Dawn Skelton

Angiotensin-I converting enzyme genotype-dependent benefit from hormone replacement therapy in isometric muscle strength and bone mineral density.

Low bone mineral density (BMD) and muscle weakness are major risk factors for postmenopausal osteoporotic fracture. Hormone replacement therapy (HRT) reverses the menopausal decline in maximum voluntary force of the adductor pollicis and reduces serum angiotensin-I converting enzyme (ACE) levels. The insertion (I) allele of the ACE gene polymorphism is associated with lower ACE activity and improved muscle efficiency in response to physical training. Therefore, we examined whether the presence of the I allele in postmenopausal women would affect the muscle response to HRT. Those taking HRT showed a significant gain in normalized muscle maximum voluntary force slope, the rate of which was strongly influenced by ACE genotype (16.0 +/- 1.53%, 14.3 +/- 2.67%, and 7.76 +/- 4.13%, mean +/- SEM for II, ID, and DD genotype, respectively; P = 0.017 for gene effect, P = 0.004 for I allele effect). There was also a significant ACE gene effect in the response of BMD to HRT in Wards triangle (P = 0.03) and a significant I allele effect in the spine (P = 0.03), but not in the neck of femur or total hip. These data suggests that low ACE activity associated with the I allele confers an improved muscle and BMD response in postmenopausal women treated with HRT.

Can exercise interventions designed to reduce falls improve bone quality [Abstract]

In this symposium, we will review the association of inflammatory arthritis with altered bone health. It has long been recognised that joint conditions such as rheumatoid arthritis and ankylosing spondylitis are associated with reduced bone density and increased fracture risk. Such conditions may be associated with high levels of inflammation, with stimulation of the inflammatory cascade and production of pro-inflammatory cytokines (Il-1, IL-10, IL-6, TNF-α), all of which are well-recognised to cause both localised and generalised osteoporosis. In addition, arthritis patients may be physically inactive because of recurrent arthritis flares, or may be receiving long term corticosteroid therapy. In this session we will review bone health in two other arthritic conditions, namely gout and HIV arthritis. We will also review novel ways of assessing bone microarchitecture in arthritis through high resolution peripheral quantitative computed tomography scans of the radius and tibia. Participants are invited to share their own observations in clinical practice, and propose a research agenda in this important area.This is an abstract of a paper presented at the Congress on Osteoporosis, Osteoarthritis and Musculoskeletal Diseases (WCO-IOF-ESCEO World), Malaga, Spain, April 14-17th. The final publication is available at Springer via http://dx.doi.org/10.1007/s00198-016-3519-5.

Can exercise protect against vertebral deformity? The proact65+bone study [Abstract]

S OF OSTEOPOROSIS CONFERENCE 2016 Invited Plenary Lecture Abstracts IS1 FROM FAMILY HISTORY TO EPIGENETICS OF OSTEOPOROSIS Trevor Cole West Midlands Regional Genetics Service and Birmingham Health Partners, Birmingham Women’s Hospital NHS Foundation Trust, Birmingham, UK With the development of greater genetic knowledge and the advent of more powerful genomic technologies there has been a greater impetus to develop more personalised service delivery and treatments for both rare diseases and common disorders. The “flagship” of such developments was in the field of oncology but similar models are now widespread and this includes disorders associated with bone fragility. Osteoporosis in the general population most frequently presents as an isolated finding, but to date, when presenting to a combined bone and genetic clinic is more likely to be seen as “compounding morbidity” in a patient or family with one of the many different rare causes of bone fragility such as osteogenesis imperfecta. Over 140 such rare bone fragility conditions are listed on the London dysmorphology database. These may present antenataly right through into old age, each with differing severity but often exacerbated by osteoporosis in those surviving into adulthood. One important lesson learnt from such clinical experience is that taking a good clinical history, including a family history, not a reliance on genomic testing, is frequently the most valuable first step in recognising the aetiology and identifying whether other family members should be seen in clinic. In past decades genetic studies in osteoporosis focused on large genomic wide association studies or rare Mendelian families in the belief that a small number of genes would be identified as the cause for more widespread osteoporosis in the general population. It was hoped such findings could be translated into simple algorithms to predict future osteoporotic risk as well as identifying novel therapeutic targets. More recently it has become apparent that this is an over-simplification and not only are there many more genetic influences present than originally suspected, but that many of these may relate to epigenetic phenomena, a mechanism by which gene expression may be modified. This now opens up a whole new therapeutic opportunity as our epigenome is modifiable by many pharmacological and nonpharmacological interventions. It also likely provides new insights into the mechanisms behind well recognised influences on osteoporosis such as physical activity. While basic research continues to focus on the genomic and epigenomic basis of osteoporosis and bone fragility disorders we will illustrate there is still plenty of scope to introduce simple practical measures, such as taking a family history, into the clinic which will improve the clinical management as well as identifying potential patient cohorts to participate in studies investigating the aetiology and future therapeutic trials. IS2 DIABETES AND BONE Serge Ferrari Geneva University Hospital and Faculty of Medicine, Geneva, Switzerland Type 1 diabetes that develops during childhood or adolescence impairs bone formation and thereby peak bone mass acquisition. Taken together with their increased risk of falls due to other diabetes complications, these bone alterations in adults with type 1 diabetes result in a 6 to 12 fold increased risk of hip fractures and also in a higher risk of vertebral and non-vertebral fractures. This increased fracture probability is also reflected in the FRAX tool when it is used without BMD in T1DM subjects. Subjects with type 2 diabetes (T2DM) also have a 50 % to two fold increased risk of fracture, depending on the skeletal site, despite the fact their aBMD is on average higher than in the non-diabetic population. Their increased Osteoporos Int (2016) 27 (Suppl 2):S609–S685 DOI 10.1007/s00198-016-3743-zThis is an abstract of a paper presented at the Osteoporosis Conference 2016, Birmingham, UK, 7-9 November 2016. The final publication is available at link.springer.com via http://dx.doi.org/10.1007/s00198-016-3743-z.This is an abstract of a paper presented at the Osteoporosis Conference 2016, Birmingham, UK, 7-9 November 2016. The final publication is available at link.springer.com via http://dx.doi.org/10.1007/s00198-016-3743-z.