Osteopaenia - a marker of low bone mass and fracture risk

Areal bone mineral density is commonly categorised into normal bone mineral density, osteopaenia and osteoporosis on the basis of nominal thresholds recommended by the World Health Organization. However, bone mineral density is a continuous variable and there is a strong association between lower bone mineral density and greater risk for fracture. Fracture risk is not negligible in persons with moderate deficits in bone mineral density. Although absolute fracture risk is greatest for individuals with osteoporosis, more than half of the fractures arise from those with osteopaenia, and even normal bone mineral density, a probable consequence of greater numbers of individuals at risk in these categories. However, areal bone mineral density measurements used commonly in clinical practice do not detect differences in bone tissue properties, geometry and microarchitecture, which contribute to bone strength. Newer technologies such as high-resolution peripheral computed tomography have the advantage of assessing trabecular and cortical components of bone separately, in addition to geometric characteristics of the skeleton. Quantifying these parameters and considering clinical risk factors that affect fracture risk independent of bone quantity and quality, may better discriminate between high- and low-risk individuals. This would improve the decision-making for targeting appropriate interventions, either lifestyle or medication, to reduce thepublic health burden of fractures

Reference Intervals for bone impact microindentation in healthy adults: a multi-centre international study

Impact microindentation (IMI) is a novel technique for assessing bone material strength index (BMSi) in vivo, by measuring the depth of a micron-sized, spherical tip into cortical bone that is then indexed to the depth of the tip into a reference material. The aim of this study was to define the reference intervals for men and women by evaluating healthy adults from the United States of America, Europe and Australia. Participants included community-based volunteers and participants drawn from clinical and population-based studies. BMSi was measured on the tibial diaphysis using an OsteoProbe in 479 healthy adults (197 male and 282 female, ages 25 to 98 years) across seven research centres, between 2011 and 2018. Associations between BMSi, age, sex and areal bone mineral density (BMD) were examined following an a posteriori method. Unitless BMSi values ranged from 48 to 101. The mean (+/- standard deviation) BMSi for men was 84.4 +/- 6.9 and for women, 79.0 +/- 9.1. Healthy reference intervals for BMSi were identified as 71.0 to 97.9 for men and 59.8 to 95.2 for women. This study provides healthy reference data that can be used to calculate T- and Z-scores for BMSi and assist in determining the utility of BMSi in fracture prediction. These data will be useful for positioning individuals within the population and for identifying those with BMSi at the extremes of the population.Metabolic health: pathophysiological trajectories and therap

Revision joint replacement surgeries of the hip and knee across geographic region and socioeconomic status in the western region of Victoria: a cross-sectional multilevel analysis of registry data

Background: Residents of rural and regional areas, compared to those in urban regions, are more likely to experience geographical difficulties in accessing healthcare, particularly specialist services. We investigated associations between region of residence, socioeconomic status (SES) and utilisation of all-cause revision hip replacement or revision knee replacement surgeries. Methods: Conducted in western Victoria, Australia, as part of the Ageing, Chronic Disease and Injury study, data from the Australian Orthopaedic Association National Joint Replacement Registry (2011–2013) for adults who underwent a revision hip replacement (n = 542; 54% female) or revision knee replacement (n = 353; 54% female) were extracted. We cross-matched residential addresses with 2011 census data from the Australian Bureau of Statistics (ABS), and using an ABS-derived composite index, classified region of residence according to local government areas (LGAs), and area-level SES into quintiles. For analyses, the control population (n = 591,265; 51% female) was ABS-determined and excluded adults already identified as cases. Mixed-effects logistic regression was performed. Results: We observed that 77% of revision hip surgeries and 83% of revision knee surgeries were performed for residents in the three most socially disadvantaged quintiles. In adjusted multilevel models, total variances contributed by the variance in LGAs for revisions of the hip or knee joint were only 1% (SD random effects ±0.01) and 3% (SD ± 0.02), respectively. No differences across SES or sex were observed. Conclusions: No differences in utilisation were identified between SES groups in the provision of revision surgeries of the hip or knee, independent of small between-LGA differences.Sharon L. Brennan-Olsen, Sara Vogrin, Stephen Graves, Kara L. Holloway-Kew, Richard S. Page, M. Amber Sajjad, Mark A. Kotowicz, Patricia M. Livingston, Mustafa Khasraw, Sharon Hakkennes, Trisha L. Dunning, Susan Brumby, Alasdair G. Sutherland, Jason Talevski, Darci Green, Thu-Lan Kelly, Lana J. Williams, and Julie A. Pasc

