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Move into the Centre for
Biomedical Research
In October this year, we moved into our new
site, the Centre for Biomedical Research (CBR)
at the NGH. The ground and 1st floors of the
old Clinical Sciences Centre have been
completely refurbished and now bear little
resemblance to the original. The ground floor
of the CBR houses both the Bone and the
Cardiovascular Biomedical Research Units.
The two units share a seminar room and
kitchen but have their own dedicated
research offices. A large biorepository is also
housed on the ground floor and will be used
for the storage of biological fluids and tissue
obtained in our research studies.
Ground floor of the CBR housing the Bone and
the Cardiovascular Biomedical Research Units
The Clinical Research Facility occupies the first
floor of the CBR. All of our diagnostic research
devices have been moved to the CRF and are
fully operational. Patients and volunteers
enrolled in our studies and clinical trials now
attend the CRF (where our clinical trials team
is based) for their study visits.
Clinical Research Facility reception area in the
Centre for Biomedical Research
Projects
Two new research studies have been initiated
in recent months. One is the Metal Ions study
led by Mark Wilkinson. Whole body bone
mineral density will be compared in patients
who have undergone metal on metal hip
resurfacing (MOMHR) or conventional total
hip arthroplasty (THA). Four patients have
been enrolled into this study to date.
Conventional THA MOMHR
The second is the High Bone Mass
multi-centre study, which is being led locally by
Eugene McCloskey. The training manual for
acquisition and analysis of bone density scans
was prepared by Margaret Paggiosi and the
Bone BRU is the lead training centre. This aim
of this research is to identify genetic
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polymorphisms in individuals and the
extended families of these individuals who
have higher than average bone mineral
density.
NIHR and BRU Developments
We have two pieces of good news to report;
firstly Richard Eastell (Bone BRU Director) was
awarded Senior NIHR investigator status
earlier this year. Secondly, the NIHR awarded
a total of £1.4 million to fill the shortfall in
funding needed to pay for the transformation
of the Clinical Sciences Building into the CBR.
Plans are now underway to apply for NIHR
Biomedical Research Centre (BRC) status
when the current funding period ends (2012).
The 1st step towards this goal has been the
formation of a BRC Strategy Board chaired by
Professor Weetman. Richard Eastell recently
attended a meeting of the NIHR ‘family’
entitled ‘Realising the Vision: the NIHR Family
Conference’ at the NEC, Birmingham.
Reassuringly, the NIHR confirmed at this
meeting that they will have £1 billion of
research funding to allocate in 2010.
Patient Panel
Members of the Bone BRU’s Patient Panel
met for a joint Christmas event with the
Cardiovascular BRU Patient Panel on the 2
ndof
December at the MEC, NGH. Professor Eastell
gave a presentation to Panel members
outlining the various roles of people involved
in research at the BRU. This was followed by a
quiz with a Christmas theme. The buffet lunch
provided an opportunity for our Panel
members to meet members of staff.
At their last meeting, on the 10
thof
November, the Panel formalised their ‘Terms
of Reference’ which included a renaming of
the Panel which will now be called the ‘
Lay
Advisory Panel for Bone Research
’. The
members also defined their role as being
‘to
give a lay perspective on and influence the
research that is being carried out in the Bone
Biomedical Research Unit.’
The Panel will meet monthly throughout 2010
to review our research protocols, participant
information sheets and lay summaries.
People
New appointments
Jemima Clarke
Jemima took up her post of Research
Coordinator in the Bone BRU in August this
year, having previously worked for CellTran
Ltd, a company specialising in regenerative
wound healing. Her duties there involved
growing autologous human tissue in a MHRA-
accredited
Class
100
laboratory
for
nationwide treatment of burns and chronic
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wounds or ulcers. The company worked to
ISO9001:2000
standards
and
therefore
Jemima gained valuable experience of Quality
Management Systems. In her role she worked
in accordance with Good Manufacturing
Practice ensuring that her work (and that of
colleagues) complied with the Human Tissue
Act and participated in several MHRA and HTA
inspections. Jemima’s role within the Bone
BRU is to work alongside Stacy Young
(Research Coordinator) and Kath Knight (Bone
BRU Manager) to maintain compliance to GCP
in all our studies. She will be responsible for
projects in the post- governance set-up phase
and for both active and archived studies.
