Stephanie M. Kaiser

2010 clinical practice guidelines for the diagnosis and management of osteoporosis in Canada: summary

See related commentary by Kanis, page [1829][1] Since the publication of the Osteoporosis Canada guidelines in 2002, there has been a paradigm shift in the prevention and treatment of osteoporosis and fractures. [1][2],[2][3] The focus now is on preventing fragility fractures and their negative

Bone turnover markers in the management of postmenopausal osteoporosis

Osteoporosis is the most common cause of fragility fractures. Bone remodelling is essential for repairing damaged areas within bone to preserve bone strength and for assisting in mineral homeostases. In young adults, bone remodelling is usually balanced with approximately as much bone replaced as is removed during each remodelling cycle. However, when remodelling becomes accelerated in combination with an imbalance that favours bone resorption over formation, such as during menopause, precipitous losses in bone mass occur. Bone turnover markers (BTMs) measure the rate of bone remodelling allowing for a dynamic assessment of skeletal status and hold promise in identifying those at highest risk of rapid bone loss and subsequent fracture. Further, the use of BTMs to monitor individuals administered osteoporosis therapy is attractive as monitoring anti-fracture efficacy with bone mineral density has significant limitations. This review details remodelling biology, pre-analytical and analytical sources of variability for BTMs, describes the most commonly used resorption and formation markers, and offers some guidelines for their use and interpretation in the laboratory and the clinic.

The impact of incident fractures on health-related quality of life: 5 years of data from the Canadian Multicentre Osteoporosis Study

Background Vertebral fractures in patients with cystic fibrosis (CF) may contribute to an accelerated decline in lung function and can be a contraindication to lung transplantation. In this study, we examined longitudinal change in bone mineral density (BMD) and the prevalence of vertebral fractures in adult CF patients, without lung-transplant, attending a Canadian specialty clinic. Methods Retrospective chart review of all patients attending an Adult Cystic Fibrosis Clinic at Hamilton Health Sciences in Hamilton, Canada. Forty-nine of 56 adults met inclusion criteria. Chest radiographs were graded by consensus approach using Genant’s semi-quantitative method to identify and grade fractured vertebrae. Dual x-ray absorptiometry (DXA) scans were also reviewed. Results The mean age of the cohort was 25.2 years (SD 9.4), 43% were male. The mean body mass index (BMI) was 19.8 (2.8) for males and 21.7 (5.1) for females. At baseline, the rate of at least one vertebral fracture was 16.3%; rising to 21.3% (prevalent and incident) after a 3-year follow-up. The mean BMD T-or Z-scores at baseline were −0.80 (SD 1.1) at the lumbar spine, −0.57 (SD 0.97) at the proximal femur, and −0.71 (SD 1.1) at the whole body. Over approximately 4-years, the mean percent change in BMD was −1.93% at the proximal femur and −0.73% at the lumbar spine. Conclusion Approximately one in five CF patients demonstrated at least one or more vertebral fractures. Moderate declines in BMD were observed. Given the high rate of vertebral fractures noted in this cohort of adult CF patients, and the negative impact they have on compromised lung functioning, regular screening for vertebral fractures should be considered on routine chest radiographs.

Construction and validation of a simplified fracture risk assessment tool for Canadian women and men: results from the CaMos and Manitoba cohorts

SummaryA procedure for creating a simplified version of fracture risk assessment tool (FRAX®) is described. Calibration, fracture prediction, and concordance were compared with the full FRAX tool using two large, complementary Canadian datasets.IntroductionThe Canadian Association of Radiologists and Osteoporosis Canada (CAROC) system for fracture risk assessment is based upon sex, age, bone mineral density (BMD), prior fragility fracture, and glucocorticoid use. CAROC does not require computer or web access, and categorizes 10-year major osteoporotic fracture risk as low (<10%), moderate (10–20%), or high (>20%).MethodsBasal CAROC fracture risk tables (by age, sex, and femoral neck BMD) were constructed from Canadian FRAX probabilities for major osteoporotic fractures (adjusted for prevalent clinical risk factors). We assessed categorization and fracture prediction with the updated CAROC system in the CaMos and Manitoba BMD cohorts.ResultsThe new CAROC system demonstrated high concordance with the Canadian FRAX tool for risk category in both the CaMos and Manitoba cohorts (89% and 88%). Ten-year fracture outcomes in CaMos and Manitoba BMD cohorts showed good discrimination and calibration for both CAROC (6.1–6.5% in low-risk, 13.5–14.6% in moderate-risk, and 22.3–29.1% in high-risk individuals) and FRAX (6.1–6.6% in low-risk, 14.4–16.1% in moderate-risk, and 23.4–31.0% in high-risk individuals). Reclassification from the CAROC risk category to a different risk category under FRAX occurred in <5% for low-risk, 20–24% for moderate-risk, and 27–30% for high-risk individuals. Reclassified individuals had 10-year fracture outcomes that were still within or close to the original nominal-risk range..ConclusionThe new CAROC system is well calibrated to the Canadian population and shows a high degree of concordance with the Canadian FRAX tool. The CAROC system provides s a simple alternative when it is not feasible to use the full Canadian FRAX tool.

