Endocrinology and Diabetes

The Geelong Osteoporosis Study (GOS) is an internationally recognized, large population-based longitudinal epidemiological study that initially recruited 1494 women beginning in 1994 and 1,538 men beginning in 2001 from the Commonwealth electoral rolls.  Participants have been evaluated with BMD, body composition, bone turnover, glucose tolerance, serum lipids, medication exposure, medical history, alcohol and tobacco exposure, muscle strength and balance, falls history, quality of life and mental health assessments.

GOS has documented the prevalence of osteoporosis in Australia and fracture incidence as well as evidence that hip fracture rates have decreased, possibly related to increased adiposity of the population. We have examined the influence of prior fracture and socioeconomic status on fracture incidence.  The interaction between socioeconomic status and risk factors for fracture has been explored.  The effect of various exposures to fracture risk such as rheumatoid arthritis, paracetamol use, diabetes and impaired glucose tolerance have been reported.  The GOS was among the first to report an association between selective serotonin receptor inhibitors, used in the treatment of mental illness and fragility fractures.  We have explored the bone densitometric definition of osteoporosis and generated normative data for calcaneal ultrasound, bone turnover markers and lean mass.  We have described the prevalence of obesity and overweight in the Australian population, how this has changed in the past decade and have examined the relationship between adiposity and bone health.

Our fracture data defined Australian population age-, gender-and BMD-specific fracture rates used extensively in preparation of the Fracture Summit Report, influenced the Prescriber Benefits Advisory Committee to approve benefits for primary fractures prevention and is the basis of the Osteoporosis Australia Burden of Disease Report the has provided an accurate assessment of the cost of fragility fractures in Australia.  We contributed data to the international meta-analysis that established that Trabecular Bone Score (TBS), a bone densitometry-derived measure improves fracture prediction and have continued to explore the utility of TBS in a variety of disease states. We have contributed data to assist in the development of a second generation of the FRAX fracture risk calculator.

Currently the GOS is leading the introduction of impact microindentation as an assessment of bone fragility using the OsteoProbe RUO (Research Use Only), developed in 2012, which measures physical properties of the tibia, the larger bone in the lower leg.  We have contributed data to an international collaboration to develop reference ranges and have published data on its use to assess skeletal fragility in patients with diabetes and chronic kidney disease.

The GOS has been evaluating the impact of diabetes mellitus on bone health.  We have reported reduced trabecular bone score and bone turnover in participants with diabetes.  We are currently evaluating the bone phenotypes in participants who have new defined subtypes of diabetes, based on cluster analysis.  In addition, we have evaluated the bone phenotype in impaired fasting glycaemia as well as describing risk factors for progression of impaired fasting glycaemia to diabetes

The GOS has been supported by grants from the Geelong Regional Research Foundation, The Victorian Health Promotion Foundation, Percy Baxter Charitable Trust, The University of Melbourne, Ronald Geoffrey Arnott Foundation, Merck, Sharp and Dohme Australia, NHMRC, Deakin University, Perpetual Trustees, The American Society for Bone and Mineral Research, BUPA, HCF, Barwon Health Foundation, Osteoporosis Australia and Amgen

Intensive care patients face health issues that extend beyond their critical illness. The current evidence indicates an association between critical illness and poor skeletal outcomes. This includes increased loss of bone mineral density (BMD), increased bone turnover markers (BTMs), increased fracture risk, and an increased rate of fragility fracture compared to matched community controls. This is most pronounced in older female survivors of critical illness.

In collaboration with Assoc Prof Neil Orford, having completed a pilot study to evaluate the safety of anti-resorptive therapies in the ICU setting, we are undertaking a MRFF-funded a randomised, placebo-controlled study to evaluate the safety of treatments that prevent bone loss in the intensive care setting.

Paget’s disease of bone is a skeletal disorder characterised by localised increases in bone cell activity at one or more sites throughout the skeleton. Genetic factors play a key role in this disorder and the most important susceptibility gene is SQSTM1. Mutations of SQSTM1 have been detected in between 40% and 50% of people with a family history of Paget’s disease and up to 15% of those who are unaware of a family history. The Zoledronate in the Prevention of Paget’s disease (ZiPP) study is a large scale study which aims to investigate the acceptability of genetic testing for Paget’s disease, coupled with offer of targeted intervention with zoledronic acid or placebo in SQSTM1 mutation carriers. This study addresses one of the unresolved questions in the management of Paget’s disease, namely, whether early intervention can prevent or delay the onset of complications associated with this disorder and has shown that a single dose of zoledronic acid can prevent the development of clinical Paget’s disease lesion in individuals at high risk.