These activities will include the monitoring
and auditing of clinical trials, submission of
ethics amendments as necessary and
maintenance of study site files.
Kathryn Watson
Kathryn has been appointed to the post of
BRU Secretary to the CBR, a joint full-time
post between the Bone and Cardiovascular
BRUs.
Kathryn worked as a medical secretary at the
King Edward VII Orthopaedic and Weston Park
Hospitals and Secretary to the Treasurer of
the Sheffield Area Health Authority before
coming to the University of Sheffield in 1989.
Kathryn was secretary to Professor Weetman
and his research team, based first at the NGH
and later at the Medical School, where she
gained invaluable knowledge of the Sheffield
NHS Foundation Trust and it’s collaboration
with the University. She welcomes her current
appointment to the BRU as an opportunity to
perform a role at the heart of a new and
evolving venture in patient-based research.
New students
Five students have recently joined the Bone
BRU. Karan Shah is a PhD student under the
joint supervision of Mark Wilkinson and Allie
Gartland. He will be examining the
mechanism of action for the effects of metal
ions on bone cell function. Annabel Burton
(supervised by Lang Yang) and Elena Del
Vescovo, Jenny Prentice (supervised by Mark
Wilkinson) and Ian Baxter (supervised by
Nicky Peel) are BMedSci students. Annabel is
working on finite element analysis of the hip
in elderly men (the MrOS study); Elena is
studying genetic polymorphisms in the Toll
signalling pathway in relation to osteolysis
around total hip prostheses; Jenny is
investigating the potential adverse health
effects of the circulating metal ions with
metal-on-metal hip replacements. Ian is
studying the response of NTX to osteoporosis
therapies in the clinical setting.
Meeting Reports
ASBMR
Members of the Bone BRU were authors or
co-authors on a total of 17 abstracts
submitted to the ASBMR meeting in Denver,
Colorado in September this year. Three of
these were presented orally, 11 were posters
and 3 were plenary posters.
Upcoming Meetings
IOF Florence, Italy 5-10 May 2010: abstract
deadline 4 February 2010.
ECTS Glasgow, UK 26-30 June 2010: abstract
deadline 18 January 2010.
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Recent publications
A randomised, double-blinded, placebo-controlled, trial to determine the individual response in bone turnover markers to lasofoxifene therapy. Rogers A, Glover SJ, Eastell R. Bone 2009 Dec;45(6):1044-52.
Showed that bone turnover markers are useful for monitoring response to lasofoxifene therapy
Rapid and robust response of biochemical markers of bone formation to teriparatide therapy. Glover SJ, Eastell R, McCloskey EV, Rogers A, et al. Bone 2009 Dec;45(6):1053-8. Bone formation markers in women with low bone density increased rapidly in response to teriparatide treatment.
Update on monthly oral bisphosphonate therapy for the treatment of osteoporosis: focus on ibandronate 150 mg and risedronate 150 mg. Epstein S, Jeglitsch M, McCloskey E. Curr Med Res Opin 2009 Dec;25(12):2951-60. Conclusions: risedronate is more effective given daily, ibandronate is more effective given monthly and is also effective when given intermittently.
The effect of cessation of raloxifene treatment on bone turnover in postmenopausal women. Naylor KE, Clowes JA, Finigan J, Paggiosi MA, Peel NF, Eastell R. Bone 2009 Nov 6 [Epub ahead of print]. Reported the reduction in bone turnover is lost 6 months after cessation of raloxifene treatment.
The effect of a fortified milk drink on vitamin D status and bone turnover in post-menopausal women from South East Asia. Kruger MC, Schollum LM, Kuhn-Sherlock B, Hestiantoro A, Wijanto P, Li-Yu J, Agdeppa I, Todd JM, Eastell R. Bone 2009 Nov 4 [Epub ahead of print]. Daily consumption of milk fortified with calcium, vitamin D, magnesium and zinc reduced vitamin D insufficiency by up to 50%.
A study of the effects of the aromatase inhibitors anastrozole and letrozole on bone metabolism in postmenopausal women with estrogen receptor-positive breast cancer. McCaig FM, Renshaw L, Williams L, Young O, Murray J, Macaskill EJ, McHugh M, Hannon R, Dixon JM. Breast Cancer Res Treat 2009 Nov 26 [Epub ahead of print]. Given after tamoxifen therapy, aromatase inhibitors induced greater increases in bone turnover than in tamoxifen-naive patients.
