• Researchers in Nashville, Tennessee, pioneer the use of 3D printing to create replica bone tissue
• Replica bone tissue used for microenvironment study of bone cancers and treatments
• Study results show remarkable difference from earlier findings about approaches to treatment

May 18, 2016, Rome, Italy. Press Dispensary. A team from Nashville, Tennessee, has used 3D printing to construct accurate replicas of human bone tissue in order to study properly, for the first time, how tumours and bones interact and how tumour-based bone disease might be treated. And already the new technique is suggesting what may be the best approach to stopping tumours being established in bone.

The new approach was described in Rome today by Dr Julie Sterling of the Department of Veterans Affairs and Vanderbilt University in Nashville, Tennessee, speaking on behalf of her colleagues from both institutions. Dr Sterling was addressing an audience at ECTS 2016, the 43rd annual congress of the European Calcified Tissue Society (ECTS).

Dr Sterling said: “Until now, it has not been possible to study the progress and treatment of bone cancers in the microenvironments of bones themselves or truly bone-like models. Instead, we have continued to grow cell cultures for study on tissue culture plates, essentially the modern answer to the Petri dish.

“So we used a combination of imaging and inkjet 3D printing technology to create 3D Tissue Engineered Constructs (TECs) that reproduce the form and mechanics of trabecular bone – the bone tissue found at the ends of long bones – as well as in the vertebrae of the spinal column and other places.”

The team made 3D-printed TECs of the tissue in three different human bone areas – the head of the femur, the tibial plateau and lumbar vertebrae – tested to show that they accurately mirrored the originals. These were used for a variety of studies that involved growing cell cultures, including stem cell cultures and bone-based breast cancer cell cultures.

Dr Sterling continued: “Importantly, we studied the behaviour of drug treatments on tumours cultured on bone-like 3D TECs and found a remarkable difference in effect when compared with tumours cultured on the conventional tissue culture plates.

“When bone-based breast cancer cells (bone-metastatic MDA-MB-231) cultured on the 3D TECs were treated with the inhibitor drugs Cilengitide or SD208 (intended to inhibit the growth and invasiveness of tumour cells), the apparent benefits that had been found in the tissue culture plates environment were not there.

“But when the treatment was the Gli2 inhibitor GANT58 (which inhibits signalling en route to the cell receptors), the treatment had a similar and significant effect whether in the 3D TEC environment or the tissue culture plate environment.

“This suggests that an effective way of blocking the establishment of tumours in bone may be to target factors downstream of cell receptors rather than targeting the cells directly.

“It also shows how important it can be to have a physical bone-like environment for the study of  tumours and treatments.”

– ends –

Click here for more info

Vitamin D insufficiency is common in fertile women

• Previous studies have shown association between vitamin D insufficiency and low birth weight, reduced fertility and adverse pregnancy outcomes.
• Daily vitamin D supplements caused fewer childbirth complications, but did not improve birth weight
• Surprisingly, high dose of vitamin D supplementation was shown to reduce chances of conceiving.

May 18, 2016, Rome, Italy. Press Dispensary. New research has established that high doses of vitamin D supplements can lead to fewer complications during childbirth but reduce a woman’s chances of getting pregnant in the first place.

The news was announced in Rome today by the Danish medical doctor and PhD Gitte Bloch Rasmussen, speaking at ECTS 2016, the 43rd annual congress of the European Calcified Tissue Society (ECTS).

Dr Rasmussen was reporting on trials that had been conducted among 193 women with low levels of vitamin D, who were all planning pregnancy and all attended a single centre in Aarhus, Denmark. The trials had been conducted by Dr Rasmussen with colleagues from Aarhus University Hospital, in Denmark.

Dr Rasmussen said: “Fertile women are often found to have low vitamin D levels, which are associated with low birth weight, reduced fertility and adverse pregnancy outcomes. Our aim was to look at the effects of vitamin D supplements on these areas in women with low levels of vitamin D.”

The 193 women were aged 20 – 40, were planning pregnancy and had levels of 25-hydroxyvitamin D (known as 25OHD, the most accurate way to measure vitamin D levels) below 50 nmol/L, which is bordering on insufficiency. Before conceiving, they were allocated to groups, one being given a 70mcg daily supplement of vitamin D3 and one a 35mcg daily dose, with matching groups given placebos. The women continued the trial until 16 weeks after birth and were evaluated for their 25OHD level, birth weight, fertility and any complications.

