Melbourne Medical School Collected Works - Research Publications
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ItemIncreased prevalence of fracture and hypoglycaemia in young adults with concomitant type 1 diabetes mellitus and coeliac disease.(Wiley, 2018-01)BACKGROUND: Both Type 1 diabetes mellitus (T1DM) and coeliac disease (CD) are independently associated with reduced bone mineral density (BMD) and increased fracture risk. Whilst poorer glycaemic control and increased microvascular complications have been described, the literature examining bone health and fractures in adults with concomitant T1DM and CD (T1DM + CD) is limited. OBJECTIVE: To evaluate fracture prevalence and explore associations with glycaemic control, hypoglycaemia and microvascular disease in T1DM + CD compared with T1DM alone. METHODS: We conducted a retrospective cross-sectional study of young adults with T1DM, who attended diabetes clinics at a large tertiary referral centre between August 2016 and February 2017. Clinical information, radiological and biochemistry results were extracted from medical records. Patients with comorbid chronic kidney disease, glucocorticoid use, hypogonadism and untreated hyperthyroidism were excluded. RESULTS: A total of 346 patients with T1DM alone (median age 23 years) and 49 patients with T1DM + CD (median age 24 years) were included. Median age, gender distribution, BMI, haemoglobin A1c, daily insulin dose and serum 25-hydroxyvitamin D levels were similar between groups. Higher adjusted fracture risk was observed in T1DM + CD compared with T1DM (12.2% vs 3.5%; OR 3.50, 95% CI 1.01-12.12, P = .01), yet BMD was only measured in 6% of patients. The adjusted risk of hypoglycaemia ≥2/week was greater for T1DM + CD (55% vs 38%, OR 3.28, 95% CI 1.61-6.69, P = .001); however, this was not independently associated with fractures. Replete vitamin D (≥ 50 nmol/L) was associated with less hypoglycaemia (OR 0.48, 95% CI 0.29-0.80; P = .005), but not with fractures. CONCLUSIONS: Coeliac disease status was independently associated with increased fracture prevalence in young adults with T1DM. Recurrent hypoglycaemia was also increased in T1DM + CD, although hypoglycaemia was not independently associated with fractures. Prospective studies are required to determine the long-term impacts of CD on bone health and glycaemic control in patients with T1DM.
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ItemLower muscle tissue is associated with higher pulse wave velocity: A systematic review and meta-analysis of observational study data(WILEY, 2017-10-01)Muscle loss and arterial stiffness share common risk factors and are commonly seen in the elderly. We aimed to synthesise the existing literature on studies that have examined this association. We searched electronic databases for studies reporting correlations or associations between a measure of muscle tissue and a measure of arterial stiffness. Meta-analysis was conducted using Fisher's Z-transformed r-correlation (rZ ) values. Pooled weighted rZ and 95% confidence intervals were calculated in an inverse-variance, random-effects model. Heterogeneity was assessed by the inconsistency index (I2 ). Study quality was assessed on a checklist using items from validated quality appraisal guidelines. 1195 records identified, 21 satisfied our inclusion criteria totalling 8558 participants with mean age 52±4 years (range 23-74). Most studies reported an inverse relationship between muscle tissue and arterial stiffness. Eight studies had data eligible for meta-analysis. Muscle tissue was inversely associated with pulse wave velocity in healthy individuals [rZ =-.15 (95% CI -0.24, -0.07); P=.0006; I2 =85%; n=3577] and in any population [rZ =-.18 (-0.26, -0.10); P<.0001; I2 =81%; n=3930]. In a leave-one-out sensitivity analysis, the results remained unchanged. Lower muscle tissue was associated with arterial stiffness. Studies were limited by cross-sectional design. Cardiovascular risk monitoring may be strengthened by screening for low muscle mass and maintaining muscle mass may be a primary prevention strategy.
