of 25(OH)D and 1,25(OH)2D by 230% (95% CI 189 to 272)%, p < 0.001 and 58% (190 to 271%), p < 0.001, respectively, and reduced PTH by 17% (- 23 to - 11%), p < 0.001. Compared with placebo, vitamin D3 significantly reduced maximal handgrip strength by 9% (- 15 to - 3%; p < 0.01) and knee flexion strength by 13% (- 24 to - 2%; p = 0.02) and increased the time spent on performing the Timed Up and Go test by 4.4%; (0.1-8.6%; p < 0.05). Levels of physical activity, total lean body mass, appendicular lean mass index, postural stability, well-being, and quality of life did not change in response to treatment. Compared with placebo, a daily supplement with a relatively high dose of vitamin D3 had no beneficial effects on any outcomes. In some measures of muscle strength and physical performance, we even saw a small unfavorable effect. Our data call for caution on use of relatively high daily doses of vitamin D3 in the treatment of vitamin D insufficiency.


Subject(s)
Cholecalciferol/pharmacology , Dietary Supplements , Muscle Strength/physiology , Muscle, Skeletal/physiology , Physical Functional Performance , Aged , Aged, 80 and over , Double-Blind Method , Female , Hand Strength/physiology , Humans , Middle Aged , Postural Balance/physiology
10.
J Clin Endocrinol Metab ; 103(9): 3574-3583, 2018 09 01.
Article in English | MEDLINE | ID: mdl-29955845

ABSTRACT

Context: Some patients with primary hyperparathyroidism (PHPT) develop renal calcifications. Investigation of urinary and nonurinary risk factors are essential. Objective: We aimed to study the prevalence and potential biochemical predictors of renal calcifications. Design: Nested case-control study. Setting: University hospital. Participants: We identified 792 patients with PHPT from 2005 to 2015. We used biochemical data to validate the diagnosis of PHPT. Main Outcome Measures: The prevalence of renal calcifications defined as nephrolithiasis or nephrocalcinosis assessed by a routine CT scan at the time of diagnosis. Results: A total of 792 patients with PHPT were identified among whom 617 patients (78%) had a CT scan preformed. We found a prevalence of renal calcifications of 23%, equally frequent between sexes. A total of 76 patients (12%) had nephrolithiasis and 75 patients (12%) had nephrocalcinosis where 7 patients (1%) had both nephrolithiasis and nephrocalcinosis. Compared with patients without renal calcifications, patients with renal calcifications had significantly higher levels of ionized calcium, parathyroid hormone, and 24-hour calcium excretion (Pall < 0.01). Patients with nephrocalcinosis had higher plasma levels of phosphate and a higher calcium-phosphate product compared with patients with nephrolithiasis (Pall < 0.05). Impaired renal function (estimated glomerular filtration rate <60 mL/min) was observed in 12% of patients. However, no differences in renal function were observed between those with and without renal calcifications. Conclusion: Renal calcifications are frequent in patients with PHPT and are associated with the severity of the disease. Impaired renal function is also common in PHPT, but renal function was not associated with renal calcifications.


Subject(s)
Calcification, Physiologic , Hyperparathyroidism, Primary/physiopathology , Kidney/physiopathology , Nephrocalcinosis/etiology , Nephrolithiasis/etiology , Aged , Biomarkers/blood , Calcium/blood , Calcium Channels/blood , Calcium Phosphates/blood , Case-Control Studies , Female , Glomerular Filtration Rate , Humans , Hyperparathyroidism, Primary/blood , Hyperparathyroidism, Primary/complications , Male , Middle Aged , Nephrocalcinosis/epidemiology , Nephrolithiasis/epidemiology , Parathyroid Hormone/blood , Phosphates/blood , Prevalence , Risk Factors
11.
Clin Endocrinol (Oxf) ; 89(5): 656-666, 2018 11.
Article in English | MEDLINE | ID: mdl-29733445