56% of the women conceived within 12 months, 38% in the placebo group, 29% taking the 70mcg supplement and 33% taking the 35mcg supplement. 44% did not conceive.

Dr Rasmussen continued: “We found a noticeable difference in two of the four areas we evaluated. Whilst the lower daily dose of vitamin D3 did not significantly affect the chances of pregnancy, the higher 70mcg daily supplement significantly reduced the chances of conceiving.  On the other hand, supplementation showed to be beneficial on risk of complications during labour, as these were significantly less frequent in the combined vitamin D3 groups (a 23% risk) than in the placebo group (a 52% risk).

“However, birth weight did not differ significantly between those treated with vitamin D3 and those receiving placebos; there were also no differences between groups on any safety measures.”

Dr Rasmussen concluded: “High doses of vitamin D3 may reduce the likelihood of conceiving, but may also be associated with fewer complications during childbirth, though without improving birth weight.”

– ends –

Click here for more info

• Rates of osteoporosis treatment rose from 1990 to 2006 in women but declined from 2006, despite growing elderly population
• Rates of osteoporosis treatment also rose in men but levelled off from 2006
• Marked differences in rates by geographic location, with highest rates in Northern Ireland and lowest in parts of England

May 18, 2016, Rome, Italy. Press Dispensary. A UK-wide study looking at the prescribing of anti-osteoporotic drugs (AOD) to people aged 50 years or above has found that, since 2006, AOD prescription rates for women have decreased and rates for men have levelled off, despite a growing elderly population and associated fracture risks. This followed a steep rise in prescribing rates since 1990. Furthermore there was marked geographic variation in prescribing rates, with greatest rates for men and women in Northern Ireland and the lowest rates for women in the East Midlands and men in Yorkshire and Humberside.

The study, funded by the UK National Osteoporosis Society and Medical Research Council, used data from the UK Clinical Practice Research Datalink, a general practice based dataset including information on 7% of the UK population. The researchers analysed AOD prescriptions from 1990 to 2012, and also found that far more women than men were prescribed AOD and that the rate of prescription increased with age, up to the age of 85-89 years where women were more than twice as likely as men to be prescribed AODs. White and Asian women were twice as likely to be receiving AOD prescriptions as black women.

The study findings were unveiled in Rome today by Robert van der Velde, speaking at ECTS 2016, the 43rd annual congress of the European Calcified Tissue Society (ECTS). The study was carried out by Dr van der Velde, Consultant Endocrinologist at the Maastricht University Medical Centre and VieCuri Medical Centre, both in the Netherlands, with colleagues from the Netherlands and Belgium as well as from Southampton, Oxford and Manchester in the UK.

Dr van der Velde said: “The finding of geographic variation in antiosteoporosis medication prescriptions is likely to reflect a range of factors, such as differences in age structure of the population, ethnic mix and socioeconomic status between the different regions of the UK. Further work will be required to investigate whether these differences also reflect variations in approaches to the prevention and treatment of osteoporosis, for example after hospital admission for a hip fracture.”

He added: “The decline in antiosteoporosis medication prescriptions over the last 10 years is concerning, particularly in the context of an ever more elderly population, in which many fracture types are becoming more common. Other work from the CPRD has demonstrated an increase in rates of treatment for osteoporosis following a hip fracture, but still only just over half such patients receive treatment – there is a clear and urgent need for the field to close this care gap.”

Professor Nicholas Harvey, Professor of Rheumatology and Clinical Epidemiology at the MRC Lifecourse Epidemiology Unit, University of Southampton, who oversaw the study, commented: “This work forms part of a larger series of studies, funded by the UK National Osteoporosis Society and Medical Research Council, in which we comprehensively assess the impact of fragility fractures in the UK. The current study, in combination with recent papers describing the burden of osteoporotic fracture in the UK population, gives really important information which will inform health planners not just in the UK, but in many other countries.”

