Reasons for referral to bone densitometry in men and women aged 20-49 years : population-based data

Introduction Osteoporosis poses a significant public health problem for ageing Australians. However, approximately 25 % of Australian adults aged 20–49 years have osteopenia, a precursor condition to osteoporosis. Despite this, little is known about bone density testing in this age group.

Methods Reasons for referral to dual energy X-ray absorptiometry (DXA) were examined in 2,264 patients aged 20–49 years, referred in 2001–2010 to the Geelong Bone Densitometry Service, Geelong Hospital, Victoria. Referral reasons were determined from clinical indication codes derived from patient records. Age, sex and bone mineral density (BMD) T scores were ascertained for each patient.

Results The most common reason for referral for women reflected glucocorticoid use, and for men reflected fracture. Compared to women, men were more likely to have been referred because of minimal trauma fracture or low BMD (41.7 versus 27.1 %, p < 0.001). No further differences were identified between the sexes, with similar numbers of referral observed for secondary osteoporosis, and monitoring of drug therapy. At the spine, and for all indications, men had a significantly greater BMD deficit compared to women (all p ≤ 0.002). After age adjustment, men who were tested due to fracture or glucocorticoid reasons had significantly greater BMD at the total hip (p ≤ 0.03). No further associations were seen after age adjustment between referral reason and BMD.

Conclusions Our study presents the first data examining reasons for referral to DXA among Australians aged 20–49 years. Understanding health service utilisation regarding bone health in young adults is fundamental to understanding future risk, informing effective public health messages and raising awareness of osteoporosis.

MMP2 and MMP9 plasma levels as markers of bone remodeling : a study on young male tennis players

Introduction
Our goal is to study the effects of tennis practice in pre-pubescent boys on bone remodeling, by means of enzyme activity involved in balance of matrix remodeling (MMP2 and MMP9).
Results
Mineral bone density has been found higher in the dominant arm (P < 0.0001) as well as MMP2 and MMP9 levels in plasma (P < 0.05).
Conclusion
Tennis practice in children increases bone remodeling, which can be assessed by MMP dosage, in addition of densitometry technique.

Peripheral quantitative computed tomography in children and adolescents : the 2007 ISCD pediatric official positions

Peripheral quantitative computed tomography (pQCT) has mainly been used as a research tool in children. To evaluate the clinical utility of pQCT and formulate recommendations for its use in children, the International Society
of Clinical Densitometry (ISCD) convened a task force to review the literature and propose areas of consensus and future research. The types of pQCT technology available, the clinical application of pQCT for bone health assessment in children, the important elements to be included in a pQCT report, and quality control monitoring techniques were evaluated. The review revealed a lack of standardization of pQCT techniques, and a paucity of data regarding differences between pQCT manufacturers, models and software versions and their impact in pediatric assessment. Measurement sites varied across studies. Adequate reference data, a critical element for interpretation of pQCT results, were entirely lacking, although some comparative data on healthy children were available. The elements of the
pQCT clinical report and quality control procedures are similar to those recommended for dual-energy X-ray absorptiometry. Future research is needed to establish evidence-based criteria for the selection of the measurement site, scan acquisition and analysis parameters, and outcome measures. Reference data that sufficiently characterize the normal range of variability in the population also need to be established.

Cortical and trabecular bone at the forearm show different adaptation patterns in response to tennis playing

Bone responds to impact-loading activity by increasing its size and/or density. The aim of this study was to compare the magnitude and modality of the bone response between cortical and trabecular bone in the forearms of tennis players. Bone area, bone mineral content (BMC), and bone mineral density (BMD) of the ulna and radius were measured by dual-energy X-ray absorptiometry (DXA) in 57 players (24.5 ± 5.7 yr old), at three sites: the ultradistal region (50% trabecular bone), the mid-distal regions, and third-distal (mainly cortical bone). At the ultradistal radius, the side-to-side difference in BMD was larger than in bone area (8.4 ± 5.2% and 4.9 ± 4.0%, respectively, p < 0.01). In the cortical sites, the asymmetry was lower (p < 0.01) in BMD than in bone area (mid-distal radius: 4.0 ± 4.3% vs 11.7 ± 6.8%; third-distal radius: 5.0 ± 4.8% vs 8.4 ± 6.2%). The asymmetry in bone area explained 33% of the variance of the asymmetry in BMC at the ultradistal radius, 66% at the mid-distal radius, and 53% at the third-distal radius. The ulna displayed similar results. Cortical and trabecular bone seem to respond differently to mechanical loading. The first one mainly increases its size, whereas the second one preferentially increases its density.