ABSTRACT

OBJECTIVE: Emerging evidence supports a positive, bidirectional and clinical relevant interaction between parathyroid hormone (PTH) and the renin-angiotensin-aldosterone-system (RAAS). A beneficial effect of the widely used RAAS inhibitors might include a PTH-lowering effect, as high PTH levels may be harmful to cardiovascular health. We aimed to investigate whether PTH levels are lowered by short-term treatment with an angiotensin 2 receptor blocker (valsartan) independently of coadministration of vitamin D3. Secondary end-points included effects on blood pressure, cardiac conduction and concentrations of renin and aldosterone. DESIGN AND METHODS: In a double-blind placebo-controlled trial, we included 81 otherwise healthy postmenopausal women with high PTH levels (>6.9 pmol/L) and vitamin D insufficiency (25(OH)D < 50 nmol/L). Participants received 2 weeks of treatment with valsartan 80 mg/d, vitamin D3 70 µg/d, valsartan plus vitamin D3 or double placebo. RESULTS: Valsartan treatment did not affect plasma PTH, although treatment reduced diastolic blood pressure (P = .01) and the aldosterone/renin ratio (P < .001). We found no associations between calciotropic hormones and RAAS markers. Vitamin D3 supplementation reduced PTH by 3.4% (25th, 75th -9.0 to 8.7) compared to a 7.1% increase (25th, 75th -2.4 to 30.9) in the placebo group (P = .01), but did not affect blood pressure, cardiac conduction or concentrations of renin and aldosterone. CONCLUSIONS: Independently of vitamin D3, short-term valsartan treatment did not reduce PTH. Vitamin D3 reduced PTH but did not affect blood pressure, cardiac conduction or the RAAS. The study does not support a direct association between PTH and aldosterone or a blood pressure-lowering effect of vitamin D3.


Subject(s)
Aldosterone/blood , Angiotensin Receptor Antagonists/therapeutic use , Cholecalciferol/therapeutic use , Parathyroid Hormone/blood , Aged , Blood Pressure/drug effects , Double-Blind Method , Electrocardiography , Female , Humans , Male , Middle Aged , Postmenopause , Valsartan/therapeutic use , Vitamin D Deficiency/blood , Vitamin D Deficiency/drug therapy
12.
J Bone Miner Res ; 33(9): 1657-1664, 2018 09.
Article in English | MEDLINE | ID: mdl-29734476

ABSTRACT

Prevalence of vertebral fractures (VFx) in primary hyperparathyroidism (PHPT) remains uncertain. We aimed to estimate the prevalence of VFx, investigate potential risk factors associated with VFx, and whether bone mineral density (BMD) differs between PHPT and osteoporotic patients with VFx. Through the Danish National Patient Register, we identified patients diagnosed with PHPT from 2005 to 2015. The diagnosis was verified by reviewing biochemical findings, and X-ray reports were reviewed by two investigators. Osteoporotic patients with VFx were identified from our outpatient clinic and matched on age and sex with PHPT patients with VFx. We identified 792 PHPT patients among whom spine X-ray was available from 588 patients. VFx were present in 122 (21%) patients and were equally frequent among sexes (77% females). Fractured patients were older (70 versus 63 years) and had lower heights (163 versus 166 cm) compared with nonfractured patients (p all < 0.02). After stratification by age groups, the prevalence of VFx differed significantly between sexes (p < 0.01). Ionized calcium and parathyroid hormone did not differ between groups. BMD at total hip and forearm were lower in fractured compared with nonfractured patients (p < 0.03 for both) after adjusting for age, sex, and body mass index (BMI). Compared with osteoporotic patients with VFx (n = 108), BMD at the lumbar spine was higher in PHPT patients with VFx (n = 108) (p < 0.01). This did not change by excluding patients with lumbar VFx (p < 0.01). The severity of PHPT assessed by biochemistry does not seem to be associated with risk of VFx. Compared with osteoporosis, VFx seems to occur at a higher BMD in PHPT. © 2018 American Society for Bone and Mineral Research.


Subject(s)
Hyperparathyroidism, Primary/complications , Spinal Fractures/complications , Spinal Fractures/epidemiology , Aged , Bone Density , Case-Control Studies , Female , Humans , Hyperparathyroidism, Primary/physiopathology , Male , Middle Aged , Osteoporosis/complications , Prevalence , Risk Assessment , Risk Factors , Spinal Fractures/diagnostic imaging , Spinal Fractures/physiopathology , Spine/diagnostic imaging , Spine/pathology , Spine/physiopathology
13.
PLoS One ; 12(7): e0180512, 2017.
Article in English | MEDLINE | ID: mdl-28686645

ABSTRACT

BACKGROUND: A large number of observational studies have reported harmful effects of low 25-hydroxyvitamin D (25OHD) levels on non-skeletal outcomes. We performed a systematic quantitative review on characteristics of randomized clinical trials (RCTs) included in meta-analyses (MAs) on non-skeletal effects of vitamin D supplementation. METHODS AND FINDINGS: We identified systematic reviews (SR) reporting summary data in terms of MAs of RCTs on selected non-skeletal outcomes. For each outcome, we summarized the results from available SRs and scrutinized included RCTs for a number of predefined characteristics. We identified 54 SRs including data from 210 RCTs. Most MAs as well as the individual RCTs reported null-findings on risk of cardiovascular diseases, type 2 diabetes, weight-loss, and malignant diseases. Beneficial effects of vitamin D supplementation was reported in 1 of 4 MAs on depression, 2 of 9 MAs on blood pressure, 3 of 7 MAs on respiratory tract infections, and 8 of 12 MAs on mortality. Most RCTs have primarily been performed to determine skeletal outcomes, whereas non-skeletal effects have been assessed as secondary outcomes. Only one-third of the RCTs had low level of 25OHD as a criterion for inclusion and a mean baseline 25OHD level below 50 nmol/L was only present in less than half of the analyses. CONCLUSIONS: Published RCTs have mostly been performed in populations without low 25OHD levels. The fact that most MAs on results from RCTs did not show a beneficial effect does not disprove the hypothesis suggested by observational findings on adverse health outcomes of low 25OHD levels.


