The effect of tenofovir disoproxil fumarate on bone mineral density: a systematic review and meta-analysis.

Baranek, Benjamin; Wang, Shaoyuan; Cheung, Angela M; Mishra, Sharmistha; Tan, Darrell Hs

BACKGROUND We conducted a systematic review and meta-analysis (CRD#42017070552) to quantify the impact of oral TDF/FTC on bone mineral density (BMD), and the risk of osteoporosis, low bone mass, and fractures, among people taking it as PrEP, HIV treatment and hepatitis B (HBV) treatment. METHODS We searched MEDLINE and EMBASE for randomized controlled trials published 1997-2018 reporting BMD, osteoporosis, low bone mass, and/or fractures in treatment-naïve patients taking compared to not taking TDF for 48±4 weeks. We pooled outcomes using DerSimonian random-effects models. RESULTS Our search yielded 5178 abstracts, representing 3865 articles, with 25 meeting the inclusion criteria. TDF was associated with greater BMD decline when taken as PrEP (lumbar spine: mean difference, MD=-0.82%, 95%CI=-1.28,-0.37%, I2=38%; total hip: MD=-0.81%, 95%CI=-1.22,-0.40%, I2=48%) and HIV treatment (lumbar spine: MD=-1.62%, 95%CI=-2.30,-0.95%, I2=93%; total hip: MD=-1.75%, 95%CI=-2.08,-1.42%, I2=83%; femoral neck: MD=-1.26%, 95%CI=-2.15,-0.38%, I2=43%) in comparison to those not taking TDF. Eight studies reported on incident osteoporosis or low bone mass, with variable results. Pooled results from five PrEP studies showed that TDF was not associated with increased fractures compared to no PrEP (RR=1.12, 95%CI=0.752,1.74, I2=26%). CONCLUSIONS TDF caused greater decreases in BMD than did comparators when used for all three indications, and the magnitude of this decrease was larger for HIV treatment compared to PrEP. Fractures were not increased among PrEP patients. The clinically-significant BMD decline caused by TDF and current expansion of PrEP use suggest attention to the adverse bone effects of TDF will increase in importance.