A new study linking low bone mass density with infections and sepsis points to the role of osteoblasts in immune system regulation.
A prospective cohort study conducted in Hong Kong has linked low bone mass density and osteoporosis with increased risk of infections and sepsis.
It’s known that bone metabolism and the immune system interact, and that low bone mass density (BMD) is a prognostic factor in patients with infections and sepsis, predicting poor outcomes in pulmonary sepsis and covid. However, the study authors found no prior research examining bone mass density or osteoporosis and subsequent risk of infections and sepsis.
For the current study, which was published in eClinicalMedicine, they hypothesised that higher BMD is associated with a reduced risk of infections and sepsis.
The participants comprised around 5700 southern Chinese community-dwelling residents of Hong Kong. Commencing in 1995, researchers recorded participants’ baseline clinical, biomedical, bone mass density, genetic and lifestyle data, with pneumonia, urinary tract infection, skin infection and sepsis the primary outcomes.
After an average follow up of 17 years, it was found that lumbar spine (L1-L4), femoral neck and total hip BMD T-scores were significantly associated with reduced risk of infections and sepsis (all P<0.001).
After adjusting for various factors including age, sex, lifestyle, comorbidities and medications, femoral neck and total hip BMD T-scores remained significantly associated with reduced risk of infections and sepsis, with hazard ratios in the range of 0.82 to 0.89.
Lumbar spine BMD was significantly associated with reduced risk of skin infection, but not with other infections or sepsis. The study authors suggested that hip BMD better reflects bone health than lumbar spine BMD, which is sensitive to environmental stimulation, such as treatment and hormonal changes.
The same patterns occurred when the criteria for osteoporosis were applied (BMD T-score < –2.5), with significant associations for femoral neck and total hip osteoporosis and increased risk of infections and sepsis, but not for lumbar spine, where only the risk of skin infections reached statistical significance. Where BMD met criteria for osteopenia (T-score –2.5 to –1), there were no significant associations for infections or sepsis.
Noting that vitamin D could potentially explain the association, the study group analysed the data controlling for serum vitamin D levels and no significant interactions were found.
One limitation of the study was that it was observational, so causality can’t be inferred. However, it’s known that osteoblasts secrete interleukin 7, important for lymphocyte production, and lipocalin-2, which can mediate immune response and inhibit bacterial growth, providing potential mechanisms for the association. The authors suggested future studies investigating the role of IL-7 and lipocalin-2 as mediators for the association.
Another limitation is that participants were southern Chinese living in Hong Kong, so findings may not be more broadly generalisable to other populations. The key strengths were the comprehensive baseline data, large sample size and long follow-up.
“Further study is warranted to examine whether improving bone health can reduce the risk of infections and sepsis,” concluded the authors.
