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

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

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

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

Reference Ranges for Trabecular Bone Score in Australian Men and Women: A Cross-Sectional Study.

Trabecular bone score (TBS) is a novel method for indirectly assessing trabecular microarchitecture at the lumbar spine, providing information complementary to areal BMD. However, limited reference ranges exist for the normative distribution of TBS, particularly in men. The aim of this study was to develop such a reference range in Australian men and women. This study included 894 men and 682 women (aged 24 to 98 years) enrolled in the Geelong Osteoporosis Study. TBS was determined retrospectively by analysis of lumbar spine DXA scans (Lunar Prodigy) using TBS iNsight software (version 2.2). Multivariable regression techniques were used to determine best-fit models for TBS incorporating age, height, and weight. Age-related differences in TBS were best modelled with a linear relationship in men and a cubic relationship in women. Combined best-fit models for TBS included age and weight in men, and age and height in women. This study provides normative reference ranges for TBS in Australian men and women, and further indicates that TBS may identify individuals at risk for fracture despite normal BMD. © 2018 The Authors. JBMR Plus Published by Wiley Periodicals, Inc. on behalf of the American Society for Bone and Mineral Research

Fracture Risk and Use of Angiotensin-Converting Enzyme Inhibitors or Angiotensin II Receptor Blockers

Published online: 14 July 2022Medications used to treat hypertension may affect fracture risk. This study investigated fracture risk for users of angiotensin converting enzyme inhibitors (ACEI) or angiotensin II receptor blockers (ARB). Participants (899 men, median age 70.3 yr (59.9–79.1), range 50.0–96.6 yr; 574 women, median age 65.5 yr (58.1–75.4), range 50.1–94.6 yr) were from the Geelong Osteoporosis Study. Medication use was self-reported and incident fractures were ascertained using radiological reports. Bone mineral density (BMD) was measured at the femoral neck. Participants were divided into four groups: (1) non-users without hypertension, (2) non-users with hypertension, (3) ACEI users and (4) ARB users. Dosage was calculated using the defined daily dose (DDD) criteria. Participants were followed from date of visit to first fracture, death or 31 December 2016, whichever occurred first. Cox proportional hazards models were used for analyses. At least one incident fracture was sustained by 156 men and 135 women over a median(IQR) of 11.5(6.2–13.2) and 10.9(6.3–11.6) years of follow-up, respectively. In unadjusted analyses, compared to non-users without hypertension, men in all three other groups had a higher risk of fracture (Hazard Ratio (HR, 95%CI) 1.54, 1.00–2.37; 1.90, 1.18–3.05; 2.15, 1.26–3.66), for non-users with hypertension, ACEI and ARB users, respectively). Following adjustment for age, prior fracture and BMD, these associations became nonsignificant. A dose effect for ARB use was observed; men using lower doses had a higher risk of fracture than non-users without hypertension, in both unadjusted (2.66, 1.34–5.29) and adjusted (2.03, 1.01–4.08) analyses, but this association was not observed at higher doses. For women, unadjusted analyses showed a higher risk for ACEI users compared to non-users without hypertension (1.74, 1.07–2.83). This was explained after adjustment for age, alcohol consumption, prior fracture and BMD (1.28, 0.74–2.22). No other differences were observed. In men, lower dose (0 < DDD ≤ 1) ARB use was associated with an increased risk of fracture. ACEI or ARB use was not associated with increased risk of incident fracture in women. These findings may be important for antihypertensive treatment decisions in individuals with a high risk of fracture.Kara L. Holloway, Kew, Amelia G. Betson, Kara B. Anderson, Filip Sepetavc, James Gaston, Mark A. Kotowicz, Wan, Hui Liao, Maciej Henneberg, Julie A. Pasc

How well do the FRAX (Australia) and Garvan calculators predict incident fractures? Data from the Geelong Osteoporosis Study.

This study reports that both FRAX and Garvan calculators underestimated fractures in Australian men and women, particularly in those with osteopenia or osteoporosis. Major osteoporotic fractures were poorly predicted, while both calculators performed acceptably well for hip fractures. This study assessed the ability of the FRAX (Australia) and Garvan calculators to predict fractures in Australian women and men. Women (n = 809) and men (n = 821) aged 50-90 years, enrolled in the Geelong Osteoporosis Study, were included. Fracture risk was estimated using FRAX and Garvan calculators with and without femoral neck bone mineral density (BMD) (FRAX &lt;sub&gt;BMD&lt;/sub&gt; , FRAX &lt;sub&gt;noBMD&lt;/sub&gt; , Garvan &lt;sub&gt;BMD&lt;/sub&gt; , Garvan &lt;sub&gt;noBMD&lt;/sub&gt; ). Incident major osteoporotic (MOF), fragility, and hip fractures over the following 10 years were verified radiologically. Differences between observed and predicted numbers of fractures were assessed using a chi-squared test. Diagnostics indexes were calculated. In women, 115 MOF, 184 fragility, and 42 hip fractures occurred. For men, there were 73, 109, and 17 fractures, respectively. FRAX underestimated MOFs, regardless of sex or inclusion of BMD. FRAX accurately predicted hip fractures, except in women with BMD (20 predicted, p = 0.004). Garvan underestimated fragility fractures except in men using BMD (88 predicted, p = 0.109). Garvan accurately predicted hip fractures except for women without BMD (12 predicted, p &lt; 0.001). Fractures were underestimated primarily in the osteopenia and osteoporosis groups; MOFs in the normal BMD group were only underestimated by FRAX &lt;sub&gt;BMD&lt;/sub&gt; and fragility fractures by Garvan &lt;sub&gt;noBMD&lt;/sub&gt; , both in men. AUROCs were not different between scores with and without BMD, except for fragility fractures predicted by Garvan in women (0.696, 95% CI 0.652-0.739 and 0.668, 0.623-0.712, respectively, p = 0.008) and men, which almost reached significance (0.683, 0.631-0.734, and 0.667, 0.615-0.719, respectively, p = 0.051). Analyses of sensitivity and specificity showed overall that MOFs and fragility fractures were poorly predicted by both FRAX and Garvan, while hip fractures were acceptably predicted. Overall, the FRAX and Garvan calculators underestimated MOF and fragility fractures, particularly in individuals with osteopenia or osteoporosis. Hip fractures were predicted better by both calculators. AUROC analyses suggest that Garvan &lt;sub&gt;BMD&lt;/sub&gt; performed better than Garvan &lt;sub&gt;noBMD&lt;/sub&gt; for prediction of fragility fractures