The use of a point of care device for monitoring the bone resorption biomarker urinary N-telopeptide in cancer patients with bone metastases. Lester JE, Brown JE, Hannon RA, Ellis SP, Horsman JM, Purohit OP, Coleman RE. Bone 2009 Nov 18 [Epub ahead of print]. Measurement of urinary NTX using the point of care device is useful in monitoring patients with metastases.
Effects of teriparatide versus alendronate for treating glucocorticoid-induced osteoporosis: thirty-six-month results of a randomized, double-blind, controlled trial. Saag KG, Zanchetta JR, Devogelaer JP, Adler RA, Eastell R, See K, Krege JH, Krohn K, Warner MR. Arthritis Rheum 2009 Nov;60(11):3346-55. Teriparatide was associated with greater increases in bone density and fewer new vertebral fractures compared to alendronate.
BMD, clinical risk factors and their combination for hip fracture prevention. Johansson H, Kanis JA, Oden A, Johnell O, McCloskey E. Osteoporos Int 2009 Oct;20(10):1675-82. FRAX in combination with bone density assessment increased the performance of fracture risk assessment.
Effect of once-yearly zoledronic acid on the spine and hip as measured by quantitative computed tomography: results of the HORIZON Pivotal Fracture Trial. Eastell R, Lang T, Boonen S, et al. Osteoporos Int. 2009 Oct 3. Once-yearly zoledronate was associated with increased bone density compared to placebo.
Effects of the Src Kinase Inhibitor Saracatinib (AZD0530) on Bone Turnover in Healthy Men: A Randomized, Double-Blind, Placebo-Controlled, Multiple Ascending Dose Phase I Trial. Hannon RA, Clack G, Rimmer M, Swaisland A, Lockton JA, Finkelman RD, Eastell R. J Bone Miner Res. 2009 Sep 23. Inhibition of Src reduced osteoclastic bone resorption; saracatinib could be useful to treat diseases linked to increased bone resorption.
Effects of yearly zoledronic acid 5 mg on bone turnover markers and relation of PINP with fracture reduction in postmenopausal women with osteoporosis. Delmas PD, Munoz F, Black DM, Cosman F, Boonen S, Watts NB, Kendler D, Eriksen EF, Mesenbrink PG, Eastell R. J Bone Miner Res 2009 Sep;24(9):1544-51. Bone turnover reduced to within the premenopausal range and remained significant after the third infusion.
Effect of once-yearly zoledronic acid five milligrams on fracture risk and change in femoral neck bone mineral density. Eastell R, Black DM, Boonen S, et al; HORIZON Pivotal Fracture Trial. J Clin Endocrinol Metab 2009 Sep;94(9):3215-25. Zoledronate was more effective in preventing vertebral fracture in younger or overweight/ obese women and women with normal renal function.
From relative risk to absolute fracture risk calculation: the FRAX algorithm. McCloskey EV, Johansson H, Oden A, Kanis JA. Curr Osteoporos Rep 2009 Sep;7(3):77-83. Describes the development of the FRAX Algorithm.
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The effects of a FRAX((R)) revision for the USA. Kanis JA, Johansson H, Oden A, Dawson-Hughes B, Melton LJ 3rd, McCloskey EV [Epub 2009 Aug 25]. The revised FRAX model for the USA did not alter fracture probability rankings but gave lower probability estimates than the earlier version.
Denosumab for prevention of fractures in postmenopausal women with osteoporosis. Cummings SR, San Martin J, McClung MR, Siris ES, Eastell R, Reid IR, Delmas P, Zoog HB, Austin M, Wang A, Kutilek S, Adami S, Zanchetta J, Libanati C, Siddhanti S, Christiansen C; FREEDOM Trial. N Engl J Med 2009 Aug 20;361(8):756-65. Erratum in: N Engl J Med. 2009 Nov 5;361(19):1914. Twice-yearly
denosumab for 36 months reduced the risk of vertebral, non-vertebral, and hip fractures.