Associations Between Aldosterone-Renin-Ratio and Bone Parameters Derived from Peripheral Quantitative Computed Tomography and Impact Microindentation in Men

OnlinePublComponents of the renin-angiotensin-aldosterone system (RAAS) are present on bone cells. One measure of RAAS activity, the aldosterone-renin-ratio (ARR), is used to screen for primary aldosteronism. Associations between ARR and bone mineral density are conflicting. This study investigated associations between ARR and peripheral quantitative computed tomography (pQCT) and impact microindentation (IMI). Male participants (n = 431) were from the Geelong Osteoporosis Study. "Likely" primary aldosteronism was defined as ARR ≥ 70 pmol/mIU. Another group, "possible" primary aldosteronism, was defined as either ARR ≥ 70 pmol/mIU or taking a medication that affects the RAAS, but not a beta blocker, and renin  0.05). There were no associations between ARR or aldosterone and pQCT-derived bone parameters. Men with likely primary aldosteronism had lower bone area, suggesting clinically high levels of ARR may have a negative impact on bone health.Kara L. Holloway-Kew, Kara B. Anderson, Pamela Rufus, Membere, Monica C. Tembo, Sophia X. Sui, Natalie K. Hyde, Mark A. Kotowicz, Stella M. Gwini, Jun Yang, Adolfo Diez, Perez, Maciej Henneberg, Wan, Hui Liao, Julie A. Pasc

Zoledronate in the prevention of Paget's (ZiPP) : protocol for a randomised trial of genetic testing and targeted zoledronic acid therapy to prevent SQSTM1-mediated Paget's disease of bone.

Introduction Paget’s disease of bone (PDB) is characterised by increased and disorganised bone remodelling affecting one or more skeletal sites. Complications include bone pain, deformity, deafness and pathological fractures. Mutations in sequestosome-1 (SQSTM1) are strongly associated with the development of PDB. Bisphosphonate therapy can improve bone pain in PDB, but there is no evidence that treatment alters the natural history of PDB or prevents complications. The Zoledronate in the Prevention of Paget’s disease trial (ZiPP) will determine if prophylactic therapy with the bisphosphonate zoledronic acid (ZA) can delay or prevent the development of PDB in people who carry SQSTM1 mutations. Methods and analysis People with a family history of PDB aged >30 years who test positive for SQSTM1 mutations are eligible to take part. At the baseline visit, participants will be screened for the presence of bone lesions by radionuclide bone scan. Biochemical markers of bone turnover will be measured and questionnaires completed to assess pain, health-related quality of life (HRQoL), anxiety and depression. Participants will be randomised to receive a single intravenous infusion of 5 mg ZA or placebo and followed up annually for between 4 and 8 years at which point baseline assessments will be repeated. The primary endpoint will be new bone lesions assessed by radionuclide bone scan. Secondary endpoints will include changes in biochemical markers of bone turnover, pain, HRQoL, anxiety, depression and PDB-related skeletal events

Trabecular Bone Score in Men and Women with Impaired Fasting Glucose and Diabetes.

Diabetes is associated with increased skeletal fragility, despite higher bone mineral density (BMD). Alternative measures are necessary to more accurately determine fracture risk in individuals with diabetes. Therefore, we aimed to describe the relationship between trabecular bone score (TBS) and normoglycaemia, impaired fasting glucose (IFG) and diabetes and determine whether TBS-adjusted FRAX (Aus) score differed between these groups. This study included 555 men (68.7 ± 12.2 years) and 514 women (62.0 ± 12.0 years), enrolled in the observational Geelong Osteoporosis Study. IFG was considered as fasting plasma glucose (FPG) ≥ 5.5 mmol/L and diabetes as FPG ≥ 7.0 mmol/L, with the use of antihyperglycaemic medication and/or self-report. Using multivariable regression, the relationship between groups and TBS was determined. Men and women (all ages) with diabetes had lower mean TBS compared to those with normoglycaemia, in models adjusted for age, height and weight/waist circumference (all p < 0.05). Men with IFG had lower mean TBS in the age-adjusted models only (all p < 0.05). The addition of TBS to the FRAX score improved the discrimination between glycaemia groups, particularly for younger women (< 65 years). There was no difference in TBS detected between normoglycaemia and IFG; however, those with diabetes had lower TBS. Thus, the increased fracture risk in men and women with diabetes may be a result of BMD-independent bone deterioration. TBS adjustment of FRAX scores may be useful for younger women (< 65 years) with diabetes. This suggests that halting or reversing progression from IFG to diabetes could be important to prevent skeletal fragility in diabetes

