Tenofovir accelerates bone mass loss of the lumbar spine in the first years of menopause in HIV‐infected women
Authors: Garlassi E , Zona S , Vescini F , Domingues da Silva A , Berardi C , Orlando G , Carli F , Menozzi M , Santoro A , Mussini C , Guaraldi G 
Published: November 2012

Background

HIV‐infected postmenopausal women have higher rates of bone loss than HIV negative women. We aimed to identify predictors of body mass density (BMD) in HIV infected women entering menopause and to evaluate the pre‐ and post‐menopausal BMD change, with regard to tenofovir (TDF) use.

Methods

Women with at least one DEXA measurement were enrolled. The observation period was divided into: “Reproductive period”, “Menopause transition period”, “Early menopause period”, “Late menopause period”. BMD of the lumbar spine (L1‐4) and femur neck were measured by DEXA. Lowess smoothing curves were drawn to analyze impact of menopause and TDF on BMD. Three different longitudinal linear regression models with random effects were built. Longitudinal regression analysis fits cross sectional time series regression models and allows to analyze repeated measures for each patient.

Results

Fifty‐five women were included. Median age at enrollment was 46 years (IQ range 44–49). Median observation period was 16 months (IQ range 8; 23) and 33 months (IQ range 23; 72) for pre‐ and post‐menopausal respectively. At enrollment mean CD4 cell count was 553 cell/mL (±269.62) and HIV‐VL was undetectable in 77.5% of patients: 6 women were not undergoing ART. Most common backbone TDF/FTC (46.9%) and ABC/3TC (20.4%). At the time of inclusion in the cohort osteopenia and ostoeporosis were present in 60% and 3.64%, respectively. At the time of last DEXA evaluation osteopenia and osteoporosis were present in 78.18% and 36.36%, respectively. The impact of menopause on lumbar BMD was depicted (fig. 1) using a lowess smoothing analysis according to current TDF exposure (as treated model). Lumbar BMD change predictors were years from menopause and TDF current exposure in the “Early menopause period” and years from menopause, Baseline lumbar BMD, BMI and vitD supplementation in the “Late menopause period”.

Discussion

This is the first study analyzing BMD across menopause. BMD was stable in the pre‐menopause period while BMD loss characterized the post‐menopause period. Traditional risk factors contributed to BMD change in the post ‐menopause period. Current TDF exposure was independently associated with BMD change in the “Early menopause period” only, but not confirmed in the “Late menopause period”, suggesting a compensating mechanism occurring after the second year post‐menopause.

image

Transitional period
Early menopause
Late menopause

β
95% CI
p‐value
β
95% CI
p‐value
β
95% CI
p‐value

Years to (from*) menopause
−0.1
−0.03; 0.01
0.407
−0.01
−0.02; − 0.01
<0.001
−0.1
−0.2; − 0.003
0.009

Baseline lumbar BMD
0.0002
−0.001; 0.003
0.078
0.0002
−0.0001; 0.0004
0.074
0.9
0.70−1.09
<0.001

PTH
−0.0005
−0.001; 0.0004
0.280
0.0001
−0.0004; 0.0002
0.535
−0.0001
−0.0002; 0.0002
0.800

BMI
0.003
−0.005; 0.010
0.489
0.004
−0.001; 0.010
0.142
0.008
0.002; 0.014
0.010

VitD supplementation
−0.003
−0.05; 0.04
0.865
0.008
−0.010; 0.026
0.392
0.03
0.001; 0.054
0.038

TDF current exposure
−0.03
−0.07; 0.01
0.125
−0.03
−0.05; −0.01
0.012
−0.04
−0.09; 0.01
0.129