Table 1.
Characteristics of included randomized controlled trials in the meta-analysis.
| Study (Author, year) | Country | Sample size (C/I group) | Blinding | Mean age, years (mean ± SD) | BMI kg/m2 (mean ± SD) | Descriptions of intervention | Comparison intervention | Duration (months) | Adherence with intervention | Outcomes | adverse events |
|---|---|---|---|---|---|---|---|---|---|---|---|
| Jansson (2019) | Sweden | 123/126 | Double blind | C: 58.1± 4.3 I: 59.1 ± 3.8 |
C: 23.9 ± 2.6 I: 24.2 ± 2.7 |
Three lactobacillus strains: L. paracasei 8700:2 (DSM 13434), L. plantarum heal 9(DSM 15312), and L. plantarum heal 19(DSM 15313) | Placebo | 12 | NR | BMD (lumbar spine and total hip) | The number of adverse events considered to be related to the treatment were similar between the groups (24% in Lactobacillus and 26% in placebo). No treatment-related serious adverse events reported |
| Takimoto (2018) | Japan | 30/31 | Double blind | C: 57.8± 5.4 I: 57.5 ± 4.3 |
C: 23.9 ± 2.6 I: 24.2 ± 2.7 |
Probiotic Bacillus subtilis C-3102 (C-3102) | Placebo | 6 | The overall mean compliance rate was 99.5% ± 0.1% (placebo = 99.6% ± 0.2%, C-3102 = 99.5% ± 0.2%) | BMD (lumbar spine and total hip) | No adverse effects were reported during the study period |
| Lambert (2017) | Denmark | 40/38 | Double blind | C: 62.9± 1 I: 60.8 ± 1.1 |
C: 26.7 ± 0.8 I: 24.8 ± 0.6 |
Lactic acid bacteria and soffavones Other treatments: twice daily red clover extract (RCE) plus vitamin and mineral tablets containing 1040 mg Ca, 487 mg Mg, and 25 mg vitamin D/d |
Placebo | 12 | The mean compliance rate was 96.44% ± 0.40%. There were no significant intergroup differences in compliance rates. | BMD (lumbar spine and hip [femoral neck]), CTX, OPG, RANKL, OC | Three participants (one in control group and two in intervention group) dropped out of the study due to gastrointestinal issues, and there was no significant difference between groups |
| Jafarnejad (2017) | Iran | 21/20 | Double blind | C: 57.3± 0.7 I: 68.9 ± 0.7 |
C: 23.8 ± 0.4 I: 24.9 ± 0.4 |
Multispecies probiotic supplement (GeriLact capsule): L. casei, Biffdobacterium longum, L. acidophilus, L. rhamnosus, L. bulgaricus, Biffdobacterium breve and Streptococcus thermophilus Other treatments: 500 mg calcium plus 200 IU vitamin D daily |
Placebo+other treatments identical to those in the intervention group | 6 | NR | BMD (lumbar spine and hip), CTX, RANKL, OPG, OC, BALP | There were no significant adverse effects reported directly attributed to the treatment |
| Nilsson (2018) | Sweden | 36/32 | Double blind | C: 76.3± 1.1 I: 76.4 ± 1.0 |
C: 25.3 ± 3.3 I: 25.5 ± 3.5 |
Freeze-dried L. reuteri 6475 (BioGaia AB, Stockholm, Sweden) | Placebo | 12 | NR | BMD (lumbar spine and total hip), CTX, BALP | Adverse events considered to be related to the treatment were similar between the groups (40% in L. reuteri 6475 and 44% in placebo) |
| Vanitchanont (2024) | Thailand | 20/20 | Double blind | C: 64.1 ± 3.6 I: 62 ± 5.1 |
C: 24.2 ± 2.8 I: 23.4 ± 3.8 |
Lactobacillus reuteri GL-104, Lactobacillus paracasei MP-137, Lactobacillus rhamnosus MP108, Lactobacillus rhamnosus F-1, Lactobacillus rhamnosus BV77, Biffdobacterium animalis ssp. lactis CP-9, Biffdobacterium longum ssp. longum OLP-01, and Bacillus coagulans Other treatments: at least 1200 mg of calcium daily and 20,000 IU of vitamin D2 per week |
