The value of whole-body dual-energy x-ray absorptiometry in assessing body composition in patients with inflammatory bowel disease: a prospective study.

OBJECTIVES: Low skeletal muscle index (SMI) is common in inflammatory bowel disease (IBD) but has an uncertain relationship with active intestinal inflammation. This study evaluated body composition by whole-body dual-energy X-ray absorptiometry (DXA) in patients with IBD and healthy controls to enable the value of formal body composition analysis to be judged. METHODS: Patients with IBD and sex/age-matched controls prospectively underwent full body composition assessment by DXA, assessment by BMI, eating questionnaires and handgrip strength. Disease activity was assessed by faecal calprotectin (active ≥150 µg/g). A cohort undergoing biologic induction therapy were assessed at baseline and after ≥13 weeks. RESULTS: Total fat mass was higher in 54 patients with IBD (56% Crohn's disease, 61% male) than in 30 controls (median 25.1 vs. 18.7 kg, P  = 0.042). DXA offered little more than BMI. Low SMI was more common than in controls (15% vs. 0%, P  = 0.027). A normal BMI was seen in many patients with low SMI and handgrip strength was a poor marker of change in SMI. Body composition was similar in 28 patients with active vs. 22 with inactive disease. However, SMI increased specifically by 9.7% ( P  = 0.004) and BMI by 6.4% ( P  = 0.012) in 9 responders to therapy. CONCLUSION: DXA identifies many patients with reduced SMI who are not detected by standard methodologies. While disease activity is not associated with low SMI, resolution of inflammation leads to improved SMI. The potential for recognition of such patients to influence therapeutic decisions underlines the need for DXA assessment in clinical practice.

Accuracy of ultrasound, bioelectrical impedance analysis and anthropometry as point-of-care measurements of skeletal muscle mass in patients with inflammatory bowel disease.

BACKGROUND: Disturbance of skeletal muscle mass has clinically important implications in patients with inflammatory bowel disease (IBD), but accurate quantification requires radiation-intense techniques. AIMS: We aimed to compare point-of-care muscle assessments and their change with therapy with those using reference-standard whole-body dual energy X-ray absorptiometry (DXA). METHODS: Adult patients with IBD and healthy controls underwent prospective assessment of muscularity by ultrasound of the dominant arm and both thighs, bioelectrical impedance analysis (BIA), anthropometric measurements, and DXA. Patients with active IBD were assessed again ≥13 weeks after initiating biologic induction therapy. RESULTS: In 54 patients with IBD and 30 controls, all muscle assessments correlated significantly with DXA-derived skeletal muscle index (SMI). In IBD, ultrasound of the arm and legs had the best agreement with DXA-derived SMI (mean difference 0 kg/m2 , 95% limits of agreement -1.3 to 1.3), while BIA overestimated DXA-derived SMI by 1.07 (-0.16 to +2.30) kg/m2 . In 17 patients who underwent biologic therapy, the percentage change in DXA-derived SMI correlated significantly with the percentage change in all other muscle assessment techniques. Responders (n = 9) increased SMI from baseline to follow-up when derived from DXA (mean 7.8-8.5 kg/m2 , p = 0.004), ultrasound of the arm and legs (300-343 cm2 , p = 0.021) and BIA (9.2-9.6 kg/m2 , p = 0.011). CONCLUSIONS: Ultrasound of the arm and legs out-performed other point-of-care methods in its accuracy of measuring muscle mass. All methods, except mid-arm circumference, were responsive to therapy-induced change. Ultrasound is the preferred non-invasive test for measuring muscle mass in patients with IBD.

Dilemmas in the Management of Osteoporosis in Younger Adults.

Osteoporosis in premenopausal women and men younger than 50 years is challenging to diagnose and treat. There are many barriers to optimal management of osteoporosis in younger adults, further enhanced by a limited research focus on this cohort. Herein we describe dilemmas commonly encountered in diagnosis, investigation, and management of osteoporosis in younger adults. We also provide a suggested framework, based on the limited available evidence and supported by clinical experience, for the diagnosis, assessment, and management of osteoporosis in this cohort. © 2021 The Authors. JBMR Plus published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research.

Challenges in the diagnosis and management of glucocorticoid-induced osteoporosis in younger and older adults.

OBJECTIVE: Glucocorticoids constitute a considerable risk for developing osteoporosis in both younger and older adults. However, currently available bone imaging modalities and fracture-risk assessment tools do not adequately capture the dramatic changes in bone microarchitecture, heterogeneity of glucocorticoid exposure, the impact of chronic disease and other osteoporosis risk factors on the assessment of osteoporosis in these individuals. DESIGN: A narrative review is presented, following a systematic search of the literature from 2000 to 2021. RESULTS: Our current appreciation of glucocorticoid-induced osteoporosis (GIO) is focused on older populations, with limited evidence to guide the investigation, risk assessment and treatment in premenopausal women and men less than 50 years. The impact of the underlying chronic disease on secondary osteoporosis in these younger adults is also poorly understood. CONCLUSION: Through this narrative review, we provide a comprehensive overview of and recommendations for optimising the management of this common cause of secondary osteoporosis younger and older adults.

