Effects of Elevated Parathyroid Hormone Levels on Muscle Health, Postural Stability and Quality of Life in Vitamin D-Insufficient Healthy Women: A Cross-Sectional Study.

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.

Bone Microstructure in Response to Vitamin D3 Supplementation: A Randomized Placebo-Controlled Trial.

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.

The effect of vitamin D3 supplementation on markers of cardiovascular health in hyperparathyroid, vitamin D insufficient women: a randomized placebo-controlled trial.

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.

Effects of Vitamin D3 Supplementation on Muscle Strength, Mass, and Physical Performance in Women with Vitamin D Insufficiency: A Randomized Placebo-Controlled Trial.

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.

Effects of treatment with an angiotensin 2 receptor blocker and/or vitamin D3 on parathyroid hormone and aldosterone: A randomized, placebo-controlled trial.

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.