Review Article

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

Table 1

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

Author (year)Target speciesSample size (n)Intervention groupProbiotic doseControl groupDurationOutcomeResults’ mean ± SD (Int vs. ctrl)

Narva et al. (2004)Six-week-old, male, Sprague-Dawley rats5 groups (n = 10-11 per group)1. L. helveticus (LBK-16H)-fermented milk + solid content of the same milk
2. Saccharomyces-fermented milk (Saccharomyces cerevisiae and L. helveticus bacteria)
1. 150 kJ/100 g
2. 200 kJ/100 g
1-sour milk fermented with a Lactococcus sp.-mixed culture
2-skim milk
3-water
14 weeksU-Ca (mg/d)Int1: 2.3 ± 0.5
Int2: 1.7 ± 0.3
Ctrl1: 0.6 ± 0.1
Ctrl2: 1.6 ± 0.2
Ctrl3: 0.7 ± 0.1
BMC (g)Int1: 0.451 ± 0.010
Int2: 0.409 ± 0.009
Ctrl1: 0.459 ± 0.008
Ctrl2: 0.474 ± 0.004
Ctrl3: 0.456 ± 0.008
BMD (g/cm2)Int1: 0.257 ± 0.018
Int2: 0.228 ± 0.003
Ctrl1: 0.243 ± 0.003
Ctrl2: 0.248 ± 0.002
Ctrl3: 0.241 ± 0.003
Femur weight (g)Int1: 0.89 ± 0.02
Int2: 0.82 ± 0.02
Ctrl1: 0.90 ± 0.02
Ctrl2: 0.92 ± 0.01
Ctrl3: 0.90 ± 0.01
Femur volume (cm3)Int1: 0.60 ± 0.01
Int2: 0.56 ± 0.01
Ctrl1: 0.61 ± 0.01
Ctrl2: 0.62 ± 0.01
Ctrl3: 0.62 ± 0.02
Femur length (cm)Int1: 3.64 ± 0.02
Int2: 3.55 ± 0.02
Ctrl1: 3.64 ± 0.02
Ctrl2: 3.68 ± 0.02
Ctrl3: 3.66 ± 0.03
Ca (mg/g)Int1: 162.0 ± 1.3
Int2: 160.9 ± 1.9
Ctrl1: 161.9 ± 1.4
Ctrl2: 164.7 ± 1.6
Ctrl3: 161.8 ± 1.8
P (mg/g)Int1: 74.8 ± 0.7
Int2: 74.6 ± 1.1
Ctrl1: 75.0 ± 0.8
Ctrl2: 76.4 ± 0.8
Ctrl3: 75.3 ± 1.1

Mutus et al. (2006)1-day-old broiler chicks (both gender)50 (n = 25 per each group)Diet (corn, soybean meal, and wheat) + Bacillus licheniformis and Bacillus subtilisEach containing 2.3 × 108 CFU/g of spores)Diet (corn, soybean meal, and wheat)6 weeksTibiotarsi weight/length index (mg/mm)79.59 vs. 77.22
Robusticity index4.94 vs. 5.01
Diaphysis diameter (mm)9.55 vs. 9.64
Thickness of medial and lateral wall (mm)1.75 vs. 1.58
3.03 vs. 2.57
Medullary canal diameter (mm)4.76 vs. 5.50
Tibiotarsal index49.99 vs. 43.26
Modulus of elasticity (kg/cm2)5192 vs. 4487
Yield stress (kg/cm2)83.48 vs. 81.56
Bone-P (%)11.26 vs. 10.06
Bone-Ca (%)23.63 vs. 22.52

Mathy et al. (2007)90-day-old female Wistar rats70,
control: 10 rats (SH),
intervention: 60 rats (OVX) (10 in each group)
1. Soy protein free powdered semipurified diet (control group)
2. Soy protein free powdered semipurified diet + genistein
3. Soy protein free powdered semipurified diet + daidzein
4. Soy protein free powdered semipurified diet + equol
5. Soy protein free powdered semipurified diet + daidzein + short chain FOS
6. Soy protein free powdered semipurified diet + daidzein + Lactobacillus casei
NMSoybean-protein-free
powdered semipurified diet
90 daysTotal BMD (g/cm2)OVX: 0.220
G: 0.234
D: 0.239
E: 0.239
D + FOS: 0.245
D + L: 0.241
SH: 0.256
Diaphyseal BMD (g/cm2)OVX: 0.209 
G: 0.221
D: 0.225 
E: 0.224
D + FOS: 0.230
D + L: 0.226
SH: 0.232
Metaphyseal BMD (g/cm2)OVX: 0.222 
G: 0.246
D: 0.248 
E: 0.251
D + FOS: 0.260
D + L: 0.255
SH: 0.267
Femoral failure loadOVX: 102.67
G: 110.38
D: 109.18
E: 116.44
D + FOS: 115.02
D + L: 109.63
SH: 108.06
OC (ng/ml)OVX: 4.98
G: 5.45
D: 5.00
E: 4.89
D + FOS: 5.21
D + L: 5.12
SH: 3.91
Trabecular thickness (um)OVX: 9.200
G: 9.637
D: 9.883
E:9.050
D + FOS: 9.891
D + L: 10.899
SH: 9.090

Narva et al. (2007)3-month-old female Sprague-Dawley rats50 (10 in each group)1. Tap water
2. 30 mg/L synthesized VPP peptide in water
3. 60 mg/L synthesized VPP peptide in water
4. Lactobacillus helveticus-fermented milk containing VPP peptide 21 mg/L
60 mlShamoperated group
receiving tap water (sham)
12 weeksTrabecular BMD of proximal tibia (mg/cm3)Sham: 245.75
OVX: 105.25
OVX + VPP30 : 112.15
OVX + VPP60 : 108.30
OVX + LH: 126.61
Cortical BMD of proximal tibia (mg/cm3)Sham: 1271
OVX: 1255
OVX + VPP30 : 1256
OVX + VPP60 : 1260
OVX + LH:1266
Cortical BMD of tibial diaphysis (mg/cm3)Sham: 1367.2
OVX: 1364.6
OVX + VPP30 : 1367.7
OVX + VPP60 : 1367.6
OVX + LH: 1369.1
Bone volume per tissue volume (%)Sham: 20.43
OVX: 3.73
OVX + VPP30: 5.31
OVX + VPP60: 2.83
OVX + LH:6.53
Trabecular thickness (um)Sham: 46.52
OVX: 44.00
OVX + VPP30: 45.67
OVX + VPP60: 38.31
OVX + LH: 46.65

Kimoto-Nira et al. (2007)SAMP male, 6 months2 (n = 1 in each group)Cornmeal + wheat + fishmeal + soya oil + calcium carbonate + vitamin/mineral (control) + strain H61Lactococcus lactis subsp. cremoris H61 (strain H61)Control diet8 monthsBone density (mg/cm2)44.42 vs. 38.49