The Relationship Between Proton Pump Inhibitor Use and Longitudinal Change in Bone Mineral Density: A Population-Based From the Canadian Multicentre Osteoporosis Study (CaMos)

OBJECTIVES:Proton pump inhibitor (PPI) use has been identified as a risk factor for hip and vertebral fractures. Evidence supporting a relationship between PPI use and osteoporosis remains scant. Demonstrating that PPIs are associated with accelerated bone mineral density (BMD) loss would provide supportive evidence for a mechanism through which PPIs could increase fracture risk.METHODS:We used the Canadian Multicentre Osteoporosis Study data set, which enrolled a population-based sample of Canadians who underwent BMD testing of the femoral neck, total hip, and lumbar spine (L1–L4) at baseline, and then again at 5 and 10 years. Participants also reported drug use and exposure to risk factors for osteoporosis and fracture. Multivariate linear regression was used to determine the independent association of PPI exposure and baseline BMD, and on change in BMD at 5 and 10 years.RESULTS:In all, 8,340 subjects were included in the baseline analysis, with 4,512 (55%) undergoing year 10 BMD testing. After adjusting for potential confounders, PPI use was associated with significantly lower baseline BMD at the femoral neck and total hip. PPI use was not associated with a significant acceleration in covariate-adjusted BMD loss at any measurement site after 5 and 10 years of follow-up.CONCLUSIONS:PPI users had lower BMD at baseline than PPI non-users, but PPI use over 10 years did not appear to be associated with accelerated BMD loss. The reasons for discordant findings between PPI use at baseline and during follow-up require further study.

Population-based Canadian hip fracture rates with international comparisons

SummaryWe identified hospitalizations throughout Canada during 2000–2005 in which the most responsible diagnosis was a proximal femoral fracture. Use of the US fracture risk assessment tool (FRAX) would be inappropriate for Canada as it would overestimate fracture risk in Canadian women and older men.IntroductionIt is recommended that the WHO fracture risk assessment tool should be calibrated to the target population.MethodsWe identified hospitalizations for women and men throughout Canada during the study period 2000–2005 in which the most responsible diagnosis was a proximal femoral fracture (147,982 hip fractures). Age-standardized hip fracture rates were compared between Canadian provinces, and national rates were compared with those reported for the USA and Germany.ResultsThere were relatively small differences in hip fracture rates between provinces, and most did not differ appreciably from the Canadian average. Hip fracture rates for women in Canada in 2001 were substantially lower than in the USA (population-weighted rate ratio 0.70) and were also lower than in Germany for 2004 (population-weighted rate ratio 0.74).ConclusionsOverall hip fracture rates for Canadian women were found to be substantially lower than those for the USA and Germany. This study underscores the importance of assessing country-specific fracture patterns prior to adopting an existing FRAX tool.

Osteoporosis Canada 2010 Guidelines for the Assessment of Fracture Risk

Osteoporosis Canadas 2010 Clinical Practice Guidelines for the Diagnosis and Management of Osteoporosis in Canada focus on the clinical impact of fragility fractures, and on the assessment and management of women and men at high risk for fragility fracture. These guidelines now integrate a 10-year absolute fracture risk prediction into an overall management approach by using validated risk assessment tools. There currently is a large gap between optimal practices and those that are now being provided to Canadians with osteoporosis. These guidelines are part of a concerted effort to close this gap. Key changes from the 2002 guidelines of interest and relevance to radiologists are highlighted in this report.

Associations of Protein Intake and Protein Source with Bone Mineral Density and Fracture Risk: A Population-Based Cohort Study.

