This recent research paper in Nature is potentially ground-breaking for the understanding of essential mechanisms involved with bone health. It's findings are related to hormonal changes during the start of mid-pregnancy lactation and early newborn nurturing that could possibly lay the foundation for a new targeted treatment for osteoporosis in both men and women. And while a mouse-study, it reflects a very disciplined research acumen on the part of its research team - one that is usually typical of research that makes its way into the journal Nature.
From the UCSF press release:
"A newly discovered hormone that keeps the bones of breastfeeding women strong could also help bone fractures heal and treat osteoporosis in the broader population. Researchers at UC San Francisco and UC Davis showed that in mice, the hormone known as Maternal Brain Hormone (CCN3) increases bone density and strength.
Their results, published July 10 in Nature, solve a long-standing puzzle about how women’s bones remain relatively robust during breastfeeding, even as calcium is stripped from bones to support milk production."
Below are links to the entire UCSF press release (1) about the research discovery and the full paper in Nature (2):
(1) Scientists Discover a New Hormone that Can Build Strong Bones - Researchers at UCSF and UC Davis solved a long-standing puzzle on how the bones of breastfeeding women stay strong even as they lose calcium to milk, By Sarah C.P. Williams, USCF News, Research, July 10,2024.
ucsf.edu/news/2024/07/42801...
(2) A maternal brain hormone that builds bone, by Muriel E. Babey, William C. Krause, Kun Chen, Candice B. Herber, Zsofia Torok, Joni Nikkanen, Ruben Rodriguez, Xiao Zhang, Fernanda Castro-Navarro, Yuting Wang, Erika E. Wheeler, Saul Villeda, J. Kent Leach, Nancy E. Lane, Erica L. Scheller, Charles K. F. Chan, Thomas H. Ambrosi & Holly A. Ingraham - Nature (2024), Article, Published: 10 July 2024.
nature.com/articles/s41586-...
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As background info and a short study-guide to the roles of testosterone and estrogen (clearly different in males and females throughout their lives), I have also linked several papers that provide some basis for a better understanding of their effects on bone health. From the evidence so far, it seems that E2 plays a more significant role than does T in the BMD of aging males - and, as is the case with T, "free" E2 (unbound by SHBG) is the primary driver of bone health.
While from 2002, this first paper (3) is by researchers at Mayo. It describes several "human experiments of nature" that provided foundational insights into the roles of both T and E2 in male bone metabolism. It also describes their trial on 59 elderly men that confirmed the predominant role of Estrogen in restraining bone resorption - which is the primary metabolic function that results in bone loss; i.e., from the paper:
"On the basis of these data, we estimated that, in normal elderly men, E accounted for approximately 70% of the total effect of sex steroids on bone resorption, with T contributing (in the absence of aromatization to E) at most 30% of the effect."
This closing passage of the report also suggests that any man on ADT, BAT, or TRT should be getting tested for E2 (free and total), T (free and total), and SHBG (their binding agent) & treated with exogenous E2 as appropriate:
"The evidence that elderly men with low bioavailable E2 levels [below ~ 40 pmol/liter (11 pg/ml)] are the ones that have the greatest increases in bone resorption markers and in rates of bone loss also suggests that age-related bone loss in men may, at least in part, be due to relative E deficiency in these men. Also, there likely is a sex steroid-independent, age-related decrease in osteoblast function (54), although given the evidence that both E and T are important or maintaining bone formation (31, 32), it is possible that even this defect is, in part, due to E and T deficiency in elderly men.
Finally, these findings suggest that not all men are likely to respond to treatment with selective ER modulators or possibly even T replacement, because the effects of the latter on the skeleton are likely mediated in large part by aromatization to E. Rather, future studies using these agents should target men with low bioavailable E2 levels, because these are the individuals who are E deficient and likely to have a favorable skeletal response to hormonal therapy. As clinicians, we already knew this to be true in the case of pre- vs. postmenopausal women, who are either E sufficient or deficient. Although this distinction may be more subtle in men, it does now appear that the same may apply to men with relative E sufficiency or deficiency."