Kimoto-Nira et al. (2009)Male, 1-month-old, SAMP6 miceEighteen per experimental groupCornmeal + wheat + fishmeal + soya oil + calcium carbonate + vitamin/mineral (control) + strain H61Lactococcus lactis G50Control diet11 monthsBone density (mg/cm2)39.7 ± 0.88 vs. 38.7 ± 0.88

Houshmand et al. (2010)1-day male broiler chicks150 (6 groups, n = 25)1. Low-calcium diet (0.67%)
2. Low-calcium diet + probiotic
3. Low-calcium diet + prebiotic
4. Low-calcium diet + synbiotic
5. Low-calcium diet + organic acids (formic acid, citric acid, malic acid, lactic acid, tartaric acid, and orthophosphoric acid)
1 × 1010 CFU/kg Bacillus subtilis and 1 × 106 CFU/kg Clostridium butyricumBasal diet containing recommended level of calcium (0.9%)21 daysTD incidenceNot detected in all groups
Tibia length (cm)Crtl: 6.87 ± 0.05
LC: 6.65 ± 0.04
LC + Pro:7.07 ± 0.09
LC + Pre: 6.92 ± 0.05
LC + Syn: 6.92 ± 0.05
LC + OA: 6.84 ± 0.06
Tibia weight (g)Crtl: 2.65 ± 0.13
LC: 2.18 ± 0.04
LC + Pro: 2.80 ± 0.14
LC + Pre: 2.82 ± 0.11
LC + Syn: 2.77 ± 0.11
LC + OA: 2.65 ± 0.08
Strength (kg/m2)Crtl:36.06 ± 2.36
LC: 33.35 ± 1.62
LC + Pro: 36.20 ± 2.10
LC + Pre: 35.84 ± 1.47
LC + Syn: 36.94 ± 3.12
LC + OA: 34.77 ± 1.49

Chiang and Pan (2011)Female 2-month-old C57BL/6J mice48 (40 mice were OVX, and 8 SH mice)1. Phosphate-buffered saline (OVX)
2. Fosamax, 0.2 mg of alendronic acid, 8 units of colecalciferol per week (FOS)
3. 0.1 g of freeze-dried powder of soy skim milk fermented by L. paracasei subsp. paracasei NTU 101 (NTU 101F)
4. 0.1 g of freeze-dried powder of soy skim milk fermented by L. plantarum
NTU 102 (NTU 102F)
5. 0.1 g of freeze-dried powder of nonfermented soy skim milk (NFSM)
(Lactobacillus paracasei subsp. paracasei NTU 101 and Lactobacillus plantarum NTU 102) 1.0 × 108 CFU/mLPhosphate-buffered saline (n = 8, sham)8 weeksCa (mg/dl)SH: 11.7 ± 0.3
OVX: 11.3 ± 0.4
FOS: 11.3 ± 0.3
NUT101F: 11.2 ± 0.4
NUT102F: 11.2 ± 0.3
NFSM: 11.1 ± 0.3
P (mg/dl)SH: 14.3 ± 1.5
OVX: 12.8 ± 1.2
FOS: 11.2 ± 0.8
NUT101F: 0.9 ± 0.7
NUT102F: 7.7 ± 1.1
NFSM: 7.7 ± 1.0
ALP (U/L)SH: 104.7 ± 14.6
OVX: 91.7 ± 11.1
FOS: 57.2 ± 15.5
NUT101F: 85.9 ± 9.0
NUT102F: 86.4 ± 11.5
NFSM: 96.3 ± 27.2
ACP (U/L)SH: 8.23 ± 0.55
OVX: 7.56 ± 0.67
FOS: 7.70 ± 0.71
NUT101F: 7.83 ± 0.75
NUT102F: 7.43 ± 0.86
NFSM: 7.01 ± 1.35
BMD (g/cm2)SH: 0.67
OVX: 0.66
FOS: 0.645
NUT101F: 0.63
NUT102F: 0.65
NFSM: 0.64
Trabecular bone volume (%)SH: 3.16
OVX: 2.00
FOS: 2.76
NUT101F: 3.08
NUT102F: 2.90
NFSM: 2.74
Trabecular thickness (mm)SH: 0.0719
OVX: 0.7266
FOS: 0.6727
NUT101F: 0.0716
NUT102F: 0.0706
NFSM: 0.0701

Chiang et al. (2011)Female BALB/c mice, 3 months old20 each group (n = 5)1. 0.05 g freeze-dried powder of soy skim milk fermented by L. plantarum NTU 101 (NTU 101F)
2. 0.05 g freeze-dried powder of soy skim milk fermented by L. plantarum NTU 102 (NTU 102F)
3. 0.05 g freeze-dried powder of nonfermented soy skim milk (NFSM)
Lactobacillus paracasei subsp. paracasei strain
NTU 101F (3.0 × 1011 CFU/g) & NTU 102F (3.9 × 1011 CFU/g)
Phosphate-buffered saline (PBS; control, ctrl)10 monthsRight femur weight (%)Ctrl: 0.6 ± 0.0
NUT101F: 0.7 ± 0.0
NUT102F: 0.6 ± 0.1
NFSM: 0.7 ± 0.0
Right femur length (cm)Ctrl: 1.5 ± 0.1
NUT101F: 1.6 ± 0.0
NUT102F: 1.6 ± 0.1
NFSM: 1.6 ± 0.1
Ca (mg/dl)Ctrl: 9.8 ± 0.5
NUT101 F: 9.8 ± 0.3
NUT102F: 9.5 ± 0.3
NFSM: 10.2 ± 0.5
P (mg/dl)Ctrl: 7.0 ± 0.7
NUT101F: 7.0 ± 0.9
NUT102F: 7.3 ± 0.7
NFSM: 8.8 ± 1.5
ALP (U/L)Ctrl: 78.7 ± 8.2
NUT101F: 74.2 ± 4.6
NUT102F: 69.2 ± 9.3
NFSM: 70.6 ± 4.6
ACP (U/L)Ctrl: 5.2 ± 0.4
NUT101F: 3.9 ± 1.1
NUT102F: 3.6 ± 5.7
NFSM: 5.6 ± 1.3
BMD (g/cm2)Ctrl: 0.715
NUT101F: 0.723
NUT102F: 0.719
NFSM: 0.716
Trabecular bone volume (%)Ctrl: 1.08
NUT101F: 3.64
NUT102F: 2.38
NFSM: 1.95
Trabecular thickness (mm)Ctrl: 0.0835
NUT101F: 0.0798
NUT102F: 0.0776
NFSM: 0.735

