Table 1.
Characteristics of included randomized controlled trials with Vitamin D supplementation.
| Authors | Country | Study Design | n | Sex (W%) | Age (Mean) |
Sample (at Baseline) | Groups | Duration of Intervention | Follow-Up | Dose of Vitamin D, Frequency | Effects on BMD | Effects on 25(OH)D and PTH | Effects on Bone Turnover Indices | Effects on Falls | Other Results |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| [18] | Brazil | Double-blind, placebo-controlled trial | 160 | 100 | 59.3 | Postmenopausal women | Intervention group (n = 80) and control group (n = 80) | 9 m | 9 m | 1000 IU | ↑ 25(OH)D ↓ PTH |
↓24.2% in s-CTX, 13.4% in P1NP, and 21.3% | - | ||
| [32] | USA | Prospective, randomized, double-blind, placebo-controlled trial | 258 | 100 | 68.2 | Healthy African American women with serum 25(OH)D 20–65 nmol/L | VitaminD3 vs. placebo | 3 y | Every 6 months | Adapted dose to achieve a concentration of 30 mg 25(OH)D in the serum >75 nmol/L | ↑BMD of spinal cord ns change in total BMD |
↑25(OH)D | NR | ns changes in risk of falling | - |
| [33] | Denmark | Double-blinded placebo-controlled randomized trial | 81 | 100 | 60–79 | Healthy postmenopausal women with 25(OH)D < 50 nmol/L and PTH> 6.9 pmol/L | Intervention group (n = 40) and control group (n = 41) | 3 m | 3 m | 70 µg (2800 IU) Daily |
↑ at the trochanter and femoral neck | ↑25(OH)D ↑1,25(OH)2D ↓PTH |
ns changes in BSAP P1NP Osteocalcin CTx |
NR | ↓failure load ↑trapezoidal thickness and ↑estimated bone strength at the tibia |
| [34] | Brazil | Double-blind, placebo-controlled trial | 160 | 100 | 58.8 | Individuals with BMD> −1.5 SD | Intervention group (n = 80) and control group (n = 81) | 9 m | 9 m | 1000 IU Daily |
NR | ↑25(OH)D in intervention group ↓ in the control group ns change in PTH |
NR | ↑ rate of falls (OR: 1.95 95% CI, 1.23–3.08) and recurrent falls (OR 2.8, 95% CI, 1.43–5.50) | |
| [35] | USA | Prospective, randomized, double-blind, placebo-controlled trial | 260 | 100 | 68.2 | Postmenopausal women | Intervention group (n = 130) and control group (n = 130) | 3 y | Annually | Adapted dose to achieve a concentration of 75–172 nmol/L (doses of 60, 90, and 120 mg) |
↓ Femoral neck BMD in all groups | ↑25(OH)D | NR | - | |
| [36] | USA | Double-blind, placebo-controlled randomized clinical trial | 218 | 100 | 59.6 | Postmenopausal women | Intervention group (n = 109) and control group (n = 109) | 12 m | 12 m | 2000 IU Daily (+ weight loss diet) |
ns changes in spine and femoral neck BMD |
↑25(OH)D | ns change in upper body muscle strength ↓leg strength in the vitamin group D compared to placebo | ||
| [37] | Finland | Double-blind, placebo-controlled trial | 350 | 100 | 74 | Elderly women | Group a (intervention): n = 102; Group b intervention): n = 103 Group c (intervention):n = 102, and Group d (control): n = 102 | 1 y | 1y, 2 y assessment | 20 μg (800 IU) +/- exercise Daily |
↓ Femoral neck BMD in all groups | ↑25(OH)D | ns change in falls | ||
| [38] | Austria | Single-center, double-blind, randomized placebo-controlled trial | 192 | 0 | 43 | Healthy men | Intervention group (n = 100) and control group (n = 100) | 3 m | 3 m | 20,000 IU Weekly |
↓ femoral neck BMD in men with baseline 25(OH)D levels ≥ 50 nmol/L (n = 115) ns changes in total body BMD, lumbar spine BMD, hip BMD |
↑25(OH)D and ns changes in PTH in subjects with 25(OH)D levels < 40 nmol/L ↑25(OH)D and ↓PTH in subjects with 25(OH)D levels > 40 nmol/L |
ns changes in CTX, OC | ns changes in BTM, TBS | |
| [40] | Great Britain | Single-center, parallel-group, participant-randomized, double-blind interventional trial | 379 | 48 | 75 | Patients in lack of treatment for osteoporosis, hyperparathyroidism, history of fractures, hypercalcemia, hypocalcemia | 3 intervention groups (~110 per group) |
1 y | 1 y | 300 μg 600 μg 1200 μg (12.000, 24.000 and 48.000 IU) Monthly |