The CTU has been involved in multiple pivotal trials of new diabetes medications, including DECLARE, SURMOUNT, COMBINE, VERTIS-CV, PIONEER PLUS, and the SURPASS series, which have ushered in a new age of diabetes medications that not only improve glycaemic control, but improve outcomes for weight management, heart health, and kidney health.

Obesity is one of the major risk factors for knee osteoarthritis and cardiovascular disease and weight reduction has shown improvement in clinical outcomes that increases with the amount of weight lost.

The purpose of the studies is to evaluate the effectiveness and safety of a once weekly injection in decreasing body weight and relieving knee pain due to osteoarthritis in participants who have obesity and the impact on cardiovascular events in Type 2 diabetics with Obesity.

These studies are commercially sponsored.

Diabetes is the commonest cause of working-age adult-onset vision loss and current treatments are not fully effective. Recent studies proved a benefit on retinopathy progression with fenofibrate in type 2 diabetes: FIELD, ACCORD Lipid trials, but it has not been studied in type 1 diabetes. This NHMRC sponsored multicentred placebo-conntrolled clinical trial aims to at least 450 participants to evaluate the effects of once daily oral fenofibrate on clinically meaningful diabetic retinopathy progression over at least 3 years in adults with type 1diabetes and existing diabetic retinopathy.

We participate in the ENDIA Study, an NHMRC-funded longitudinal observational study of 1500 babies Australia-wide who have a first degree relative with type 1 diabetes. Participants include:

• Pregnant women with type 1 diabetes
• Men with type 1 diabetes whose partner is pregnant
• Children with type 1 diabetes whose mother is pregnant
• Babies under 6 months of age with a first degree relative (mum, dad, brother or sister) who has type 1 diabetes.

ENDIA researchers are investigating factors that may contribute to the development of islet autoimmunity and type 1 diabetes in children, such as:

• The genes of the participating child and their family member with type 1 diabetes
• The method of delivery (natural birth versus caesarean section)
• The mother’s nutrition during pregnancy and breast feeding
• Exposure to viruses during pregnancy and early life

Identifying the factors that initiate islet autoimmunity in early life could lead to a means of preventing type 1 diabetes before it begins. For more information visit www.endia.org.au.

Congratulations to Barwon Health and Deakin University researchers Pamela Rufus-Membere, Kara Holloway-Kew, Mark Kotowicz and Julie Pasco, whose 2019 Endocrinology publication “Associations Between Bone Impact Microindentation and Clinical Risk Factors for Fracture” has been selected for inclusion in the 2020 Endocrine Society Bone Health Thematic Issue. This special issue is a curated collection of journal articles focused on bone health that were published in 2018–2020.

In this publication, the team establishes that risk factors for fracture are associated with poor bone impact microindentation (BMSi), a way of assessing bone hardness, and would be consistent with BMSi being a valuable for assessing fracture risk.

Described by the Society as a cutting-edge, influential contribution to the endocrine community, this selection recognises the significant impact of the team’s work on osteoporosis research across the world.

• Read the original article here.
• Read more about Mark Kotowicz’s research here.
• Read more about Julie Pasco’s research here.

Congratulations to our research team for two recent awards recognising the impact of their publications on the worldwide research effort into improving patient outcomes.

1. The International Osteoporosis Foundation Award for Publishing Excellence 2019 was awarded to Kara Holloway-Kew et al for the publication: Trabecular bone score in men and women with dysglycaemia. Calcif Tissue Int 2018 Jan;102(1):32-40.
2. The Clinical Endocrinology (Oxford) top downloaded paper 2018-9 was ‘Assessment and management of bone health in women with oestrogen receptor-positive breast cancer receiving endocrine therapy: Position statement of the Endocrine Society of Australia, the Australian and New Zealand Bone & Mineral Society, the Australian Menopause Society and the Clinical Oncology Society of Australia’, co-authored by Mark Kotowicz. Clin Endocrinol (Oxf) 2018: 89(3):280-296

Congratulations to Dr Muhammad Amber Sajjad and Dr Pamela Rufus-Membre, who have been awarded PhDs by publication from Deakin University

Dr Sajjad’s project investigated the use of acute health services in diabetes mellitus, and Dr Rufus-Membre undertook an evaluation of Impact microindentation in men.