Takasugi et al. (2011)Male rats, aged 3 weeks, Sprague–Dawley rats32 (n = 8 in each group)1. DFL
2. DFL + PPI
Dairy product fermented by Lactobacillus bulgaricus and Streptococcus thermophilus (DFL)1. Casein-based diet
2. Casein-based diet + PPI
9 daysCortical BMD (mg/cm3)Ctrl: 559 ± 12
Ctrl + PPI: 492 ± 9
DFL: 556 ± 8
DFL + PPI: 533 ± 9
Cancellous BMD (mg/cm3)Ctrl: 250 ± 7
Ctrl + PPI: 200 ± 5
DFL: 251 ± 8
DFL + PPI: 237 ± 6
Total BMD (mg/cm3)Ctrl: 357 ± 9
Ctrl + PPI: 303 ± 6
DFL: 359 ± 8
DFL + PPI: 341 ± 7
Ca-left femur (mg)Ctrl: 24.6 ± 0.9
Ctrl + PPI: 19.7 ± 0.6
DFL: 23.8 ± 0.7
DFL + PPI:22.5 ± 0.5
P-left femur(mg)Ctrl: 13.2 ± 0.5
Ctrl + PPI: 10.6 ± 0.3
DFL: 12.7 ± 0.4
DFL + PPI: 12.1 ± 0.3
Total Ca (ug/ml)Ctrl: 108 ± 2
Ctrl + PPI: 105 ± 2
DFL: 109 ± 3
DFL + PPI: 107 ± 2
Total P (ug/ml)Ctrl: 143 ± 9
Ctrl + PPI: 152 ± 6
DFL: 150 ± 6
DFL + PPI: 156 ± 8
OC (ng/ml)Ctrl: 756 ± 47
Ctrl + PPI: 965 ± 60
DFL: 755 ± 26
DFL + PPI: 784 ± 53
CTX (ng/ml)Ctrl: 74.8 ± 3.0
Ctrl + PPI: 92.1 ± 6.0
DFL: 77.8 ± 3.7
DFL + PPI: 78.3 ± 2.9
PTH (pg/ml)Ctrl: 61 ± 21
Ctrl + PPI: 215 ± 28
DFL: 73 ± 16
DFL + PPI: 163 ± 40
25-OH-D (nmol/l)Ctrl: 34.5 ± 1.8
Ctrl + PPI: 33.3 ± 2.2
DFL: 36.4 ± 1.7
DFL + PPI: 33.8 ± 2.2

Rodrigues et al. (2012)Male Wistar rats, (aged = NM)32 (n = 8 in each group)1. Yacon flour (Y)
2. Diet + B. longum (B)
3. Yacon flour + B. longum (YB)
Bifidobacterium longum; 109 CFU mL−11. Ctrl: AIN-93G diet28 daysALP (UI)Ctrl: 156.88 ± 46.83
Y: 142.75 ± 25.89
B: 148.00 ± 29.71
YB: 139.12 ± 32.63
Femur weight (g)Ctrl: 0.60 ± 0.04
Y: 0.63 ± 0.04
B: 0.64 ± 0.04
YB: 0.64 ± 0.04
Femur length (mm)Ctrl: 3 2.30 ± 0.47 Y: 32.04 ± 0.87
B: 32.27 ± 0.59
YB: 31.40 ± 0.95
Femur thickness (mm)Ctrl: 4.60 ± 0.22
Y: 4.58 ± 0.32
B: 4.42 ± 0.25
YB: 4.50 ± 0.32
Force of fracture (N)Ctrl: 92.35 ± 11.19
Y: 99.86 ± 7.30
B: 100.33 ± 9.60
YB: 105.81 ± 21.70
Bone weight (g)Ctrl: 0.45 ± 0.03
Y: 0.47 ± 0.04
B: 0.45 ± 0.06
YB: 0.46 ± 0.02
Bone-CaCtrl: 7.55 ± 1.20
Y: 7.82 ± 1.07
B: 9.50 ± 0.57
YB: 8.91 ± 0.77
Bone-PCtrl: 8.88 ± 1.21
Y: 9.18 ± 1.09
B: 10.75 ± 1.42
YB: 10.27 ± 0.57

Shim et al. (2012)Sprague-Dawley female rats, 10 weeks48 (sham, n= 8; OVX, n= 40)1. Bilaterally OVX (OVX)
2. Bilaterally OVX + 0.3 g/kg of HRT (HRT-0.3)
3. Bilaterally OVX + 1.0 g/kg of HRT (HRT-1.0)
4. Bilaterally OVX followed by 0.3 g/kg of fHRT (fHRT-0.3)
5. Bilaterally OVX + 1.0 g/kg of fHRT (fHRT-1.0)
Lactobacillus casei KFRI-127 1–5 × 106 CFU/mLSham operated (sham): normal diet without supplement3 monthsBMD (g/cm3)Sham: 0.331
OVX: 0.094
HRT-0.3: 0.125
HRT-1: 0.095
fHRT-0.3: 0.107
fHRT-1: 0.276
Bone volume (%)Sham: 25.39
OVX: 8.98
HRT-0.3: 10.24
HRT-1: 7.94
fHRT-0.3: 8.96
fHRT-1: 18.68
Trabecular thickness (mm)Sham: 0.113
OVX: 0.098
HRT-0.3: 0.103
HRT-1: 0.105
fHRT-0.3: 0.103
fHRT-1: 0.124

McCabe et al. (2013)C57Bl/6 mice, 14 weeks (both gender)20 (n = 10 in each group)Normal diet with supplement formulaLactobacillus reuteri ATCC PTA 6475 (300 μl of 1 × 109 CFU/ml)Normal diet without supplement4 weeksFemur trabecular bone volume28.8 ± 1.8 vs. 19.8 ± 1.7
Femur trabecular thickness (mm)49 ± 2 vs. 39 ± 2
Femur trabecular BMC (mg)0.58 ± 0.02 vs. 0.50 ± 0.02
Femur trabecular BMD (mg/cc)193 ± 7 vs. 166 ± 6
Vertebral trabecular volume56.9 ± 2.7 vs. 38.8 ± 2.7
Vertebral trabecular thickness (mm)61.3 ± 3.3 vs. 42.8 ± 1.7
Vertebral trabecular BMC (mg)0.61 ± 0.02 vs. 0.49 ± 0.02
Vertebral trabecular BMD (mg/cc)270 ± 7 vs. 216 ± 8

Takasugi et al. (2013)3-week-old male Sprague–Dawley rats56 (n = 8 in each group)1. Normal (ctrl diet + vehicle)
2. Low GOL (LO) + PPI
3. High GOL (HO) + PPI
4. DFL + PPI
5. DFL + LO + PPI
6. DFL + HO + PPI
Dairy product fermented by Lactobacillus bulgaricus and Streptococcus thermophilus (DFL1. Ctrl: modified AIN-93G diet + PPI9 daysCortical BMD (mg/cm3)Normal: 518 ± 36
Ctrl: 475 ± 21
LO: 483 ± 21
HO: 515 ± 24
DFL: 542 ± 21
DFL + LO: 535 ± 13
DFL + HO:542 ± 30
Cancellous BMD (mg/cm3)Normal: 232 ± 14
Ctrl: 197 ± 12
LO: 203 ± 10
HO: 225 ± 18
DFL: 238 ± 13
DFL + LO: 236 ± 16
DFL + HO: 246 ± 20
Total BMD (mg/cm3)Normal: 330 ± 19
Ctrl: 294 ± 16
LO: 301 ± 13
HO: 327 ± 20
DFL: 345 ± 18
DFL + LO: 341 ± 15
DFL + HO: 349 ± 23