Determination of human body composition

This thesis deals with two electrical methods designed to enable rapid, safe and noninvasive measurement of body composition, both for clinical and community use. The first section provides a review of the literature related to measurement of body composition in humans and outlines the approach of the research project. The second section deals with established methods of determining body composition, the two most important being hydrostatic densitometry and deuterium oxide dilution. In this part of the report, a novel method for measuring lung volume by hydrogen dilution at the time of underwater weighing is described. The main findings of the thesis are contained in the third section which deals with the assessment of body opposition by electrical means. There are two components to this part of the study. The first involved the testing of a commercially available bioelectric impedance analyser (BIA) which measures impedance to a flow of current through the body. Studies on the reproducibility and reliability of measurements were performed. Results showed the importance of correct electrode placement and revealed that subjects can consume a light meal and a drink before being measured with the BIA without adversely affecting impedance readings. Results suggested, however, that subjects empty their bladders before measurements are made. Strong correlations were found between height 2/ resistance and measurements of total body water (r = 0.839) and fat-free weight derived from densitometry (r = 0.821), Moderate correlations (r = 0.6 to 0.7) were also found when height /resistance was related to fat-free weight derived from anthropometric measurements. The second and major consonant of the third section deals with the development of a method based on the absorption of energy from a weak electromagnetic field established in a capacitor or chamber large enough to accommodate an adult human subject. The method involves measurement of the effect of the body on the electromagnetic field, and is based on differential absorption of energy by body fat and fat-free tissues. Regression equations were developed for predicting the weight of fat and fat-free tissue in the body from measurement of electromagnetic field effects in a test capacitor and in a resonating chamber. The test capacitor comprised a large aluminum cylinder with a copper rod as a central conductor. The following equation was derived for the relationship of fat-free weight (FEW) based on body density, with measurements of change in resonant frequency (ΔfR), height (H) and weight (W) : FFW = -4.39 + 0.690 W + 19.9 H + 37.6 ΔfR In a study of 17 subjects, a value of 0.891 was found for R2, and S.E.E. was 1.63. The resonating chamber consisted of a large enclosed aluminium cylinder with a copper rod as a central conductor. The following equation was derived for the relationship of fat weight (FW) based on the mean of estimates from body density and total body water, with measurements of change in signal attenuation (ΔA), change in resonant frequency (ΔfR), and height (H) and weight (W) : FW = 73.48 + 0.291 (W/√(ΔA) - 49.2 H - 0.53 ΔfR In a study of 27 subjects, a value of 0.956 was found for R2, and S.E.E. was 1.97. In these equations, variables were measured in the following units : FEW, FW and W (kg), ΔfR (MHz) and H (m).

A gel-capture assay for characterizing the sialyl-glycan selectivity of influenza viruses

Sialic acids (SA) usually linked to galactose (Gal) in an α2,6- or α2,3-configuration are considered the main cell receptors for influenza viruses, in particular for their hemagglutinins (HA). The typing of influenza virus HA receptor selectivity is relevant for understanding the transmissibility of avian and swine viruses to the human population. In this study we developed a simple and inexpensive gel-capture assay (GCA) of the influenza virus HA receptor-binding selectivity. Its principle is the binding of soluble influenza virus to pentasaccharide analogs, representatives of receptors of human and avian influenza viruses, immobilized on a gel resin. The human and avian analogs consisted of a sialyllactose-N-tetraose c (LSTc) [Neu5Ac(α2,6)Gal(β1-3)GlcNAc(β1-3)Gal(β1-4)Glc] and a sialyllactose-N-tetraose a (LSTa) [Neu5Ac(α2,3)Gal(β1-3)GlcNAc(β1-3)Gal(β1-4)Glc], respectively. Following equilibration, the unbound virus is washed away and the bound one is assayed via HA by densitometry as a function of the analog concentration. Using GCA, the receptor selectivity of three influenza viruses of different HA subtype was investigated. The results showed that the egg-adapted A/California/07/2009 (H1N1) virus exhibited an avian α2,3-linked LSTa selectivity, however, it retained the ability to bind to the α2,6-linked LSTc human receptor analog. Influenza B virus B/Florida/4/2006 showed α2,6-linked LSTc selectivity and a poor α2,3-linked LSTa avidity. The H3N2 virus A/Wisconsin/15/2009 displayed almost comparable avidity for both receptor analogs with a marginally greater α2,3-linked LSTa avidity. The described assay protocol provides a simple and rapid method for the characterization of influenza virus HA receptor binding selectivity. Keywords: influenza virus; hemagglutinin; receptor; sialyllactose-N-tetraose; gel-capture assay.

