Lactoferrin's Role in Bone Growth

Lactoferrin's Role in Bone Growth

Professor Jillian Cornish is a biomedical researcher living in New Zealand and currently teaching at The University of Auckland. Stephanie Drax, Leapfrog's founder, met Professor at the Lactoferrin Conference in Rome in 2023, where she presented her research on Lactoferrin.

When Professor Cornish published her first paper in 2004, little research had been conducted into Lactoferrin's effects on bone. Her studies have established Lactoferrin as a potent novel anabolic factor in osteoblasts, which also reduces bone resorption and increases bone mass when administered in humans. These findings posed important questions regarding the role of Lactoferrin in bone physiology, both during growth and in adulthood, and provided a potential target for drug development in the therapeutics of osteoporosis (1). Stephanie Drax spoke to Professor Cornish to get more detail on her groundbreaking work. 

SD: How long have you been working with Lactoferrin and what sparked your interest in it?

JC: Lactoferrin became my favourite molecule over 20 years ago when a dairy company in New Zealand asked me to find something in milk that increased bone health. My answer was that indeed many factors in milk favour bone health….but they said "Yes, but we want you to find something new!" So after analysing many fractions of milk, we identified Lactoferrin as being a potent bone growth factor.

SD: How would you briefly describe Lactoferrin and its potential for health?

JC: One of Lactoferrin’s primary roles in mammals is iron sequestration as well as modulating gut microbiota. Lactoferrin has immuno-modulatory activity, modulating the immune system to respond to disease or illness. Lactoferrin’s use in the treatment of cancer suggests a role in homeostasis that could be explained by iron metabolism or immuno-modulatory activity. The most promising therapy of the decade for Lactoferrin has been the treatment of preterm sepsis, so the role of Lactoferrin is credible and consistent with the physiological presence of Lactoferrin in milk, with high levels in colostrum. The data is substantially positive regarding H. pylori and supports that Lactoferrin assists with microbiome balance, favouring beneficial bacteria over pathogenic, and improving gastroenteritis. Periodontal disease is tightly intertwined with osteoimmunology, and with the oral cavity being an obvious location for Lactoferrin to act. Published data supports many potential targets for improved human health and wellness, although the lack of clear mechanistic data weakens the support of clinically significant findings.

SD: Why - and for who - is bone loss an issue? How does it happen?

JC: Bone loss can be an issue throughout life if you suffer from some bone-wasting disease. Osteoporosis though is what my work was initially linked with as I was working with endocrinologists. Osteoporosis is a condition of ageing. Your entire skeleton is renewed approximately every 10 years throughout life.  As your bones are growing in childhood bone formation exceeds bone resorption, then for many years formation and resorption are equal. As menopause is reached, bone resorption exceeds bone formation and ultimately bone loss causes an osteoporotic condition.

SD: How can Lactoferrin help and how has your research on its potential for bone health evolved?

JC: My research on Lactoferrin evolved as I led a bone cell biology lab. We tested the different milk fractions on the bone-forming osteoblasts and the bone-resorbing osteoclasts to establish that Lactoferrin is a potent bone growth stimulating molecule. We also showed this in a rat critical-sized calvarial defect model (2).

SD: Can you outline some of the most exciting results?

JC: The exciting recent results we are showing now is that Lactoferrin also has some anti-microbial properties in bone infections in which Lactoferrin acts as an anti-microbial adjuvant when it is mixed with antibiotics that orthopaedic surgeons use (we have been working on this for the US Department of Defence). It makes the antibiotics 10 times more effective as it helps break down the biofilm - or slimy layer - that bacteria form to protect themselves. In bone infections, bone loss also occurs so Lactoferrin can support this bone regeneration.

SD: Have there been any human studies on the effect of bone growth or strengthening with Lactoferrin supplementation? Can both topical and ingested Lactoferrin have effects?

JC: Yes, please look at the clinical trial data that gives evidence of this.

SD: Could Lactoferrin be considered as a supplement for promoting youthful cellular activity, taken earlier in life to mitigate say peri-menopausal and menopausal loss of bone density, or any other conditions?

JC: Lactoferrin is beneficial to all bones, and we aim to use it in paediatric conditions in the future.

References: 

(1) Miao Tian et al. 2023 "The role of lactoferrin in bone remodeling: evaluation of its potential in targeted delivery and treatment of metabolic bone diseases and orthopedic conditions" Frontiers in Endocrinology, PMC10482240

(2) Gao R et al Local application of Lactoferrin promotes bone regeneration in a rat critical-sized calvarial defect model as demonstrated by micro-CT and histological analysis. J Tissue Eng Regen Med DOI: 10.1002/term.2348, 2017)

Jillian Cornish et al. 2010 "Lactoferrin as an effector molecule in the skeleton" Biometals, PMID: 20232111