Britton et al. (2014)BALB/c mice 12 weeks of age, non-OVX and OVX, female24 (n = 8 in each group)1. OVX with normal diet
2. OVX + L. reuteri with normal diet
300 μl (1 × 109 CFU/ml) L. reuteri ATCC PTA 6475 or MRS gavaging
1.5 × 108 CFU/ml L. reuteri added water
Non-OVX (ctrl) with normal dietFour weeksFemur trabecular BMD (mg/cc)Ctrl: 230 ± 1.2
OVX: 179 ± 7
OVX + Lr: 222 ± 11
Femur trabecular BMC (mg)Ctrl: 0.38 ± 0.02
OVX: 0.27 ± 0.01
OVX + Lr: 0.35 ± 0.02
Femur trabecular thickness (um)Ctrl: 45.4 ± 1.2
OVX: 35.8 ± 2.2
OVX + Lr: 41.3 ± 1.9
Vertebrae trabecular BMD (mg/cc)Ctrl: 218 ± 8
OVX: 182 ± 8
OVX + Lr: 204 ± 10
Vertebrae trabecular BMC (mg)Ctrl: 0.36 ± 0.01
OVX: 0.29 ± 0.01
OVX + Lr: 0.36 ± 0.01
Vertebrae trabecular thickness (um)Ctrl: 47.4 ± 1.81
OVX: 37.5 ± 1.00
OVX + Lr: 40.8 ± 1.48

Ohlsson et al. (2014)Six-week-old C57BL/6N female mice60 (n = 10 in each group)1. OVX vehicle
2. OVX L. para
3. OVX L. mix
Lactobacillus strain, L. paracasei DSM13434 (L. para) or a mixture of three strains, L. paracasei DSM13434, L. plantarum DSM 15312 and DSM 15313 supplementation1. Vehicle sham
2. L. para sham
3. L. mix sham
6 weeksTrabecular bone volume (%)Vehicle sham: 16.2 ± 0.7
L. para sham: 16.8 ± 0.8
L. mix sham: 17.4 ± 0.8
OVX vehicle: 13.2 ± 0.7
OVX L. para: 14.4 ± 0.6
OVX L. mix: 13.8 ± 0.5
BMD (mg/cm2)Vehicle sham: 322 ± 9
L. para sham:331 ± 12
L. mix sham:344 ± 8
OVX vehicle:285 ± 9
OVX L. para:302 ± 7
OVX L. mix:298 ± 7
Trabecular thickness (mm)Vehicle sham: 45.3 ± 0.7
L. para sham: 46.0 ± 0.7
L. mix sham: 47.9 ± 1.0
OVX vehicle: 43.2 ± 0.8
OVX L. para: 42.7 ± 0.8
OVX L. mix: 44.6 ± 1.0
OC (ng/ml)Vehicle sham: 90.9 ± 10.4
L. para sham: 97.1 ± 6.7
L. mix sham: 105.6 ± 6.1
OVX vehicle: 159.9 ± 11.8
OVX L. para: 142.1 ± 7.9
OVX L. mix: 136.9 ± 6.5
Ca (mg/dl)Vehicle sham: 9.1 ± 0.4
L. para sham: 9.2 ± 0.4
L. mix sham: 8.5 ± 0.3
OVX vehicle: 10.3 ± 0.4
OVX L. para: 9.3 ± 0.4
OVX L. mix:8.7 ± 0.3
25 (OH) D3 (ng/ml)Vehicle sham: 16.5 ± 1.3
L. para sham: 17.5 ± 1.7
L. mix sham: 16.5 ± 1.8
OVX vehicle: 16.7 ± 1.1
OVX L. para: 17.6 ± 1.0
OVX L. mix: 16.8 ± 1.2

Parvaneh et al. (2015)10-week-old female mature Sprague-Dawley rats24 (n = 8)G2 : OVX,
G3 : OVX + Bifidobacterium longum (OVX + B. longum).
1 mL of Bifidobacterium longum
(108-109) (CFU/mL)
G1: sham-ovariectomized (sham)16 weeksOsteocalcin (ng/ml)Sham: 184.61 ± 6.93
OVX: 76.81 ± 6.44
OVX + B: 101.31 ± 9.21
Ca (mmol/L)Sham: 2.27 ± 0.12
OVX: 2.23 ± 0.12
OVX + B: 2.27 ± 0.06
Ca-femur (mg/g)Sham: 246.23 ± 10.14
OVX: 242.09 ± 5.16
OVX + B: 242.45 ± 15.26
Bone volume (%)Sham: 73.66 ± 6.45
OVX: 49.60 ± 5.69
OVX + B: 60.55 ± 3.57
Trabecular thickness (mm)Sham:7.33 ± 0.65
OVX: 4.83 ± 0.27
OVX + B: 7.21 ± 0.48
BMD (g/cm3)Sham: 1.06 ± 0.02
OVX: 0.59 ± 0.07
OVX + B: 0.89 ± 0.06

Zhang et al. (2015)Adult (14 weeks old) C57BL/6 male mice40 (n = 10 in each group)1. Normal diet + gavage L. reuteri (ctrl mice)
2. Normal diet + gavage L. reuteri (diabetic mice)
3. Normal diet (diabetic mice)
Lactobacillus reuteri ATCC PTA 6475 (109 colony-forming units/mL)Normal diet without gavage (ctrl mice)4 weeksBMD (mg/cc)Ctrl: 223.05
D: 177.23
Ctrl + LR: 238.62
D + LR: 237.75
BMC (mg)Ctrl: 0.581
D: 0.502
Ctrl + LR: 0.634
D + LR: 0.657
Trabecular thickness(um)Ctrl: 42.59
D: 35.77
Ctrl + LR: 48.71
D + LR: 50.99
Bone volume (%)Ctrl: 31.23
D: 21.81
Ctrl + LR: 35.74
D + LR: 34.94

Collins et al. (2016)Female BALB/c mice 11 weeks of age4 group (n = 9–18 per group)1. Nonsurgery (NS)+L.
2. Dorsal surgical incision (DSI)+L.
300 μl (1 × 109 CFU/ml) Lactobacillus reuteri 6475 or MRS1. NS
2. DSI
4 or 8 weekBone volume (%)NS: 22.4 ± 2.1
DSI: 24.1 ± 1.7
NS + L: 20.9 ± 2.8
DSI + L: 31.4 ± 2.3
Femur trabecular thickness (um)NS: 48 ± 2
DSI: 45 ± 2
NS + L: 47 ± 3
DSI + L: 50 ± 2
BMD (mg/cc)NS: 857 ± 17
DSI: 905 ± 32
NS + L: 844 ± 10
DSI + L: 821 ± 32
BMC(mg)NS: 14.5 ± 0.5
DSI: 16.9 ± 0.5
NS + L: 14.7 ± 0.3
DSI + L.:16.2 ± 0.8

