Probiotics as a New Regulator for Bone Health: A Systematic Review and Meta-Analysis

Table 2

Characteristics of studies that reported the relationship between probiotic consumption and bone health in humans.

Author (year)	Country	Study design	Population sex and age (y)	Sample size (n)	Intervention group (strain of probiotics)	Probiotic dose	Control group	Duration	Outcome	Results mean ± SD (Int vs. ctrl)	Quality score
Narva et al. (2004)	Finland	Randomized double-blind crossover study	Postmenopausal women; 50 to 78 y (65 y)	20	Lactobacillus helveticus LBK-16H bacteria/milk fermented 14.5 g/100 g IPP &VPP	Portion size 220 ml	Normal sour milk fermented with a Lactococcus sp. mixed culture (420 ml)	1 day Int; 6 day washout; 1 day Int	Ca (mmol/l)	0.09 ± 0.01 vs. 0.05 ± 0.02 (↑)	H
									P (mmol/l)	−0.09 ± 0.02 vs. −0.09 ± 0.02
									iCa (mmol/l)	0.03 ± 0.005 vs. 0.03 ± 0.004
									PTH (ng/l)	−20.8 ± 5.3 vs. −15.4 ± 6.4 (↓)
									ICTP (ug/l)	−1.09 ± 0.28 vs. −1.15 ± 0.20
									U-Ca (mmol/l)	0.19 ± 0.5 vs. 0.17 ± 0.5
					Orange juice + peptide fraction from L. helveticus fermented milk whey with the same amount of IPP and VPP as in the first product	400 ml	Orange juice + calcium lactate gluconate (220 ml)	1 day Int; 6 day washout; 1 day Int	Ca (mmol/l)	0.10 ± 0.02 vs. 0.07 ± 0.01 (↓)
									P (mmol/l)	−0.12 ± 0.02 vs. −0.11 ± 0.01
									iCa (mmol/l)	0.005 ± 0.004 vs. 0.026 ± 0.005
									PTH (ng/l)	−13.0 ± 4.7 vs. −23.7 ± 5.9 (↑)
									ICTP (ug/l)	−1.10 ± 0.10 vs. −1.08 ± 0.18
									U-Ca (mmol/l)	0.15 ± 0.04 vs. 0.21 ± 0.07 (↓)
Jones et al. (2013)	Canada	Double-blind, placebo-controlled,; randomized, parallel-arm study	Hypercholesterolemic adults; 34–64 y (50 y)/both gender	127 (61 Pbo); (66 Int)	Capsule supplement/Lactobacillus reuteri NCIMB 30242	2 capsules (130 mg L. reuteri (2.9 × 10^9) + 170 mg MD)	300 mg MD	13 week	Ca (umol/l)	−0.01 ± 0.001 vs. 0.01 ± 0.02	H
									P (umol/l)	−0.03 ± 0.001 vs. −0.01 ± 0.04
									25 (OH) D (nmol/L)	14.73 ± 13.38 vs. −3.19 ± 5.63 (↑)
Jafarnejad et al. (2017)	Iran	Randomized, double-blind, placebo-controlled study	Women with osteopenia 50–72 y (58 y)	41 (20 Int) (21 Pbo)	Multispecies probiotic capsules (GeriLact) (7 bacteria; species: Lactobacillus casei 1.3 × 10^10, Bifidobacterium longum 5 × 10^10, Lactobacillus acidophilus 1.5 × 10^10, Lactobacillus rhamnosus 3.5 × 10^9, Lactobacillus bulgaricus 2.5 × 10^8, Bifidobacterium breve 1 × 10^10, and Streptococcus thermophilus 1.5 × 10^8)	1 capsule 500 mg	Placebo capsule 500 mg of corn starch	6 months	Spinal BMD (g/cm^2)	0.001 ± 0.01 vs. 0.002 ± 0.01	H
									Total hip BMD (g/cm^2)	−0.015 ± 0.01 vs. −0.016 ± 0.02
									BALP (U/L)	−3.12 ± 0.76 vs. 0.82 ± 0.06 (↓)
									OC (ng/ml)	−0.16 ± 0.07 vs. −1.62 ± 0.2
									CTX (ng/ml)	−0.06 ± 0.001 vs. −0.03 ± 0.001 (↓)
									PTH (pg/ml)	−2.87 ± 0.14 vs. 2.16 ± 0.28 (↓)
									ALP (U/L)	7.4 ± 0.7 vs. 7.5 ± 0.4
									Ca (mg/dl)	0.75 ± 0.12 vs. −0.52 ± 0.04
									P (mg/dl)	0.29 ± 0.04 vs. 0.05 ± 0.001
