Identifying the inflammatory and hormonal paths of bone loss

Category: Blog

We are going to follow a path in exploring what is causing bone loss in a patient. This is not the path every person follows, but it is a common path.

Recently, doctors at the University of Arkansas published fascinating insights into how low hormone levels. especially that of estrogen,  in maturing men affect their bones. (1) Here are the highlights of their research.

  • Aging men and women are subject to two distinct types of bone loss mechanisms:

1 low estrogen and
2 oxidative stress.

  • Bone loss in both sexes are caused by increased osteoclastogenesis caused by estrogen deficiency.
    • What this means is that bone cells responsible for breaking down bone so it can be replaced by new bone – is breaking down more bone than can be replaced.
  • The second cause of bone loss is independent of estrogen deficiency. It is caused by oxidative stress.

So we are following the path of bone loss. Both men and women are losing bone because:

  1. They are low in estrogen and this is preventing replacement or remodeling bone from forming.
  2. They are suffering from oxidative stress, that is, chronic inflammation. Inflammation is dissolving their bones.

Recently doctors at the University of Florence (2) wrote that negative changes in our body’s antioxidant systems (low antioxidants or nutrients) significantly impacts our ability to make new bone. The researchers recommended that patients with bone loss should be given  antioxidants  for the treatment and prevention of bone loss as a means to regulate the oxidative stress and the inflammation it causes.

As we travel down this patient’s path we have found hormones to be a problem for them, now we find inflammation is a problem for them This is not however weher this path ends.

A third independent cause of bone loss – disruption of the Gut Microbiota

Scientists at Emory University and Georgia State University (3) reported that hormone deficiency increases gut permeability (the ability of harmful lipids and other cells to pass through the gut wall into the rest of the body) and the production of osteoclastogenic cytokines (cells that send messages to increase bone destruction through inflammation.)

So in recap – hormone  deficiency increases gut inflammation which sends inflammatory messages to the bone marrow to break down bone.

How is this for a summary of this research:

  • treatment with probiotics prevents the increase in gut permeability, the production of intestinal and bone marrow cytokines, and the bone loss induced by sex steroid (hormone) depletion.

A 2018 study from Michigan State University (4) had this to say: “There are many studies supporting the role for the microbiome in the regulation of bone heath. Direct supplementation of beneficial probiotic bacteria can affect bone health by regulating aspects of gut such as preventing dysbiosis (imbalance) and/or increases in gut permeability and inflammation.”

The path does not end here, especially for men.

Estrogen, progesterone and testosterone – a focus on bone loss in men

Doctors have further suggested a  connection between testosterone and estrogen and bone health in aging men. Writing in the journal Bone and Mineral Research, (5) doctors say that estrogen is the dominant regulator of bone metabolism in men and that a legitimate argument can be made that testosterone is largely a prohormone (a building block precursor) for the male skeleton, with its effects on bone mediated principally via aromatization (synthesis) to estrogen.

What does all that mean? It is another example that the balance of hormones in men is equally as challenging to that in women. In the example above the challenges of balancing estrogen and providing enough testosterone in men to help build and maintain bone is highlighted.

Male osteoporosis is a health problem which deserves more attention as nearly 30% of osteoporotic fractures happen in men aged 50 years and above.

  • Observations from epidemiological studies indicate that elderly men with higher testosterone can preserve their Bone Mass Density better and thus are less prone to fracture.
  • Observations on men with estrogen resistance or aromatase deficiency indicate that estrogen is equally important in the maintenance of bone health status.

This had been validated in several epidemiological studies which found that the relationships between estrogen and bone health indices are significant and sometimes stronger than testosterone.

  • Doctors writing in the International Journal of Endocrinology wrote “both testosterone and estrogen are important in the maintenance of bone health in men.”(6)
  • Doctors at the University of Gothenburg wrote,”Even though estradiol has been considered the ‘female hormone’, levels of serum estradiol in elderly men are higher than those in postmenopausal women. Estradiol levels are more strongly associated with bone mass density, bone turnover and bone loss than testosterone levels are in adult men…” (7)
  • Doctors at the US Veterans Affairs Medical Center also confirmed that older men with total testosterone or estradiol deficiency were more likely to be osteoporotic. (8)

So Estrogen plays an important role in preventing bone weakening and osteoporosis in men, especially in men over 70.

1 Ucer S, Iyer S, Kim HN, et al.  The Effects of Aging and Sex Steroid Deficiency on the Murine Skeleton Are Independent and Mechanistically Distinct. J Bone Miner Res. 2016 Oct 7. doi: 10.1002/jbmr.3014.
2 Domazetovic V, Marcucci G, Iantomasi T, Brandi ML, Vincenzini MT. Oxidative stress in bone remodeling: role of antioxidants. Clin Cases Miner Bone Metab. 2017;14(2):209-216.2 Li J-Y,
3 Chassaing B, Tyagi AM, et al. Sex steroid deficiency–associated bone loss is microbiota dependent and prevented by probiotics. The Journal of Clinical Investigation. 2016;126(6):2049-2063. doi:10.1172/JCI86062.
4 Schepper JD, Irwin R, Kang J, et al. Probiotics in Gut-Bone Signaling. Adv Exp Med Biol. 2017;1033:225-247.
5. Khosla S.Commentary: New Insights Into Androgen and Estrogen Receptor Regulation of the Male Skeleton. J Bone Miner Res. 2015 Apr 9. doi: 10.1002/jbmr.2529.
6 Chin KY, Ima-Nirwana S. Sex steroids and bone health status in men. Int J Endocrinol. 2012;2012:208719. doi: 10.1155/2012/208719. Epub 2012 Oct 24.
7. Vandenput L, Ohlsson C. Estrogens as regulators of bone health in men. Nat Rev Endocrinol. 2009 Aug;5(8):437-43. Epub 2009 Jun 16.
8. Fink HA, Ewing SK, Ensrud KE, Barrett-Connor E, Taylor BC, Cauley JA, Orwoll ES. Association of Testosterone and Estradiol Deficiency with Osteoporosis and Rapid Bone Loss in Older Men. J Clin Endocrinol Metab. 2006 Jul 18