Stuart Jackson

The influence of osteoporotic fractures on health-related quality of life in community-dwelling men and women across Canada.

Abstract: Health-related quality of life (HRQL) was examined in relation to prevalent fractures in 4816 community-dwelling Canadian men and women 50 years and older participating in the Canadian Multicentre Osteoporosis Study (CaMos). Fractures were of three categories: clinically recognized main fractures, subclinical vertebral fractures and fractures at other sites. Main fractures were divided and analyzed at the hip, spine, wrist/forearm, pelvis and rib sites. Baseline assessments of anthropometric data, medical history, therapeutic drug use, spinal radiographs and prevalent fractures were obtained from all participants. The SF-36 instrument was used as a tool to measure HRQL. A total of 652 (13.5%) main fractures were reported. Results indicated that hip, spine, wrist/forearm, pelvis and rib fractures had occurred in 78 (1.6%), 40 (0.8%), 390 (8.1%), 19 (0.4%) and 125 (2.6%) individuals, respectively (subjects may have had more than one main fracture). Subjects who had experienced a main prevalent fracture had lower HRQL scores compared with non-fractured participants. The largest differences were observed in the physical functioning (−4.0; 95% confidence intervals (CI): −6.0, −2.0) and role-physical functioning domains (−5.8; 95% CI: −9.5, −2.2). In women, the physical functioning domain was most influenced by hip (−14.9%; 95% CI: −20.9, −9.0) and pelvis (−18.1; 95% CI: −27.6, −8.6) fractures. In men, the role-physical domain was most affected by hip fractures (−35.7; 95% CI: −60.4, −11.1). Subjects who experienced subclinical vertebral fractures had lower HRQL scores than those without prevalent fractures. In conclusion, HRQL was lower in the physical functioning domain in women and the role-physical domain in men who sustained main fractures at the hip. Subclinical vertebral fractures exerted a moderate effect on HRQL.

Vertebral fracture definition from population-based data: preliminary results from the Canadian Multicenter Osteoporosis Study (CaMos).

Abstract: The Canadian Multicenter Osteoporosis Study is a large population-based prospective study of osteoporosis in the Canadian population. The study involves 9424 subjects, both male and female, from nine centers and seven regions of Canada. Each subject completed an extensive interview to obtain medical, demographic and lifestyle information, and was examined by dual-energy X-ray absorptiometry of the spine and hip, ultrasound of the heel and, for subjects over 50 years of age, lateral spine radiographs. Spinal morphometry of the initial radiographs was performed to determine the prevalence of vertebral deformity. A method is utilized to extract reference norms for vertebral shape from a subset of the population data, which is then used to categorize any deformity within the whole data set. Using 3 standard deviations (SD) as a limit of normality, the male prevalence of 21.5% was similar to the female prevalence of 23.5%. Using 4 SD this reduced to 7.3% and 9.3% respectively. The younger men (50–59 years) showed a higher prevalence of deformity than the women and a lower increase of prevalence with age. In the older age group (over 80 years) the female prevalence of 45% compared with 36% for the men using 3 SD (grade 1) to define the limit of normality. The female group presented with more severe deformities on average than the male group. This continuing study will provide longitudinal information regarding the development of osteoporosis and associated risk factors which will eventually be of use to develop public health policies.

Peak Bone Mass From Longitudinal Data: Implications for the Prevalence, Pathophysiology, and Diagnosis of Osteoporosis

We estimated peak bone mass (PBM) in 615 women and 527 men aged 16 to 40 years using longitudinal data from the Canadian Multicentre Osteoporosis Study (CaMos). Individual rates of change were averaged to find the mean rate of change for each baseline age. The age range for PBM was defined as the period during which bone mineral density (BMD) was stable. PBM was estimated via hierarchical models, weighted according to 2006 Canadian Census data. Lumbar spine PBM (1.046 ± 0.123 g/cm2) occurred at ages 33 to 40 years in women and at 19 to 33 years in men (1.066 ± 0.129 g/cm2). Total hip PBM (0.981 ± 0.122 g/cm2) occurred at ages 16 to 19 years in women and 19 to 21 years in men (1.093 ± 0.169 g/cm2). Analysis of Canadian geographic variation revealed that the levels of PBM and of mean BMD in those over age 65 sometimes were discordant, suggesting that PBM and subsequent rates of bone loss may be subject to different genetic and/or environmental influences. Based on our longitudinally estimated PBM values, the estimated Canadian prevalences of osteoporosis (T‐score < –2.5) were 12.0% (L1–L4) and 9.1% (total hip) in women aged 50 years and older and 2.9% (L1–L4) and 0.9% (total hip) in men aged 50 years and older. These were higher than prevalences using cross‐sectional PBM data. In summary, we found that the age at which PBM is achieved varies by sex and skeletal site, and different reference values for PBM lead to different estimates of the prevalence of osteoporosis. Furthermore, lack of concordance of PBM and BMD over age 65 suggests different determinants of PBM and subsequent bone loss.