– ends –

Click here for more info

• New rodent study uncovers novel mechanism by which chronic stress leads to bone loss
• Study also finds the phenomenon restricted to males

May 18, 2016, Rome, Italy. Press Dispensary. A new study has helped to unveil the mystery of why chronic stress and depression can lead to bone loss and increase the risk of fractures. The effect of chronic stress on the health of bones is already known but how one leads to the other is not entirely understood. The study, whose results have just been announced by Holger Henneicke of the University of Sydney, set out to investigate the mechanism.

Dr Henneicke was speaking to an audience of specialists at ECTS 2016, the 43rd annual congress of the European Calcified Tissue Society (ECTS) being held in Rome. He described how the study examined the impact of chronic stress on skeletal metabolism and structure in mice, comparing a group of wildtype mice with a group in which the signals of a hormone, suspected of being responsible, had been disrupted.

Holger Henneicke said: “We know stress and depression are linked to poor bone health but not how one results in the other, so we set out to determine the role played by stress hormones, known as glucocorticoids, in the cells which synthesise bone.

“Eight week old male and female mice were exposed to chronic but mild stress. In some mice, the glucocorticoid signalling was selectively disrupted in bone-forming osteoblasts, while their littermates were left ‘wild’.”

There was also a control group not exposed to the mild stress.

Dr Henneicke continued: “After four weeks of stress exposure, the mice were examined and a portion of the spine – the L3-vertebrae – plus tibia and blood were analysed.

“When compared to the non-stressed control group, the wildtype mice, with normal intact stress hormone signalling, experienced a loss of bone mass in the analysed vertebrae and a reduction in the area of the tibial cortex, as well as an increase in the activity of osteoclasts, a type of bone cell that breaks down bone tissue for maintenance and repair purposes. Meanwhile, the stressed mice whose glucocorticoid signalling had been disrupted did not experience this effect.

“And interestingly, this only applied to males. In stressed females, neither the vertebral nor tibial structures were affected.”

Mr Henneicke concluded: “So in male mice, glucocorticoid signalling in osteoblasts and the subsequent activation of osteoclasts is part of what lies behind bone loss during chronic mild stress.

“In female mice, it is a different story altogether, chronic stress did not seem to influence bone health and we are currently looking into why not.”

– ends –

Click here for More info

The European Calcified Tissue Society (ECTS) Establishes the ECTS Academy for Top PostDoctoral Researchers

The future of excellence in European research requires efficient support structures to enable the best next generation researchers to develop their career. Key aspects include training and networking. With these considerations in mind the European Calcified Tissue Society has established the ECTS Academy to support young musculoskeletal researchers. The concept follows the model of interdisciplinary Young Academies: young researchers self-organise their society to foster personal contact and networking among the most talented young scientists.

“The ECTS Academy will represent the most talented PostDoc researchers in the musculoskeletal field in Europe” said Dr. Claus–C. Glüer, Professor of Medical Physics at the Christian-Albrechts-Universität in Kiel, Germany and ECTS President, “scientific excellence and cooperative engagement for advancing musculoskeletal research are key requirements for being elected to the membership. Its establishment should strengthen the future of musculoskeletal research by attracting top scientists and assisting them in setting up their research network”.

Ten members will be elected every year for a membership duration of five years. The ECTS Academy will not exceed 50 members and during their membership, each fellow will receive a wide range of benefits including free participation at ECTS Annual Congress, personal research grants and scholarships for ECTS supported meetings.

A key benefit is also the access to ECTS members and supporters which include top level scientists in Europe. The ECTS Academy members will be able to network and establish personal contacts. The ECTS Academy will receive funds to support Academy activities. The financial support has been made possible by unrestricted educational grants by corporate sponsors of ECTS including Amgen Europe and AgNovos.

The ECTS together with its Affiliated Societies in more than 20 European Countries will nominate a group of respected European mentors, covering the background of basic, translational, methodological, and clinical science. Mentors will assist candidates in the selection process and also provide valuable career advice.

The ECTS will accept applications for the ECTS Academy between March 1 and April 8, 2016. The first 10 successful applicants will be announced and invited to participate in the ECTS Academy Founding Reception at the ECTS Annual Congress in Rome, May 14-17, 2016.

Interested Mentors, Mentees and Affiliated Societies will find all information on how to become involved on the ECTS Website. More info