Scholz-Ahren et al. (2016)Virgin female Fisher-344 rats 21-week age80 (n = 15–16 in each group)1. PRO : L. acidophilus NCC90
2. PRE: corn starch 2.5%
3. SYN : PRO + PRE
f 1–5 × 108 CFU
per 100 g
Sham
OVX
16 weeksTrabecular thickness (mm)OVX: 0.020 ± 0.002
PRO: 0.020 ± 0.004
PRE: 0.020 ± 0.003
SYN: 0.021 ± 0.003
U-Ca (mg/7 d)OVX: 9.01
PRO: 8.70
PRE: 10.42
SYN: 10.82
Ca-femur (mg)OVX: 8.41
PRO: 8.64
PRE: 8.56
SYN: 8.78
Ca-lumber vertebra (mg)OVX: 41.14
PRO: 41.64
PRE: 43.35
SYN: 44.71
U-P (mg/7 d)OVX: 9.07
PRO: 8.93
PRE: 8.49
SYN: 8.34
P-femur (mg)OVX: 39.23
PRO: 40.25
PRE: 39.64
SYN: 4046
P-lumber vertebra (mg)OVX:19.38
PRO: 21.20
PRE: 21.12
SYN:21.56
Bone alkaline phosphatase (BAP) (U/L)OVX: 154.61
PRO: 158.85
PRE: 137.12
SYN: 126.93

Bayat et al. (2018)Male Sprague-Dawley rats (aged = NM)65 (n = 13 in each group)1. Diabetic group (STZ): they were fed 1 ml/day of distilled water
2. Soy milk group (STZ + SM): diabetic rats were fed 1 ml/day of soy milk
3. Probiotic soy milk group (STZ + PSM): diabetic rats were fed 1 ml/day of probiotic soy milk
4. Omega-3 probiotic soy milk group (STZ + OPSM): diabetic rats were fed 1 ml/day of omega-3-enriched probiotic soy milk
Lactobacillus casei (1.5 × 108 CFU/mL)Nondiabetic group (control): they were fed 1 ml/day of distilled water2 monthsTibia weight (mg)Ctrl: 405 ± 14
D: 229 ± 29
SM: 310 ± 75
PSM: 312 ± 70
OPSM: 334 ± 42
Tibia volume (mm3)Ctrl: 243 ± 18
D: 124 ± 20
SM: 178 ± 56
PSM: 179 ± 39
OPSM: 191 ± 30
Tibia trabeculae volume (mm3)Ctrl: 119 ± 23
D: 57 ± 31
SM: 72 ± 25
PSM: 80 ± 26
OPSM: 88 ± 13
Vertebra weight (mg)Ctrl: 318 ± 34
D: 239 ± 50
SM: 275 ± 31
PSM: 293 ± 29
OPSM: 311 ± 41
Vertebra volume (mg)Ctrl: 207 ± 42
D: 116 ± 22
SM: 154 ± 49
PSM: 155 ± 37
OPSM: 182 ± 37
Vertebra trabeculae volume (mm3)Ctrl:8 6 ± 23
D: 45 ± 10
SM: 50 ± 25
PSM: 56 ± 14
OPSM: 60 ± 17

Blanton et al. (2018)Male 8-month-old ND4 Swiss Webster retired breeder mice181–10% grape powder
2–20% grape powder
3–10% grape powder + 1% probiotic
4–20% grape powder + 1% probiotic
5-1% probiotic
Bifidobacterium bifidum, B. breve, Lactobacillus casei, L. plantarum, and L. bulgaricus at a concentration of 1.0 × 1011 CFU/g20% sugar6 monthsTibia bone volume (%)10%G: 5.9 ± 3.7
20%G: 6.4 ± 3.3
10%G + 1%P: 6.1 ± 2.2
20%G + %P: 3.67 ± 1.8
1%P: 6.1 ± 1.8
Ctrl: 6.4 ± 2.7
Tibia thickness (mm)10%G: 0.0392 ± 0.007
20%G: 0.042 ± 0.007
10%G + 1%P:0.038 ± 0.003
20%G + %P: 0.041 ± 0.006
1%P: 0.041 ± 0.004
Ctrl:0.035 ± 0.004
Femur bone volume (%)10%G: 8.4 ± 3.4
20%G: 8.5 ± 3.8
10%G + 1%P: 7.6 ± 3.5
20%G + %P: 5.6 ± 1.7
1%P: 7.4 ± 2.6
Ctrl: 7.2 ± 3.7
Femur thickness (mm)10%G: 0.050 ± 0.006
20%G: 0.046 ± 0.003
10%G + 1%P: 0.046 ± 0.002
20%G + %P: 0.044 ± 0.004
1%P: 0.048 ± 0.009
Ctrl: 0.044 ± 0.003

Dar et al. (2018)Female mice (BALB/c) of 8–10 weeks30 (n = 10 in each group)Group B: OVX
Group C: OVX + LA
200 μl (of 109 CFU/ml Lactobacillus acidophilus (LA) ATCC 4356Group A: no probiotic + shamoperated6 weeksBMD of LV5(mgHA/cm3)Sham: 2.14 ± 0.07
OVX: 1.74 ± 0.20
OVX + LA: 2.8 ± 0.08
BMD of femur trabecular (mgHA/cm3)Sham: 3.23 ± 0.08
OVX: 1.77 ± 0.40
OVX + LA: 3.54 ± 0.24
BMD of tibia trabecular (mgHA/cm3)Sham: 3.62 ± 0.58
OVX: 2.77 ± 0.19
OVX + LA: 3.51 ± 0.24
BMD of femur cortical (mgHA/cm3)Sham: 0.91 ± 0.02
OVX: 1.02 ± 0.016
OVX + LA:1.12 ± 0.02
BMD of tibia cortical (mgHA/cm3)Sham: 0.99 ± 0.012
OVX: 1 ± 0.03
OVX + LA: 1.11 ± 0.03
Bone volume of LV5 (%)Sham: 23.5 ± 0.04
OVX: 16.53 ± 1.61
OVX + LA:21.83 ± 0.04
Bone volume of femur trabecular (%)Sham:30.71 ± 0.32
OVX:13.21 ± 3.21
OVX + LA: 25.41 ± 1.51
Bone volume of tibia trabecular (%)Sham: 26.67 ± 0.35
OVX: 20.11 ± 0.35
OVX + LA: 25.31 ± 0.24
Thickness of LV5 (mm)Sham: 1.65 ± 0.08
OVX: 0.64 ± 0.16
OVX + LA: 1.42 ± 0.07
Thickness of femur trabecular (mm)Sham: 1.73 ± 0.14
OVX: 0.74 ± 0.16
OVX + LA:1.45 ± 0.08
Thickness of tibia trabecular (mm)Sham: 1.88 ± 0.02
OVX: 1.10 ± 0.02
OVX + LA: 1.76 ± 0.03

