Children in the Gaza Strip are facing a grave new threat: paralysis by poliovirus. Traces of the virus, derived from vaccine using a live but weakened strain, have been found in six wastewater samples from two sites there, Gaza’s Ministry of Health announced on 16 July. www.science.org/content/article/news-glance-pricey-stegosaurus-alzheimer-s-drug-company-resignations-and-monitoring-co2?
No cases of paralysis have been reported yet, according to the international Global Polio Eradication Initiative (GPEI). The Ministry of Health and international partners are scrambling to find any undetected polio cases. Many of Gaza’s 1.9 million displaced people are crammed into unhygienic camps without clean water or sanitation—an ideal environment for the poliovirus. Tens of thousands of children are at risk. Widespread immunization campaigns with a different vaccine tailored to the virus will be necessary to stop the outbreak, GPEI says. But, it says, that is impossible in areas of active conflict.
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The near-extinction of vultures in India from poisoning during the 1990s likely led to the spread of pathogens that later contributed to the deaths of more than a half-million people, a study has estimated. Farmers in India have disposed of dead livestock by leaving them in open fields, and historically birds of prey have reduced the spread of disease by consuming the carcasses. But after 1994, when farmers began to use a cattle medication poisonous to Indian vultures, the birds’ population fell precipitously. www.science.org/content/article/news-glance-pricey-stegosaurus-alzheimer-s-drug-company-resignations-and-monitoring-co2?
A research team examined human health records and maps of vulture habitats; they found that by the end of 2005, areas that had hosted many vultures recorded a 4.7% hike in the annual human death rate while other areas saw no increase. The team estimated the result was 100,000 additional deaths per year from 2000 to 2005 across India. The government banned the use of the cattle medication, diclofenac, in 2006, but the vulture population has not recovered. The study, which could inform policies tying wildlife conservation to human health, is described in a working paper to be published in the American Economic Review.
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www.medscape.com/viewarticle/osteoporosis-medication-could-soothe-arthritic-fingers-2024a1000cis?
A promising approach for the erosive form of finger polyarthritis is treatment with an osteoporosis medication: The monoclonal antibody denosumab, which targets the receptor activator of nuclear factor-kappa B ligand. The corresponding study was also mentioned by Willem Lems, professor of immunology at the University of Amsterdam, Amsterdam, in a session on osteoporosis.
Finger polyarthritis often takes a back seat to arthritis of the knees and hips, which is why it is referred to as a “forgotten disease.” It is not a rarity, however. “Up to 10%-25% of older women suffer from it.”
The term “hand arthritis” may be misleading. “It sounds so simple, as if it were just one joint,” says Margreet Kloppenburg, professor of rheumatology at Leiden University in Leiden. In fact, it is mostly a polyarticular disease that affects various finger joints, usually middle and end joints, and the thumb saddle joint. Arthritis leads to deformities, painful movement restrictions, and sometimes erosive joint changes. “This is seen in around 10% of people with symptomatic, radiologically detectable finger polyarthritis, often accompanied by inflammation,” says Kloppenburg.
“What we really lack are medications that can stop, reverse, or prevent structural damage,” said Kloppenburg. In other words, disease-modifying osteoarthritis drugs are needed. The understanding that there are apparently different endotypes of arthritis helps in the search for potentially suitable agents. “The best known are synovitis-driven, cartilage-driven, and bone-driven endotypes.”
“We know that osteoclast and osteoblast activation play a role in arthritis, and that’s also what we see in erosive finger polyarthritis,” said Kloppenburg. Studies suggest that osteoclasts resorb the subchondral bone, leading to bone remodelling at the cartilage interface. MRI studies, such as a meta-analysis with data from nearly 2000 patients, support this observation.
These findings appear to be clinically relevant. “Bone marrow lesions are also associated with radiographic progression,” said Kloppenburg.
There seems to be a link to osteoporosis, she added, describing long-term data from the population-based Rotterdam Study over 4-8 years. “Especially patients with vertebral fractures at study baseline had a higher incidence of finger polyarthritis over time.”
Could osteoporosis medications help? That question was exactly what researchers from Belgium investigated in a randomized, placebo-controlled phase 2a study. They enrolled 101 patients with at least one erosive or pre-erosive interphalangeal joint, a soft swelling in at least one interphalangeal joint with ultrasound evidence of synovitis, and temporary inflammatory activations. Over 48 weeks, participants received subcutaneous denosumab or placebo every 12 weeks. A significant improvement was achieved, which was even more pronounced after 48 weeks.
“What I find promising is that the number of new erosive joints after 48 weeks in the denosumab group was lower than in the placebo group,” said Kloppenburg. Erosions first appeared in nine joints in the denosumab group, compared with 38 in the placebo group.
“This is a really exciting study,” said Kloppenburg, despite one disappointment. “Unfortunately, they could not demonstrate an improvement in pain and function.” The difference on the numerical rating scale from 0 to 10 was only 0.3 points in favour of denosumab at week 24, which was not significant. Kloppenburg attributed it to the study design and suggested new randomized controlled studies with pain as an outcome.
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Researchers have called osteoporosis a “silent” disease because it often isn’t recognized until a person suffers a debilitating injury. But it is widespread: Globally, an estimated one-third of women and one-fifth of men over age 50 will experience fractures related to osteoporosis. In India, reliable statistics are scarce, but more than 61 million people are believed to have the condition.