Association between vitamin D receptor gene polymorphisms, falls, balance and muscle power: results from two independent studies (APOSS and OPUS). Barr R, Macdonald H, Stewart A, McGuigan F, Rogers A, Eastell R, Felsenberg D, Glüer C, Roux C, Reid DM. Osteoporos Int. 2009 Jul 24 [Epub ahead of print]. Reports an association between the Bsm1 polymorphism and risk of falling.
A Randomised Controlled Dose-Ranging Study of Risedronate in Children with Moderate and Severe Osteogenesis Imperfecta. Bishop N, Harrison R, Ahmed F, Shaw N, Eastell R, et al. Bone Miner Res. 2009 Jul 6 [Epub ahead of print]. Increasing doses of risedronate produced greater increases in bone mass and fewer bowing deformities. The fracture rate was reduced irrespective of dose.
The cost-effectiveness of risedronate in the UK for the management of osteoporosis using the FRAX(R). Borgström F, Ström O, Coelho J, Johansson H, Oden A, McCloskey EV, Kanis JA.
Osteoporos Int 2009 Jun 30 [Epub ahead of print].
Risedronate was cost-effective for treatment of women with osteoporosis at age 65+ or with established osteoporosis at age 50+.
Prevalence of Osteonecrosis of the Jaw in Patients With Oral Bisphosphonate Exposure. Lo JC, O'Ryan FS, Gordon NP, Yang J, Hui RL, Martin D, Hutchinson M, Lathon PV, Sanchez G, Silver P, Chandra M, McCloskey CA, Staffa JA, Willy M, Selby JV, Go AS; Predicting Risk of Osteonecrosis of the Jaw with Oral Bisphosphonate Exposure (PROBE) Investigators. J Oral Maxillofac Surg. 2009 Jun 30 [Epub ahead of print]. ONJ cases occurred in 1/952 respondents with oral bisphosphonate exposure; a similar number had features that did not meet the criteria.
Bone turnover markers in postmenopausal breast cancer treated with fulvestrant--a pilot study. Agrawal A, Hannon RA, Cheung KL, Eastell R,
Robertson JF. Breast 2009 Jun;18(3):204-7. Long-term stability of bone markers may be exploited by early use of fulvestrant.
Subtrochanteric and diaphyseal femur fractures in patients treated with alendronate: a register-based national cohort study. Abrahamsen B, Eiken P, Eastell R. J Bone Miner Res. 2009 Jun;24(6):1095-102. Subtrochanteric/diaphyseal and classic hip fracture had similar epidemiologies and similar responses to alendronate.
The cost-effectiveness of strontium ranelate in the UK for the management of osteoporosis. Borgström F, Ström O, Coelho J, Johansson H, Oden A, McCloskey E, Kanis JA. Osteoporos Int 2009 Jun 10 [Epub ahead of print]. Strontium ranelate is
cost-effective in older women with established
osteoporosis and possibly in younger women with additional clinical risk factors.
Bazedoxifene reduces vertebral and clinical fractures in postmenopausal women at high risk assessed with FRAX. Kanis JA, Johansson H, Oden A, McCloskey EV. Bone 2009 Jun;44(6):1049-54. Bazedoxifene decreased clinical fracture and morphometric vertebral fracture risk in women ≥ a FRAX-based fracture probability threshold.
Biochemical Markers of Bone Turnover, Hip Bone Loss and Fracture in Older Men: The MrOS Study. Bauer DC, Garnero P, Harrison S, Cauley J, Eastell R, Ensrud K, Orwoll E; For the Osteoporotic Fractures in Men (MrOS) Research Group. J Bone Miner Res 2009 May 19 [Epub ahead of print]. Higher bone turnover was associated with greater loss of bone at the hip, but was not an independent predictor of hip or non-spine fracture.
Can fall risk be incorporated into fracture risk assessment algorithms: a pilot study of responsiveness to clodronate. Kayan K, Johansson H, Oden A, Vasireddy S, Pande K, Orgee J, Kanis JA, McCloskey EV. Osteoporos Int 2009 May 13 [Epub ahead of print]. Fall risk did not significantly impact on the anti-fracture efficacy of clodronate.
Ten-year fracture probability identifies women who will benefit from clodronate therapy--additional results from a double-blind, placebo-controlled randomised study. McCloskey EV, Johansson H, Oden A, et al. Osteoporos Int 2009 May;20(5):811-7. Estimation of 10-year fracture probability by FRAX in elderly women identifies those at high risk of fracture.
