Lactobacillus reuteri reduces bone loss in older women with low bone mineral density: a randomized, placebo-controlled, double-blind, clinical trial

被引:243
作者
Nilsson, A. G. [1 ,2 ,3 ]
Sundh, D. [1 ]
Backhed, F. [4 ,5 ]
Lorentzon, M. [1 ,6 ,7 ]
机构
[1] Univ Gothenburg, Sahlgrenska Acad, Inst Med, Dept Internal Med & Clin Nutr,Geriatr Med, Gothenburg, Sweden
[2] Sahlgrens Univ Hosp, Dept Endocrinol, Internal Med, Gothenburg, Sweden
[3] Sahlgrens Univ Hosp, Dept Endocrinol, Internal Med, Molndal, Sweden
[4] Univ Gothenburg, Sahlgrenska Acad, Inst Med,Wallenberg Lab, Dept Mol & Clin Med, Gothenburg, Sweden
[5] Univ Copenhagen, Ctr Basic Metab Res, Sect Metab Receptol & Enteroendocrinol, Fac Hlth Sci,Novo Nordisk Fdn, Copenhagen, Denmark
[6] Sahlgrens Univ Hosp, Geriatr Med Clin, Gothenburg, Sweden
[7] Sahlgrens Univ Hosp, Geriatr Med Clin, Molndal, Sweden
基金
瑞典研究理事会;
关键词
lactobacillus reuteri; osteoporosis; probiotics; volumetric bone mineral density; OSTEOPOROSIS; MICROBIOME; FRACTURES;
D O I
10.1111/joim.12805
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
BackgroundThe importance of the gut microbiome for bone metabolism in mice has recently been demonstrated, but no studies are available in humans. Lactobacillus reuteri ATCCPTA 6475 (L. reuteri 6475) has been reported to increase bone mineral density (BMD) in mice but its effect on the human skeleton is unknown. The objective of this trial was to investigate if L. reuteri 6475 affects bone loss in older women with low BMD. MethodsIn this double-blind, placebo-controlled study, women from the population who were 75 to 80 years old and had low BMD were randomized to orally receive 10(10) colony-forming units of L. reuteri 6475 daily or placebo. The predefined primary end-point was relative change after 12 months in tibia total volumetric BMD (vBMD). ResultsNinety women were included and 70 completed the study. L. reuteri 6475 reduced loss of total vBMD compared to placebo both in the intention-to-treat (ITT) analysis [-0.83% (95% confidence interval [CI], -1.47 to -0.19%) vs. -1.85% (95% CI, -2.64 to -1.07%); mean difference 1.02% (95% CI, 0.02-2.03)] and per protocol analysis [-0.93% (95% CI, -1.45 to -0.40) vs. -1.86% (95% CI, -2.35 to -1.36); mean difference 0.93% (95% CI, 0.21-1.65)]. In general, similar but smaller effects were observed in the secondary bone variable outcomes, but these differences did not reach statistical significance in the ITT population. Adverse events did not differ between groups. ConclusionsSupplementation with L. reuteri 6475 should be further explored as a novel approach to prevent age-associated bone loss and osteoporosis.
引用
收藏
页码:307 / 317
页数:11
相关论文
共 29 条
[1]   Managing Osteoporosis in Patients on Long-Term Bisphosphonate Treatment: Report of a Task Force of the American Society for Bone and Mineral Research [J].
Adler, Robert A. ;
El-Hajj Fuleihan, Ghada ;
Bauer, Douglas C. ;
Camacho, Pauline M. ;
Clarke, Bart L. ;
Clines, Gregory A. ;
Compston, Juliet E. ;
Drake, Matthew T. ;
Edwards, Beatrice J. ;
Favus, Murray J. ;
Greenspan, Susan L. ;
McKinney, Ross, Jr. ;
Pignolo, Robert J. ;
Sellmeyer, Deborah E. .
JOURNAL OF BONE AND MINERAL RESEARCH, 2016, 31 (10) :1910-1910
[2]   Defining a Healthy Human Gut Microbiome: Current Concepts, Future Directions, and Clinical Applications [J].
Backhed, Fredrik ;
Fraser, Claire M. ;
Ringel, Yehuda ;
Sanders, Mary Ellen ;
Sartor, R. Balfour ;
Sherman, Philip M. ;
Versalovic, James ;
Young, Vincent ;
Finlay, B. Brett .
CELL HOST & MICROBE, 2012, 12 (05) :611-622
[3]  
Black DM, 2016, NEW ENGL J MED, V374, P2096, DOI 10.1056/NEJMc1602599
[4]  
BLACK DM, 2007, NEW ENGL J MED, V356, P1809, DOI [DOI 10.1056/NEJMOA067312, 10.1056/NEJMoa067312]
[5]   Osteoclast precursors: cytokine-stimulated immunomodulators of inflammatory bone disease [J].
Boyce, Brendan F. ;
Schwarz, Edward M. ;
Xing, Lianping .
CURRENT OPINION IN RHEUMATOLOGY, 2006, 18 (04) :427-432
[6]   Probiotic L. reuteri Treatment Prevents Bone Loss in a Menopausal Ovariectomized Mouse Model [J].
Britton, Robert A. ;
Irwin, Regina ;
Quach, Darin ;
Schaefer, Laura ;
Zhang, Jing ;
Lee, Taehyung ;
Parameswaran, Narayanan ;
McCabe, Laura R. .
JOURNAL OF CELLULAR PHYSIOLOGY, 2014, 229 (11) :1822-1830
[7]   Incidence and economic burden of osteoporosis-related fractures in the United States, 2005-2025 [J].
Burge, Russel ;
Dawson-Hughes, Bess ;
Solomon, Daniel H. ;
Wong, John B. ;
King, Alison ;
Tosteson, Anna .
JOURNAL OF BONE AND MINERAL RESEARCH, 2007, 22 (03) :465-475
[8]   Lactobacillus reuteri 6475 Increases Bone Density in Intact Females Only under an Inflammatory Setting [J].
Collins, Fraser L. ;
Irwin, Regina ;
Bierhalter, Hayley ;
Schepper, Jonathan ;
Britton, Robert A. ;
Parameswaran, Narayanan ;
McCabe, Laura R. .
PLOS ONE, 2016, 11 (04)
[9]   Lactobacillus reuteri Prevents Diet-Induced Obesity, but not Atherosclerosis, in a Strain Dependent Fashion in Apoe-/- Mice [J].
Fak, Frida ;
Backhed, Fredrik .
PLOS ONE, 2012, 7 (10)
[10]   Skeletal changes through the lifespan-from growth to senescence [J].
Farr, Joshua N. ;
Khosla, Sundeep .
NATURE REVIEWS ENDOCRINOLOGY, 2015, 11 (09) :513-521