Associations among disease conditions, bone mineral density, and prevalent vertebral deformities in men and women 50 years of age and older: Cross-sectional results from the canadian Multicentre Osteoporosis Study

This cross‐sectional cohort study of 5566 women and 2187 men 50 years of age and older in the population‐based Canadian Multicentre Osteoporosis Study was conducted to determine whether reported past diseases are associated with bone mineral density or prevalent vertebral deformities. We examined 12 self‐reported disease conditions including diabetes mellitus (types 1 or 2), nephrolithiasis, hypertension, heart attack, rheumatoid arthritis, thyroid disease, breast cancer, inflammatory bowel disease, neuromuscular disease, Pagets disease, and chronic obstructive pulmonary disease. Multivariate linear and logistic regression analyses were performed to determine whether there were associations among these disease conditions and bone mineral density of the lumbar spine, femoral neck, and trochanter, as well as prevalent vertebral deformities. Bone mineral density measurements were higher in women and men with type 2 diabetes compared with those without after appropriate adjustments. The differences were most notable at the lumbar spine (+0.053 g/cm2), femoral neck (+0.028 g/cm2), and trochanter (+0.025 g/cm2) in women, and at the femoral neck (+0.025 g/cm2) in men. Hypertension was also associated with higher bone mineral density measurements for both women and men. The differences were most pronounced at the lumbar spine (+0.022 g/cm2) and femoral neck (+0.007 g/cm2) in women and at the lumbar spine (+0.028 g/cm2) in men. Although results were statistically inconclusive, men reporting versus not reporting past nephrolithiasis appeared to have clinically relevant lower bone mineral density values. Bone mineral density differences were −0.022, −0.015, and −0.016 g/cm2 at the lumbar spine, femoral neck, and trochanter, respectively. Disease conditions were not strongly associated with vertebral deformities. In summary, these cross‐sectional population‐based data show that type 2 diabetes and hypertension are associated with higher bone mineral density in women and men, and nephrolithiasis may be associated with lower bone mineral density in men. The importance of these associations for osteoporosis case finding and management require further and prospective studies.

Comparison of Fracture Risk Prediction among Individuals with Reduced and Normal Kidney Function

BACKGROUND AND OBJECTIVES The Fracture Risk Assessment Tool (FRAX) is widely used to predict the 10-year probability of fracture; however, the clinical utility of FRAX in CKD is unknown. This study assessed the predictive ability of FRAX in individuals with reduced kidney function compared with individuals with normal kidney function. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS The discrimination and calibration (defined as the agreement between observed and predicted values) of FRAX were examined using data from the Canadian Multicentre Osteoporosis Study (CaMos). This study included individuals aged ≥40 years with an eGFR value at year 10 of CaMos (defined as baseline). The cohort was stratified by kidney function at baseline (eGFR<60 ml/min per 1.73 m(2) [72.2% stage 3a, 23.8% stage 3b, and 4.0% stage 4/5] versus ≥60 ml/min per 1.73 m(2)) and followed individuals for a mean of 4.8 years for an incident major osteoporotic fracture (clinical spine, hip, forearm/wrist, or humerus). RESULTS There were 320 individuals with an eGFR<60 ml/min per 1.73 m(2) and 1787 with an eGFR≥60 ml/min per 1.73 m(2). The mean age was 67±10 years and 71% were women. The 5-year observed major osteoporotic fracture risk was 5.3% (95% confidence interval [95% CI], 3.3% to 8.6%) in individuals with an eGFR<60 ml/min per 1.73 m(2), which was comparable to the FRAX-predicted fracture risk (6.4% with bone mineral density; 8.2% without bone mineral density). A statistically significant difference was not observed in the area under the curve values for FRAX in individuals with an eGFR<60 ml/min per 1.73 m(2) versus ≥60 ml/min per 1.73 m(2) (0.69 [95% CI, 0.54 to 0.83] versus 0.76 [95% CI, 0.70 to 0.82]; P=0.38). CONCLUSIONS This study showed that FRAX was able to predict major osteoporotic fractures in individuals with reduced kidney function; further study is needed before FRAX should be routinely used in individuals with reduced kidney function.