Subject(s)
Dietary Supplements/adverse effects , Vitamin D/analogs & derivatives , Vitamin D/therapeutic use , Cardiovascular Diseases/diet therapy , Cardiovascular Diseases/epidemiology , Cardiovascular Diseases/pathology , Diabetes Mellitus, Type 2/diet therapy , Diabetes Mellitus, Type 2/epidemiology , Diabetes Mellitus, Type 2/pathology , Humans , Neoplasms/diet therapy , Neoplasms/epidemiology , Neoplasms/pathology , Nutrition Therapy , Randomized Controlled Trials as Topic , Risk Factors , Vitamin D/adverse effects , Weight Loss/drug effects
14.
J Bone Miner Res ; 31(7): 1440-8, 2016 07.
Article in English | MEDLINE | ID: mdl-26865527

ABSTRACT

Total thyroidectomy causes postsurgical hypothyroidism (HypoT). Besides HypoT, as a complication patients may also develop hypoparathyroidism (HypoPT). The aim of this study was to assess quality of life (QoL), muscle function, and postural stability in patients with postsurgical hypothyroidism and hypoparathyroidism (HypoT+PT) as compared to patients with postsurgical HypoT and healthy controls. Age- and gender-matched patients on treatment for HypoT+PT and HypoT were recruited from our outpatient clinic. Matched healthy controls were recruited from the general background population. Compared with controls, HypoT was associated with a significantly lower mental summary score, whereas patients with HypoT+PT had a significantly lower physical summary score (Short Form 36 Health Survey questionnaire version 2). Moreover, the physical component score was significantly lower in patients with HypoT+PT compared with HypoT. WHO-5 well-being index was significantly lower in both groups of patients compared with controls, but did not differ between groups of patients. Compared with controls, muscle strength and maximal force production was significantly reduced in HypoT+PT, but not in HypoT. In HypoT+PT, the time spent on the Timed Up & Go test and the Repeated Chair Stands test were significantly longer than in the HypoT group and the control group. Postsurgical HypoT+PT is associated with a more severe impairment of QoL, in particular regarding physical functioning, than HypoT. HypoT+PT patients are also hampered by impaired muscle function. Studies on how to improve well-being and muscle function in HypoT+PT patients are warranted. © 2016 American Society for Bone and Mineral Research.


Subject(s)
Exercise , Hypoparathyroidism/physiopathology , Hypothyroidism/physiopathology , Muscle Strength , Postural Balance , Quality of Life , Thyroidectomy , Adult , Female , Humans , Hypoparathyroidism/etiology , Hypothyroidism/etiology , Male , Middle Aged
15.
Dan Med J ; 62(9)2015 Sep.
Article in English | MEDLINE | ID: mdl-26324087

ABSTRACT

INTRODUCTION: Danish patients diagnosed with cancer who present with unspecific signs and symptoms are diagnosed with unfavourable delay, which has led to the establishment of a national fast-track (cancer) pathway. The aim of this study was to estimate the prevalence of cancer and other diagnoses in patients referred to this programme at Aarhus University Hospital from general practitioners. Furthermore, we aimed to characterise the patient cohort, assess survival and estimate the predictive values of symptoms, signs and biochemical abnormalities. METHODS: From 1 March 2011 to 31 December 2013, data of interest were consecutively collected from the electronic patient record by two medical doctors. RESULTS: Overall, 18% (58/323) had cancer, but the prevalence decreased from 22% in 2011 to 16% in 2013. Haematological cancers and cancers originating from the digestive system were the predominant cancer diagnoses. Patients diagnosed with cancer unfortunately had a high mortality suggesting that we diagnose cancer in the late, non-curable stages. Patients referred to the fast-track pathway had a median of four symptoms, most commonly weight loss and fatigue. In one fourth of the patients, a final diagnosis was not reached at discharge. For the rest (n = 185), gastrointestinal conditions, infectious and rheumatological diseases were most common. The predictive value of the presenting symptoms was poor. Age and biochemical markers considered as unspecific markers of cancer were better predictors. Anaemia was seen in 71% versus 34% of patients with/without diagnosed cancer, respectively. CONCLUSIONS: Unspecific signs and symptoms that may be indicative of cancer represent a clinical challenge. A fast-track (cancer) pathway is a new option for patients not entitled to enter an organ-specific programme.


