Frailty increases the risk of fragility fractures in men living with HIV: data collected in routine HIV care can help predict risk

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 age.

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 score.

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 was 13.5gm/dl.

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.”

Womack JA et al. Physiologic frailty and fragility fracture in HIV infected male veterans. Clin Infect Dis, online edition, 2013.