Antibodies Against Oxidized Phospholipids Protect Against Osteoporosis

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It has long been known that hyperlipidemia adversely affects bone, but the exact pathologic mechanism(s) underlying hyperlipidemia-induced bone loss has not been fully understood. Until now.

Pathogenesis of Osteoporosis

New research by Ambrogini and colleagues shows that oxidation-specific epitopes derived from lipid peroxidation contribute to the pathogenesis of osteoporosis.¹ Importantly, the research shows that innate immune antibodies against these epitopes can offer a protective effect against the disease—at least in mice.

“There are antibodies against oxidized phospholipids that are protective against osteoporosis,” says lead author of the study, Elena Ambrogini, MD, PhD, assistant professor, Division of Endocrinology and Metabolism, Center for Osteoporosis and Metabolic Bone Diseases, University of Arkansas for Medical Sciences and Central Arkansas Veterans HealthCare System, directed by Stavros C. Manolagas, MD, PhD, in Little Rock, Ark. “We have shown in mice that if you overexpress these antibodies, the mice have more bone.”

“This is the first proof-of-principle that oxidation-specific epitopes are involved in bone metabolism,” she says.

Pathogenesis of Atherosclerosis

Dr. Ambrogini

The study by Ambrogini et al. comes on the heels of another recently published study by Que et al. that demonstrates for the first time what has long been recognized without demonstrable proof—oxidized phospholipids contribute to the pathogenesis of atherosclerosis.² Although it has long been suspected that oxidized phospholipids and oxidized low-density lipoprotein are involved in the pathogenesis of atherosclerosis, the study by Que et al. was the first to demonstrate this in vivo in murine models, according to senior author of the study, Joseph Witztum, MD, professor of medicine, Division of Endocrinology and Metabolism, University of California, San Diego.

Dr. Witztum, who is also a co-investigator in the osteoporosis study, emphasizes the implication of these results for humans. “We believe this is relevant to humans [because] oxidized phospholipids can be demonstrated to be abundant in almost all atherosclerotic lesions in humans,” he says.

As for osteoporosis, Dr. Witztum says further research is needed to determine the relevance to humans of the finding that oxidized phospholipids contribute to this disease as well.

If such research pans out, the hope is that one day a new therapeutic agent will be able to simultaneously target both osteoporosis and atherosclerosis.

‘This is the first proof-of-principle that oxidation-specific epitopes are involved in bone metabolism.’ —Dr. Ambrogini

Common Pathogenesis/Common Treatment

Epidemiological data have shown that osteoporosis, atherosclerosis and a high fat diet are linked. The new research demonstrates for the first time, in vivo in murine models, that oxidation-specific epitopes are an important common pathogenic factor that may underlie these links. In specific, the research shows that oxidized phospholipids impair the function of osteoblasts, the cells that build new bone.