Antibodies Against Oxidized Phospholipids Protect Against Osteoporosis

For atherosclerosis, the potential involvement of these oxidation-specific epitopes has long been recognized, says Dr. Witztum. What is truly novel, he emphasizes, is demonstrating this same pathogenic mechanism underlies osteoporosis.

Ambrogini et al. discovered the common mechanisms underlying osteoporosis by examining the role of oxidation-specific epitopes in bone homeostasis in murine models. Using mice overexpressing antibodies that block the effects of oxidation-specific epitopes, the investigators found they could attenuate the high-fat-diet-induced loss of bone mass in these mice.

Importantly, the study also found that one of those antibodies increases bone mass not only in mice fed a high-fat diet, but also in mice fed a normal diet.

Dr. Witztum

According to Dr. Witztum, this strongly implies “that even under physiological conditions, oxidized phospholipids impair bone anabolism.” As such, he emphasized the need to better understand where the oxidation-specific epitopes are coming from. “This remains to be determined, but we have shown that as cells undergo apoptosis there is generation of oxidized phospholipids and that oxidized phospholipids are frequently present on vesicles released from cells, so in a period of rapid growth and bone turnover early in life one might speculate that this could be a source,” he says.

Given the attenuation of bone loss in the mice overexpressing the antibodies that block the oxidation-specific epitopes, the study does suggest these epitopes as a new potential therapeutic target for osteoporosis.

“It is known that these antibodies are already protective against cardiovascular disease in humans,” says Dr. Ambrogini. “Now we have to look at whether this is true for osteoporosis.”

Emphasizing that the study by Ambrogini and colleagues showed antibodies targeting oxidized phospholipids ameliorated their adverse effects on bone, Dr. Witztum says further study is needed to fully understand the pathogenetic mechanisms of these oxidation-specific epitopes. “Importantly, it remains to be determined if treatment to neutralize oxidized phospholipids after the diseases have been established will lead to prevention of advancement or even regression,” he says.

Mary Beth Nierengarten is a freelance medical journalist based in Minneapolis.

References

1. Ambrogini E, Que X, Wang S, et al. Oxidation-specific epitopes restrain bone formation. Nat Commun. 2018 Jun 6;9(1):2193.
2. Que X, Hung MY, Yeang C, et al. Oxidized phospholipids are proinflammatory and proatherogenic in hypercholesterolaemic mice. Nature. 2018 Jun; 558(7709):301–306.