Reference ranges for bone densitometers adopted Australia-wide : Geelong Osteoporosis Study

Bone densitometry reports a measure of fracture risk in comparison with young adults (T-scores) and age-matched peers (Z-scores). To date, each manufacturer has provided its own reference range resulting in lack of uniformity. The Australia and New Zealand Bone and Mineral Society and Osteoporosis Australia have recognized the need to standardize the reference range and have recommended that data generated by the Geelong Osteoporosis Study (GOS) be used Australia-wide. The GOS recruited a random, population-based sample of adult women and measured bone mineral density (BMD) at the proximal femur and spine using a Lunar DPX-L. These data were used to establish reference ranges for Lunar machines and, using conversion equations, for Norland and Hologic machines. The new standardized Australian reference ranges for BMD will enable consistent diagnosis of osteoporosis and categorization of fracture risk across different types of densitometers.

Morphometric vertebral fractures of the lower thoracic and lumbar spine, physical function and quality of life in men

The epidemiology and sequelae of morphometric vertebral fracture (MVF) are poorly documented. We found that MVFs of the lower thoracic and lumbar spine were associated with poor quality of life and impaired physical function in men. We recommend that morphometric X-ray absorptiometry be included in routine requests for bone densitometry.

β-Adrenergic blockers reduce the risk of fracture partly by increasing bone mineral density : Geelong Osteoporosis Study

This population-based study documented β-blocker use in 59/569 cases with incident fracture and 112/775 controls. OR for fracture associated with β-blocker use was 0.68 (95%CI, 0.49–0.96). β-Blockers were associated with higher BMD at the total hip (2.5%) and UD forearm (3.6%) after adjusting for age, anthropometry, and thiazide use. β-Blocker use is associated with reduced fracture risk and higher BMD.

Introduction: Animal data suggests that bone formation is under β-adrenergic control and that β-blockers stimulate bone formation and/or inhibit bone resorption.

Materials and Methods: We evaluated the association between β-blocker use, bone mineral density (BMD), and fracture risk in a population-based study in Geelong, a southeastern Australian city with a single teaching hospital and two radiological centers providing complete fracture ascertainment for the region. β-Blocker use was documented for 569 women with radiologically confirmed incident fractures and 775 controls without incident fracture. Medication use and lifestyle factors were documented by questionnaire.

Results: Odds ratio for fracture associated with β-blocker use was 0.68 (95% CI, 0.49–0.96) for any fracture. Adjusting for age, weight, medications, and lifestyle factors had little effect on the odds ratio. β-Blocker use was associated with a higher BMD at the total hip (2.5%, p = 0.03) and ultradistal forearm (3.6%, p = 0.04) after adjustment for age, anthropometry, and thiazide use.

Conclusion: β-Blockers are associated with a reduction in fracture risk and higher BMD.

Determination of lung volume by hydrogen dilution at the time of underwater weighing

A method for measuring the volume of air in the lungs at the time of underwater weighing is described. A low concentration of hydrogen is used as a tracer gas in a closed-circuit rebreathing system. At the end of a normal exhalation the subject is connected to a respiratory bladder containing 2 L of air with a small admixture of hydrogen. After an equilibration period of five breaths the subject submerges completely, together with the bladder, and underwater weight is measured. Lung volume, at the time of weighing, is determined by hydrogen dilution. Using this method, the coefficient of variation for body density in the same individual was 0.23%.

The exclusion of high trauma fractures may underestimate the prevalence of bone fragility fractures in the community : the Geelong Osteoporosis Study

Fractures associated with severe trauma are generally excluded from estimates of the prevalence of osteoporotic fractures in the community. Because the degree of trauma is difficult to quantitate, low bone mass may contribute to fractures following severe trauma. We ascertained all fractures in a defined population and compared the bone mineral density (BMD) of women who sustained fractures in either 'low' or 'high' trauma events with the BMD of a random sample of women from the same population. BMD was measured by dual-energy X-ray absorptiometry and expressed as a standardized deviation (Z score) adjusted for age. The BMD Z scores (mean ± SEM) were reduced in both the low and high trauma groups, respectively: spine-posterior-anterior (- 0.50 ± 0.05 and -0.21 ± 0.08), spine-lateral (-0.28 ± 0.06 and -0.19 ± 0.10), femoral neck (-0.42 ± 0.04 and -0.26 ± 0.09), Ward's triangle (- 0.44 ± 0.04 and -0.28 ± 0.08), trochanter (-0.44 ± 0.05 and -0.32 ± 0.08), total body (-0.46 ± 0.06 and -0.32 ± 0.08), ultradistal radius (- 0.47 ± 0.05 and -0.42 ± 0.07), and midradius (-0.52 ± 0.06 and -0.33 ± 0.09). Except at the PA spine, the deficits were no smaller in the high trauma group. Compared with the population, the age-adjusted odds ratio for osteoporosis (t-score < -2.5) at one or more scanning sites was 3.1 (95% confidence interval 1.9, 5.0) in the high trauma group and 2.7 (1.9, 3.8) in the low trauma group. The data suggest that the exclusion of high trauma fractures in women over 50 years of age may result in underestimation of the contribution of osteoporosis to fractures in the community. Bone density measurement of women over 50 years of age who sustain fractures may be warranted irrespective of the classification of trauma.

