Important physiologic markers of frailty
are associated with fragility fractures in men living with HIV, according to
research conducted in the United States and published in the online edition of Clinical Infectious Diseases.
“Among HIV-infected men, physiologic
frailty…is strongly associated with risk of fragility fracture,” write the
authors. “The association…was driven by increasing age and anaemia.”
The study population comprised
approximately 40,000 men living with HIV who received care from the Department of
Veterans Affairs between 1997 and 2009. Investigators used the Veterans Aging
Cohort Study (VACS) Index to assess their patients’ risk of fragility fractures
– hip, vertebra and upper arm. The VACS Index assesses a number of markers
known to be associated with physical frailty in older people. These include
all-cause mortality, hospitalisation and functional performance, as well as of markers
of inflammation, such as IL-6, D-dimer and soluble CD14.
VACS Index scores are based on data
collected during routine HIV clinical follow-up, including hepatitis C status,
liver fibrosis status (assessed by FIB-4), kidney function (estimated
glomerular filtration rate [eGFR]), haemoglobin, CD4 cell count, viral load and
Investigators explored the association
between the overall VACS Index score and the risk of fragility fractures, and
also the relationship between such fractures and individual components of the
At baseline, the patients had a mean age of
46 years. Approximately a third were white. Mean BMI was 25m/kg2.
However, there was a high prevalence of known risk factors for fragility
fractures. Some 16% of patients had alcohol-related diagnoses, 19% had drug use
issues, 75% were smokers (past or current) and 12% had a history of depression.
However, few patients had a diagnosis of cerebrovascular disease/stroke (2%) or
coronary artery disease/diabetes (7%).
The mean duration of follow-up was six
years. There were a total of 588 fragility fractures. This provided an
incidence of 2.6 per 1000 patient-years.
The median VACS Index score at baseline was
33, indicating a five-year mortality risk of 14%. Median CD4 cell count was 280
cells/mm3 and mean viral load was approximately 10,000 copies/ml.
Just over a quarter of the sample (27%) were infected with hepatitis C and 7%
of patients had a FIB-4 score above 3.25 suggesting the presence of advanced
liver fibrosis or cirrhosis. The median eGFR was 97ml/min and mean haemoglobin
Analysis survival curves relating to VACS
Index score showed that patients with the highest scores had the shortest
fracture-free time, whereas patients with the lowest scores had the longest
time without fracture (p < 0.001).
Closer examination of VACS Index scores
indicated that the 10% of individuals with the highest scores had an almost
four-fold increase in their risk of fragility fracture compared to the 10% of
patients with the lowest scores (HR = 3.83; 95% CI, 2.49-5.90).
Further analysis showed that VACS Index
score (HR = 1.15; 95% CI, 1.1-1.19) had a significant association with fracture
risk. Other factors included white race, BMI, alcohol-related diagnoses,
cerebrovascular disease, use of PPI inhibitors (an antacid therapy) and
treatment with a protease inhibitor.
The investigators then explored the
relationship between individual components of the VACS Index score and fracture
risk. Increasing age emerged as a strong risk factor, each ten-year increment
in age increasing the risk of fracture by 40% (HR = 1.40; 95% CI, 1.27-1.54).
Anaemia was also significant. The investigators note this is an established
risk factor for fragility fractures among older people in the general
population. “Anaemia may increase fracture risk through its association with
decreased bone mass and density…inflammation may drive this relationship,”
suggest the authors. “Anaemia may also increase the risk of fracture by
increasing the risk of falls through its negative impact on physical
performance and muscle strength.”
A surprise finding of the study was an
association between lower viral load and increased fracture risk. The
researchers suggest that “this association is an example of competing risk:
individuals with high viral load are sicker than those with lower viral loads
and died before they experienced a fracture.”
“Our work is the first to explore the
association between physiologic frailty and fracture risk among HIV infected
individuals,” conclude the investigators. “As women are more likely to be frail
than men in the general population, a similar analysis should be conducted
among HIV infected women.”