									25 (OH) D (ng/ml)	28.20 ± 0.97 vs. 29.08 ± 1
									U-Ca (mg/dl)	14.5 ± 0.5 vs. 3.8 ± 0.3
Lambert et al. (2017)	Denmark	Double-blind, parallel design, placebo-controlled,; randomized controlled trial	Postmenopausal osteopenic women; 59–64 y (61 y)	78 (38 Int) (40 Pbo)	60 mg isoflavone aglycones and acid lactic probiotics, cold fermentation	2 Sachet 95 ml (RCE extract + probiotic)	2 Sachet 95 ml (water + food color)	12 month	CTX (ng/ml)	−0.05 ± 0.13 vs. 0.03 ± 0.16 (↓)	H
									P1NP (ng/ml)	1.56 ± 0.53 vs. 0.7 ± 0.56
									OC (ng/ml)	−0.03 ± 0.29 vs. 0.69 ± 0.22
									BMD changes L2–L4 (g/cm^2)	−0.0085 (−0.017, 0.00006) vs. −0.022 (−20.032, 20.012) (↓)
									BMD changes FN (g/cm^2)	−0.008 (−0.015, 0.00003) vs. −0.022 (−0.03, −0.15) (↓)
									BMD changes troch (g/cm^2)	−0.004 (−0.01,0.004) vs. −0.017 (−0.025, −0.008) (↓)
Takimoto et al. (2018)	Japan	Randomized, placebo-controlled, double-blind clinical trial	Healthy women 50-69 y (57 y)	61 (31 Int, 30 Pbo)	Tables contain soybean oil residue (0.34 mg) + Bacillus subtilis C-3102	0.19 g (3.4 × 10^9)	0.19 g	26 weeks	BMD changes L2–L4 (g/cm^2)	0.18 ± 0.50 vs. −0.68 ± 0.63	H
									BMD changes total hip (g/cm^2)	2.53 ± 0.52 vs. 0.83 ± 0.35 (↑)
Nilsson et al. (2018)	Sweden	Double-blind, placebo-controlled study	Women 75–80 y (76 y)	90 (45 Int, 45 Pbo)	Capsules contain Lactobacillus reuteri ATCCPTA 6475 + MD	2 capsules 5 × 10^9	MD	12 months	Tibia total vBMD changes	−0.83 (−1.47, −0.19) vs. −1.85 (−2.64, −1.07) (↓)	H
									BMD changes L2–L4 (g/cm^2)	0.78 (−0.54, 2.10) vs. 0.08 (−1.02, 1.19)
									BMD changes total hip (g/cm^2)	−0.13 (−1.33, 1.07) vs. −0.90 (−2.07, 0.27)
									BAP (U/L)	−4.83 (−13.8, 13.1) vs. 5.43 (−12.8, 22.0)
Sergeev et al. (2020)	The USA	Placebo-controlled clinical trial	Overweight and obese adults 31–62 y (47 y)/both gender	20 (10 Int, 10 Pbo)	Capsule (Lactobacillus acidophilus DDS‐1,; Bifidobacterium lactis UABla‐12, Bifidobacterium longum UABl‐14, and Bifidobacterium bifidum UABb‐10) + a trans‐galactooligosaccharide (GOS)	69 mg (15 × 10^9); 5.5 g	Placebo capsule	3 month	BMC changes (kg)	0.75 ± 0.05 vs. 0.16 ± 0.01	L

Intervention (Int), placebo (Pbo), calcium (Ca), phosphate (P), serum ionised calcium (iCa), parathyroid hormone (PTH), carboxyterminal telopeptide of type I collagen (ICTP), urinary calcium (U-Ca), isoleycyl-prolyl-proline (IPP), valyl-prolyl-proline (VPP), maltodextrin (MD), bone-specific alkaline phosphatase (BALP), osteocalcin (OC), control (ctrl), collagen type 1 cross-linked C-telopeptide (CTX), bone mineral density (BMD), bone mineral content (BMC), alkaline phosphatase (ALP), bone-specific alkaline phosphatase (BAP), femoral neck (FN), lumber spine (L), trochanter (Troch), procollagen type I N-terminal propeptide (P1NP), 25-hydroxy vitamin D (25-OH-D), volumetric bone mineral density (vBMD), red clover extract (RCE), year (y), and gram (g). Results are presented with mean differences and standard deviation, and red color results are significant .