Eaimworawuthikul et al. (2018)Six-week-old male Wistar rats48 (n = 6 in each group)1. High fat diet + vehicle (HFV)
2. High fat diet + probiotic (HFPO)
3. High fat diet + prebiotic (HFPE)
4. High fat diet + symbiotic (HFS)
Lactobacillus paracasei HII01
1 × 108 CFU/ml/day
1. Normal diet + vehicle (NDV)
2. Normal diet + probiotic (NDPO)
3. Normal diet + prebiotic (NDPE)
4. Normal diet + symbiotic (NDS)
24 weeksTrabecular volumetric BMD (g/cm3)NDV: 0.978
NDPO: 0.881
NDPE: 0.878
NDS: 0.872
HFV: 0.844
HFPO: 0.877
HFPE: 0.858
HFS: 0.835
Bone volume (%)NDV: 24.11
NDPO: 32.39
NDPE: 35.57
NDS: 34.56
HFV: 20.72
HFPO: 19.58
HFPE: 21.71
HFS: 22.14
Trabecular thickness (mm)NDV: 0.325
NDPO: 0.387
NDPE: 0.343
NDS: 0.399
HFV: 0.306
HFPO: 0.265
HFPE: 0.267
HFS: 0.327

Montazeri-Najafabady et al. (2018)Adult female Sprague-Dawley rats (12–14 weeks old)49 (n = 7 in each group)1. OVX (normal diet)
2. OVX + Lactobacillus acidophilus
3. OVX + Lactobacillus Casei
4. OVX + Bacillus coagulans
5. OVX + Bifidobacterium
6. OVX + Lactobacillus reuteri
Lactobacillus, Streptococcus,
Bifidobacterium
1.5 × 108 CFU/mL
Ctrl: normal diet4 weeks1,25 (OH) 2 D3 (Pmol/ml)Ctrl: 19.86
OVX: 12.81
LBA: 14.48
LBC: 18.65
BCO: 16.14
BB: 15.40
LBR: 16.34
P (mg/dl)Ctrl: 6.48
OVX: 5.36
LBA: 4.13
LBC: 4.57
BCO: 4.49
BB: 5.11
LBR: 5.25
Ca (mg/dl)Ctrl: 10.06
OVX: 9.43
LBA: 9.77
LBC: 10.16
BCO: 9.43
BB: 9.77
LBR: 9.38
ALP (IU/L)Ctrl: 330.43
OVX: 512.76
LBA: 705.87
LBC: 743.05
BCO: 554.45
BB: 580.84
LBR: 690.63
Global BMC (g)Ctrl: 11.29
OVX: 9.09
LBA: 10.93
LBC: 10.69
BCO: 9.94
BB: 9.91
LBR: 10.17
Femur BMC (g)Ctrl: 0.600
OVX: 0.326
LBA: 0.603
LBC: 0.547
BCO: 0.574
BB: 0.569
LBR: 0.554
Spine BMC (g)Ctrl: 0.756
OVX: 0.717
LBA: 0.781
LBC: 0.762
BCO: 0.762
BB: 0.722
LBR: 0.745
Tibia BMC (g)Ctrl: 0.513
OVX: 0.288
LBA: 0.321
LBC: 0.500
BCO: 0.348
BB: 0.304
LBR: 0.287

Parvaneh et al. (2018)Mature Sprague-Dawley rats, aged 10 weeks, female24 (n = 8 in each group)G2: OVX
G3: OVX + L. helveticus
Lactobacillus helveticus (ATCC 27558) 1 mL of 108–109 CFU of L. helveticus in phosphate buffer salineG1: sham16 weeksBone volume (%)Sham: 76 ± 6.30
OVX: 49 ± 5.7
OVX + L: 57 ± 6.6
Trabecular thickness (mm)Sham: 7.6 ± 0.5
OVX: 5.3 ± 0.4
OVX + L: 5.8 ± 0.5
BMD (g/cm3)Sham: 1.07 ± 0.02
OVX: 0.76 ± 0.06
OVX + L: 0.91 ± 0.05

Yan et al. (2018)1-day-old Ross 708 broiler chicks, both gender360 (n = 120 in each group)1. 0.5X: regular diet + 0.5 g/kg symbiotic
2. 1X: regular diet + 1 g/kg symbiotic
Enterococcus faecium,
Pediococcus acidilactici, Bifidobacterium animalis, and Lactobacillus reuteri
Ctrl: regular diet40 daysTibia BMD (g/cm3)Ctrl: 0.209
0.5X: 0.216
1X: 0.226
Tibia BMC (g)Ctrl: 2.82
0.5X: 3.02
1X: 3.30
Femur BMD (g/cm3)Ctrl: 0.180
0.5X: 0.185
1X: 0.199
Femur BMC (g)Ctrl: 1.80
0.5X: 1.92
1X: 2.21
Humerus BMD (g/cm3)Ctrl: 0.215
0.5X: 0.214
1X: 0.234
Humerus BMC (g)Ctrl: 1.60
0.5X: 1.62
1X: 1.87

Yan et al. (2018)56-week-old White Leghorn laying hens of the Hy-Line W-36 strain96 (n = 24 in each group)1-0.5X = 0.5 g/kg (0.5 × 106 CFU/g)
2-1X: 1 g/kg (1.0 × 2 × 106 CFU/g)
3-2X: 2 g/kg (2.0 × 4 × 106 CFU/g)
Enterococcus faecium,
Pediococcus acidilactici, Bifidobacterium animalis, and Lactobacillus reuteri
Ctrl: regular diet7 weeksTibia BMD (g/cm2)Ctrl: 0.1912
0.5X: 0.2018
1X: 0.1978
2X: 0.2034
Femur BMD (g/cm2)Ctrl: 0.1931
0.5X: 0.2048
1X: 0.2023
2X: 0.2100
Humerus BMD (g/cm2)Ctrl: 0.1069
0.5X: 0.1102
1X: 0.1124
2X: 0.1136
Keel BMD (g/cm2)Ctrl: 0.1109
0.5X: 0.1122
1X: 0.1164
2X: 0.1138
Tibia BMC (g)Ctrl: 2.25
0.5X: 2.35
1X: 2.35
2X: 2.36
Femur BMC (g)Ctrl: 1.71
0.5X: 1.83
1X: 1.83
2X:1.86
Humerus BMC (g)Ctrl: 1.04
0.5X: 1.07
1X: 1.10
2X: 1.15
Keel BMC(g)Ctrl: 0.69
0.5X: 0.71
1X: 0.73
2X: 0.72
CTX (c-terminal telopeptide of type I collagen) (ng/ml)Ctrl:1.17
0.5X:0.97
1X: 1.05
2X: 0.99

