Growth hormone reduces risk of osteoporosis fractures in older women

 

For years after it was administered, growth hormone continued to reduce the risk of fractures and helped maintain bone density in postmenopausal women who had osteoporosis, according to a new study published in the Endocrine Society's Journal of Clinical Endocrinology & Metabolism. Osteoporosis is a progressive condition that causes the bones to become weak and more likely to break.  80 percent of the people being treated for the condition nationwide are women, according to the Society's Endocrine Facts and Figures Report. Women are three times more likely to experience an osteoporosis-related bone fracture in their lifetimes than men. "Our study is the largest and longest controlled study of growth hormone treatment for osteoporosis in postmenopausal women to date," said one of the study's authors, Emily Krantz, MD, of Södra Älvsborgs Hospital in Borås, Sweden. "Years after treatment stopped, women who were treated with growth hormone still experienced improved bone density and reduced fracture risk." During an 18-month-long randomized, double-blind trial, 80 postmenopausal women with osteoporosis received daily injections of either placebo, a single unit of growth hormone or a 2.5-unit dose of growth hormone. The women were between the ages of 50 and 70 when they were recruited for the decade-long study. After 18 months, the women who received the placebo halted the injections. Women who received growth hormone continued to receive injections for another 18 months. The researchers continued to follow up with the women for seven years after the growth hormone treatment was halted to monitor their bone density, fractures and perception of their quality of life. The researchers compared the participants' bone density and rate of fractures to those of a group of 120 women who did not have osteoporosis. The controls were identified using the city census in Gothenburg, Sweden. A decade after the study began, the women who received the larger growth hormone dose still had higher bone mineral density levels than the participants who received the lower dose or the placebo. The rate of fractures in the treated women who had osteoporosis declined by 50 percent during the 10-year-long study. More than half of the participants had fractured bones prior to the start of the study. In contrast, the rate of fractures rose four-fold in the control group as some of those women were diagnosed with osteoporosis. "The findings indicate the beneficial effects of growth hormone remained long after the treatment ceased," Krantz said. Story Source: The above post is reprinted from materials provided by The Endocrine Society.Note: Materials may be edited for content and length. Journal Reference: Emily Krantz, Penelope Trimpou, Kerstin Landin-Wilhelmsen. Effect of Growth Hormone Treatment on Fractures and Quality of Life in Postmenopausal Osteoporosis: A 10-Year Follow-Up Study. The Journal of Clinical Endocrinology & Metabolism, 2015; jc.2015-1757 DOI:10.1210/jc.2015-1757   The Endocrine Society. "Growth hormone reduces risk of osteoporosis fractures in older women: Long-term follow-up study shows benefits lasted for years after randomized trial." ScienceDaily. ScienceDaily, 27 August 2015. www.sciencedaily.com/releases/2015/08/150827141905.htm

Osteoporosis: Genetic researchers take major step towards better diagnosis, treatment

 

May 30, 2014

European Society of Human Genetics (ESHG)

A new target that may be critical for the treatment of osteoporosis, a disease which affects about 25% of post-menopausal women, has been discovered by a group of researchers. New studies in zebrafish and mice have shown that injection of human plastin 3 (PLS3) or related proteins in zebrafish where PLS3 action has been suppressed can replace its loss and repair the bone development anomalies associated with this deficiency.

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A new target that may be critical for the treatment of osteoporosis, a disease which affects about 25% of post-menopausal women, has been discovered by a group of researchers in The Netherlands and in Germany.

Professor Brunhilde Wirth, Head of the Institute of Human Genetics, University of Cologne, Germany, will tell the annual conference of the European Society of Human Genetics tomorrow (Sunday) that new studies in zebrafish and mice have shown that injection of human plastin 3 (PLS3) or related proteins in zebrafish where PLS3 action has been suppressed can replace its loss and repair the bone development anomalies associated with this deficiency. Furthermore, overexpression of human (PLS3) in normal mice had a significant impact on bone development and maintenance, making them more resistant to fractures.

