Protein Intake and Bone Mineral Density‐ a Systematic Review and Meta‐Analysis of Randomized Controlled Trials
Authors: Shams‐White Marissa , Sackey Joachim , Fu Zhuxuan , Karlsen Micaela , Du Mengxi , Insogna Karl , LeBoff Meryl , Shapses Sue , Weaver Connie , Chung Mei 
Published: November 2023

ObjectiveTo conduct a systematic review and meta‐analysis evaluating the effects of protein intake on bone mineral density (BMD) in healthy adults, as well as its synergistic effects with calcium or vitamin D. [Registered on International Prospective Register of Systematic Reviews: PROSPERO CRD42015017751].MethodsThis study is a sub‐analysis of a larger systematic review. Search strategies were conducted through April 19, 2015. Inclusion criteria: randomized controlled trials (RCTs) at least one year in duration that examined effects of high versus low or animal versus plant protein intake on total body, total hip, lumbar spine or femoral neck BMD in healthy adults. Two scientists independently conducted abstract and full‐text screenings, data extractions and risk of bias assessments, with discrepancies resolved via group consensus. Random effect meta‐analyses were performed using Stata.ResultsOf the 869 citations identified in the literature search, 12 studies were included in qualitative and quantitative synthesis. Nine of the studies were in post‐menopausal women, two of which had recent hip fractures. In the three remaining studies, two were conducted in men and one was in both men and women. The majority of studies (N=10) supplemented all groups with calcium, vitamin D or both, and none examined their interaction with protein. There were no significant differences in BMD outcomes across studies comparing different sources of protein intake (animal vs plant, N=4). Meta‐analysis results showed that high protein groups had less lumbar spine BMD loss than low protein groups, with small heterogeneity (N=3, SMD: 0.25, 95% CI: −0.03, 0.53, I2: 22.4%). Individual study findings were mixed for total hip and total body BMD outcomes, sites that contain more cortical bone than the spine. Meta‐analysis results showed nonsignificant, negligible to small effect sizes with wide confidence intervals (total hip: N=4, SMD: 0.04, 95% CI: −0.18, 0.27, I2:0%; total body: N=4, SMD: 0.26, 95% CI: −0.21, 0.73, I2: 60.9%; femoral neck: N=3, SMD: 0.09, 95% CI: −0.25, 0.44, I2: 21.9%). While risk of bias assessment indicated all studies’ groups were comparable at baseline, half did not provide adequate randomization information, had <80% compliance or significant differences in compliance between groups and had incomplete outcome data.ConclusionsResults suggest that higher protein intake, rather than the type of protein, may have a small effect on attenuating BMD loss, but the effects were not consistent across BMD sites. Moreover, existing studies were heterogeneous and limited in number and quality, weakening our confidence in the meta‐analysis findings. Future studies are needed, including those examining the effects of different protein sources on BMD and the interaction of protein with calcium and vitamin D.Support or Funding InformationNational Osteoporosis Foundation