(3) Estrogen and the Male Skeleton, by Sundeep Khosla, L. Joseph Melton III, and B. Lawrence Riggs, Endocrine Research Unit (S.K., B.L.R.) and Department of Health Sciences Research (L.J.M.), Mayo Clinic and Mayo Foundation, Rochester, Minnesota 55905, The Journal of Clinical Endocrinology & Metabolism, Volume 87, Issue 4, 1 April 2002, Pages 1443–1450
academic.oup.com/jcem/artic...
The second paper (4) is on the effects of various endocrine therapies on both breast and prostate cancers.
This passage on ADT should get the attention of all PCa patients:
"Androgen deprivation therapy induces a high rate of bone turnover that results in a reduction of BMD of about 4% in the spine after 12 months of treatment. Notably, patients with untreated prostate cancer already have a high prevalence of osteoporosis (4–38%), and this increases to 53% in patients with prostate cancer receiving androgen deprivation therapy.
In a large meta-analysis of 14 trials, men who had androgen deprivation therapy had an increased risk of overall fracture of 23% compared with men with prostate cancer who did not receive androgen deprivation therapy. The fracture risk is directly correlated with the number of GnRH agonist doses given. Although patients who received one to four doses of GnRH agonist had an unchanged fracture risk of 14% over 5 years compared with patients with prostate cancer not receiving androgen deprivation therapy, those who received more than nine doses had an increased fracture risk of 28%.
In another study that included roughly 76 000 men, the fracture rate increased from 52·9 to 73·0 per 1000 person-years in patients receiving more than 18 doses of GnRH agonists, and was associated with a higher overall mortality risk of 1·4 (95% CI 1·34–1·43) compared with patients who received no GnRH agonists. In a smaller study of 195 men with androgen suppression,49 of which had a history of skeletal fracture since diagnosis, the overall median survival of men was 121 months for those with a history of skeletal fracture and 160 months for those without (p=0·04). Furthermore, in men being treated with androgen deprivation therapy, the increased bone complications of osteoporosis and fracture risk are associated with a substantially increased economic burden.
Except for tamoxifen in postmenopausal women, endocrine therapy has pronounced negative effects on bone health, although their positive effects on survival warrant their routine use. Therefore, bone health should be actively monitored and managed in patients receiving endocrine therapy for cancer treatment."
And, as with the first paper, this closing paragraph suggests initial BMD testing and regular monitoring for anyone on endocrine therapy, such as ADT:
"Each patient receiving endocrine therapy should be stringently assessed for their individual fracture risk when therapy is initiated, and this risk should be reassessed in adequate intervals or whenever major changes to disease status or treatment occur."
(4) Bone health during endocrine therapy for cancer, by Tilman D Rachner, Robert Coleman, Peyman Hadji, Lorenz C Hofbauer, Lancet Diabetes Endocrinology 2018, Published online March 20, 2018.
sci-hub.st/10.1016/S2213-85...
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Lastly, here is a link to a series of animated Amgen videos (5-9) on bone biology. These very short video animations explain the most basic bone biology and essential functions of osteoclasts and osteoblasts:
(5) Introduction to Bone Biology, Amgen - 2012
youtube.com/watch?v=inqWoak...
(6) Osteoblasts and Osteoclasts, Amgen - 2012
youtube.com/watch?v=78RBpWS...
(7) Bone Remodeling and Modeling, Amgen - 2012
youtube.com/watch?v=0dV1Bwe...
(8) Regulation of Osteoclast Activity, Amgen -2012
youtube.com/watch?v=GpMV197...
(9) Anatomy of a Fracture as a Result of Systemic Bone Loss, Amgen - 2012
youtube.com/watch?v=P5HwYWS...
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BTW - None of the above should prevent PCa patients from engaging in the sorts of weight-bearing exercises that are proven to help build and maintain BMD. Just Do It!
And keep staying S&W - Ciao, Cujoe