Post-transplant nuclear renal scans correlate with renal injury biomarkers and early allograft outcomes

BACKGROUND Clinical- and histopathology-based scores are limited predictors of allograft outcome. In addition, more objective markers of early transplant function are needed to identify and validate biomarkers and predictive scores. We evaluated existing scores and transcriptome biomarkers of kidney injury as predictors of early transplant function measured by renal scan. METHODS Clinical, histopathologic and transcriptome data were collected in 143 consecutive kidney transplant recipients. A post-operative renal scan was performed within 48 h. Prediction scores for early outcomes were calculated. RESULTS Patients were stratified into three groups by renal scan: normal, mild-to-moderate or severe dysfunction. Kidneys with severe dysfunction were more often from deceased donors (P < 0.001), had greater HLA antigen mismatches (P < 0.001), were transplanted into older recipients (P = 0.040), had lower urine output during the first 8 h (P < 0.001), higher Day 7 serum creatinine (P < 0.001) and higher incidence of delayed graft function (P < 0.001). Clinical- and pathology-based scores did not discriminate between scan groups. In contrast, the overall transcriptome (P < 0.001) and transcripts of preselected acute kidney injury (AKI) genes were significantly different between the groups, with kidney injury molecule 1 (P = 0.001) and neutrophil gelatinase-associated lipocalin (P = 0.002) being most highly expressed and genes associated with glutathione metabolism (GSTA1, 3 and 4) most down-regulated in kidneys with subsequent severe dysfunction. CONCLUSIONS Renal scans reflect early transplant function and allow for a more objective assessment of scores predicting early outcome and for identification of biomarkers. The study shows that transcript levels of AKI genes correlate better with renal scans than clinical- or histopathology-based scores.

Planar imaging quantification using 3D attenuation correction data and Monte Carlo simulated buildup factors

A new method to correct for attenuation and the buildup of scatter in planar imaging quantification is presented. The method is based on the combined use of 3D density information provided by computed tomography to correct for attenuation and the application of Monte Carlo simulated buildup factors to correct for buildup in the projection pixels. CT and nuclear medicine images were obtained for a purpose-built nonhomogeneous phantom that models the human anatomy in the thoracic and abdominal regions. The CT transverse slices of the phantom were converted to a set of consecutive density maps. An algorithm was developed that projects the 3D information contained in the set of density maps to create opposing pairs of accurate 2D correction maps that were subsequently applied to planar images acquired from a dual-head gamma camera. A comparison of results obtained by the new method and the geometric mean approach based on published techniques is presented for some of the source arrangements used. Excellent results were obtained for various source-phantom configurations used to evaluate the method. Activity quantification of a line source at most locations in the nonhomogeneous phantom produced errors of less than 2%. Additionally, knowledge of the actual source depth is not required for accurate activity quantification. Quantification of volume sources placed in foam, Perspex and aluminium produced errors of less than 7% for the abdominal and thoracic configurations of the phantom.