Primary hyperparathyroidism in adults-(Part II) surgical management and postoperative follow-up: Position statement of the Endocrine Society of Australia, The Australian & New Zealand Endocrine Surgeons, and The Australian & New Zealand Bone and Mineral Society.

OBJECTIVE: To develop evidence-based recommendations to guide the surgical management and postoperative follow-up of adults with primary hyperparathyroidism. METHODS: Representatives from relevant Australian and New Zealand Societies used a systematic approach for adaptation of guidelines (ADAPTE) to derive an evidence-informed position statement addressing eight key questions. RESULTS: Diagnostic imaging does not determine suitability for surgery but can guide the planning of surgery in suitable candidates. First-line imaging includes ultrasound and either parathyroid 4DCT or scintigraphy, depending on local availability and expertise. Minimally invasive parathyroidectomy is appropriate in most patients with concordant imaging. Bilateral neck exploration should be considered in those with discordant/negative imaging findings, multi-gland disease and genetic/familial risk factors. Parathyroid surgery, especially re-operative surgery, has better outcomes in the hands of higher volume surgeons. Neuromonitoring is generally not required for initial surgery but should be considered for re-operative surgery. Following parathyroidectomy, calcium and parathyroid hormone levels should be re-checked in the first 24 h and repeated early if there are risk factors for hypocalcaemia. Eucalcaemia at 6 months is consistent with surgical cure; parathyroid hormone levels do not need to be re-checked in the absence of other clinical indications. Longer-term surveillance of skeletal health is recommended. CONCLUSIONS: This position statement provides up-to-date guidance on evidence-based best practice surgical and postoperative management of adults with primary hyperparathyroidism.

Primary hyperparathyroidism in adults-(Part I) assessment and medical management: Position statement of the endocrine society of Australia, the Australian & New Zealand endocrine surgeons, and the Australian & New Zealand bone and mineral society.

OBJECTIVE: To formulate clinical consensus recommendations on the presentation, assessment, and management of primary hyperparathyroidism (PHPT) in adults. METHODS: Representatives from relevant Australian and New Zealand Societies used a systematic approach for adaptation of guidelines (ADAPTE) to derive an evidence-informed position statement addressing nine key questions. RESULTS: PHPT is a biochemical diagnosis. Serum calcium should be measured in patients with suggestive symptoms, reduced bone mineral density or minimal trauma fractures, and in those with renal stones. Other indications are detailed in the manuscript. In patients with hypercalcaemia, intact parathyroid hormone, 25-hydroxy vitamin D, phosphate, and renal function should be measured. In established PHPT, assessment of bone mineral density, vertebral fractures, urinary tract calculi/nephrocalcinosis and quantification of urinary calcium excretion is warranted. Parathyroidectomy is the only definitive treatment and is warranted for all symptomatic patients and should be considered for asymptomatic patients without contraindications to surgery and with >10 years life expectancy. In patients who do not undergo surgery, we recommend annual evaluation for disease progression. Where the diagnosis is not clear or the risk-benefit ratio is not obvious, multidisciplinary discussion and formulation of a consensus management plan is appropriate. Genetic testing for familial hyperparathyroidism is recommended in selected patients. CONCLUSIONS: These clinical consensus recommendations were developed to provide clinicians with contemporary guidance on the assessment and management of PHPT in adults. It is anticipated that improved health outcomes for individuals and the population will be achieved at a decreased cost to the community.

Models of care for osteoporosis: A systematic scoping review of efficacy and implementation characteristics.

BACKGROUND: Osteoporosis affects over half of adults over 50 years worldwide. With an ageing population, osteoporosis, fractures and their associated costs are increasing. Unfortunately, despite effective therapies, many with osteoporosis remain undiagnosed and untreated. Models of care (MoC) to improve outcomes include fracture liaison services, screening, education, and exercise programs, however efficacy for these is mixed. The aim of this study is to summarise MoC in osteoporosis and describe implementation characteristics and evidence for improving outcomes. METHODS: This systematic scoping review identified articles via Ovid Medline and Embase, published in English between 01/01/2009 and 15/06/2021, describing MoC for adults aged ≥18 years with, or at risk of, osteoporosis and / or health professionals caring for this group. All included at least one of clinical, consumer or clinician outcomes, with fractures and bone mineral density (BMD) change the primary clinical outcomes. Exclusion criteria were studies assessing pharmaceuticals or procedures without other interventions, or insufficient operational details. All study designs were included, with no comparator necessary. Title and abstract were reviewed by two reviewers. Full text review and data extraction was performed by these reviewers for 20% of article and, thereafter by a single author. As the review was predominantly descriptive, no comparator statistics were used. FINDINGS: 314 articles were identified describing 289 MoC with fracture liaison services (n=89) and education programs (n=86) predominating. The population had prior fragility fracture in 77 studies, the median (IQR) patient number was 210 (87, 667) and the median (IQR) follow-up duration for outcome assessment was 12 (6, 12·5) months. Fracture reduction was reported by 65 studies, with 16 (37%) graded as high quality, and 19 / 47 studies with a comparator group found a reduction in fractures. BMD change was reported by 73 studies, with 41 finding improved BMD. Implementation characteristics including reach, fidelity and loss to follow-up were under-reported, and consumer and clinician perspectives rare. INTERPRETATION: This comprehensive review of MoC for osteoporosis demonstrated inconsistent evidence for improving outcomes despite similar types of models. Future studies should include implementation outcomes, consumer and clinician perspectives, and fracture or BMD outcomes with sufficient duration of follow-up. Authors should consider pragmatic trial designs and co-design with clinicians and consumers.