Is trabecular bone score less affected by degenerative-changes at the spine than lumbar spine BMD?

It has been established that degenerative-changes at the spine elevate bone mineral density at the lumbar spine. This study in men reports that trabecular bone score may be less affected by spinal degenerative-changes. A recent tool for assessing trabecular microarchitecture at the lumbar spine, trabecular bone score (TBS), provides information about bone health complementary to lumbar spine areal BMD (here referred to as BMD). In men, mean BMD increases with increasing age due to degenerative-changes at the spine including osteophytes and aortic calcification. The aim of this study was to investigate whether TBS is similarly affected by the presence of degenerative-changes in men. This study included 728 men aged 40-90 years enrolled in the Geelong Osteoporosis Study. Lumbar spine DXA scans (Lunar Prodigy) were used to determine TBS retrospectively (TBS iNsight software, Version 2.2), and for identification of degenerative-changes. Using multivariable regression techniques, the relationships between TBS or BMD and degenerative-changes were assessed, further adjusting for age and weight. The difference between each of the two methods was examined through testing interactions between method, degenerative-changes and age. Of 728 men, 439 (60.3%) were identified as having one or more degenerative-changes at the lumbar spine. Adjusted mean TBS was 1.219 (1.203-1.232) and 1.196 (1.179-1.212) for those with and without degenerative-changes, respectively. Adjusted mean BMD was 1.317 g/cm <sup>2</sup> (1.297-1.336) and 1.198 g/cm <sup>2</sup> (1.173-1.223) for those with and without degenerative-changes, respectively. Partial r <sup>2</sup> for degenerative-changes in the model for TBS was 0.076 and for BMD, 0.257 (both p < 0.05). The three-way interaction between method, degenerative-changes and age was significant (p = 0.05) indicating significant effect of artefacts on the standardised values, affected by age and method. This study suggests that TBS is less affected by degenerative-changes at the spine than is BMD. Thus, TBS may prove useful in the assessment of fracture risk in men with degenerative-changes at the spine

Physical and lifestyle factors associated with trabecular bone score values.

TBS is associated with age, weight, childhood physical activity, and BMD in men and age, height, BMD, and mobility in women. Trabecular bone score (TBS) indirectly assesses trabecular microarchitecture at the lumbar spine, providing complementary information to areal BMD. Many studies have investigated the relationships between BMD and lifestyle factors known to affect bone, but such research is limited for TBS. The aim of this study was to assess the relationship between TBS and lifestyle factors in Australian men and women. This cross-sectional study involved 894 men and 682 women (ages 24-98 years) enrolled in the Geelong Osteoporosis Study. TBS was assessed by analysis of lumbar spine DXA scans (Lunar Prodigy) using TBS iNsight software (Version 2.2). Bivariate and multivariable linear regression models were used to explore the associations between TBS and physical and lifestyle factors, including anthropometry, alcohol consumption, childhood physical activity, mobility, smoking status, prior low trauma fracture, medication use, and intakes of calcium and vitamin D. In bivariate regression modelling, low mobility and the use of antiresorptive medication were associated with lower TBS in both men and women. Low childhood physical activity was also associated with lower TBS in men. Prior fracture, use of glucocorticosteroids, and total calcium intake were also associated with lower TBS in women. The final adjusted model for men included age, weight, childhood physical activity, and BMD, and for women, age, height, BMD, and mobility. No interaction terms were identified in the models. Lower TBS is associated with older age, increased weight, low childhood physical activity, and lower BMD in men and older age, shorter stature, lower BMD, and low mobility in women