The discovery that PLS3 mutations could cause osteoporosis was published last year in The New England Journal of Medicine. The results came as a surprise to the researchers, since mutations in the PLS3 gene had not previously been known to be related to osteoporosis and fractures, or to play a role in bone formation. “In our most recent research, we started out by using zebrafish embryos in which PLS3 was knocked-out and studying their development at the three and five day-old stage,” says Professor Wirth, “and we found that they had massive impairment of craniofacial skeletal development. However, this was fully restored when we added human PLS3. The same thing happened when we added two other proteins, actinin 1 and actinin 4, F-actin proteins2 which are involved in ‘bundling’ or building the ‘scaffolding’ for cells, and it seems that these proteins can compensate for the loss of PLS3.  Thus we have been able to verify the essential role of actin in bone development and maintenance.”

The subsequent mouse studies confirmed the findings in zebrafish, the researchers say, and open up possibilities for new treatments. They now intend to use PLS3 knock-out mice, where the PLS3 gene has been removed, in the search for the disease-causing mechanism involved.  PLS3 is expressed in three different types of cells - osteocytes and osteoclasts, both involved in bone growth and remodelling, as well as in muscle cells.  Using a transgenic mouse that overexpresses PLS3, they will also investigate whether this overexpression could be effective in other diseases involving in bone weakness.

“Since we know that about five percent of the human population expresses higher than normal levels of PLS3, we can hypothesise that these people may be protected against osteoporosis,” says Professor Wirth.

Once the researchers understand the exact disease-causing mechanism, it may be possible to translate the knowledge into therapy, they say. PLS3 overexpression is also protective against spinal muscular atrophy, the second most frequent autosomal recessive disorder in humans.3 This implies that understanding the protective role of PLS3 is crucial in both disorders. “We are currently trying to unravel the whole protein network and, once we have understood the signalling pathways influencing PLS3 expression, we should be able to identify drugs or molecules that influence PLS3 expression or actin proteins,” she says.

Osteoporosis affects not only post-menopausal women, but also older men, and the condition currently causes more than 8.9 million fractures per year or an osteoporitic fracture every three seconds. Worldwide one in three women over 50 will experience fractures due to osteoporosis, as will one in five men. Currently, emphasis for sufferers is on the prevention of falls that can cause broken bones. Although bisphosphonates are useful in decreasing the risk of future fractures in those who have already sustained an osteoporotic fracture, they are otherwise of little use.

“Osteoporosis poses an urgent health problem that is going to become more important as years go with the numbers of elderly people in the community continuing to increase,” says Professor Wirth.  “Although in itself it is not a fatal illness, large numbers of people die prematurely as a result of health complications following falls. We believe that our work has led to a better understanding of the condition and has pointed the way towards improved diagnosis and prevention, and, we hope, an effective treatment in the future.”

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Story Source:

The above story is based on materials provided by European Society of Human Genetics (ESHG). Note: Materials may be edited for content and length.

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Journal Reference:

1. Fleur S. van Dijk, M. Carola Zillikens, Dimitra Micha, Markus Riessland, Carlo L.M. Marcelis, Christine E. de Die-Smulders, Janine Milbradt, Anton A. Franken, Arjan J. Harsevoort, Klaske D. Lichtenbelt, Hans E. Pruijs, M. Estela Rubio-Gozalbo, Rolf Zwertbroek, Youssef Moutaouakil, Jaqueline Egthuijsen, Matthias Hammerschmidt, Renate Bijman, Cor M. Semeins, Astrid D. Bakker, Vincent Everts, Jenneke Klein-Nulend, Natalia Campos-Obando, Albert Hofman, Gerard J. te Meerman, Annemieke J.M.H. Verkerk, André G. Uitterlinden, Alessandra Maugeri, Erik A. Sistermans, Quinten Waisfisz, Hanne Meijers-Heijboer, Brunhilde Wirth, Marleen E.H. Simon, Gerard Pals. PLS3Mutations in X-Linked Osteoporosis with Fractures. New England Journal of Medicine, 2013; 369 (16): 1529 DOI: 10.1056/NEJMoa1308223