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ItemSerum phosphorus levels and fracture following renal transplantation.(Wiley, 2017-08)PURPOSE: Increased fracture rates are observed in renal transplant recipients (RTRs) compared with the general population. Risk factors include age, diabetes, dialysis vintage, immunosuppression and mineral and bone disorders.1 Low serum phosphorus levels occur post-transplantation; however, its relationship with fracture risk has not been evaluated. The purpose of this study was to evaluate risk factors for fracture in RTRs at a single tertiary referral centre. METHODS: A retrospective cross-sectional analysis of 146 patients (75 M, 71 F) who had been referred for dual energy X-ray densitometry (DXA) post-renal transplantation was performed. Aetiology of end stage kidney disease (ESKD), duration of dialysis, parathyroidectomy history, immunosuppression regimen, bone mineral density (BMD), biochemistry and fractures were documented. Statistical analyses included univariable and multivariable regression. RESULTS: The mean age of patients was 54 years and mean time post-transplantation 6.7 years. A total of 79 fractures occurred in 52 patients (35%), with 40 fractures occurring post-transplantation. Ankle/foot fractures were most common (48%). Lower serum phosphorus levels and declining femoral neck (FN) T-score and were associated with fractures in both univariable and multivariable regression analyses after adjusting for age, gender, weight, estimated glomerular filtration rate and pre-transplant history of fracture (P=.011 and P=.042 respectively). The relationship between serum phosphorus and fracture remained significant independent of FN T-score, parathyroid hormone levels, parathyroidectomy status and prednisolone use. CONCLUSION: Fracture was common post-renal transplantation. Lower serum phosphorus levels and declining FN T-scores were associated with fractures. The mechanism of this previously unreported observation requires further evaluation in prospective studies.
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ItemManagement of mineral and bone disorders in renal transplant recipients.(Wiley, 2017-03)The management of post-transplantation bone disease is a complex problem that remains under-appreciated in clinical practice. In these patients, pre-existing metabolic bone disorder is further impacted by the use of immunosuppressive medications (glucocorticoids and calcineurin-inhibitors), variable post-transplantation renal allograft function and post-transplantation diabetes mellitus. The treatment of post-transplantation bone loss should begin pre-transplantation. All patients active on transplant waiting lists should be screened for bone disease. Patients should also be encouraged to take preventative measures against osteoporosis such as regular weight-bearing exercise, smoking cessation and reducing alcohol consumption. Biochemical abnormalities of disordered mineral metabolism should be corrected prior to transplantation wherever possible, and because these abnormalities commonly persist, post transplant hypophosphatemia, persistent hyperparathyroidism and low vitamin D levels should be regularly monitored and treated. Bone loss is greatest in the first 6-12 months post-transplantation, during which period any intervention is likely to be of greatest benefit. There is strong evidence that bisphosphonates prevent post-transplantation bone loss; however, data are lacking that this clearly extends to a reduction in fracture incidence. Denosumab is a potential alternative to vitamin D receptor agonists and bisphosphonates in reducing post-transplantation bone loss; however, further studies are needed to demonstrate its safety in patients with a significantly reduced estimated glomerular filtration rate. Clinical judgement remains the cornerstone of this complex clinical problem, providing a strong rationale for the formation of combined endocrinology and nephrology clinics to treat patients with Chronic Kidney Disease-Mineral and Bone Disorder, before and after transplantation.
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ItemThe Birth of JBMR Plus.(Wiley, 2017-02)
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ItemSelf-Reported Changes in Sun-Protection Behaviors at Different Latitudes in Australia(WILEY, 2016-05-01)Sun exposure is the most important source of vitamin D, but is also a risk factor for skin cancer. This study investigated attitudes toward vitamin D, and changes in sun-exposure behavior due to concern about adequate vitamin D. Participants (n = 1002) were recruited from four regions of Australia and completed self- and interviewer-administered surveys. Chi-square tests were used to assess associations between participants' latitude of residence, vitamin D-related attitudes and changes in sun-exposure behaviors during the last summer. Multivariate logistic regression analyses were used to model the association between attitudes and behaviors. Overall, people who worried about their vitamin D status were more likely to have altered sun protection and spent more time in the sun people not concerned about vitamin D. Concern about vitamin D was also more common with increasing latitude. Use of novel item response theory analysis highlighted the potential impact of self-reported behavior change on skin cancer predisposition due concern to vitamin. This cross-sectional study shows that the strongest determinants of self-reported sun-protection behavior changes due to concerns about vitamin D were attitudes and location, with people at higher latitudes worrying more.
