Bone mineral density decreases with antiretroviral therapy
(ART)-initiation, although the pathogenesis, including the role of tenofovir
(TDF), is unclear. This study assessed changes in bone-turnover markers,
osteoprotegerin (OPG), soluble receptor activator for nuclear factor kappa
β ligand (sRANKL), and inflammation in subjects initiating TDF- vs.
non-TDF-containing regimens, and determined the relationship between bone
turnover, OPG/sRANKL, and inflammation.
This was a longitudinal, observational study comparing levels of
bone-turnover markers (C-terminal telopeptide of type I collagen, CTX;
osteocalcin (OC)), OPG, sRANKL, and inflammatory cytokines (soluble tumor
necrosis factor-α receptor-I, -II (sTNFR-I,-II), interleukin-6)
prior to ART and 6–12 months after ART-initiation with a TDF- vs.
non-TDF-containing regimen in HIV-infected subjects 18–50 years
87 subjects were enrolled (TDF=44; non-TDF=43). Groups were similar
except subjects on TDF had a lower CD4 nadir (P<0.01) and were more
likely to receive a protease inhibitor (PI) (P=0.03). At pre-ART,
35% and 1% of subjects had CTX and OC above normal range,
respectively. Both increased with ART initiation, whereas OPG, sRANKL, and
inflammatory markers significantly decreased. In multivariate models,
increases in OC were associated with TDF-use, PI-use, and pre-ART levels of
sTNFR-I, while increases in CTX were associated with CD4 nadir <50
cell/mm3. Increases in bone markers were unrelated to pre-ART
levels of OPG/sRANKL and changes in OPG/sRANKL after ART-initiation.
TDF-use, PI-use, TNF-α activity, and advanced HIV disease are
associated with changes in bone-turnover markers, underscoring the
complicated interaction between ART, bone turnover, inflammation, and immune
status, which extend beyond the OPG/RANKL system.