Examining the impact of reimbursement on referral to bone density testing for older adults: 8 years of data from the Barwon Statistical Division, Australia

Summary
In 2007, Medicare Australia revised reimbursement guidelines for dual energy X-ray absorptiometry (DXA) for Australians aged ≥70 years; we examined whether these changes increased DXA referrals in older adults. Proportions of DXA referrals doubled for men and tripled for women from 2003 to 2010; however, rates of utilization remained low.

Introduction
On April 1, 2007 Medicare Australia revised reimbursement guidelines for DXA for Australians aged ≥70 year; changes that were intended to increase the proportion of older adults being tested. We examined whether changes to reimbursement increased DXA referrals in older adults, and whether any sex differences in referrals were observed in the Barwon Statistical Division.

Methods
Proportions of DXA referrals 2003–2010 based on the population at risk ascertained from Australian Census data and annual referral rates and rate ratios stratified by sex, year of DXA, and 5-year age groups. Persons aged ≥70 years referred to the major public health service provider for DXA clinical purposes (n = 6,096; 21 % men).

Results
DXA referrals. Proportions of DXA referrals for men doubled from 0.8 % (2003) to 1.8 % (2010) and tripled from 2.0 to 6.3 % for women (all p < 0.001). For 2003–2006, referral ratios of men/women ranged between 1:1.9 and 1:3.0 and for 2007–2010 were 1:2.3 to 1:3.4. Referral ratios <2007:≥2007 were 1:1.7 for men aged 70–79 years (p < 0.001), 1:1.2 for men aged 80–84 years (p = 0.06), and 1:1.3 for men 85+ years (p = 0.16). For women, the ratios <2007:≥2007 were 1:2.1 (70–79 years), 1.1.5 (80–84 years), and 1:1.4 (85+ years) (all p < 0.001).

Conclusions
DXA referral ratios were 1:1.6 (men) and 1:1.8 (women) for 2007–2010 vs. 2003–2006; proportions of referrals doubled for men and tripled for women from 2003 to 2010. Overall, rates of DXA utilization remained low. Policy changes may have had minimal influence on referral; thus, ongoing evaluation over time is warranted.

Fracture prediction from repeat BMD measurements in clinical practice

Summary: We investigated whether repeat BMD measurements in clinical populations are useful for fracture risk assessment. We report that repeat BMD measurements are a robust predictor of fracture in clinical populations; this is not affected by preceding BMD change or recent osteoporosis therapy. Introduction: In clinical practice, many patients selectively undergo repeat bone mineral density (BMD) measurements. We investigated whether repeat BMD measurements in clinical populations are useful for fracture risk assessment and whether this is affected by preceding change in BMD or recent osteoporosis therapy. Methods: We identified women and men aged ≥50 years who had a BMD measurement during 1990–2009 from a large clinical BMD database for Manitoba, Canada (n = 50,215). Patient subgroups aged ≥50 years at baseline with repeat BMD measures were identified. Data were linked to an administrative data repository, from which osteoporosis therapy, fracture outcomes, and covariates were extracted. Using Cox proportional hazards models, we assessed covariate-adjusted risk for major osteoporotic fracture (MOF) and hip fracture according to BMD (total hip, lumbar spine, femoral neck) at different time points. Results: Prevalence of osteoporosis therapy increased from 18 % at baseline to 55 % by the fourth measurement. Total hip BMD was predictive of MOF at each time point. In the patient subgroup with two repeat BMD measurements (n = 13,481), MOF prediction with the first and second measurements was similar: adjusted-hazard ratio (HR) per SD 1.45 (95 % CI 1.34–1.56) vs. 1.64 (95 % CI 1.48–1.81), respectively. No differences were seen when the second measurement results were stratified by preceding change in BMD or osteoporosis therapy (both p-interactions >0.2). Similar results were seen for hip fracture prediction and when spine and femoral neck BMD were analyzed. Conclusion: Repeat BMD measurements are a robust predictor of fracture in clinical populations; this is not affected by preceding BMD change or recent osteoporosis therapy.