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ItemFracture risk in young and middle-aged adults with type 1 diabetes mellitus: A systematic review and meta-analysis.(Wiley, 2018-09)BACKGROUND: Type 1 diabetes mellitus (T1DM) is associated with skeletal fragility. While previous meta-analyses have demonstrated an increased risk of fracture in individuals with T1DM, little is known about fracture risk in T1DM, in the absence of age-related confounders. AIMS: To determine the risk of fracture in young and middle-aged adults with T1DM aged 18-50 years old. DESIGN: Systematic review and meta-analysis. DATA SOURCES: Ovid MEDLINE, PubMed, EMBASE, EBM reviews and relevant conference abstracts. STUDY INCLUSION CRITERIA: Studies of adults aged between 18-50 years with type 1 diabetes mellitus, with reported fracture outcomes. PRIMARY OUTCOMES: Incident or prevalent fracture. RESULTS: Six studies were included in the meta-analysis. A total of 1724 fractures occurred in 35 925 patients with T1DM and 48 253 fractures occurred in 2 455 016 controls. RR for all fractures was 1.88 (95% CI 1.52-2.32, P < .001). Fifty-six hip fractures occurred among 34 707 patients with T1DM and 594 hip fractures occurred in 2 295 177 controls. The RR of hip fractures was 4.40 (95% CI 2.58-7.50, P < .001). Females and males with T1DM had a RR of 5.79 (95% CI 3.55-9.44, P < .001) and 3.67 (95% CI 2.10-6.41, P < .001), respectively. CONCLUSIONS: In the absence of age-related comorbidities, fracture risk remains significantly elevated in young and middle-aged adults with T1DM. Younger age does not mitigate against hip fracture risk in T1DM, and health professionals need to be aware of this risk. Further studies are needed to evaluate the mechanisms of fracture in T1DM.
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ItemThe prevalence of sarcopenia and relationships between muscle and bone in ageing West-African Gambian men and women.(Wiley, 2018-10)BACKGROUND: The rapidly rising ageing population in low and middle-income countries (LMIC) will lead to a concurrent increase in musculoskeletal diseases. Sarcopenia is a disease caused by progressive loss of skeletal muscle mass and strength, leading to adverse outcomes including frailty, falls, fractures, and premature mortality. We investigated the prevalence of sarcopenia, assessed the suitability of current diagnostic guidelines and explored muscle-bone relationships in ageing men and women from rural Gambia. METHODS: A total of 249 women and 239 men aged 40-75+ years were recruited. Body composition was measured using dual energy X-ray absorptiometry. Comparisons of the Foundations for the National Institutes of Health (FNIH) and European Working Group On Sarcopenia (EWGSOP) definitions of sarcopenia to define prevalence and to identify poor physical capability were determined. Functional ability was assessed by jumping mechanography to calculate lower limb muscle force and power; grip strength was assessed by a hand dynamometer. Peripheral quantitative computed tomography was used to assess muscle-bone relationships. RESULTS: The prevalence of sarcopenia in Gambian men and women significantly varied depending on the definition used; in men 20% and 19% and in women 45% and 10% for FNIH and EWGSOP, respectively. The FNIH appendicular lean mass cut-off had greatest sensitivity and specificity in identifying low functional ability in Gambian adults. Muscle force was positively associated with measures of tibial bone size, strength, and mineral content. CONCLUSIONS: The variation in the prevalence of sarcopenia depends on the definition used and highlights the importance of measuring functional capability across ethnic populations.