AbstractBackground: As HIV-positive patients live longer, they are experiencing age-related comorbidities,
including bone and renal disease. The aetiology is multifactorial, comprising
traditional and HIV-related factors, including antiretroviral therapy (ART). However, whether
reduced bone mineral density (BMD) translates into a higher fracture risk remains unclear.
Aims: My main aim in my thesis was to conduct a cross-sectional study with changes over
time to investigate BMD and renal tubular dysfunction (RTD) in a relatively homogenous
group of white, ART-experienced HIV-positive men in the UK, who were mostly men who
have sex with men (MSM) and mainly on tenofovir disoproxil fumarate (TDF). The aims I
1. The prevalence and risk factors associated with reduced BMD at baseline and the
change in BMD over 12 months and the factors associated with loss of BMD.
2. The utility of the FRAX®
score and peripheral dual-energy x-ray absorptiometry
(pDXA) as screening tools.
3. The utility of albumin/protein ratio (APR) in differentiating RTD from other proteinuria
and the relationship between RTD and bone.
Methods: I designed a prospective cohort study of HIV-positive men attending an HIV
outpatient clinic. Participants underwent central DXA (cDXA) and pDXA, fasting blood and
urine tests (including bone turnover markers [BTMs] and retinol binding protein creatinine
ratio [RBPCR]) and completed a questionnaire at baseline and at 12 months.
Results: I found a low prevalence of reduced BMD. Mainly ‘traditional’ risk factors were
associated with reduced BMD. The change seen in absolute BMD at 12 months was small,
reflecting the short follow-up period. The only factor associated with a greater than smallest
detectable difference (SDD) reduction in BMD was a detectable HIV viral load. FRAX® was
not sensitive enough as a screening tool, and pDXA was slightly more sensitive, although
combining FRAX® and pDXA was not much better than FRAX®
alone. RTD prevalence was
too low to conduct meaningful analyses. Overall, 20.7% had RBPCR-defined RTD and there
was a borderline association between severe RTD and BMD at the lumbar spine, but not
Conclusions: In my cohort of mainly white, ART-experienced (mainly exposed to TDF) HIVpositive
MSM in the UK, the prevalences of reduced BMD and RTD were low. The factors
associated with reduced BMD were mainly ‘traditional’ factors and probably reflects a ‘return
to health’ with ART in these men. There was not much change in BMD over 12 months,
which is probably reflective of the short follow-up period. Using FRAX® and pDXA may be
useful as screening tools, but further work is needed before any firm conclusions can be
made in this cohort. Although one-fifth had RBPCR-defined RTD, the clinical significance of
these findings and the impact on bone health is yet to be fully elucidated.
|Date of Award||Feb 2018|
|Supervisor||Kevin A. Davies (Supervisor)|