Achi et al. (2019)Male Wistar rats, aged = NM48 (n = 8 in each group)1-B. breve NCIM 5671,
2-B. longum NCIM 5672,
3-B. bifidum NCIM 5697
4-arthritic
5-standard anti-inflammatory drug (piroxicam)
Bifidobacteria strains B. breve NCIM 5671,
B. longum NCIM 5672
B. bifidum NCIM 5697
Ctrl: regular diet15 daysCa-bone (mg/g)B. breve: 182.94 ± 21.28
B. longum: 160.86 ± 18.71
B. bifidum: 163.20 ± 7.76
Arthritic: 139.15 ± 18.49
Piroxicam: 165.43 ± 14.02
Ctrl: 204.85 ± 4.15
K-bone (mg/g)B. breve: 3.013 ± 0.60
B. longum: 2.575 ± 0.68
B. bifidum: 2.839 ± 0.83
Arthritic: 2.007 ± 0.44
Piroxicam: 2.071 ± 0.77
Ctrl: 3.143 ± 0.56

Collins et al. (2019)Male mice (12 weeks of age) wild-type (C57BL/6) and Rag knockout (Rag1tm1Mm, C57BL/6 background)42 (n = 10–11 in each group)1-WT + LR
2-RK + LR
3.3 × 108 CFU/ml of Lactobacillus reuteri ATCC PTA 64751-WT
2-RK
4 weeksFemur trabecular bone volume (%)WT: 2.28 ± 3.33
WT + LR: 44.45 ± 4.16
RK: 40.53 ± 2.23
RK + LR:46.05 ± 5.25
Femur trabecular BMD (mg/ml)WT: 243.5 ± 8.13
WT + LR: 282.5 ± 12.41
RK: 265.2 ± 6.27
RK + LR: 290.3 ± 18.44
Femur trabecular BMC (mg)WT: 0.46 ± 0.02
WT + LR: 0.52 ± 0.01
RK: 0.51 ± 0.01
RK + LR: 0.52 ± 0.02
Femur trabecular thickness (mm)WT: 0.04 ± 0.002
WT + LR: 0.06 ± 0.004
RK: 0.05 ± 0.002
RK + LR:0.07 ± 0.006
Femur cortical BMD (mg/ml)WT: 784.3 ± 13.43
WT + LR: 779.7 ± 7.17
RK: 784.1 ± 7.14
RK + LR: 800 ± 11.65
Femur cortical BMC (mg)WT: 0.01 ± 0.001
WT + LR: 0.02 ± 
0.00
RK: 0.01 ± 0.00
RK + LR: 0.02 ± 0.00

Lee et al. (2019)Eight-week-old
female Sprague-Dawley (SD) rats
40 (n = 10 per group)1. Shamoperated (sham),
2 OVX 17-beta-estradioltreated (E2),
3. 500
mg/kg LABE-treated OVX (LAB)
Lactobacillus casei (LAB)
LAB extract (LABE)
OVX-control (OVX)8 weeksAlp (U/L)Sham: 112.53
OVX: 161.00
E2: 62.95
LABE: 75.21
Ca (uM)Sham: 44.06
OVX: 17.28
E2: 39.98
LABE: 22.78
BMD (%)Sham: 71.14
OVX: 42.62
E2: 54.42
LABE: 52.13
Bone volume (%)Sham: 16.83
OVX: 4.28
E2: 8.50
LABE: 7.45
Bone trabecular thickness (mm)Sham: 0.105
OVX: 0.096
E2: 0.111
LABE: 0.114

Levi et al. (2019)Male Wistar rats (Rattus norvegicus albinus), aged = NM40 (n = 10 per group)Group PROB (control + probiotic);
group CSI (cigarette smoke inhalation)
group CSI + PROB (CSI + probiotic)
Lactobacillus acidophilus (1 × 109 CFU/kg) Enterococcus faecium (2.1 × 109 CFU/kg)
Bacillus subtilis (2.9 × 109 CFU/kg)
Bifidobacterium bifidum (2 × 109 CFU/kg)
Group ctrl (control, without CSI and probiotic)6 monthsBMD (%)Ctrl: 0.780
PROB: 0.901
CSI: 0.478
CSI + PROB: 0.713
Bone mineral volume (%)Ctrl: 79.74
PROB: 80.10
CSI: 72.10
CSI + PROB: 74.56

Liu et al. (2019)Six-week-old male C57BL6/J mice1. Sham group: normal saline;
2. LGG group: Tenofovir disoproxil fumarate (TDF) (43 mg/kg) and LGG
Lactobacillus rhamnosus GG
(5 × 108 CFU, ATCC)
1. TDF group (negative control):
2. ZOL (zoledronate) group (positive control)
8 weeksCa (mmol/L)Sham: 2.02
LGG: 1.98
TDF: 1.97
ZOL: 1.87
P (mmol/L)Sham: 2.93
LGG: 3.36
TDF: 3.04
ZOL: 3.18
Mandibular BMD (mg/cm3)
Sham: 1219
LGG: 1177
TDF: 1011
ZOL: 1286
Mandibular BMC (mg)Sham: 1.23
LGG: 1.16
TDF: 0.72
ZOL: 1.30
Bone volume (%)Sham: 58.85
LGG: 57.66
TDF: 44.92
ZOL: 64.18
Trabecular thickness (mm)Sham: 0.063
LGG: 0.064
TDF: 0.048
ZOL: 0.074

Liu et al. (2019)Mice aged 6 weeks and male (C57BL6/J)5 group (n = 10–12)(a) Sham group: normal saline (NS)
(b) LGG + TDF group: 0.86 mg TDF (43 mg/kg body weight) + 5 × 108 CFU LGG
(c) E. coli + TDF group: TDF (43 mg/kg body weight) + 5 × 108 CFU E. coli
LGG (accession number 53103)
Escherichia coli (accession number 25922)
(d) TDF group: TDF (43 mg/kg body weight) (negative control). (e) ZOL + TDF group: TDF (43 mg/kg body weight) + ZOL (100 μg/kg as a positive control)8 weeksFemur BMD (mg/cm3)Sham: 544.172 ± 46.588
LGG + TDF: 565.929 ± 57.65
E. coli + TDF: 415.57 ± 18.319
TDF: 421.582 ± 14.481
ZOL + TDF: 1231.783 ± 124.543
Femur BMC (mg)Sham: 0.739 ± 0.132
LGG + TDF: 0.868 ± 0.169
E. coli + TDF: 0.551 ± 0.555
TDF: 0.623 ± 0.056
ZOL + TDF: 2.387 ± 0.324
Bone volume (%)Sham: 25.407 ± 3.821
LGG + TDF: 27.872 ± 0.671
E. coli + TDF: 16.757 ± 2.158
TDF: 16.223 ± 0.822
ZOL + TDF: 94.028 ± 2.278
Trabecular thickness (mm)Sham: 0.045 ± 0.01
LGG + TDF: 0.044 ± 0.003
E. coli + TDF: 0.038 ± 0.003
TDF: 0.039 ± 0.001
ZOL + TDF: 0.194 ± 0.017