ns change in bone density | ↑25(OH)D | NR | ns changes in falls | - |
| [41] | Canada | Double-blind, randomized clinical trial | 311 | 47 | 62.2 | lumbar spine and total ischial BMD T score >−2.5 SD, serum 25(OH)D: 30–125 nmol/L and normal serum Ca 2.10–2.55 mmol/L | 3 parallel groups and control group (n~100 per group, total n = 400) | 3 y | DXA: 12, 24 and 36 months (HR-pQCT: 6, 12, 24 and 36 months |
400 IU 4000 IU 10,000 IU Daily |
↓ radial BMD at 4000 IU/day or 10,000 IU/day ↓tibial BMD at 10,000 IU per day |
↑25(OH)D ↓PTH |
↑CTx | ns change in falls | ns changes in failure load ns differences in bone strength in either the stapes or the tibia |
| [42] | Canada | Randomized clinical trial | 311 | 47 | 62.2 | total hip BMD total hip T score >−2.5 SD, serum 25(OH)D between 30 and 125 nmol/L and serum Ca 2.10–2.55 mmol/L | 3 parallel groups (n~100 per group) | 3 y | DXA: 12, 24, and 36 months (HR-pQCT: 6, 12, 24, and 36 months | 400 IU 4000 IU 10,000 IU Daily |
↓ BMD in women but not men ↓1.8% (400 IU), 3.8% (4000 IU) and 5.5% (10,000 IU) at the radius. Men ↓ 0.9% (400 IU), 1.3% (4000 IU), and 1.9% (10,000 IU) at the radius. In the tibia, losses in tBMD were smaller but followed a similar trend |
↑25(OH)D ns PTH |
ns CTx | NR | ns bone strength changes |
| [43] | Iran | Single blind Clinical trial | 400 | 48.5 | 20–60 | Healthy adults | Vitamin D (n = 76) | 8 w | 8 w | 50,000 Weekly |
↓ osteoporosis in the intervention group | - | |||
| [44] | Shanghai | Randomized, double-blind, Placebo-controlled trial | 448 | 69 | 31.9 | Vitamin D-deficient adults’ serum 25(OH)D: 12.5–50 nmol/L | Placebo (n = 222) Intervention group (n = 226) |
20 w | 20 w | 2000 IU Daily |
↑25(OH)D | ↑bALP ns change in serum PINP, β-CTX, or TRAP5b In intervention group, subjects with 25(OH)D ≥75 nmol/L ↑β-CTX and TRAP5b, but smaller ↓ in Ca and Ca product phosphorus |
|||
| [46] | Austria | Randomized, double-blind, placebo-controlled trial | 289 | 37.5% control g and 35.3 vitamin D |
62.2 control and 60.3 vitamin D |
Patients in ICU | Placebo (n =136) Vitamin D (n = 153) | 6 m | 6 m | Initial: 540,000 IU 90,000 IU Monthly |
ns change in BMD at the lumbar spine and femoral neck | ↑25(OH)D ↓ PTH |
ns changes in CTX and OC | ns changes in falls | - |
| [47] | New Zealand | Randomized, double-blind, placebo-controlled trial | 452 | 35% control and 38% vitamin d |
69 | Adults living in the community | Placebo (n = 224) Vitamin D (n = 228) | 2y | 2y | 100,000 IU (2.5 mg) Monthly First dose was double |
ns change in lumbar spine BMD ↓ proximal femur and total body BMD in all groups |
↑25(OH)D | |||
| [48] | India | Controlled trial | 16 | 0 | 18–35 | Men with vitamin D deficiency | Intervention group (n = 8 and a control group (n = 4) |
3 y | 3 y | 60,000 IU Weekly |
↑25(OH)D | ↑ Bone mineral balance | |||
| [49] | Austria | Single-center, double-blind, placebo-controlled, parallel-group study | 197 | 47 | 62.4 | People with arterial hypertension and serum 25(OH)D concentration <75 nmol/L | Vitamin D (n = 98) Placebo (n = 99) | 8 w | 8 y | 2800 IU | ns changes in bALP, CTX, OC and P1NP values ↑ OC in men. |
- |
25(OH)D = 25-hydroxyvitamin D; BMD = bone mineral density; PTH = parathormone; vBMD = volumetric bone mineral density; HR-pQCT = high-resolution peripheral quantitative computed tomography; TtBMD= total volumetric bone mineral density; BTM= bone turnover markers; TBS = trabecular bone score; lbs = pounds; s-CTX = serum carboxy-terminal collagen crosslinks; P1NP = propeptide of type 1 procollagen; CI = confidence interval; ICU = Intensive care unit; bALP = bone alkaline phosphatase; CTX = C-terminal telopeptide; OC = osteocalcin; β-CTX = β-isomerized C-terminal telopeptides; TRAP5b = Tartrate-resistant acid phosphatase; y = year; m = month; w = week; WM = women; ns = non-significant; OR = odds ratio.