Comparative Analysis of the Radiology of Osteoporotic Vertebral Fractures in Women and Men: Cross-Sectional and Longitudinal Observations from the Canadian Multicentre Osteoporosis Study (CaMos)†

We compared two methods for osteoporotic vertebral fracture (VF) assessment on lateral spine radiographs, the Genant semiquantitative (GSQ) technique and a modified algorithm‐based qualitative (mABQ) approach. We evaluated 4465 women and 1771 men aged ≥50 years from the Canadian Multicentre Osteoporosis Study with available X‐ray images at baseline. Observer agreement was lowest for grade 1 VFs determined by GSQ. Among physician readers, agreement was greater for VFs diagnosed by mABQ (ranging from 0.62 [95% confidence interval (CI) 0.00–1.00] to 0.88 [0.76–1.00]) than by GSQ (ranging from 0.38 [0.17–0.60] to 0.69 [0.54–0.85]). GSQ VF prevalence (16.4% [95% CI 15.4–17.4]) and incidence (10.2/1000 person‐years [9.2; 11.2]) were higher than with the mABQ method (prevalence 6.7% [6.1–7.4] and incidence 6.3/1000 person‐years [5.5–7.1]). Women had more prevalent and incident VFs relative to men as defined by mABQ but not as defined by GSQ. Prevalent GSQ VFs were predominantly found in the mid‐thoracic spine, whereas prevalent mABQ and incident VFs by both methods co‐localized to the junction of the thoracic and lumbar spine. Prevalent mABQ VFs compared with GSQ VFs were more highly associated with reduced adjusted L1 to L4 bone mineral density (BMD) (–0.065 g/cm2 [–0.087 to –0.042]), femoral neck BMD (–0.051 g/cm2 [–0.065 to –0.036]), and total hip BMD (–0.059 g/cm2 [–0.076 to –0.041]). Prevalent mABQ VFs compared with prevalent GSQ were also more highly associated with incident VF by GSQ (odds ratio [OR] = 3.3 [2.2–5.0]), incident VF by mABQ (9.0 [5.3–15.3]), and incident non‐vertebral major osteoporotic fractures (1.9 [1.2–3.0]). Grade 1 mABQ VFs, but not grade 1 GSQ VFs, were associated with incident non‐vertebral major osteoporotic fractures (OR = 3.0 [1.4–6.5]). We conclude that defining VF by mABQ is preferred to the use of GSQ for clinical assessments.

A neural network approach to risk factor analysis in osteoporosis

MINERAL DENSITY OF THE TIBIA AND HIP M. Bouxsein, B. Colin, Beth Israel Hospital and Harvard Medical School, Orthopedic Biomedmnics Laboratory, Boston, MA The measurement of ultrasound velocity (SOS) in the cortical bone of the tibia is currently being investigated as a potential diagnostic tool for asteoporosis. This technique is of interest as it may reveal information about skeletal status without the use of ionizing radiation. However, it is not known whell~er massunng ultrasound transmission along the cortical bone at the mid-tibia will here the ability to predict fracture risk at other sites. The objective of this study was to assess the relationships among tibial SOS, tibial bone mineral density (BMD), and femoral BMD in human cadaverio specimens. In addition we daterminad the coefficient of variation (CV, %) end standardized CV (sCV, Miller el EJ, Ostcop Int, 3:31-35,1993) for tri~icate tibial SOS measurements. We obtained 20 in~ct legs from the local anatomic gifts program. The donom included 11 women and 9 men with 8 mean age of 82 years (range 62-98 yrs). The specimens were obtained fresh, stored frozen, End thawed before testing. We assessed tibtal SOS (m/s) using the Mydad SoundS(an 2000 system. For each specimen, scans were performed three limes with rspositioning. BMD (g/cm 2) of the mid-tibia End proximal femur were messed using DXA. Tibial BMD was very strongly correlated to femoral net;k, trechanteric, and total femoral BMD (r-0.81 0.85, p<0.01, Figure). Tibial SOS was strongly correlated with tibial BMD (r-0.72, p<0.01, Figure) and moderately correlatedwith femoral BMD (r=0.46-O.51, IO<0.05). The mean CV for triplicsts measurements of tibiE SOS was 0.62%. The sCV, defined as the mean SD divided by the sample range (taken to be the 5-95% range), was 2.9%. In condasion, we found slreng correlations between SOS and mid-tibial BMD, and between mid-tibial BMD and femoral BMD. Thus, tibial ultrasound measurements may be useful for assessing bone status to predict future hip fracture dsk. Tibial SOS explained only about 50% of the vEdation in tidal BMD. This may be because ultrasound reflects aspects of bone status that ~e, in part, independent of BMD, but that may be related to fracture risk.