Research suggests many factors contribute to osteoporosis, including hormonal changes, a lack of exercise, and drinking alcohol and smoking tobacco. All play a role in India, but so may another factor: exposure to air pollution. www.science.org/content/article/breathing-polluted-air-increases-risk-osteoporosis-growing-evidence-shows?
Epidemiological studies in numerous nations suggest rates of osteoporosis are higher in areas that have sooty, highly polluted air—for which Indian cities and villages have become notorious. Researchers are still trying to understand the biological mechanisms that might link smog to brittle bones. But, “There is growing recognition that … air pollution is a risk factor for bone health,” says environmental epidemiologist Cathryn Tonne of the Barcelona Institute for Global Health (ISGlobal)
A study conducted in Norway in 2007 first called attention to a possible connection to air pollution. That study, published in Osteoporosis International, found a weak but statistically significant correlation between modelled exposure to air pollution and reduced bone density in 590 men ages 75 or 76. Three years later, the same researchers found a correlation between air pollution exposure and an increased prevalence of self-reported forearm fractures in men who smoked.
Since then, researchers working in other nations have jumped into the field. In the United States, a team led by Diddier Prada, an environmental and molecular epidemiologist at the Icahn School of Medicine at Mount Sinai, has been probing large data sets assembled by the U.S. government and researchers. One study, published in 2017 in The Lancet Planetary Health, examined a cohort of 9.2 million people above the age of 65 who lived in the northeastern U.S. as well as 692 middle-age men living in low-income communities. In both cohorts, the researchers found that exposure to higher levels of two especially dangerous forms of air pollution—particulate matter less than 2.5 microns in diameter (PM2.5) and soot known as black carbon—was associated with higher rates of bone fractures and other markers of osteoporosis. Last year in eClinical Medicine Prada’s team reported finding an association between osteoporosis markers and exposure to another major air pollutant, nitrogen oxides, among a group of more than 160,000 U.S. women who had already experienced menopause.
In the United Kingdom, an analysis of more than 446,000 participants in the UK Biobank, published in the Journal of Bone and Mineral Research, found that those living in more polluted areas had a 15% greater risk of fractures. Epidemiologist Otavio Ranzani of ISGlobal found a similar pattern in health data collected from 3717 people living in 28 villages near Hyderabad in southern India. Ranzani says his team launched the study, in part, because studies had suggested that “some harmful components from tobacco smoke have similarities with ambient air pollution.” The researchers found individuals living in more polluted villages were more likely to have lower bone mineral content and density, they reported in 2020 in JAMA Network Open.
In China, which has some of the world’s worst air pollution and a rapidly aging population, researchers are finding similar links. One recent study of more than 5000 urban residents of Shandong province, published in the Archives of Osteoporosis, found that even short-term exposure to traffic-related air pollutants appeared to increase the risk of osteoporotic fractures. People living in China’s rural areas also face risks, a 2020 study published in Environmental Research showed. Researchers used satellite, weather, and land use data to estimate the pollution levels experienced by some 8000 residents of a rural area. Even relatively small increases in PM2.5 and other pollutants seemed to increase rates of osteoporosis, they found.
The study’s “substantial sample size” and “robust statistical model” make its results convincing, says environmental health scientist Yuming Guo of Monash University, one of its authors. Prada agrees that the statistical correlations between pollution and osteoporosis are strong. But actually proving causation is difficult, he and other researchers note, because it’s difficult to document exactly how much pollution a person is breathing in—as well as the specific chemicals in the smog. “Individual assessment of exposure is logistically really complicated and quite expensive,” Prada says. It can also be difficult to sift out confounding variables; people who live in highly polluted areas may have other risk factors, such as poor nutrition, that contribute to osteoporosis.
Despite that complexity, researchers have begun to identify some of the ways that air pollutants likely lead to bone damage. One is in plain sight: Ground-level ozone catalysed by pollutants can block sunlight, dimming the ultraviolet radiation that enables the body to produce vitamin D, which plays a key role in bone development.
Other potential mechanisms are buried deep within cells. There, compounds found in air pollution can spur the formation of unstable molecules called free radicals that can bind to and damage DNA, proteins, and other cellular components. Pollutants can also promote inflammation and other immune responses, which could interfere with cellular processes that replace old bone tissue with new, Prada’s team noted in 2020 in Environmental Research.
If air pollution does cause osteoporosis, the findings could have major implications in India, where a growing population—now 1.4 billion—is breathing increasingly dirty air. From 1998 to 2021, India’s average annual particulate pollution increased by almost 68%, according to the Energy Policy Institute at the University of Chicago. The burning of fossil fuels is partly to blame, but so is the common practice of burning agricultural residues in rural areas. And many Indians, cook over smoky stoves fuelled with dung, firewood, or charcoal.
Such pollution is already known to take a toll on heart and lung health, but it’s likely link to osteoporosis provides yet another reason for India to “implement policies leading to [air pollution] reduction,” Ranzani says. The nation also faces a pressing need to improve osteoporosis diagnosis, says Uma Kumar, head of the rheumatology department at the All India Institute of Medical Sciences. Many cases are currently missed, she says, because of a shortage of standard bone density testing equipment, especially machines used to perform dual-energy x-ray absorptiometry, or DEXA, scans. India currently has just about one DEXA scanner for every 4 million people, mostly in big cities. (The scans can also be prohibitively expensive for many Indians.)
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Lalita Panicker is Consulting Editor, Views and Editor, Insight, Hindustan Times, New Delhi
