Frailty is associated with loss of bone mineral density in middle-aged HIV-positive men and women

Frailty is associated with loss of bone mineral density (BMD) in HIV-positive people, investigators from France report in AIDS. They found that people living with HIV who were frail were more likely to show signs of bone loss in the spine and femur among women, and femoral osteoporosis in men. 

The study also found that around around 1 in 12 people with HIV in middle age were already frail and at least one-third were showing some signs of early frailty. In contrast, but using somewhat stricter criteria, the English Longitudinal Study of Ageing found that these rates of frailty are not matched in the general population until people reach their 70s.

Frailty is a common feature of ageing and is defined as any three of: unintentional weight loss of more than 4kg in the previous year, reduced grip strength, reduced walking speed, self-reported exhaustion and a low level of physical activity (walking for less than 30 minutes three times a week). Frailty develops as a result of multiple medical conditions, muscle loss and reduced nutrient intake, and often accompanies long-term medical conditions.

Frailty places people at greater risk of falls, broken bones and social isolation, but may go undiagnosed, especially in late middle-aged people. Frailty can also be exacerbated by depression, low mood, cognitive impairment, hearing loss or tremor.

Research has already shown that frailty appears at an earlier age in HIV-positive people compared to individuals in the general population. Similarly, loss of BMD, a condition of ageing, has been associated with HIV infection and long-term antiretroviral therapy, especially regimens containing tenofovir or protease inhibitors.

A connection between frailty and BMD loss among elderly people in the general population is well documented. However, it is unknown if this connection is also present in people with HIV, and whether it becomes apparent at a younger age.

Investigators from Marseille therefore designed a cross-sectional, observational study involving 175 HIV-positive outpatients who had a BMD assessment using densitometry. The patients received care between 2010 and 2016.

Frailty was measured using criteria of the Cardiovascular Health Study (CHS) and Study of Osteoporotic fractures (SOF). Markers of frailty were weight loss, exhaustion, physical activity, walking speed, grip strength and standing from a sitting position. Using CHS criteria, frailty was defined as the presence of at least three markers, and prefrailty as the presence of one of two markers. Frailty according to SOF criteria was the presence of two or more markers, with prefrailty the presence of a single marker.

The majority of individuals (69%) were male and the median age was 56 years in men and 53 years in women.

There was a very high prevalence of previous or current therapy with anti-HIV drugs associated with bone loss, with 79% having used tenofovir and 88% a protease inhibitor.

Low physical activity was the most prevalent marker of frailty (40%), followed by exhaustion (39%), weakness and weight loss (16%), slow walking speed (13%) and chair stands (5%). Prevalence of these markers did not differ by sex.

According to CHS definitions, 8% of patients were frail and 63% were prefrail; use of SOF showed a frailty prevalence of 10% and prefrail prevalence of 37%.

Prevalence of osteopenia and osteoporosis in the spine were 22% and 10%, respectively and 34% and 6% for the femur neck. Significantly lower spinal and femoral BMD and T-scores were present in women compared to men, though rates of osteopenia and osteoporosis were similar.

Among women, the investigators found a significant relationship between SOF-defined frailty and spinal BMD/T-score (p < 0.05). All the SOF-defined frail female patients presented with femoral osteopenia.

After adjusting for potential founders such as age, smoking, duration of HIV infection, CD4 cell count and nadir and use of tenofovir and protease inhibitors, there was a strong association between femoral osteoporosis and SOF-defined frailty among men (OR = 28.79; 95% CI, 2.15-286.4).

“Our results indicate that, like in the elderly, frailty defined by the SOF index is associated with BMD less in HIV-infected patients,” conclude the investigators. “As frail HIV-infected patients that do no fulfill the criteria for densitometry may also be at risk of BMD loss, further studies should establish whether the diagnosis of frailty should trigger the prescription of densitometry.”

Where access to bone mineral density testing is limited, the researchers say that frailty testing using the SOF criteria – any two out of weight loss, inability to perform three chair stands in 15 seconds and negative response to the question 'do you feel full of energy?' – should be used to identify individuals at higher risk of bone loss, for further follow-up and interventions.