High dietary protein has been hypothesized to cause lower bone mineral density (BMD) and greater fracture risk. Previous results are conflicting and few studies have assessed potential differences related to differing protein sources.Participants/MeasuresProtein intake was assessed as percent of total energy intake (TEI) at Year 2 (1997-99) using a food frequency questionnaire (N=6510). Participants were contacted annually to ascertain incident fracture. Total hip and lumbar spine BMD was measured at baseline and Year 5. Analyses were stratified by group (men 25-49 y, men 50+ y, premenopausal women 25-49 y, and postmenopausal women 50+ y) and adjusted for major confounders. Fracture analyses were limited to those 50+ y.ResultsIntakes of dairy protein (with adjustment for BMI) were positively associated with total hip BMD among men and women aged 50+ y, and in men aged 25-49. Among adults aged 50+ y, those with protein intakes of <12% TEI (women) and <11% TEI (men) had increased fracture risk compared to those with intakes of 15% TEI. Fracture risk did not significantly change as intake increased above 15% TEI, and was not significantly associated with protein source. Conclusions: In contrast to hypothesized risk of high protein, we found that for adults 50+ y, low protein intake (below 15% TEI) may lead to increased fracture risk. Source of protein was a determinant of BMD, but not fracture risk.

Anemia is an independent risk for mortality after acute myocardial infarction in patients with and without diabetes

IntroductionAnemia and diabetes are risk factors for short-term mortality following an acute myocardial infarction(AMI). Anemia is more prevalent in patients with diabetes. We performed a retrospective study to assess the impact of the combination of diabetes and anemia on post-myocardial infarction outcomes.MethodsData relating to all consecutive patients hospitalized with AMI was obtained from a population-based disease-specific registry. Patients were divided into 4 groups: diabetes and anemia (group A, n = 716), diabetes and no anemia (group B, n = 1894), no diabetes and anemia (group C, n = 869), and no diabetes and no anemia (group D, n = 3987). Mortality at 30 days and 31 days to 36 months were the main outcome measures.Results30-day mortality was 32.3% in group A, 16.1% in group B, 21.5% in group C, 6.6% in group D (all p < 0.001). 31-day to 36-month mortality was 47.6% in group A, 20.8% in group B, 34.3% in group C, and 10.4% in group D (all p < 0.001). Diabetes and anemia remained independent risk factors for mortality with odds ratios of 1.61 (1.41–1.85, p < 0.001) and 1.59 (1.38–1.85, p < 0.001) respectively at 36 months. Cardiovascular death from 31-days to 36-months was 43.7% of deaths in group A, 54.1% in group B, 47.0% in group C, 50.8% group D (A vs B, p < 0.05).InterpretationPatients with both diabetes and anemia have a significantly higher mortality than those with either diabetes or anemia alone. Cardiovascular death remained the most likely cause of mortality in all groups.

Ten-year incident osteoporosis-related fractures in the population-based Canadian Multicentre Osteoporosis Study — Comparing site and age-specific risks in women and men

BACKGROUND Population-based incident fracture data aid fracture prevention and therapy decisions. Our purpose was to describe 10-year site-specific cumulative fracture incidence by sex, age at baseline, and degree of trauma with/without consideration of competing mortality in the Canadian Multicentre Osteoporosis Study adult cohort. METHODS Incident fractures and mortality were identified by annual postal questionnaires to the participant or proxy respondent. Date, site and circumstance of fracture were gathered from structured interviews and medical records. Fracture analyses were stratified by sex and age at baseline and used both Kaplan-Meier and competing mortality methods. RESULTS The baseline (1995-97) cohort included 6314 women and 2789 men (aged 25-84 years; mean±SD 62±12 and 59±14, respectively), with 4322 (68%) women and 1732 (62%) men followed to year-10. At least one incident fracture occurred for 930 women (14%) and 247 men (9%). Competing mortality exceeded fracture risk for men aged 65+years at baseline. Age was a strong predictor of incident fractures especially fragility fractures, with higher age gradients for women vs. men. Major osteoporotic fracture (MOF) (hip, clinical spine, forearm, humerus) accounted for 41-74% of fracture risk by sex/age strata; in women all MOF sites showed age-related increases but in men only hip was clearly age-related. The most common fractures were the forearm for women and the ribs for men. Hip fracture incidence was the highest for the 75-84 year baseline age-group with no significant difference between women 7.0% (95% CI 5.3, 8.9) and men 7.0% (95% CI 4.4, 10.3). INTERPRETATION There are sex differences in the predominant sites and age-gradients of fracture. In older men, competing mortality exceeds cumulative fracture risk.