Schepper et al. (2019)Eleven-week-old male BALB/c mice88 (n = 10–18 per group)1. ABX: antibiotic-treated (ampicillin 1.0 g/L and neomycin 0.5 g/L)
2. ABX + LR
3. ABX + LGG
4. ABX + EC
5. ABX + MDY (high-molecular-weight polymer)
300 mL of L. reuteri 6475 (LR), Lactobacillus rhamnosus (LGG),
nonpathogenic Escherichia coli (EC; ATCC O6 : B1)
(1 × 109 CFU/mL)
Ctrl: normal diet4 weekBMD (mg/cc)Ctrl: 1019 ± 24.34
ABX: 1024 ± 18.5
ABX + LR: 1045 ± 39.05
ABX + LGG: 1044 ± 55.7
ABX + EC: 1043 ± 27.23
ABX + MDY: 1021 ± 
27.02
BMC (mg)Ctrl: 0.022 ± 0.001
ABX: 0.021 ± 0.0005
ABX + LR: 0.022 ± 0.001
ABX + LGG: 0.022 ± 0.001
ABX + EC: 0.023 ± 0.0007
ABX + MDY: 0.021 ± 0.001
Cortical thickness (mm)Ctrl: 0.29 ± 0.01
ABX: 0.28 ± 0.003
ABX + LR: 0.29 ± 0.003
ABX + LGG: 0.29 ± 0.003
ABX + EC: 0.28 ± 0.005
ABX + MDY: 0.28 ± 0.005

Lawenius et al. (2019)Twelve-week-old female C57BL/6 mice(n = 8–12/groupSham + pAkk
OVX + pAkk
Pasteurized Akkermansia muciniphila (pAkk) (2 × 108 CFU/150 µl)Sham + Veh
OVX + Veh
4 weekFemur length (mm)Sham + Veh: 15.37 ± 0.15
Sham + pAkk: 15.19 ± 0.07
OVX + Veh: 15.61 ± 0.08
OVX + pAkk: 15.27 ± 0.13
Femur cortical thickness (mm)Sham + Veh:0.197 ± 0.002
Sham + pAkk:0.192 ± 0.002
OVX + Veh: 0.186 ± 0.003
OVX + pAkk: 0.184 ± 0.002
Vertebra length (mm)Sham + Veh: 3.02 ± 0.02
Sham + pAkk: 3.04 ± 0.02
OVX + Veh: 3.06 ± 0.01
OVX + pAkk: 3.06 ± 0.01
Vertebra cortical thickness (mm)Sham + Veh: 0.065 ± 0.001
Sham + pAkk: 0.060 ± 0.002
OVX + Veh: 0.056 ± 0.001
OVX + pAkk: 0.056 ± 0.001
25 (OH) D3 (ng/ml)Sham + Veh: 41.7 ± 1.2
Sham + pAkk: 38.1 ± 
2.8
OVX + Veh: 44.5 ± 1.3
OVX + pAkk: 42.9 ± 1.0
OC (ng/ml)Sham + Veh: 96.8 ± 3.8
Sham + pAkk: 104.1 ± 
8.6
OVX + Veh: 116.3 ± 8.8
OVX + pAkk: 119.4 ± 7.3
BMD (mg/cm2)Sham + Veh: 77.62
Sham + pAkk: 70.54
OVX + Veh: 70.24
OVX + pAkk: 67.98
Bone volume (%)Sham + Veh: 15.63
Sham + pAkk: 14.34
OVX + Veh: 14.03
OVX + pAkk: 13.50
Trabecular thickness (mm)Sham + Veh: 0.0478
Sham + pAkk: 0.0442
OVX + Veh: 0.459
OVX + pAkk: 0.0436
PTH (pg/ml)Sham + Veh: 276
Sham + pAkk: 235
OVX + Veh: 506
OVX + pAkk: 330
Ca (mg/dl)Sham + Veh: 9.24
Sham + pAkk: 9.44
OVX + Veh: 9.16
OVX + pAkk: 9.33
U–CaSham + Veh: 0.237
Sham + pAkk: 0.484
OVX + Veh: 0.169
OVX + pAkk: 0.230

Kim et al. (2019)Female C57BL/6 mice (6 weeks old for GV-induced BV
and 11 weeks old for ovariectomy-induced osteoporosis)
56 (n = 8 in each group)1. SH: vehicle (1% maltose)
2. OVX: vehicle (1% maltose)
3. OLP: 1 × 109 CFU LP
4. OBL: 1 × 109 CFU BL
5. OMX: 1 × 109 CFU LP + BL
6. OCP: 1 mg/kg beta-estradiol
1 × 109 CFU
Lactobacillus plantarum NK3 and Bifidobacterium longum NK49
Ctrl: vehicle (1% maltose)2 weeks (6 days per week)Femur weight (g)Ctrl: 0.178
SH: 0.173
OVX: 0.130
OLP: 0.171
OBL: 0.176
OMX: 0.177
OCP: 0.175
Ca (mmol/L)Ctrl: 0.280
SH: 0.288
OVX: 0.178
OLP: 0.269
OBL: 0.304
OMX: 0.258
OCP: 0.285
P (mmol/L)Ctrl: 0.871
SH: 0.920
OVX: 0.681
OLP: 0.861
OBL: 0.862
OMX: 0.945
OCP: 0.836
OC (pg/ml)Ctrl: 0.448
SH: 0.472
OVX: 0.059
OLP: 0.469
OBL: 0.441
OMX: 0.570
OCP: 0.609

Tibiotarsal index = (diaphysis diameter − medullary canal diameter)/diaphysis diameter × 100 (Barnet and Nordin, 1960). Robusticity index = bone length/cube root of bone weight (Reisenfeld, 1972). Calcium (Ca), phosphorus (P), urinary calcium (U-Ca), parathyroid hormone (PTH), osteocalcin (OC), isoleycyl-prolyl-proline (IPP), valyl-prolyl-proline (VPP), collagen type 1 cross-linked C-telopeptide (CTX), 25-hydroxy vitamin D (25-OH-D), alkaline phosphatase (ALP), acid phosphatase (ACP), bone mineral density (BMD), bone mineral content (BMC), Hwangryun-haedok-tang (HRT), fermented HRT (fHRT), sham-operated (SH), ovariectomized (OVX), tibia dyschondroplasis (TD), senescence-accelerated mouse (SAMP), and dorsal surgical incision (DSI). Final results in each group were reported in the Results column. Results with red color are significant ( value <0.05).