Subject(s)
Critical Pathways/statistics & numerical data , Neoplasms/epidemiology , Referral and Consultation/statistics & numerical data , Symptom Assessment/methods , Adolescent , Adult , Aged , Aged, 80 and over , Denmark/epidemiology , Female , Humans , Male , Middle Aged , Neoplasms/diagnosis , Prevalence , Symptom Assessment/statistics & numerical data , Young Adult
16.
Dan Med J ; 62(6)2015 Jun.
Article in English | MEDLINE | ID: mdl-26036884

ABSTRACT

INTRODUCTION: Concomitant somatic and mental illness is associated with excess mortality compared with the general population. To prevent this, a number of health initiatives relating to somatic illness in psychiatric patients have recently been introduced. One of the means used to screen for and treat somatic disease in psychiatric patients is highly qualified referral for somatic specialist assessment. The aim of this study was to assess the quality of referral of psychiatric patients to specialists in internal medicine. METHODS: A total of 110 consecutive referrals were collected from August to November in 2012 and 2013. Regional guidelines define the requirement for the satisfactory referral scheme and using these guidelines as a reference, each referral was rated based on indexation and an overall assessment. A report about the 2012 results was presented to the hospital management. The management of the hospital was not informed about the 2013 replication of the study. RESULTS: Half of the topics assessed were inadequately completed. Information about somatic co-morbidity was missing in 76% of the referrals. Description of relevant tests and physical examinations was missing in 53%. By overall assessment, 40% of the referrals were rated as being insufficient. The resident physicians stand out by producing the most informative referrals. The 2013 results improved compared with 2012. CONCLUSION: We call for improvement in the quality of the referrals among psychiatric in-patients to somatic specialists. We propose an expansion of the use of standardised schemes and a strengthening of the skills needed to write a good referral.


Subject(s)
Internal Medicine , Medical Records/standards , Mental Health Services/standards , Referral and Consultation/standards , Comorbidity , Humans , Mental Disorders/mortality , Mental Disorders/therapy , Practice Guidelines as Topic/standards , Quality Assurance, Health Care
17.
Calcif Tissue Int ; 95(4): 374-81, 2014 Oct.
Article in English | MEDLINE | ID: mdl-25086672

ABSTRACT

The objective of this study was to assess the effect on calcium homeostasis of changing PTH replacement therapy (PTH-RT) from intact PTH (PTH(1-84)) to teriparatide (PTH(1-34)). This study is a consecutive case series. All patients with postoperative hypoparathyroidism who changed medication from PTH(1-84) (100 µg) to PTH(1-34) (20 µg) were included. Plasma ionized calcium, daily dose of 1α-hydroxylated-vitamin D metabolites alfacalcidol, calcium, TSH and PTH was collected. Eight patients (women = 88%) with a mean age of 54 ± 12 years and a duration of hypoPT of 13 ± 6 years were included. Before initiation of PTH(1-84), the mean daily dose of alfacalcidol was 1.9 ± 1.1 µg/d and calcium supplements were 1,550 ± 705 mg. Alfacalcidol dose was reduced with 88 ± 29% (p < 0.01) after 6 months of PTH(1-84) treatment and terminated in six patients. Calcium levels were reduced with 78 ± 36% (p = 0.02) to 273 ± 353 mg/d and stopped in five patients. Six patients received 100 µg PTH(1-84) daily, the seventh 2 out of 3 days and the last every second day. When changing from PTH(1-84) to PTH(1-34), plasma ionized calcium initially dropped and the demand for supplements increased. Alfacalcidol was resumed in five patients; mean daily dose increased to 1.50 ± 1.56 µg/d, (p = 0.02) and calcium increased to 329 ± 368 mg/d, (p = 0.72). Five patients received 20 µg PTH(1-34) a day, two patients twice-a-day and one 20/40 µg/d alternately. Compared with PTH(1-34), PTH(1-84) has a longer plasma half-life and a higher calcemic response. We have shown a need for higher doses of alfacalcidol and calcium supplements to maintain normal serum calcium when treated with PTH(1-34) compared to PTH(1-84) and in some a need for more than one daily PTH(1-34) dose.


Subject(s)
Calcium/blood , Hypoparathyroidism/metabolism , Parathyroid Hormone/administration & dosage , Teriparatide/therapeutic use , Adult , Aged , Calcitriol/blood , Calcium/administration & dosage , Female , Homeostasis , Hormone Replacement Therapy , Humans , Hydroxycholecalciferols/administration & dosage , Hypoparathyroidism/drug therapy , Male , Middle Aged , Parathyroid Hormone/therapeutic use , Teriparatide/administration & dosage , Time Factors , Young Adult
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