Placebo+other treatments identical to those in the intervention group | 3 | NR | CTX, P1NP | Four participants in the placebo group and two in the multispecies probiotic group reported adverse reactions during the study period. There were no significant differences between groups in these adverse reactions. |
| Gregori (2024) | Sweden | 79/160 | Double blind | C: 55(53-56) High-dose: 55(52-56) Low-dose: 55(53-56) |
C:23.7(21.4-28.3) High-dose:23.9(22.1-27.5) Low-dose:24.5(21.9-27.9) |
High-dose: L reuteri 6475 (BioGaia AB) (5 × 109 colony-forming units) Low-dose: L reuteri 6475 (BioGaia AB) (5 × 108 colony-forming units) Other treatments: 200 IU of cholecalciferol per day |
Placebo+other treatments identical to those in the intervention group | 24 | Overall, mean (SD) adherence to the study product was high, ranging from 87.5% (24.6%) in the high-dose L reuteri group to 93.6% (12.9%) in the placebo group | BMD (lumbar spine and total hip), CTX, P1NP | No significant adverse effects were observed. |
| Harahap (2024) | Poland | 32/32 | Double blind | Overall: 45-70 | C: 28.6 ± 4.4 I: 25.3 ± 4.8 |
L. acidophilus UALa-01 | Placebo | 3 | NR | BMD (lumbar spine and hip [femoral neck]), PINP, CTX, BALP | A significant increase in glucose concentration was observed in the probiotic group |
| Zhao (2023) | China | 20/20 | Double blind | C:61.6 ± 7.9 I: 62.8 ± 6.0 |
C: 23.4 ± 2.5 I: 23.1 ± 2.2 |
Bifdobacterium animalis subsp. lactis Probio-M8, Probio-M8 Other treatments: daily 600 mg of calcium and 0.25µg of calcitriol |
Placebo+other treatments identical to those in the intervention group | 3 | NR | BMD (lumbar spine and hip [femoral neck]), PINP, CTX, OC | NR |
| Li (2021) | China | 73/73 | Unclear | C: 69.8 ± 21.5 I: 68.2 ± 22.4 |
C: 24.9 ± 7.4 I: 26.3 ± 8.4 |
Bifidobacterium quadruple viable bacteria tablets 0.5 g Tid + oral alendronate sodium 10 mg Qd + subcutaneous or intramuscular injection of salmon calcitonin 50 IU Qd. | Oral alendronate sodium 10 mg Qd + subcutaneous or intramuscular injection of salmon calcitonin 50 IU Qd. | 6 | NR | BMD (lumbar spine and hip [femoral neck]), CTX, OC, BALP | There were no significant differences between groups in adverse reactions. |
| Guo (2020) | China | 24/30 | Double blind | C: 63.4 ± 5.7 I: 61.9 ± 6.4 |
C: 23.9 ± 3.2 I: 23.6 ± 3.4 |
Dry Probio-M8 lactic acid bacteria | placebo | 6 | NR | BMD (lumbar spine and hip [femoral neck]), CTX, OC | NR |
| Zhang (2018) | China | 50/53 | Unclear | C:58.6 ± 7.5 I:56.8 ± 6.2 |
C:25.9 ± 3.7 I:25.9 ± 3.0 |
Bifidobacterium quadruple viable bacteria tablets 0.5 g Tid+ calcium carbonate 600mg/d+vitamin D3 (125IU/d) | calcium carbonate 600mg/d+vitamin D3 125IU/d | 6 | NR | BMD (lumbar spine), CTX, BALP | NR |
C, control; CTX, collagen type 1 cross-l inked C-telopeptide; I, intervention; BMD, bone mineral density; RANKL, Receptor activator of nuclear factor-κ B ligand; OC, osteocalcin; OPG, osteoprotegerin; PINP, N-terminal propeptide of type I procollagen; BSAP, bone-specific alkaline phosphatase; NR, not reported; BALP, bone-specific alkaline phosphatase.