Frailty associated with bone mineral density loss in HIV patients

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Frailty is associated with loss of bone mineral density (BMD) in HIV-positive patients, investigators from the Service d’Immuno-hématologie clinique, Aix-Marseille Université, APHM Sainte-Marguerite, and INSERM U912 (SESSTIM), Marseille, France report. 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 one in twelve 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 patients 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 patients in the general population is well documented. However, it is unknown if this connection is also present in patients 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 pre-frailty 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 the patients (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 using 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 not 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 patients at higher risk of bone loss, for further follow-up and interventions.

Abstract 1
Objective: The study aims to assess the association between bone mineral density (BMD) and frailty in a cohort of HIV-infected patients.
Design: A cross-sectional study in an HIV outpatient unit where nearly 1000 patients are monitored.
Methods: Study participants undergoing bone densitometry were proposed an evaluation of frailty using criteria of the Cardiovascular Health Study (CHS) and the Study of Osteoporotic Fractures (SOF). Frailty markers were weight-loss, self-reported exhaustion, physical activity, grip strength, chair stands, and slow gait. Patients’ characteristics were collected from an electronic medical record. Associations of frailty with BMD and osteoporosis were tested using multivariate linear and logit regression models, respectively.
Results: In total, 175 HIV-infected patients, 121 (69.14%) men, were analyzed. Prevalence of frailty markers, osteopenia, and osteoporosis were comparable among sexes. Despite a younger age, spinal and femoral neck BMD were lower in women (P < 0.05). Linear regression model adjusting by age, duration of HIV follow-up, BMI, smoking status, osteoarthritis, osteoporosis treatment, and the age at menopause showed a negative association of spinal and femoral BMD with frailty according to SOF criteria in women (P < 0.05). In men, SOF-defined frailty was associated with osteoporosis (odds ratio 28.79; 95% confidence interval 2.15–386.4) in a model adjusting for age, duration of HIV follow-up, CD4+ nadir, CD4+ T-cell count, tobacco consumption, exposure to tenofovir (TDF) and protease inhibitors. No significant associations were found between BMD and CHS-defined frailty.
Conclusion: Our study shows that frailty according to SOF criteria is associated with low spinal BMD values in female and osteoporosis in male HIV-infected patients.

Authors
Bregigeon, Sylvie; Galinier, Anne; Zaegel-Faucher, Olivia; Cano, Carla E.; Obry, Véronique; Laroche, Hélène; Trijau, Sophie; Saout, Armelle; Poizot-Martin, Isabelle

Abstract 2
Objective: to examine the prevalence of frailty and disability in people aged 60 and over and the proportion of those with disabilities who receive help or use assistive devices. Methods: participants were 5,450 people aged 60 and over from the English Longitudinal Study of Ageing. Frailty was defined according to the Fried criteria. Participants were asked about difficulties with mobility or other everyday activities. Thosewith difficulties were asked whether they received help or used assistive devices. Results: the overallweighted prevalence of frailty was 14%.Prevalence rosewith increasing age, from6.5% in those aged 60–69 yearsto65%inthoseaged 90orover.Frailtyoccurredmorefrequentlyinwomen thanin men (16 versus12%).Mobilitydifficulties were very common: 93% of frail individuals had such difficulties versus 58% of the non-frail individuals. Among frail individuals, difficulties in performing activities or instrumental activities of daily living were reported by 57 or 64%, respectively, versus 13or15%, respectively, among thenon-frailindividuals. Amongthosewith difficulties with mobilityorotherdailyactivities, 71% offrailindividualsand31% of non-frail individualssaidthat they received help. Ofthosewith difficulties, 63%of frailindividuals and20%ofnon-frailindividualsusedawalkingstick,buttheuseofotherassistivedeviceswasuncommon. Conclusions: frailty becomes increasingly common in older age groups and is associated with a sizeable burden as regards difficulties with mobilityand othereverydayactivities.

Authors
Catherine R Gale, Cyrus Cooper, Avan Aihie Sayer

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