Osteoporosis Risk Rises With Air Pollution Levels 

Jeff Evans

June 21, 2022

COPENHAGEN — Chronic exposure to high levels of particulate matter (PM) air pollution 2.5 micrometers (PM2.5) or larger, and 10 micrometers (PM10) or larger, in size is associated with a significantly higher likelihood of having osteoporosis, according to research presented at the European Alliance of Associations for Rheumatology (EULAR) 2022 Annual Meeting.

Dr Giovanni Adami

The results of the 7-year longitudinal study carried out across Italy from 2013-2019 dovetail with other recent published accounts from the same team of Italian researchers, led by Giovanni Adami, MD, of the rheumatology unit at the University of Verona, Italy. In addition to the current report presented at EULAR 2022, Adami and associates have reported an increased risk of flares of both rheumatoid arthritis and psoriasis following periods of elevated pollution, as well as an overall elevated risk for autoimmune diseases with higher concentrations of PM2.5 and PM10.

The pathogenesis of osteoporosis is thought to involve both genetic and environmental input, such as smoking, which is itself environmental air pollution, Adami said. The biological rationale for why air pollution might contribute to risk for osteoporosis comes from studies showing that exposure to indoor air pollution from biomass combustion raises serum levels of RANKL (receptor activator of nuclear factor-kappa ligand 1) but lowers serum osteoprotegerin — suggesting an increased risk of bone resorption — and that toxic metals such as lead, cadmium, mercury, and aluminum accumulate in the skeleton and negatively affect bone health.

In their study, Adami and colleagues found that, overall, the average exposure during the period 2013-2019 across Italy was 16.0 µg/m3 for PM2.5 and 25.0 µg/m3 for PM10.

"I can tell you that [25.0 µg/m3 for PM10] is a very high exposure. It's not very good for your health," Adami said.

Data on More Than 59,000 Italian Women

Adami and colleagues used clinical characteristics and densitometric data from Italy's osteoporosis fracture risk and osteoporosis screening reimbursement tool known as DeFRAcalc79, which has amassed variables from more than 59,000 women across the country. They used long-term average PM concentrations across Italy during 2013-2019 that were obtained from the Italian Institute for Environmental Protection and Research's 617 air quality stations in 110 Italian provinces. The researchers linked individuals to a PM exposure value determined from the average concentration of urban, rural, and near-traffic stations in each person's province of residence.

For 59,950 women across Italy who were at high risk for fracture, the researchers found 64.5% with bone mineral density that was defined as osteoporotic. At PM10 concentrations of 30 µg/m3 or greater, there was a significantly higher likelihood of osteoporosis at both the femoral neck (odds ratio [OR], 1.15) and lumbar spine (OR, 1.17).

The likelihood of osteoporosis was slightly greater with PM2.5 at concentrations of 25 µg/m3 or more at the femoral neck (OR, 1.22) and lumbar spine (OR, 1.18). These comparisons were adjusted for age, body mass index (BMI), presence of prevalent fragility fractures, family history of osteoporosis, menopause, glucocorticoid use, comorbidities, and for residency in northern, central, or southern Italy.

Both thresholds of PM10 >30 µg/m3 and PM2.5 >25 µg/m3 "are considered safe…by the World Health Organization," Adami pointed out.

"If you live in a place where the chronic exposure is less than 30 µg/m3, you probably have slightly lower risk of osteoporosis as compared to those who live in a highly industrialized, polluted zone," he explained.

"The cortical bone — femoral neck — seemed to be more susceptible, compared to trabecular bone, which is the lumbar spine. We have no idea why this is true, but we might speculate that somehow chronic inflammation like the [kind] seen in rheumatoid arthritis might be responsible for cortical bone impairment and not trabecular bone impairment," Adami said.

One audience member, Kenneth Poole, BM, PhD, senior lecturer and honorary consultant in Metabolic Bone Disease and Rheumatology at the University of Cambridge, United Kingdom, asked whether it was possible to account for the possibility of confounding caused by areas with dense housing in places where the particulate matter would be highest, and where residents may be less active and use stairs less often.

Adami noted that confounding is indeed a possibility, but he said Italy is unique in that its most polluted area — the Po River valley — is also its most wealthy area and in general has less crowded living situations with a healthier population, which could have attenuated, rather than reinforced, the results.

Does Air Pollution Have an Immunologic Effect?

In interviews with Medscape Medical News, session co-moderators Filipe Araújo, MD, and Irene Bultink, MD, PhD, said that the growth in evidence for the impact of air pollution on risk for, and severity of, various diseases suggests air pollution might have an immunologic effect.

"I think it's very important to point this out. I also think it's very hard to rule out confounding, because when you're living in a city with crowded housing you may not walk or ride your bike but instead go by car or metro, and…[the lifestyle is different]," said Bultink, of Amsterdam University Medical Center, the Netherlands.

"It stresses that these diseases [that are associated with air pollution], although they are different in their pathophysiology, it points toward the systemic nature of rheumatic diseases, including osteoporosis," said Araújo, of Hospital Cuf Cascais, Cascais, Portugal, and Hospital Ortopédico de Sant'Ana, Parede, Portugal.

The study was independently supported.Adami disclosed being a shareholder of Galapagos and Theramex.

European Alliance of Associations for Rheumatology (EULAR) 2022 Annual Meeting: Abstract OP0242. Presented June 3, 2022.

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