Paediatric and young adult manifestations and outcomes of multiple endocrine neoplasia type 1.

CONTEXT: Multiple endocrine neoplasia 1 (MEN 1) is an autosomal dominant disease presenting as hyperplasia and neoplasia of parathyroid, pituitary and enteropancreatic tissues. Over 90% of gene carriers develop phenotypic disease by age 30 years, potentially with onset of asymptomatic disease during childhood and adolescence. OBJECTIVE: To describe the paediatric and young adult manifestations of MEN 1. DESIGN: Descriptive retrospective study of 180 patients with a common MEN1 genotype. The paediatric and young adult (age <22 years) manifestations were determined using hospital records and disease surveillance data. RESULTS: Primary hyperparathyroidism (PHPT) was identified in 42 patients (mean age 17.2 ± 3.3 years). Parathyroidectomy was performed in 16 (38.1%; mean age 17.8 ± 3.2). Four patients experienced recurrent PHPT (25%), and six (37.5%) developed permanent hypoparathyroidism. Pituitary disease was identified in 13 patients. Prolactinoma was found in nine patients (mean age 16.6 ± 2.6 years) of whom four (44.4%) had macroprolactinoma. Two patients required surgical intervention; dopamine agonists showed efficacy in six patients. Two patients with Cushing's disease were successfully treated surgically. Three patients with nonfunctioning pituitary microadenoma managed conservatively. Pancreatic neuroendocrine neoplasms (pNENs) were diagnosed in 12 patients (mean age 17.0 ± 2.6 years): three patients with insulinoma successfully resected (two resected and one exhibiting perineural invasion) and nine patients with nonfunctioning adenomas (NFAs). CONCLUSION: Pituitary adenomas, PHPT and pNENs are encountered in the paediatric and young adult MEN 1 population. Successful outcomes are typically achieved using standard medical and surgical paradigms; however, parathyroidectomy was associated with a substantial complication rate.

Fracture risk in young and middle-aged adults with type 1 diabetes mellitus: A systematic review and meta-analysis.

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.

Minimal-trauma ankle fractures predominate during pregnancy: a 17-year retrospective study.

This study assessed all fractures occurring in pregnancy at a tertiary referral centre over a 17-year period. Most fractures were due to minimal trauma, and those involving the ankle were the most common. Women tended to fracture during their second and third trimesters and most required surgical intervention during pregnancy. PURPOSE: To characterise fractures in pregnancy over a 17-year period at a tertiary referral health service. METHODS: Medical records at the Monash Health in Australia were examined from 2000-2016 for fractures in pregnancy using the birthing outcome system database and the tenth revision of the International Statistical Classification of Diseases and Related Health Problems coding. Site, mechanism, investigations, management and outcomes were documented. RESULTS: Of the 114,673 live births during this period, 33 women (mean age 30.3 ± 1.9 years) were identified with fracture in pregnancy (~ 2.9 maternal fractures/10,000 live births). Minimal-trauma fractures (MTFs) occurred in 28 women whilst 5 were due to motor vehicle accidents. Of the MTF, 2/28 (7.1%), 13/28 (46.4%) and 13/28 (46.4%) occurred in the first, second and third trimesters, respectively. MTF involved the lower limb (60.7%), upper limb (25.0%), ribs (10.7%) and clavicle (3.6%). The ankle was involved in 39.3% of MTFs. Diabetes (14.3%), asthma (10.7%) and thyroid dysfunction (7.1%) affected these women with MTF; vitamin D levels were not routinely measured. Surgical interventions requiring anaesthesia were required in 57.1% with MTF: 50.0% during their second, 31.3% in their third and 12.5% in their first trimesters; 6.3% had surgery post partum. Pre-term birth and emergency caesarean section complicated 6/28 (21.4%) of MTF pregnancies. One patient received post-partum bisphosphonate therapy; only two 2/32 (6.25%) received medical follow-up. CONCLUSIONS: Fractures in pregnancy are uncommon. Lower limb fractures are frequently due to minimal trauma, and surgical intervention is often required. The low rate of medical follow-up in MTF is of concern and reinforces the need for greater recognition of potential osteoporosis in this population.